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Management of schizophrenia usually involved many aspects including psychological, pharmacological, social, educational, and employment-related interventions directed to recovery, reducing the impact of the disease on quality of life, social functioning, and longevity.^[1]

Hospitalization

Hospitalization may occur with severe episodes of schizophrenia. This can be voluntary or (if mental health legislation allows it) involuntary (called civil or involuntary commitment). Long-term inpatient stays are now less common due to deinstitutionalization, although still occur.^[2] Following (or in lieu of) a hospital admission, support services available can include drop-in centers, visits from members of a community mental health team or Assertive Community Treatment team, supported employment^[3] and patient-led support groups. Efforts to avoid repeated hospitalization include the obtaining of community treatment orders which, following judicial approval, coerce the affected individual to receive psychiatric treatment including long-acting injections of anti-psychotic medication. This legal mechanism has been shown to increase the affected patient's time out of the hospital.^[4]

Medication

The mainstay of psychiatric treatment for schizophrenia is antipsychotic medication.^[5] Medication might improve a number of outcomes found to be important to patients, including positive, acute and psychotic symptoms, and social and vocational functioning.^[6] Medication can reduce the "positive" symptoms of psychosis. Most antipsychotics are thought to take around 7 to 14 days to have their main effect. However, these drugs fail to significantly ameliorate the negative symptoms and cognitive dysfunction.^[7]^[8] There is evidence of clozapine, amisulpride, olanzapine and risperidone being the most effective medications, although a high proportion of studies of risperidone were undertaken by its manufacturer, Janssen-Cilag, and should be interpreted with this in mind.^[9] In those on antipsychotics, continued use decreases the risk of relapse.^[10]^[11] There is little evidence regarding consistent benefits from their use beyond two or three years.^[11]

Treatment of schizophrenia changed dramatically in the mid-1950s with the development and introduction of the first antipsychotic chlorpromazine.^[12] Others such as haloperidol and trifluoperazine soon followed.

It remains unclear whether the newer antipsychotics reduce the chances of developing neuroleptic malignant syndrome, a rare but serious and potentially fatal neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs.^[13]

Most people on antipsychotics get side effects. People on typical antipsychotics tend to have a higher rate of extrapyramidal side effects while some atypicals are associated with considerable weight gain, diabetes, and risk of metabolic syndrome; this is most pronounced with olanzapine, while risperidone and quetiapine are also associated with weight gain.^[9] Risperidone has a similar rate of extrapyramidal symptoms to haloperidol.^[9] The American Psychiatric Association generally recommends that atypicals be used as first line treatment in most patients, but further states that therapy should be individually optimized for each patient.^[14]

The response of symptoms to medication is variable; "Treatment-resistant schizophrenia" is the failure to respond to two or more antipsychotic medications given in therapeutic doses for six weeks or more.^[15] Patients in this category may be prescribed clozapine, a medication that may be more effective at reducing symptoms of schizophrenia, but treatment may come with a higher risk of several potentially lethal side effects including agranulocytosis and myocarditis.^[16]^[17] Clozapine is the only medication proven to be more effective for people who do not respond to other types of antipsychotics.^[18] It also appears to reduce suicide in people with schizophrenia. As clozapine suppresses the development of bone marrow, in turn reducing white blood cells which can lead to infection, blood tests are taken for the first six months on this medication.^[19] The risk of experiencing agranulocytosis due to clozapine treatment is higher in elderly people, children, and adolescents.^[16] The effectiveness in the studies also needs to be interpreted with caution as the studies may have an increased risk of bias.^[16]

Add on agents

Note: Only adjuncts for which at least one double-blind randomized placebo-controlled trial has provided support are listed in this table.

Adjuncts^[20]^[21]	Symptoms against which efficacy is known	Notable adverse effects seen in clinical trials	Highest quality of clinical data available	N	Notes
Adjuncts to clozapine^[22]^[23]
Antipsychotics
Amisulpride	Global	Extrapyramidal side effects (e.g. tremor, dystonia, akathisia, etc.), headache, somnolence, insomnia, elevated serum prolactin, etc.	1 DB-RPCTs	16	Not approved for use in the US or Canada. Approved for use in Australia, Europe and several countries in East Asia. Can prolong the QT interval, some in vivo evidence^[24] suggests it may have anti-diabetogenic effects and hence may improve metabolic parameters in patients on clozapine.
Aripiprazole	Global, esp. negative	Akathisia	1 DB-RPCT	61	Can also improve metabolic side effects of clozapine (including body weight). Six studies so far; only one negative.
Risperidone	Global	Impaired cognitive functioning, prolactin elevation and hyperglycaemia	2 DB-RPCTs, 1 DB-RCT	357 (DB-RPCTs) & 24 (DB-RCT)	11 studies have been conducted, 5 negative. A meta-analysis^[22] found no clinically significant difference between risperidone augmentation and placebo augmentation.
Sulpiride	Global	Increased serum prolactin	1 DB-RPCT	28	Not approved for use in the US, Canada and Australia.
Ziprasidone	Global	QTc interval prolongation	1 DB-RCT	24	Was compared with risperidone in the one DB-RCT.
Antidepressants
Citalopram	Negative symptoms	Well-tolerated	1 DB-RPCT	61	Can prolong the QT interval and since clozapine can prolong the QT interval too it's advisable to avoid their concurrent use in patients with cardiovascular risk factors.
Fluvoxamine	Negative and depressive symptoms	Elevated serum levels of clozapine (via inhibition of P450 cytochromes)	Open-label studies	NA	Improved metabolic parameters
Mirtazapine	Negative, depressive and cognitive symptoms	Weight gain	2 DB-RPCTs (1 negative)	80	5-HT_2A/2C/3 & α₂ adrenoceptor antagonist
Anticonvulsants
Lamotrigine	Negative & depressive symptoms	Stevens-Johnson syndrome, toxic epidermal necrolysis, etc.	4 DB-RPCTs (2 negative)	108	Usually a relatively well-tolerated anticonvulsant, but because of risk of potentially-fatal dermatologic AEs the dose must be slowly titrated up in order to prevent these AEs. A meta-analysis^[22] found that it was ineffective.
Topiramate	Negative symptoms	Cognitive impairment, sedation, asthenia	2 DB-RPCTs (1 negative)	57	Can cause cognitive impairment and hence should probably be avoided in patients with cognitive impairments.
Valproate	Reduced anxiety & depression	Weight gain, hair loss	One open-label study comparing it with lithium	NA	Increases the expression of mGluR2 and GAD67 via histone deacetylase (HDAC) inhibition.
Glutamatergic agents^[25]^[26]
CX-516	Global	Well-tolerated	1 DB-RPCT	18	Statistically significant improvement in total symptoms but no significant improvement in negative and positive symptoms when considered separately.
Memantine	Global	Well-tolerated	1 DB-RPCT	21	Statistically significant improvement in negative and total symptomtology.
Other
Lithium	Global	Weight gain, hypersalivation	1 DB-RPCT, 1 DB-RCT	10 (DB-RPCT), 20 (DB-RCT)	Increased risk of neurological side effects such as neuroleptic malignant syndrome.
E-EPA	Global (especially negative and cognitive symptoms)	Well-tolerated	3 DB-RPCT (1 negative)	131	Ester of the ω-3 fatty acid, eicosapentaenoic acid.
Adjuncts to other antipsychotics
Anti-inflammatory agents^[27]^[28]
Aspirin^[29]	Global (especially positive symptoms)	Well-tolerated	1 DB-RPCT	70	Increased risk of bleeding, but seems relatively well-tolerated.
Celecoxib	Global (especially negative symptoms)	Well-tolerated	3 DB-RPCTs (1 negative)	147	May increased the risk of cardiovascular events (which is particularly worrisome as schizophrenia patients are a higher risk group for cardiovascular events). Case series (N=2) suggests efficacy in augmenting clozapine.
Minocycline^[30]^[31]^[32]^[33]	Global	Well-tolerated	4 DB-RPCTs	164	Increased risk of blood dyscarsias.
ω-3 fatty acids	Global	Well-tolerated	6 DB-RPCTs (1 negative)^[34]	362	May have protective effects against depression.
Pregnenolone^[35]^[36]^[37]^[38]	Global	Well-tolerated	3 DB-RPCTs	100	Levels of this neurosteroid in the body are elevated by clozapine treatment.
Glutamatergics^[25]^[39]
D-alanine^[40]^[41]	Global	Well-tolerated	1 DB-RPCT	31	A D-amino acid with affinity towards the glycine site on the NMDA receptor.
D-serine	Global (especially negative symptoms)	Well-tolerated	4 DB-RPCTs	183	Affinity towards the glycine site on NMDA receptors. D. Souza 2013,^[42] Heresco-Levy 2005,^[43] Lane 2005,^[44] Lane 2010,^[45] Tsai 1999,^[46] Weiser 2012^[47]
Glycine	Global (predominantly positive symptoms)	Well-tolerated	5 DB-RPCTs	219	Endogenous NMDA receptor ligand.
N-acetylcysteine^[48]	Global (especially negative symptoms)	Well-tolerated	3 DB-RPCTs	140	Cystine and glutathione prodrug.^[49]^[50] Cystine increases intracellular glutamate levels via the glutamate-cystine anti porter. Berk 2008,^[51] Berk 2011,^[52] Carmeli 2012,^[53] Lavoie 2008^[54]
Sarcosine	Global (especially negative symptoms)	Well-tolerated	3 DB-RPCTs	112	GlyT1 antagonist (i.e. glycine reuptake inhibitor). Also known as N-methylglycine. Lane 2005,^[44] Lane 2006,^[55] Lane 2008,^[56] Lane 2010,^[45] Tsai 2004^[57]
Cholinergics^[58]^[59]^[60]
Donepezil	Global	Well-tolerated	6 DB-RPCTs (5 negative; or 12 DB-RPCTs if one includes cross-over trials; 8 negative in total)	378, 474 (including cross-over trials)	Possesses antidepressant effects according to one trial.
Galantamine	Cognition	Well-tolerated	5 DB-RPCTs (1 negative)	170	Robust nootropic
Rivastigmine	Cognition	Well-tolerated	3 DB-RPCTs (all 3 negative; 5 trials including cross-over trials; 4 negative)	93, 131 (including cross-over trials)	Seems to be a weaker nootropic
Tropisetron†^[61]^[62]^[63]^[64]	Cognitive and negative symptoms	Well-tolerated	3 DB-RPCTs	120	Agonist at α₇ nAChRs; antagonist at 5-HT₃. Expensive (>$20 AUD/tablet).
Antidepressants^[65]
Escitalopram†^[66]	Negative symptoms	Well-tolerated	1 DB-RPCT	40	May increase risk of QT interval prolongation.
Fluoxetine	Negative symptoms	Well-tolerated	4 DB-RPCTs (3 negative)	136	The safest of antidepressants listed here in overdose.^[67] Risk of QT interval prolongation is lower than with escitalopram (but still exists).
Mianserin^[68]	Negative and cognitive symptoms	Well-tolerated	2 DB-RPCTs	48	Weight gain, sedation, dry mouth, constipation and dizziness. Blood dyscarsias are a possible adverse effect and both the Australian Medicines Handbook and British National Formulary 65 (BNF 65) recommend regular complete blood counts to be taken.^[69]^[70]
Mirtazapine^[68]	Cognition,^[71]^[72] negative and positive symptoms†^[73]	Well-tolerated	≥4 DB-RPCTs (one negative)	127	Relatively safe in overdose. Produces significant sedation and weight gain, however, which could potentially add to the adverse effects of atypical antipsychotics. Can reduce antipsychotic-induced akathisia.^[74]
Ritanserin	Negative symptoms	Well-tolerated	2 DB-RPCTs	73	5-HT_2A/2C antagonist. Not clinically available.
Trazodone	Negative symptoms	Well-tolerated	2 DB-RPCTs	72	5-HT_2A antagonist and SSRI. Has sedative effects and hence might exacerbate some of the side effects of atypical antipsychotics.
Other
Alpha-lipoic acid^[75]^[76]	Weight gain	Well-tolerated	1 DB-RPCT	360	Offset antipsychotic drug-induced weight gain. Increased total antioxidant status. May also increase GSH:GSSG (reduced glutathione:oxidized glutathione) ratio.^[77]
L-Theanine^[78]^[79]^[80]	Positive, activation, and anxiety symptoms	Well-tolerated	2 DB-RPCTs	40	Glutamic acid analog. Primary study noted reduction in positive, activation, and anxiety symptoms. Additional studies have noted improvements in attention.^[81]^[82]^[83]^[84] Research suggests that theanime has a regulatory effect on the nicotine acetylcholine receptor-dopamine reward pathway, and was shown to reduced dopamine production in the midbrain of mice.^[85]
Famotidine†^[86]	Global	Well-tolerated	1 DB-RPCT	30	May reduce the absorption of vitamin B12 from the stomach. Might also increase susceptibility to food poisoning.
Ginkgo biloba	Tardive dyskinesia, positive symptoms	Well-tolerated	4 DB-RPCTs	157	Atmaca 2005,^[87] Doruk 2008,^[88] Zhang 2001,^[89] Zhang 2001,^[90] Zhang 2006,^[91] Zhang 2011,^[92] Zhou 1999^[93]
Ondansetron^[94]	Negative and cognitive symptoms	Well-tolerated	3 DB-RPCTs	151	5-HT₃ antagonist. May prolong the QT interval. Expensive (>$4 AUD/tablet).
SAM-e^[95]	Aggression	Well-tolerated	1 DB-RPCT	18	Study noted improvement of aggressive behavior and quality of life impairment. while in another another study SAM-e has been purported to have a contributory effect on psychosis ^[96]
Vitamin C^[97]^[98]^[99]^[100]	Global	Well-tolerated	1 DB-RPCT	40	Improves BPRS scores.

Acronyms used:
DB-RPCT — Double-blind randomized placebo-controlled trial.
DB-RCT — Double-blind randomized controlled trial.

Note: Global in the context of schizophrenia symptoms here refers to all four symptom clusters.

N refers to the total sample sizes (including placebo groups) of DB-RCTs.

† No secondary sources could be found on the utility of the drug in question, treating the symptom in question (or any symptom in the case of where † has been placed next to the drug's name).

Psychosocial

Psychotherapy is also widely recommended, though not widely used in the treatment of schizophrenia, due to reimbursement problems or lack of training. As a result, treatment is often confined to psychiatric medication.^[101]

Cognitive behavioral therapy (CBT) is used to target specific symptoms and improve related issues such as self-esteem and social functioning. Although the results of early trials were inconclusive^[102] as the therapy advanced from its initial applications in the mid-1990s, meta-analytic reviews suggested CBT to be an effective treatment for the psychotic symptoms of schizophrenia.^[103]^[104] Nonetheless, more recent meta analyses have cast doubt upon the utility of CBT as a treatment for the symptoms of psychosis^[105]^[106]^[107]

Another approach is cognitive remediation therapy, a technique aimed at remediating the neurocognitive deficits sometimes present in schizophrenia. Based on techniques of neuropsychological rehabilitation, early evidence has shown it to be cognitively effective, resulting in the improvement of previous deficits in psychomotor speed, verbal memory, nonverbal memory, and executive function, such improvements being related to measurable changes in brain activation as measured by fMRI.^[108]

Metacognitive training: In view of many empirical findings ^[109] suggesting deficits of metacognition (thinking about one’s thinking, reflecting upon one’s cognitive process) in patients with schizophrenia, metacognitive training (MCT) ^[109]^[110] is increasingly adopted as a complementary treatment approach. MCT aims at sharpening the awareness of patients for a variety of cognitive biases (e.g. jumping to conclusions, attributional biases, over-confidence in errors), which are implicated in the formation and maintenance of schizophrenia positive symptoms (especially delusions),^[111] and to ultimately replace these biases with functional cognitive strategies.

The training consists of 8 modules and can be obtained cost-free from the internet in 15 languages.^[109]^[110] Studies confirm the feasibility ^[112] and lend preliminary support to the efficacy ^[109]^[113]^[114] of the intervention. Recently, an individualized format has been developed which combines the metacognitive approach with methods derived from cognitive-behavioral therapy.^[115]

Family Therapy or Education, which addresses the whole family system of an individual with a diagnosis of schizophrenia, may be beneficial, at least if the duration of intervention is longer-term.^[116]^[117]^[118] A 2010 Cochrane review concluded that many of the clinical trials that studied the effectiveness of family interventions were poorly designed, and may over estimate the effectiveness of the therapy. High-quality randomized controlled trials in this area are required.^[118] Aside from therapy, the impact of schizophrenia on families and the burden on careers has been recognized, with the increasing availability of self-help books on the subject.^[119]^[120] There is also some evidence for benefits from social skills training, although there have also been significant negative findings.^[121]^[122] Some studies have explored the possible benefits of music therapy and other creative therapies.^[123]^[124]^[125]

The Soteria model is alternative to inpatient hospitalization using full non professional care and a minimal medication approach.^[126] Although evidence is limited, a review found the programme equally as effective as treatment with medications but due to the limited evidence did not recommend it as a standard treatment.^[127] Training in the detection of subtle facial expressions has been used to improve facial emotional recognition.^[128]

Diet

An unconventional approach is the use of omega-3 fatty acids, with one study finding some benefits from their use as a dietary supplement.^[129]

A 2003 review of four randomized controlled trials of EPA (an omega-3 fatty acid) vs. placebo as adjunctive treatment for schizophrenia found that two of the trials detected a significant improvement on positive and negative symptoms, and suggested that EPA may be an effective adjunct to antipsychotics.^[130] The most recent meta-analysis (2006) failed however to find a significant effect.^[131] A 2007 review found that studies of omega-3 fatty acids in schizophrenia, despite being mostly of high quality, have produced inconsistent results and small effect sizes of doubtful clinical significance.^[132] Individualized nutrition interventions and supplementation has been proposed as an adjunct to pharmacological therapy in people with schizophrenia, though this approach has not been evaluated in clinical trials to determine the efficacy of such an approach in improving symptoms.^[133]

Other

A 2015 Cochrane review found unclear evidence regarding if transcranial magnetic stimulation (TMS) is useful for schizophrenia.^[134]

Electroconvulsive therapy is not considered a first-line treatment but may be prescribed in cases where other treatments have failed. It is more effective where symptoms of catatonia are present,^[135] and is recommended for use under NICE guidelines in the UK for catatonia if previously effective, though there is no recommendation for use for schizophrenia otherwise.^[136] Psychosurgery has now become a rare procedure and is not a recommended treatment for schizophrenia.^[137]

A study in 2014 conducted by an Australian researcher indicated that the pericarp powder of Garcinia mangostana L. have the ability to reduce oxidative stress as an effective treatment for schizophrenia by increasing glutathione S-transferase levels which enhances mitochondrial activity over a period of 180 days under a sustained intake of 1000 mg/day.^[138]^[139]

There may be some benefit in trying several treatment modalities at the same time, especially those that could be classed as lifestyle interventions.^[140]

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-'''Management of schizophrenia''' usually involved many aspects including psychological, pharmacological, social, educational, and employment-related interventions directed to recovery, reducing the impact of the disease on quality of life, social functioning, and longevity.<ref>{{cite web |url=http://www.nice.org.uk/guidance/CG178/chapter/Key-priorities-for-implementation |title=Psychosis and schizophrenia in adults: treatment and management &#124; Key-priorities-for-implementation &#124; Guidance and guidelines &#124; NICE |format= |work= |accessdate=}}</ref>
+'''Management of schizophrenia''' usually involved many aspects including psychological, pharmacological, social, educational, and employment-related interventions directed to recovery, reducing the impact of the disease on quality of life, social functioning, and longevity.<ref>{{cite web |url=http://www.nice.org.uk/guidance/CG178/chapter/Key-priorities-for-implementation |title=Psychosis and schizophrenia in adults: treatment and management &#124; Key-priorities-for-implementation &#124; Guidance and guidelines &#124; NICE |format= |website= |accessdate=}}</ref>
 ==Hospitalization==
-Hospitalization may occur with severe episodes of schizophrenia. This can be voluntary or (if mental health legislation allows it) involuntary (called civil or [[involuntary commitment]]). Long-term inpatient stays are now less common due to [[deinstitutionalization]], although still occur.<ref name="BeckerKilian2006">{{cite journal |vauthors=Becker T, Kilian R | year = 2006 | title = Psychiatric services for people with severe mental illness across western Europe: what can be generalized from current knowledge about differences in provision, costs and outcomes of mental health care? | url = | journal = [[Acta Psychiatrica Scandinavica]] Supplement | volume = 113 | issue = 429| pages = 9–16 | pmid = 16445476 | doi=10.1111/j.1600-0447.2005.00711.x}}</ref> Following (or in lieu of) a hospital admission, support services available can include drop-in centers, visits from members of a community mental health team or [[Assertive Community Treatment]] team, supported employment<ref>{{cite journal | last1 = McGurk | first1 = SR | last2 = Mueser | first2 = KT | last3 = Feldman | first3 = K | last4 = Wolfe | first4 = R | last5 = Pascaris | first5 = A | title = Cognitive training for supported employment: 2-3 year outcomes of a randomized controlled trial. | journal = The American Journal of Psychiatry | volume = 164 | issue = 3 | pages = 437–41 | year = 2007 | pmid = 17329468 | doi = 10.1176/appi.ajp.164.3.437 }}</ref> and patient-led support groups.
+Hospitalization may occur with severe episodes of schizophrenia. This can be voluntary or (if mental health legislation allows it) involuntary (called civil or [[involuntary commitment]]). Long-term inpatient stays are now less common due to [[deinstitutionalization]], although still occur.<ref name="BeckerKilian2006">{{cite journal |vauthors=Becker T, Kilian R | year = 2006 | title = Psychiatric services for people with severe mental illness across western Europe: what can be generalized from current knowledge about differences in provision, costs and outcomes of mental health care? | url = | journal = Acta Psychiatrica Scandinavica Supplement | volume = 113 | issue = 429| pages = 9–16 | pmid = 16445476 | doi=10.1111/j.1600-0447.2005.00711.x}}</ref> Following (or in lieu of) a hospital admission, support services available can include drop-in centers, visits from members of a community mental health team or [[Assertive Community Treatment]] team, supported employment<ref>{{cite journal | last1 = McGurk | first1 = SR | last2 = Mueser | first2 = KT | last3 = Feldman | first3 = K | last4 = Wolfe | first4 = R | last5 = Pascaris | first5 = A | title = Cognitive training for supported employment: 2-3 year outcomes of a randomized controlled trial | journal = The American Journal of Psychiatry | volume = 164 | issue = 3 | pages = 437–41 | year = 2007 | pmid = 17329468 | doi = 10.1176/appi.ajp.164.3.437 }}</ref> and patient-led support groups.
 Efforts to avoid repeated hospitalization include the obtaining of community treatment orders which, following judicial approval, coerce the affected individual to receive psychiatric treatment including long-acting injections of anti-psychotic medication. This legal mechanism has been shown to increase the affected patient's time out of the hospital.<ref>Effects of compulsory treatment orders on time to [[Hospital Readmission|hospital readmission]] (2005).</ref>
 ==Medication==
 [[File:Risperdal tablets.jpg|thumb|right|150px|[[Risperidone]] (trade name Risperdal) is a common [[atypical antipsychotic]] medication.]]
-The mainstay of psychiatric treatment for schizophrenia is [[antipsychotic]] medication.<ref name="fn_72">The Royal College of Psychiatrists & The British Psychological Society (2003). [http://www.nice.org.uk/download.aspx?o=289559 ''Schizophrenia. Full national clinical guideline on core interventions in primary and secondary care''] {{webarchive|url=https://web.archive.org/web/20070927014932/http://www.nice.org.uk/download.aspx?o=289559 |date=2007-09-27 }} (PDF). London: Gaskell and the British Psychological Society.  Retrieved on 2007-05-17.</ref> Medication might improve a number of outcomes found to be important to patients, including positive, acute and psychotic symptoms, and social and vocational functioning.<ref>{{cite journal | year = 2015 | title = What matters to patients? A systematic review of preferences for medication-associated outcomes in mental disorders | url = | journal = BMJ Open | volume = 5 | issue = 4| page = e007848 | doi=10.1136/bmjopen-2015-007848| last1 = Eiring | first1 = O. | last2 = Landmark | first2 = B. F. | last3 = Aas | first3 = E. | last4 = Salkeld | first4 = G. | last5 = Nylenna | first5 = M. | last6 = Nytroen | first6 = K. }}</ref> Medication can reduce the "positive" symptoms of psychosis. Most antipsychotics are thought to take around 7 to 14 days to have their main effect. However, these drugs fail to significantly ameliorate the negative symptoms and cognitive dysfunction.<ref name=AFP10>{{cite journal |vauthors=Smith T, Weston C, Lieberman J |title=Schizophrenia (maintenance treatment) |journal=Am Fam Physician |volume=82 |issue=4 |pages=338–9 |date=August 2010  |pmid=20704164 }}</ref><ref name="pmid18291627">{{cite journal |vauthors=Tandon R, Keshavan MS, Nasrallah HA |title=Schizophrenia, "Just the Facts": what we know in 2008 part 1: overview |journal=[[Schizophrenia Research]] |volume=100 |issue=1–3 |pages=4–19 |date=March 2008  |pmid=18291627 |doi=10.1016/j.schres.2008.01.022 |url=http://download.journals.elsevierhealth.com/pdfs/journals/0920-9964/PIIS0920996408000716.pdf| format=PDF}}</ref> There is evidence of [[clozapine]], [[amisulpride]], [[olanzapine]] and [[risperidone]] being the most effective medications, although a high proportion of studies of risperidone were undertaken by its manufacturer, [[Janssen-Cilag]], and should be interpreted with this in mind.<ref name="barry 2012"/> In those on antipsychotics, continued use decreases the risk of relapse.<ref name=Relapse2012>{{cite journal  |vauthors=Leucht S, Tardy M, Komossa K, etal |title=Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis |journal=Lancet |volume=379 |issue=9831 |pages=2063–71 |date=June 2012  |pmid=22560607 |doi=10.1016/S0140-6736(12)60239-6 }}</ref><ref name=Harrow2013>{{cite journal|vauthors=Harrow M, Jobe TH |title=Does long-term treatment of dchizophrenia with antipsychotic medications facilitate recovery?|journal=Schizophrenia bulletin|date=19 March 2013|pmid=23512950|volume=39|issue=5|pages=962–5|doi=10.1093/schbul/sbt034|pmc=3756791}}</ref> There is little evidence regarding consistent benefits from their use beyond two or three years.<ref name=Harrow2013/>
+The mainstay of psychiatric treatment for schizophrenia is [[antipsychotic]] medication.<ref name="fn_72">The Royal College of Psychiatrists & The British Psychological Society (2003). [http://www.nice.org.uk/download.aspx?o=289559 ''Schizophrenia. Full national clinical guideline on core interventions in primary and secondary care''] {{webarchive|url=https://web.archive.org/web/20070927014932/http://www.nice.org.uk/download.aspx?o=289559 |date=2007-09-27 }} (PDF). London: Gaskell and the British Psychological Society.  Retrieved on 2007-05-17.</ref> Medication might improve a number of outcomes found to be important to patients, including positive, acute and psychotic symptoms, and social and vocational functioning.<ref>{{cite journal | year = 2015 | title = What matters to patients? A systematic review of preferences for medication-associated outcomes in mental disorders | url = | journal = BMJ Open | volume = 5 | issue = 4| page = e007848 | doi=10.1136/bmjopen-2015-007848| pmid = 25854979 | pmc = 4390680 | last1 = Eiring | first1 = O. | last2 = Landmark | first2 = B. F. | last3 = Aas | first3 = E. | last4 = Salkeld | first4 = G. | last5 = Nylenna | first5 = M. | last6 = Nytroen | first6 = K. }}</ref> Medication can reduce the "positive" symptoms of psychosis. Most antipsychotics are thought to take around 7 to 14 days to have their main effect. However, these drugs fail to significantly ameliorate the negative symptoms and cognitive dysfunction.<ref name=AFP10>{{cite journal |vauthors=Smith T, Weston C, Lieberman J |title=Schizophrenia (maintenance treatment) |journal=Am Fam Physician |volume=82 |issue=4 |pages=338–9 |date=August 2010  |pmid=20704164 }}</ref><ref name="pmid18291627">{{cite journal |vauthors=Tandon R, Keshavan MS, Nasrallah HA |title=Schizophrenia, "Just the Facts": what we know in 2008 part 1: overview |journal=[[Schizophrenia Research]] |volume=100 |issue=1–3 |pages=4–19 |date=March 2008  |pmid=18291627 |doi=10.1016/j.schres.2008.01.022 |url=http://download.journals.elsevierhealth.com/pdfs/journals/0920-9964/PIIS0920996408000716.pdf| format=PDF}}</ref> There is evidence of [[clozapine]], [[amisulpride]], [[olanzapine]] and [[risperidone]] being the most effective medications, although a high proportion of studies of risperidone were undertaken by its manufacturer, [[Janssen-Cilag]], and should be interpreted with this in mind.<ref name="barry 2012"/> In those on antipsychotics, continued use decreases the risk of relapse.<ref name=Relapse2012>{{cite journal  |vauthors=Leucht S, Tardy M, Komossa K, etal |title=Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis |journal=Lancet |volume=379 |issue=9831 |pages=2063–71 |date=June 2012  |pmid=22560607 |doi=10.1016/S0140-6736(12)60239-6 }}</ref><ref name=Harrow2013>{{cite journal|vauthors=Harrow M, Jobe TH |title=Does long-term treatment of dchizophrenia with antipsychotic medications facilitate recovery?|journal=Schizophrenia Bulletin|date=19 March 2013|pmid=23512950|volume=39|issue=5|pages=962–5|doi=10.1093/schbul/sbt034|pmc=3756791}}</ref> There is little evidence regarding consistent benefits from their use beyond two or three years.<ref name=Harrow2013/>
 Treatment of schizophrenia changed dramatically in the mid-1950s with the development and introduction of the first antipsychotic [[chlorpromazine]].<ref name="Turner2007">{{cite journal | author=Turner T. | title=Unlocking psychosis | journal=Br J Med | year=2007 | volume=334 | issue=suppl | pages=s7 | doi=10.1136/bmj.39034.609074.94 | pmid=17204765 }}</ref> Others such as [[haloperidol]] and [[trifluoperazine]] soon followed.
@@ Line 13: / Line 13: @@
 It remains unclear whether the newer antipsychotics reduce the chances of developing [[neuroleptic malignant syndrome]], a rare but serious and potentially fatal neurological disorder most often caused by an adverse reaction to [[neuroleptic]] or antipsychotic drugs.<ref name="Ananth_et_al_2004">{{cite journal | doi = 10.4088/JCP.v65n0403 |vauthors=Ananth J, Parameswaran S, Gunatilake S, Burgoyne K, Sidhom T | year = 2004 | title = Neuroleptic malignant syndrome and atypical antipsychotic drugs | url = | journal = Journal of Clinical Psychiatry | volume = 65 | issue = 4| pages = 464–70 | pmid = 15119907 }}</ref>
-Most people on antipsychotics get side effects. People on typical antipsychotics tend to have a higher rate of [[extrapyramidal side effects]] while some atypicals are associated with considerable weight gain, diabetes, and risk of [[metabolic syndrome]]; this is most pronounced with olanzapine, while risperidone and [[quetiapine]] are also associated with weight gain.<ref name="barry 2012">{{cite journal|vauthors=Barry SJ, Gaughan TM, Hunter R |date=2012 |title=Schizophrenia |journal=BMJ Clinical Evidence |pmid=23870705 |url=http://www.clinicalevidence.bmj.com/x/systematic-review/1007/archive/06/2012.html |archive-url=https://archive.is/20140911114812/http://www.clinicalevidence.bmj.com/x/systematic-review/1007/archive/06/2012.html |dead-url=yes |archive-date=2014-09-11 |pmc=3385413 |volume=2012 }}</ref> Risperidone has a similar rate of extrapyramidal symptoms to haloperidol.<ref name="barry 2012"/> The American Psychiatric Association generally recommends that atypicals be used as first line treatment in most patients, but further states that therapy should be individually optimized for each patient.<ref>{{cite web|url=http://psychiatryonline.org/content.aspx?bookID=28&sectionID=1665359#46267 |archive-url=https://archive.is/20140306093804/http://psychiatryonline.org/content.aspx?bookID=28&sectionID=1665359%2346267#46267 |dead-url=yes|title=PsychiatryOnline &#124; APA Practice Guidelines &#124; Practice Guideline for the Treatment of Patients With Schizophrenia Second Edition |format= |work= |accessdate= }}</ref>
+Most people on antipsychotics get side effects. People on typical antipsychotics tend to have a higher rate of [[extrapyramidal side effects]] while some atypicals are associated with considerable weight gain, diabetes, and risk of [[metabolic syndrome]]; this is most pronounced with olanzapine, while risperidone and [[quetiapine]] are also associated with weight gain.<ref name="barry 2012">{{cite journal|vauthors=Barry SJ, Gaughan TM, Hunter R |date=2012 |title=Schizophrenia |journal=BMJ Clinical Evidence |pmid=23870705 |url=http://www.clinicalevidence.bmj.com/x/systematic-review/1007/archive/06/2012.html |archive-url=https://archive.is/20140911114812/http://www.clinicalevidence.bmj.com/x/systematic-review/1007/archive/06/2012.html |dead-url=yes |archive-date=2014-09-11 |pmc=3385413 |volume=2012 }}</ref> Risperidone has a similar rate of extrapyramidal symptoms to haloperidol.<ref name="barry 2012"/> The American Psychiatric Association generally recommends that atypicals be used as first line treatment in most patients, but further states that therapy should be individually optimized for each patient.<ref>{{cite web|url=http://psychiatryonline.org/content.aspx?bookID=28&sectionID=1665359#46267 |archive-url=https://archive.is/20140306093804/http://psychiatryonline.org/content.aspx?bookID=28&sectionID=1665359%2346267#46267 |dead-url=yes|title=PsychiatryOnline &#124; APA Practice Guidelines &#124; Practice Guideline for the Treatment of Patients With Schizophrenia Second Edition |format= |website= |accessdate= }}</ref>
-The response of symptoms to medication is variable; "Treatment-resistant schizophrenia" is the failure to respond to two or more antipsychotic medications given in therapeutic doses for six weeks or more.<ref>Semple.David"Oxford Handbook Of Psychiatry". Oxford Press. 2005. p 207.</ref> Patients in this category may be prescribed [[clozapine]], a medication that may be more effective at reducing symptoms of schizophrenia, but treatment may come with a higher risk of several potentially lethal side effects including [[agranulocytosis]] and [[myocarditis]].<ref name=Essali2009 /><ref>{{cite journal |vauthors=Haas SJ, Hill R, Krum H | title = Clozapine-associated myocarditis: a review of 116 cases of suspected myocarditis associated with the use of clozapine in Australia during 1993–2003 | journal = Drug Safety | volume = 30 | pages = 47–57 | year = 2007 | pmid=17194170 | doi = 10.2165/00002018-200730010-00005 | issue = 1 }}</ref>  Clozapine is the only medication proven to be more effective for people who do not respond to other types of antipsychotics.<ref>{{cite journal |doi=10.1056/NEJMoa051688 |title=Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia |year=2005 |last1=Lieberman |first1=Jeffrey A. |last2=Stroup |first2=T. Scott |last3=McEvoy |first3=Joseph P. |last4=Swartz |first4=Marvin S. |last5=Rosenheck |first5=Robert A. |last6=Perkins |first6=Diana O. |last7=Keefe |first7=Richard S.E. |last8=Davis |first8=Sonia M. |last9=Davis |first9=Clarence E. |last10=Lebowitz |first10=Barry D. |last11=Severe |first11=Joanne |last12=Hsiao |first12=John K. |journal=New England Journal of Medicine |volume=353 |issue=12 |pages=1209–23 |pmid=16172203 |author13=Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators}}</ref> It also appears to reduce suicide in people with schizophrenia. As clozapine suppresses the development of bone marrow, in turn reducing white blood cells which can lead to infection, blood tests are taken for the first six months on this medication.<ref>Kozier, B et al. (2008). Fundamentals Of Nursing, Concepts, Process, and Practice. London: Pearson Education. p. 189.</ref> The risk of experiencing agranulocytosis due to clozapine treatment is higher in elderly people, children, and adolescents.<ref name=Essali2009 /> The effectiveness in the studies also needs to be interpreted with caution as the studies may have an increased risk of bias.<ref name=Essali2009>{{Cite book|url=http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000059.pub2/abstract|title=Cochrane Database of Systematic Reviews|last=Essali|first=Adib|last2=Al-Haj Haasan|first2=Nahla|last3=Li|first3=Chunbo|last4=Rathbone|first4=John|date=2009-01-21|publisher=John Wiley & Sons, Ltd|issn=1465-1858|language=en|doi=10.1002/14651858.cd000059.pub2}}</ref>
+The response of symptoms to medication is variable; "Treatment-resistant schizophrenia" is the failure to respond to two or more antipsychotic medications given in therapeutic doses for six weeks or more.<ref>Semple.David"Oxford Handbook Of Psychiatry". Oxford Press. 2005. p 207.</ref> Patients in this category may be prescribed [[clozapine]], a medication that may be more effective at reducing symptoms of schizophrenia, but treatment may come with a higher risk of several potentially lethal side effects including [[agranulocytosis]] and [[myocarditis]].<ref name=Essali2009 /><ref>{{cite journal |vauthors=Haas SJ, Hill R, Krum H | title = Clozapine-associated myocarditis: a review of 116 cases of suspected myocarditis associated with the use of clozapine in Australia during 1993–2003 | journal = Drug Safety | volume = 30 | pages = 47–57 | year = 2007 | pmid=17194170 | doi = 10.2165/00002018-200730010-00005 | issue = 1 }}</ref>  Clozapine is the only medication proven to be more effective for people who do not respond to other types of antipsychotics.<ref>{{cite journal |doi=10.1056/NEJMoa051688 |title=Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia |year=2005 |last1=Lieberman |first1=Jeffrey A. |last2=Stroup |first2=T. Scott |last3=McEvoy |first3=Joseph P. |last4=Swartz |first4=Marvin S. |last5=Rosenheck |first5=Robert A. |last6=Perkins |first6=Diana O. |last7=Keefe |first7=Richard S.E. |last8=Davis |first8=Sonia M. |last9=Davis |first9=Clarence E. |last10=Lebowitz |first10=Barry D. |last11=Severe |first11=Joanne |last12=Hsiao |first12=John K. |journal=New England Journal of Medicine |volume=353 |issue=12 |pages=1209–23 |pmid=16172203 |author13=Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators}}</ref> It also appears to reduce suicide in people with schizophrenia. As clozapine suppresses the development of bone marrow, in turn reducing white blood cells which can lead to infection, blood tests are taken for the first six months on this medication.<ref>Kozier, B et al. (2008). Fundamentals Of Nursing, Concepts, Process, and Practice. London: Pearson Education. p. 189.</ref> The risk of experiencing agranulocytosis due to clozapine treatment is higher in elderly people, children, and adolescents.<ref name=Essali2009 /> The effectiveness in the studies also needs to be interpreted with caution as the studies may have an increased risk of bias.<ref name=Essali2009>{{Cite journal|title=Cochrane Database of Systematic Reviews|journal = Cochrane Database of Systematic Reviews|issue = 1|pages = CD000059|last=Essali|first=Adib|last2=Al-Haj Haasan|first2=Nahla|last3=Li|first3=Chunbo|last4=Rathbone|first4=John|date=2009-01-21|language=en|doi=10.1002/14651858.cd000059.pub2|pmid = 19160174}}</ref>
 === Add on agents ===
@@ Line 21: / Line 21: @@
 {| class="wikitable"
 |-
-! Adjuncts<ref>{{cite book | isbn = 9789400758056 | title = Polypharmacy in Psychiatry Practice, Volume I | author = Ritsner, MS | year = 2013 | publisher = Springer Science+Business Media Dordrecht | url = https://link.springer.com/book/10.1007/978-94-007-5805-6/ | pages =  | doi = 10.1007/978-94-007-5805-6 | access-date = 2017-08-28 | archive-url = https://wayback.archive-it.org/all/20151219171020/http://link.springer.com/book/10.1007%2F978-94-007-5805-6 | archive-date = 2015-12-19 | dead-url = yes | df =  }}</ref><ref>{{cite book | isbn = 9789400757998 | author = Ritsner, MS | title = Polypharmacy in Psychiatry Practice, Volume II | year = 2013 | publisher = Springer Science+Business Media Dordrecht | url = https://link.springer.com/book/10.1007/978-94-007-5799-8/  | pages =  | doi = 10.1007/978-94-007-5799-8 }}</ref> !! Symptoms against which efficacy is known !! Notable adverse effects seen in clinical trials !! Highest quality of clinical data available !! N !! Notes
+! Adjuncts<ref>{{cite book | isbn = 9789400758056 | title = Polypharmacy in Psychiatry Practice, Volume I | author = Ritsner, MS | year = 2013 | publisher = Springer Science+Business Media Dordrecht | pages =  | doi = 10.1007/978-94-007-5805-6 | df =  }}</ref><ref>{{cite book | isbn = 9789400757998 | author = Ritsner, MS | title = Polypharmacy in Psychiatry Practice, Volume II | year = 2013 | publisher = Springer Science+Business Media Dordrecht | pages =  | doi = 10.1007/978-94-007-5799-8 }}</ref> !! Symptoms against which efficacy is known !! Notable adverse effects seen in clinical trials !! Highest quality of clinical data available !! N !! Notes
 |-
 | colspan="6" align=center | '''Adjuncts to [[clozapine]]'''<ref name = CLZ>{{cite journal|author1=Porcelli, S |author2=Balzarro, B |author3=Serretti, A |title=Clozapine resistance: augmentation strategies|journal=European Neuropsychopharmacology|volume=22|issue=3|pages=165–182|doi=10.1016/j.euroneuro.2011.08.005|pmid=21906915|date=March 2012}}</ref><ref>{{cite journal|title=Pharmacological Augmentation Strategies for Schizophrenia Patients With Insufficient Response to Clozapine: A Quantitative Literature Review|author1=Sommer, IE |author2=Begemann, MJ |author3=Temmerman, A |author4=Leucht, S |journal=Schizophrenia Bulletin|date=September 2012|volume=38|issue=5|pages=1003–1011|doi=10.1093/schbul/sbr004|pmid=21422107|pmc=3446238|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446238/pdf/sbr004.pdf}}</ref>
@@ Line 53: / Line 53: @@
 | [[Valproate]] || Reduced anxiety & depression || Weight gain, hair loss || One open-label study comparing it with lithium || NA || Increases the expression of [[metabotropic glutamate receptor 2|mGluR2]] and [[GAD67]] via [[histone deacetylase]] (HDAC) inhibition.
 |-
-| colspan="6" align=center | '''Glutamatergic agents'''<ref name = Glut>{{cite journal|title=Meta-Analysis of the Efficacy of Adjunctive NMDA Receptor Modulators in Chronic Schizophrenia|author1=Singh, SP |author2=Singh, V |journal=CNS Drugs|volume=25|issue=10|pages=859–885|doi=10.2165/11586650-000000000-00000|url=https://link.springer.com/article/10.2165/11586650-000000000-00000|pmid=21936588|date=October 2011}}</ref><ref>{{cite journal|title=Adjunctive pharmacotherapy for cognitive deficits in schizophrenia: meta-analytical investigation of efficacy|journal=The British Journal of Psychiatry|author1=Choi, KH |author2=Wykes, T |author3=Kurtz, MM |volume=203|issue=3|pages=172–178|doi=10.1192/bjp.bp.111.107359|pmid=23999481|date=September 2013 |pmc=3759029}}</ref>
+| colspan="6" align=center | '''Glutamatergic agents'''<ref name = Glut>{{cite journal|title=Meta-Analysis of the Efficacy of Adjunctive NMDA Receptor Modulators in Chronic Schizophrenia|author1=Singh, SP |author2=Singh, V |journal=CNS Drugs|volume=25|issue=10|pages=859–885|doi=10.2165/11586650-000000000-00000|pmid=21936588|date=October 2011}}</ref><ref>{{cite journal|title=Adjunctive pharmacotherapy for cognitive deficits in schizophrenia: meta-analytical investigation of efficacy|journal=The British Journal of Psychiatry|author1=Choi, KH |author2=Wykes, T |author3=Kurtz, MM |volume=203|issue=3|pages=172–178|doi=10.1192/bjp.bp.111.107359|pmid=23999481|date=September 2013 |pmc=3759029}}</ref>
 |-
 | [[CX-516]] || Global || Well-tolerated || 1 DB-RPCT || 18 || Statistically significant improvement in total symptoms but no significant improvement in negative and positive symptoms when considered separately.
@@ Line 75: / Line 75: @@
 | [[Minocycline]]<ref>{{Cite journal | doi = 10.1016/j.schres.2014.01.011| pmid = 24503176| title = Minocycline supplementation for treatment of negative symptoms in early-phase schizophrenia: A double blind, randomized, controlled trial| journal = Schizophrenia Research| volume = 153| issue = 1–3| pages = 169–76| year = 2014| last1 = Liu | first1 = F. | last2 = Guo | first2 = X. | last3 = Wu | first3 = R. | last4 = Ou | first4 = J. | last5 = Zheng | first5 = Y. | last6 = Zhang | first6 = B. | last7 = Xie | first7 = L. | last8 = Zhang | first8 = L. | last9 = Yang | first9 = L. | last10 = Yang | first10 = S. | last11 = Yang | first11 = J. | last12 = Ruan | first12 = Y. | last13 = Zeng | first13 = Y. | last14 = Xu | first14 = X. | last15 = Zhao | first15 = J. }}</ref><ref>{{Cite journal | doi = 10.1016/j.psychres.2013.12.051| pmid = 24480077| title = Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: Randomized double-blind placebo-controlled study| journal = Psychiatry Research| volume = 215| issue = 3| pages = 540–6| year = 2014| last1 = Khodaie-Ardakani | first1 = M. R. | last2 = Mirshafiee | first2 = O. | last3 = Farokhnia | first3 = M. | last4 = Tajdini | first4 = M. | last5 = Hosseini | first5 = S. M. R. | last6 = Modabbernia | first6 = A. | last7 = Rezaei | first7 = F. | last8 = Salehi | first8 = B. | last9 = Yekehtaz | first9 = H. | last10 = Ashrafi | first10 = M. | last11 = Tabrizi | first11 = M. | last12 = Akhondzadeh | first12 = S. }}</ref><ref>{{Cite journal | last1 = Chaudhry | first1 = I. B. | last2 = Hallak | first2 = J. | last3 = Husain | first3 = N. | last4 = Minhas | first4 = F. | last5 = Stirling | first5 = J. | last6 = Richardson | first6 = P. | last7 = Dursun | first7 = S. | last8 = Dunn | first8 = G. | last9 = Deakin | first9 = B. | doi = 10.1177/0269881112444941 | title = Minocycline benefits negative symptoms in early schizophrenia: A randomised double-blind placebo-controlled clinical trial in patients on standard treatment | journal = Journal of Psychopharmacology | volume = 26 | issue = 9 | pages = 1185–1193 | year = 2012 | pmid =  22526685| pmc = }}</ref><ref>{{Cite journal | last1 = Levkovitz | first1 = Y. | last2 = Mendlovich | first2 = S. | last3 = Riwkes | first3 = S. | last4 = Braw | first4 = Y. | last5 = Levkovitch-Verbin | first5 = H. | last6 = Gal | first6 = G. | last7 = Fennig | first7 = S. | last8 = Treves | first8 = I. | last9 = Kron | first9 = S. | doi = 10.4088/JCP.08m04666yel | title = A Double-Blind, Randomized Study of Minocycline for the Treatment of Negative and Cognitive Symptoms in Early-Phase Schizophrenia | journal = The Journal of Clinical Psychiatry | volume = 71 | issue = 2 | pages = 138–149 | year = 2010 | pmid =  19895780| pmc = }}</ref> || Global || Well-tolerated || 4 DB-RPCTs || 164 || Increased risk of blood dyscarsias.
 |-
-| [[Omega-3 fatty acids|ω-3 fatty acids]] || Global || Well-tolerated || 6 DB-RPCTs (1 negative)<ref>{{cite journal|title=Polyunsaturated fatty acid supplementation for schizophrenia(Review)|journal=Cochrane Database of Systematic Reviews|issue=3|pages=CD001257|doi=10.1002/14651858.CD001257.pub2|pmid=16855961|url=http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001257.pub2/pdf|date=July 2006|author1=Irving, CB |author2=Mumby-Croft, R |author3=Joy, LA }}</ref> || 362 || May have protective effects against depression.
+| [[Omega-3 fatty acids|ω-3 fatty acids]] || Global || Well-tolerated || 6 DB-RPCTs (1 negative)<ref>{{cite journal|title=Polyunsaturated fatty acid supplementation for schizophrenia(Review)|journal=Cochrane Database of Systematic Reviews|issue=3|pages=CD001257|doi=10.1002/14651858.CD001257.pub2|pmid=16855961|date=July 2006|author1=Irving, CB |author2=Mumby-Croft, R |author3=Joy, LA }}</ref> || 362 || May have protective effects against depression.
 |-
 | [[Pregnenolone]]<ref>{{Cite journal | last1 = Ritsner | first1 = M. S. | last2 = Gibel | first2 = A. | last3 = Shleifer | first3 = T. | last4 = Boguslavsky | first4 = I. | last5 = Zayed | first5 = A. | last6 = Maayan | first6 = R. | last7 = Weizman | first7 = A. | last8 = Lerner | first8 = V. | doi = 10.4088/JCP.09m05031yel | title = Pregnenolone and Dehydroepiandrosterone as an Adjunctive Treatment in Schizophrenia and Schizoaffective Disorder | journal = The Journal of Clinical Psychiatry | volume = 71 | issue = 10 | pages = 1351–1362 | year = 2010 | pmid =  20584515| pmc = }}</ref><ref>{{Cite journal | last1 = Marx | first1 = C. E. | last2 = Keefe | first2 = R. S. E. | last3 = Buchanan | first3 = R. W. | last4 = Hamer | first4 = R. M. | last5 = Kilts | first5 = J. D. | last6 = Bradford | first6 = D. W. | last7 = Strauss | first7 = J. L. | last8 = Naylor | first8 = J. C. | last9 = Payne | first9 = V. M. | last10 = Lieberman | first10 = J. A. | last11 = Savitz | first11 = A. J. | last12 = Leimone | first12 = L. A. | last13 = Dunn | first13 = L. | last14 = Porcu | first14 = P. | last15 = Morrow | first15 = A. L. | last16 = Shampine | first16 = L. J. | title = Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia | doi = 10.1038/npp.2009.26 | journal = Neuropsychopharmacology | volume = 34 | issue = 8 | pages = 1885–1903 | year = 2009 | pmid =  19339966| pmc =3427920 }}</ref><ref>{{Cite journal | last1 = Wong | first1 = P. | last2 = Chang | first2 = C. C. R. | last3 = Marx | first3 = C. E. | last4 = Caron | first4 = M. G. | last5 = Wetsel | first5 = W. C. | last6 = Zhang | first6 = X. | editor1-last = Hashimoto | editor1-first = Kenji | title = Pregnenolone Rescues Schizophrenia-Like Behavior in Dopamine Transporter Knockout Mice | doi = 10.1371/journal.pone.0051455 | journal = PLoS ONE | volume = 7 | issue = 12 | pages = e51455 | year = 2012 | pmid =  23240026| pmc =3519851 | bibcode = 2012PLoSO...751455W }}</ref><ref>{{Cite journal | last1 = Marx | first1 = C. E. | last2 = Stevens | first2 = R. D. | last3 = Shampine | first3 = L. J. | last4 = Uzunova | first4 = V. | last5 = Trost | first5 = W. T. | last6 = Butterfield | first6 = M. I. | last7 = Massing | first7 = M. W. | last8 = Hamer | first8 = R. M. | last9 = Morrow | first9 = A. L. | last10 = Lieberman | first10 = J. A. | title = Neuroactive Steroids are Altered in Schizophrenia and Bipolar Disorder: Relevance to Pathophysiology and Therapeutics | doi = 10.1038/sj.npp.1300952 | journal = Neuropsychopharmacology | year = 2005 | pmid =  16319920| pmc = | volume=31 | issue = 6 | pages=1249–63}}</ref> || Global || Well-tolerated || 3 DB-RPCTs || 100 || Levels of this neurosteroid in the body are elevated by clozapine treatment.
@@ Line 83: / Line 83: @@
 | [[D-alanine]]<ref>{{Cite journal | last1 = Hatano | first1 = T. | last2 = Ohnuma | first2 = T. | last3 = Sakai | first3 = Y. | last4 = Shibata | first4 = N. | last5 = Maeshima | first5 = H. | last6 = Hanzawa | first6 = R. | last7 = Suzuki | first7 = T. | last8 = Arai | first8 = H. | doi = 10.1016/j.psychres.2010.02.014 | title = Plasma alanine levels increase in patients with schizophrenia as their clinical symptoms improve—Results from the Juntendo University Schizophrenia Projects (JUSP) | journal = Psychiatry Research | volume = 177 | issue = 1–2 | pages = 27–31 | year = 2010 | pmid =  20226539| pmc = }}</ref><ref>{{Cite journal | last1 = Tsai | first1 = G. E. | last2 = Yang | first2 = P. | last3 = Chang | first3 = Y. C. | last4 = Chong | first4 = M. Y. | title = D-Alanine Added to Antipsychotics for the Treatment of Schizophrenia | doi = 10.1016/j.biopsych.2005.06.032 | journal = Biological Psychiatry | volume = 59 | issue = 3 | pages = 230–234 | year = 2006 | pmid =  16154544| pmc = }}</ref> || Global || Well-tolerated || 1 DB-RPCT || 31 || A D-amino acid with affinity towards the glycine site on the [[NMDA receptor]].
 |-
-| [[D-serine]] || Global (especially negative symptoms) || Well-tolerated || 4 DB-RPCTs || 183 || Affinity towards the glycine site on NMDA receptors. D. Souza 2013,<ref>{{Cite journal | last1 = d'Souza | first1 = D. C. | last2 = Radhakrishnan | first2 = R. | last3 = Perry | first3 = E. | last4 = Bhakta | first4 = S. | last5 = Singh | first5 = N. M. | last6 = Yadav | first6 = R. | last7 = Abi-Saab | first7 = D. | last8 = Pittman | first8 = B. | last9 = Chaturvedi | first9 = S. K. | last10 = Sharma | first10 = M. P. | last11 = Bell | first11 = M. | last12 = Andrade | first12 = C. | doi = 10.1038/npp.2012.208 | title = Feasibility, Safety, and Efficacy of the Combination of D-Serine and Computerized Cognitive Retraining in Schizophrenia: An International Collaborative Pilot Study | journal = Neuropsychopharmacology | volume = 38 | issue = 3 | pages = 492–503 | year = 2012 | pmid =  23093223| pmc =3547200 }}</ref> Heresco-Levy 2005,<ref>{{Cite journal | last1 = Heresco-Levy | first1 = U. | last2 = Javitt | first2 = D. C. | last3 = Ebstein | first3 = R. | last4 = Vass | first4 = A. | last5 = Lichtenberg | first5 = P. | last6 = Bar | first6 = G. | last7 = Catinari | first7 = S. | last8 = Ermilov | first8 = M. | doi = 10.1016/j.biopsych.2004.12.037 | title = D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia | journal = Biological Psychiatry | volume = 57 | issue = 6 | pages = 577–585 | year = 2005 | pmid =  15780844| pmc = }}</ref> Lane 2005,<ref name="doi10.1001/archpsyc.62.11.1196">{{Cite journal | last1 = Lane | first1 = H. Y. | last2 = Chang | first2 = Y. C. | last3 = Liu | first3 = Y. C. | last4 = Chiu | first4 = C. C. | last5 = Tsai | first5 = G. E. | title = Sarcosine or D-Serine Add-on Treatment for Acute Exacerbation of Schizophrenia | doi = 10.1001/archpsyc.62.11.1196 | journal = Archives of General Psychiatry | volume = 62 | issue = 11 | pages = 1196–1204 | year = 2005 | pmid =  16275807| pmc = }}</ref> Lane 2010,<ref name="doi10.1017/S1461145709990939">{{Cite journal | last1 = Lane | first1 = H. Y. | last2 = Lin | first2 = C. H. | last3 = Huang | first3 = Y. J. | last4 = Liao | first4 = C. H. | last5 = Chang | first5 = Y. C. | last6 = Tsai | first6 = G. E. | doi = 10.1017/S1461145709990939 | title = A randomized, double-blind, placebo-controlled comparison study of sarcosine ( N-methylglycine) and d-serine add-on treatment for schizophrenia | journal = The International Journal of Neuropsychopharmacology | volume = 13 | issue = 4 | pages = 451–460 | year = 2009 | pmid =  19887019| pmc = }}</ref> Tsai 1999,<ref>{{Cite journal | last1 = Tsai | first1 = G. E. | last2 = Yang | first2 = P. | last3 = Chung | first3 = L. C. | last4 = Tsai | first4 = I. C. | last5 = Tsai | first5 = C. W. | last6 = Coyle | first6 = J. T. | title = D-serine added to clozapine for the treatment of schizophrenia | journal = The American Journal of Psychiatry | volume = 156 | issue = 11 | pages = 1822–1825 | year = 1999 | pmid = 10553752 | doi = 10.1176/ajp.156.11.1822 }}</ref> Weiser 2012<ref>{{Cite journal | last1 = Weiser | first1 = M. | last2 = Heresco-Levy | first2 = U. | last3 = Davidson | first3 = M. | last4 = Javitt | first4 = D. C. | last5 = Werbeloff | first5 = N. | last6 = Gershon | first6 = A. A. | last7 = Abramovich | first7 = Y. | last8 = Amital | first8 = D. | last9 = Doron | first9 = A. | last10 = Konas | first10 = S. | last11 = Levkovitz | first11 = Y. | last12 = Liba | first12 = D. | last13 = Teitelbaum | first13 = A. | last14 = Mashiach | first14 = M. | last15 = Zimmerman | first15 = Y. | title = A Multicenter, Add-On Randomized Controlled Trial of Low-Dosed-Serine for Negative and Cognitive Symptoms of Schizophrenia | doi = 10.4088/JCP.11m07031 | journal = The Journal of Clinical Psychiatry | volume = 73 | issue = 6 | pages = e728 | year = 2012 | pmid =  22795211| pmc = }}</ref>
+| [[D-serine]] || Global (especially negative symptoms) || Well-tolerated || 4 DB-RPCTs || 183 || Affinity towards the glycine site on NMDA receptors. D. Souza 2013,<ref>{{Cite journal | last1 = d'Souza | first1 = D. C. | last2 = Radhakrishnan | first2 = R. | last3 = Perry | first3 = E. | last4 = Bhakta | first4 = S. | last5 = Singh | first5 = N. M. | last6 = Yadav | first6 = R. | last7 = Abi-Saab | first7 = D. | last8 = Pittman | first8 = B. | last9 = Chaturvedi | first9 = S. K. | last10 = Sharma | first10 = M. P. | last11 = Bell | first11 = M. | last12 = Andrade | first12 = C. | doi = 10.1038/npp.2012.208 | title = Feasibility, Safety, and Efficacy of the Combination of D-Serine and Computerized Cognitive Retraining in Schizophrenia: An International Collaborative Pilot Study | journal = Neuropsychopharmacology | volume = 38 | issue = 3 | pages = 492–503 | year = 2012 | pmid =  23093223| pmc =3547200 }}</ref> Heresco-Levy 2005,<ref>{{Cite journal | last1 = Heresco-Levy | first1 = U. | last2 = Javitt | first2 = D. C. | last3 = Ebstein | first3 = R. | last4 = Vass | first4 = A. | last5 = Lichtenberg | first5 = P. | last6 = Bar | first6 = G. | last7 = Catinari | first7 = S. | last8 = Ermilov | first8 = M. | doi = 10.1016/j.biopsych.2004.12.037 | title = D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia | journal = Biological Psychiatry | volume = 57 | issue = 6 | pages = 577–585 | year = 2005 | pmid =  15780844| pmc = }}</ref> Lane 2005,<ref name="doi10.1001/archpsyc.62.11.1196">{{Cite journal | last1 = Lane | first1 = H. Y. | last2 = Chang | first2 = Y. C. | last3 = Liu | first3 = Y. C. | last4 = Chiu | first4 = C. C. | last5 = Tsai | first5 = G. E. | title = Sarcosine or D-Serine Add-on Treatment for Acute Exacerbation of Schizophrenia | doi = 10.1001/archpsyc.62.11.1196 | journal = Archives of General Psychiatry | volume = 62 | issue = 11 | pages = 1196–1204 | year = 2005 | pmid =  16275807| pmc = }}</ref> Lane 2010,<ref name="doi10.1017/S1461145709990939">{{Cite journal | last1 = Lane | first1 = H. Y. | last2 = Lin | first2 = C. H. | last3 = Huang | first3 = Y. J. | last4 = Liao | first4 = C. H. | last5 = Chang | first5 = Y. C. | last6 = Tsai | first6 = G. E. | doi = 10.1017/S1461145709990939 | title = A randomized, double-blind, placebo-controlled comparison study of sarcosine ( N-methylglycine) and d-serine add-on treatment for schizophrenia | journal = The International Journal of Neuropsychopharmacology | volume = 13 | issue = 4 | pages = 451–460 | year = 2009 | pmid =  19887019| pmc = }}</ref> Tsai 1999,<ref>{{Cite journal | last1 = Tsai | first1 = G. E. | last2 = Yang | first2 = P. | last3 = Chung | first3 = L. C. | last4 = Tsai | first4 = I. C. | last5 = Tsai | first5 = C. W. | last6 = Coyle | first6 = J. T. | title = D-serine added to clozapine for the treatment of schizophrenia | journal = The American Journal of Psychiatry | volume = 156 | issue = 11 | pages = 1822–1825 | year = 1999 | pmid = 10553752 | doi = 10.1176/ajp.156.11.1822 | doi-broken-date = 2018-09-07 }}</ref> Weiser 2012<ref>{{Cite journal | last1 = Weiser | first1 = M. | last2 = Heresco-Levy | first2 = U. | last3 = Davidson | first3 = M. | last4 = Javitt | first4 = D. C. | last5 = Werbeloff | first5 = N. | last6 = Gershon | first6 = A. A. | last7 = Abramovich | first7 = Y. | last8 = Amital | first8 = D. | last9 = Doron | first9 = A. | last10 = Konas | first10 = S. | last11 = Levkovitz | first11 = Y. | last12 = Liba | first12 = D. | last13 = Teitelbaum | first13 = A. | last14 = Mashiach | first14 = M. | last15 = Zimmerman | first15 = Y. | title = A Multicenter, Add-On Randomized Controlled Trial of Low-Dosed-Serine for Negative and Cognitive Symptoms of Schizophrenia | doi = 10.4088/JCP.11m07031 | journal = The Journal of Clinical Psychiatry | volume = 73 | issue = 6 | pages = e728-34 | year = 2012 | pmid =  22795211| pmc = }}</ref>
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 | [[Glycine]] || Global (predominantly positive symptoms) || Well-tolerated || 5 DB-RPCTs || 219 || Endogenous NMDA receptor ligand.
 |-
-| [[Acetylcysteine|N-acetylcysteine]]<ref>{{Cite journal | last1 = Dean | first1 = O. | last2 = Giorlando | first2 = F. | last3 = Berk | first3 = M. | title = N-acetylcysteine in psychiatry: Current therapeutic evidence and potential mechanisms of action | journal = Journal of psychiatry & neuroscience : JPN | volume = 36 | issue = 2 | pages = 78–86 | year = 2011 | doi = 10.1503/jpn.100057 | pmid = 21118657 | pmc =3044191 }}</ref> || Global (especially negative symptoms) || Well-tolerated || 3 DB-RPCTs || 140 || Cystine and glutathione prodrug.<ref>{{Cite journal | last1 = Aoyama | first1 = K. | last2 = Watabe | first2 = M. | last3 = Nakaki | first3 = T. | doi = 10.1254/jphs.08R01CR | title = Regulation of Neuronal Glutathione Synthesis | journal = Journal of Pharmacological Sciences | volume = 108 | issue = 3 | pages = 227–238 | year = 2008 | pmid =  19008644| pmc = }}</ref><ref>{{Cite journal | doi = 10.1073/pnas.88.5.1913 | last1 = Jain | first1 = A. | last2 = Mårtensson | first2 = J. | last3 = Stole | first3 = E. | last4 = Auld | first4 = P. A. | last5 = Meister | first5 = A. | title = Glutathione deficiency leads to mitochondrial damage in brain | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 5 | pages = 1913–1917 | year = 1991 | pmid = 2000395 | pmc = 51136| bibcode = 1991PNAS...88.1913J }}</ref> Cystine increases intracellular glutamate levels via the glutamate-cystine anti porter.
+| [[Acetylcysteine|N-acetylcysteine]]<ref>{{Cite journal | last1 = Dean | first1 = O. | last2 = Giorlando | first2 = F. | last3 = Berk | first3 = M. | title = N-acetylcysteine in psychiatry: Current therapeutic evidence and potential mechanisms of action | journal = Journal of Psychiatry & Neuroscience : JPN | volume = 36 | issue = 2 | pages = 78–86 | year = 2011 | doi = 10.1503/jpn.100057 | pmid = 21118657 | pmc =3044191 }}</ref> || Global (especially negative symptoms) || Well-tolerated || 3 DB-RPCTs || 140 || Cystine and glutathione prodrug.<ref>{{Cite journal | last1 = Aoyama | first1 = K. | last2 = Watabe | first2 = M. | last3 = Nakaki | first3 = T. | doi = 10.1254/jphs.08R01CR | title = Regulation of Neuronal Glutathione Synthesis | journal = Journal of Pharmacological Sciences | volume = 108 | issue = 3 | pages = 227–238 | year = 2008 | pmid =  19008644| pmc = }}</ref><ref>{{Cite journal | doi = 10.1073/pnas.88.5.1913 | last1 = Jain | first1 = A. | last2 = Mårtensson | first2 = J. | last3 = Stole | first3 = E. | last4 = Auld | first4 = P. A. | last5 = Meister | first5 = A. | title = Glutathione deficiency leads to mitochondrial damage in brain | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 5 | pages = 1913–1917 | year = 1991 | pmid = 2000395 | pmc = 51136| bibcode = 1991PNAS...88.1913J }}</ref> Cystine increases intracellular glutamate levels via the glutamate-cystine anti porter.
 Berk 2008,<ref>{{Cite journal | last1 = Berk | first1 = M. | last2 = Copolov | first2 = D. | last3 = Dean | first3 = O. | last4 = Lu | first4 = K. | last5 = Jeavons | first5 = S. | last6 = Schapkaitz | first6 = I. | last7 = Anderson-Hunt | first7 = M. | last8 = Judd | first8 = F. | last9 = Katz | first9 = F. | last10 = Katz | first10 = P. | last11 = Ording-Jespersen | first11 = S. | last12 = Little | first12 = J. | last13 = Conus | first13 = P. | last14 = Cuenod | first14 = M. | last15 = Do | first15 = K. Q. | last16 = Bush | first16 = A. I. | title = N-Acetyl Cysteine as a Glutathione Precursor for Schizophrenia—A Double-Blind, Randomized, Placebo-Controlled Trial | doi = 10.1016/j.biopsych.2008.03.004 | journal = Biological Psychiatry | volume = 64 | issue = 5 | pages = 361–368 | year = 2008 | pmid =  18436195| pmc = }}</ref> Berk 2011,<ref>{{Cite journal | last1 = Berk | first1 = M. | last2 = Munib | first2 = A. | last3 = Dean | first3 = O. | last4 = Malhi | first4 = G. S. | last5 = Kohlmann | first5 = K. | last6 = Schapkaitz | first6 = I. | last7 = Jeavons | first7 = S. | last8 = Katz | first8 = F. | last9 = Anderson-Hunt | first9 = M. | last10 = Conus | first10 = P. | last11 = Hanna | first11 = B. | last12 = Otmar | first12 = R. E. | last13 = Ng | first13 = F. | last14 = Copolov | first14 = D. L. | last15 = Bush | first15 = A. I. | title = Qualitative Methods in Early-Phase Drug Trials | doi = 10.4088/JCP.09m05741yel | journal = The Journal of Clinical Psychiatry | volume = 72 | issue = 7 | pages = 909–913 | year = 2011 | pmid =  20868637| pmc = }}</ref> Carmeli 2012,<ref>{{Cite journal | last1 = Carmeli | first1 = C. | last2 = Knyazeva | first2 = M. G. | last3 = Cuénod | first3 = M. | last4 = Do | first4 = K. Q. | editor1-last = Burne | editor1-first = Thomas | title = Glutathione Precursor N-Acetyl-Cysteine Modulates EEG Synchronization in Schizophrenia Patients: A Double-Blind, Randomized, Placebo-Controlled Trial | doi = 10.1371/journal.pone.0029341 | journal = PLoS ONE | volume = 7 | issue = 2 | pages = e29341 | year = 2012 | pmid =  22383949| pmc =3285150 | bibcode = 2012PLoSO...729341C }}</ref> Lavoie 2008<ref>{{Cite journal | last1 = Lavoie | first1 = S. | last2 = Murray | first2 = M. M. | last3 = Deppen | first3 = P. | last4 = Knyazeva | first4 = M. G. | last5 = Berk | first5 = M. | last6 = Boulat | first6 = O. | last7 = Bovet | first7 = P. | last8 = Bush | first8 = A. I. | last9 = Conus | first9 = P. | last10 = Copolov | first10 = D. | last11 = Fornari | first11 = E. | last12 = Meuli | first12 = R. | last13 = Solida | first13 = A. | last14 = Vianin | first14 = P. | last15 = Cuénod | first15 = M. | last16 = Buclin | first16 = T. | last17 = Do | first17 = K. Q. | title = Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients | doi = 10.1038/sj.npp.1301624 | journal = Neuropsychopharmacology | volume = 33 | issue = 9 | pages = 2187–2199 | year = 2007 | pmid =  18004285| pmc = }}</ref>
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 | [[Sarcosine]] || Global (especially negative symptoms) || Well-tolerated || 3 DB-RPCTs || 112 || [[Glycine transporter 1|GlyT1]] antagonist (i.e. glycine reuptake inhibitor). Also known as N-methylglycine. Lane 2005,<ref name="doi10.1001/archpsyc.62.11.1196" /> Lane 2006,<ref>{{Cite journal | last1 = Lane | first1 = H. Y. | last2 = Huang | first2 = C. L. | last3 = Wu | first3 = P. L. | last4 = Liu | first4 = Y. C. | last5 = Chang | first5 = Y. C. | last6 = Lin | first6 = P. Y. | last7 = Chen | first7 = P. W. | last8 = Tsai | first8 = G. | doi = 10.1016/j.biopsych.2006.04.005 | title = Glycine Transporter I Inhibitor, N-methylglycine (Sarcosine), Added to Clozapine for the Treatment of Schizophrenia | journal = Biological Psychiatry | volume = 60 | issue = 6 | pages = 645–649 | year = 2006 | pmid =  16780811| pmc = }}</ref> Lane 2008,<ref>{{Cite journal | last1 = Lane | first1 = H. Y. | last2 = Liu | first2 = Y. C. | last3 = Huang | first3 = C. L. | last4 = Chang | first4 = Y. C. | last5 = Liau | first5 = C. H. | last6 = Perng | first6 = C. H. | last7 = Tsai | first7 = G. E. | doi = 10.1016/j.biopsych.2007.04.038 | title = Sarcosine (N-Methylglycine) Treatment for Acute Schizophrenia: A Randomized, Double-Blind Study | journal = Biological Psychiatry | volume = 63 | issue = 1 | pages = 9–12 | year = 2008 | pmid =  17659263| pmc = }}</ref> Lane 2010,<ref name="doi10.1017/S1461145709990939" /> Tsai 2004<ref>{{Cite journal | last1 = Tsai | first1 = G. | last2 = Lane | first2 = H. Y. | last3 = Yang | first3 = P. | last4 = Chong | first4 = M. Y. | last5 = Lange | first5 = N. | title = Glycine transporter I inhibitor, N-Methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia | doi = 10.1016/j.biopsych.2003.09.012 | journal = Biological Psychiatry | volume = 55 | issue = 5 | pages = 452–456 | year = 2004 | pmid =  15023571| pmc = }}</ref>
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-| colspan="6" align=center | '''Cholinergics'''<ref>{{cite journal|title=Acetylcholinesterase inhibitors for schizophrenia|journal=Cochrane Database of Systematic Reviews|volume=1|pages=CD007967|date=January 2012|doi=10.1002/14651858.CD007967.pub2|pmid=22258978|author1=Singh, J |author2=Kour, K |author3=Jayaram, MB |url=http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001257.pub2/pdf}}</ref><ref>{{cite journal|title=Adjunctive pharmacotherapy for cognitive deficits in schizophrenia: meta-analytical investigation of efficacy|journal=The British Journal of Psychiatry|volume=203|issue=3|pages=172–178|doi=10.1192/bjp.bp.111.107359|pmid=23999481|date=September 2013|author1=Choi, KH |author2=Wykes, T |author3=Kurtz, MM|pmc=3759029}}</ref><ref>{{cite journal|title=Cholinesterase Inhibitors as Adjunctive Therapy in Patients with Schizophrenia and Schizoaffective Disorder A Review and Meta-Analysis of the Literature|journal = CNS Drugs|date=April 2010|volume=24|issue=4|pages=303–317|doi=10.2165/11530260-000000000-00000|pmid=20297855|author1=Ribeiz, SR |author2=Bassitt, DP |author3=Arrais, JA |author4=Avila, R |author5=Steffens, DC |author6=Bottino, CM }}</ref>
+| colspan="6" align=center | '''Cholinergics'''<ref>{{cite journal|title=Acetylcholinesterase inhibitors for schizophrenia|journal=Cochrane Database of Systematic Reviews|volume=1|pages=CD007967|date=January 2012|doi=10.1002/14651858.CD007967.pub2|pmid=22258978|author1=Singh, J |author2=Kour, K |author3=Jayaram, MB }}</ref><ref>{{cite journal|title=Adjunctive pharmacotherapy for cognitive deficits in schizophrenia: meta-analytical investigation of efficacy|journal=The British Journal of Psychiatry|volume=203|issue=3|pages=172–178|doi=10.1192/bjp.bp.111.107359|pmid=23999481|date=September 2013|author1=Choi, KH |author2=Wykes, T |author3=Kurtz, MM|pmc=3759029}}</ref><ref>{{cite journal|title=Cholinesterase Inhibitors as Adjunctive Therapy in Patients with Schizophrenia and Schizoaffective Disorder A Review and Meta-Analysis of the Literature|journal = CNS Drugs|date=April 2010|volume=24|issue=4|pages=303–317|doi=10.2165/11530260-000000000-00000|pmid=20297855|author1=Ribeiz, SR |author2=Bassitt, DP |author3=Arrais, JA |author4=Avila, R |author5=Steffens, DC |author6=Bottino, CM }}</ref>
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 | [[Donepezil]] || Global || Well-tolerated || 6 DB-RPCTs (5 negative; or 12 DB-RPCTs if one includes cross-over trials; 8 negative in total) || 378, 474 (including cross-over trials) || Possesses antidepressant effects according to one trial.
@@ Line 110: / Line 110: @@
 | [[Mianserin]]<ref name = Alpha>{{cite journal|title=Alpha-2 receptor antagonist add-on therapy in the treatment of schizophrenia; a meta-analysis|journal=Schizophrenia Research|pages=202–206|volume=134|issue=2–3|doi=10.1016/j.schres.2011.11.030|pmid=22169246|author1=Hecht, EM |author2=Landy, DC |date=February 2012}}</ref> || Negative and cognitive symptoms || Well-tolerated || 2 DB-RPCTs || 48 || Weight gain, sedation, dry mouth, constipation and dizziness. Blood dyscarsias are a possible adverse effect and both the [[Australian Medicines Handbook]] and [[British National Formulary]] 65 (BNF 65) recommend regular complete blood counts to be taken.<ref>{{cite book | editor = Rossi, S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }}</ref><ref>{{cite book | isbn = 978-0-85711-084-8 | title = British National Formulary (BNF) | last1 = Joint Formulary Committee | year = 2013 | publisher = Pharmaceutical Press | location = London, UK | edition = 65 | page = 247  }}</ref>
 |-
-| [[Mirtazapine]]<ref name = Alpha /> || Cognition,<ref>{{cite book| isbn = 9789400758056| title = Polypharmacy in Psychiatry Practice, Volume I| author = Ritsner, MS| year = 2013| publisher = Springer Science+Business Media Dordrecht| url = https://link.springer.com/book/10.1007/978-94-007-5805-6/| doi = 10.1007/978-94-007-5805-6| access-date = 2017-08-28| archive-url = https://wayback.archive-it.org/all/20151219171020/http://link.springer.com/book/10.1007%2F978-94-007-5805-6| archive-date = 2015-12-19| dead-url = yes| df = }}</ref><ref>{{cite journal|title=Meta-Analysis of Efficacy of Mirtazapine as an Adjunctive Treatment of Negative Symptoms in Schizophrenia|journal=Clinical Schizophrenia & Related Psychoses|publisher=Walsh Medical Media|issn=1935-1232|doi=10.3371/CSRP.VIRE.030813|date=March 2013|pages=1–24|pmid=23491969|author1=Vidal, C |author2=Reese, C |author3=Fischer, BA |author4=Chiapelli, J |author5=Himelhoch, S |volume=9|issue=2}}</ref> negative and positive symptoms†<ref>{{cite journal| title = More evidence on proneurocognitive effects of add-on mirtazapine in schizophrenia | journal = Progress in Neuro-Psychopharmacology and Biological Psychiatry | pages = 1080–1086 | volume = 35 | issue = 4 | doi = 10.1016/j.pnpbp.2011.03.004 | pmid = 21402120 |author1=Stenberg, JH |author2=Terevnikov, V |author3=Joffe, M |author4=Tiihonen, J |author5=Tchoukhine, E |author6=Burkin, M |author7=Joffe, G | date = June 2011 }}</ref>|| Well-tolerated || ≥4 DB-RPCTs (one negative) || 127 || Relatively safe in overdose. Produces significant sedation and weight gain, however, which could potentially add to the adverse effects of atypical antipsychotics. Can reduce antipsychotic-induced akathisia.<ref>{{cite journal|title=Akathisia and Second-generation Antipsychotic Drugs| journal = Current Opinion in Psychiatry | volume=22 | issue = 3 | pages = 293–299 | doi = 10.1097/YCO.0b013e32832a16da | date = May 2009 |author1=Kumar, R |author2=Sachdev, PS | pmid = 19378382 |url=http://www.medscape.com/viewarticle/703492}}</ref>
+| [[Mirtazapine]]<ref name = Alpha /> || Cognition,<ref>{{cite book| isbn = 9789400758056| title = Polypharmacy in Psychiatry Practice, Volume I| author = Ritsner, MS| year = 2013| publisher = Springer Science+Business Media Dordrecht| doi = 10.1007/978-94-007-5805-6| df = }}</ref><ref>{{cite journal|title=Meta-Analysis of Efficacy of Mirtazapine as an Adjunctive Treatment of Negative Symptoms in Schizophrenia|journal=Clinical Schizophrenia & Related Psychoses|issn=1935-1232|doi=10.3371/CSRP.VIRE.030813|date=March 2013|pages=1–24|pmid=23491969|author1=Vidal, C |author2=Reese, C |author3=Fischer, BA |author4=Chiapelli, J |author5=Himelhoch, S |volume=9|issue=2}}</ref> negative and positive symptoms†<ref>{{cite journal| title = More evidence on proneurocognitive effects of add-on mirtazapine in schizophrenia | journal = Progress in Neuro-Psychopharmacology and Biological Psychiatry | pages = 1080–1086 | volume = 35 | issue = 4 | doi = 10.1016/j.pnpbp.2011.03.004 | pmid = 21402120 |author1=Stenberg, JH |author2=Terevnikov, V |author3=Joffe, M |author4=Tiihonen, J |author5=Tchoukhine, E |author6=Burkin, M |author7=Joffe, G | date = June 2011 }}</ref>|| Well-tolerated || ≥4 DB-RPCTs (one negative) || 127 || Relatively safe in overdose. Produces significant sedation and weight gain, however, which could potentially add to the adverse effects of atypical antipsychotics. Can reduce antipsychotic-induced akathisia.<ref>{{cite journal|title=Akathisia and Second-generation Antipsychotic Drugs| journal = Current Opinion in Psychiatry | volume=22 | issue = 3 | pages = 293–299 | doi = 10.1097/YCO.0b013e32832a16da | date = May 2009 |author1=Kumar, R |author2=Sachdev, PS | pmid = 19378382 |url=http://www.medscape.com/viewarticle/703492}}</ref>
 |-
 | [[Ritanserin]] || Negative symptoms || Well-tolerated || 2 DB-RPCTs || 73 || 5-HT<sub>2A/2C</sub> antagonist. Not clinically available.
@@ Line 118: / Line 118: @@
 | colspan="6" align=center | '''Other'''
 |-
-| [[Alpha-lipoic acid]]<ref>{{Cite journal | last1 = Koh | first1 = E. H. | last2 = Lee | first2 = W. J. | last3 = Lee | first3 = S. A. | last4 = Kim | first4 = E. H. | last5 = Cho | first5 = E. H. | last6 = Jeong | first6 = E. | last7 = Kim | first7 = D. W. | last8 = Kim | first8 = M. S. | last9 = Park | first9 = J. Y. | last10 = Park | first10 = K. G. | last11 = Lee | first11 = H. J. | last12 = Lee | first12 = I. K. | last13 = Lim | first13 = S. | last14 = Jang | first14 = H. C. | last15 = Lee | first15 = K. H. | last16 = Lee | first16 = K. U. | title = Effects of Alpha-Lipoic Acid on Body Weight in Obese Subjects | doi = 10.1016/j.amjmed.2010.08.005 | journal = The American Journal of Medicine | volume = 124 | pages = 85.e1 | year = 2011 | pmid =  | pmc = }}</ref><ref>{{Cite journal | last1 = Kim | first1 = E. | last2 = Park | first2 = D. W. | last3 = Choi | first3 = S. H. | last4 = Kim | first4 = J. J. | last5 = Cho | first5 = H. S. | title = A Preliminary Investigation of α-Lipoic Acid Treatment of Antipsychotic Drug-Induced Weight Gain in Patients with Schizophrenia | doi = 10.1097/JCP.0b013e31816777f7 | journal = Journal of Clinical Psychopharmacology | volume = 28 | issue = 2 | pages = 138–146 | year = 2008 | pmid =  18344723| pmc = }}</ref> || Weight gain || Well-tolerated || 1 DB-RPCT || 360 || Offset antipsychotic drug-induced weight gain. Increased total antioxidant status. May also increase GSH:GSSG (reduced glutathione:oxidized glutathione) ratio.<ref>{{Cite journal | last1 = Jariwalla | first1 = R. J. | last2 = Lalezari | first2 = J. | last3 = Cenko | first3 = D. | last4 = Mansour | first4 = S. E. | last5 = Kumar | first5 = A. | last6 = Gangapurkar | first6 = B. | last7 = Nakamura | first7 = D. | doi = 10.1089/acm.2006.6397 | title = Restoration of Blood Total Glutathione Status and Lymphocyte Function Followingα-Lipoic Acid Supplementation in Patients with HIV Infection | journal = The Journal of Alternative and Complementary Medicine | volume = 14 | issue = 2 | pages = 139–146 | year = 2008 | pmid =  18315507| pmc = }}</ref>
+| [[Alpha-lipoic acid]]<ref>{{Cite journal | last1 = Koh | first1 = E. H. | last2 = Lee | first2 = W. J. | last3 = Lee | first3 = S. A. | last4 = Kim | first4 = E. H. | last5 = Cho | first5 = E. H. | last6 = Jeong | first6 = E. | last7 = Kim | first7 = D. W. | last8 = Kim | first8 = M. S. | last9 = Park | first9 = J. Y. | last10 = Park | first10 = K. G. | last11 = Lee | first11 = H. J. | last12 = Lee | first12 = I. K. | last13 = Lim | first13 = S. | last14 = Jang | first14 = H. C. | last15 = Lee | first15 = K. H. | last16 = Lee | first16 = K. U. | title = Effects of Alpha-Lipoic Acid on Body Weight in Obese Subjects | doi = 10.1016/j.amjmed.2010.08.005 | journal = The American Journal of Medicine | volume = 124 | issue = 1 | pages = 85.e1-85.e8 | year = 2011 | pmid =  21187189| pmc = }}</ref><ref>{{Cite journal | last1 = Kim | first1 = E. | last2 = Park | first2 = D. W. | last3 = Choi | first3 = S. H. | last4 = Kim | first4 = J. J. | last5 = Cho | first5 = H. S. | title = A Preliminary Investigation of α-Lipoic Acid Treatment of Antipsychotic Drug-Induced Weight Gain in Patients with Schizophrenia | doi = 10.1097/JCP.0b013e31816777f7 | journal = Journal of Clinical Psychopharmacology | volume = 28 | issue = 2 | pages = 138–146 | year = 2008 | pmid =  18344723| pmc = }}</ref> || Weight gain || Well-tolerated || 1 DB-RPCT || 360 || Offset antipsychotic drug-induced weight gain. Increased total antioxidant status. May also increase GSH:GSSG (reduced glutathione:oxidized glutathione) ratio.<ref>{{Cite journal | last1 = Jariwalla | first1 = R. J. | last2 = Lalezari | first2 = J. | last3 = Cenko | first3 = D. | last4 = Mansour | first4 = S. E. | last5 = Kumar | first5 = A. | last6 = Gangapurkar | first6 = B. | last7 = Nakamura | first7 = D. | doi = 10.1089/acm.2006.6397 | title = Restoration of Blood Total Glutathione Status and Lymphocyte Function Followingα-Lipoic Acid Supplementation in Patients with HIV Infection | journal = The Journal of Alternative and Complementary Medicine | volume = 14 | issue = 2 | pages = 139–146 | year = 2008 | pmid =  18315507| pmc = }}</ref>
 |-
-| [[L-Theanine]]<ref>{{Cite journal | last1 = Ritsner | first1 = M. S. | last2 = Miodownik | first2 = C. | last3 = Ratner | first3 = Y. | last4 = Shleifer | first4 = T. | last5 = Mar | first5 = M. | last6 = Pintov | first6 = L. | last7 = Lerner | first7 = V. | doi = 10.4088/JCP.09m05324gre | title = L-Theanine Relieves Positive, Activation, and Anxiety Symptoms in Patients with Schizophrenia and Schizoaffective Disorder | journal = The Journal of Clinical Psychiatry | volume = 72 | issue = 1 | pages = 34–42 | year = 2011 | pmid =  21208586| pmc = }}</ref><ref>{{Cite journal | last1 = Miodownik | first1 = C. | last2 = Maayan | first2 = R. | last3 = Ratner | first3 = Y. | last4 = Lerner | first4 = V. | last5 = Pintov | first5 = L. | last6 = Mar | first6 = M. | last7 = Weizman | first7 = A. | last8 = Ritsner | first8 = M. S. | doi = 10.1097/WNF.0b013e318220d8c6 | title = Serum Levels of Brain-Derived Neurotrophic Factor and Cortisol to Sulfate of Dehydroepiandrosterone Molar Ratio Associated with Clinical Response to l-Theanine as Augmentation of Antipsychotic Therapy in Schizophrenia and Schizoaffective Disorder Patients | journal = Clinical Neuropharmacology | volume = 34 | issue = 4 | pages = 155–160 | year = 2011 | pmid =  21617527| pmc = }}</ref><ref>{{Cite journal | last1 = Lardner | first1 = A. L. | title = Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders | doi = 10.1179/1476830513Y.0000000079 | journal = Nutritional Neuroscience | pages = 140123093232009 | year = 2013 | pmid =  | pmc = | volume=17| issue = 4 }}</ref> || Positive, activation, and anxiety symptoms || Well-tolerated || 2 DB-RPCTs || 40 ||  [[Glutamic acid]] analog. Primary study noted reduction in positive, activation, and anxiety symptoms. Additional studies have noted improvements in attention.<ref>{{Cite journal | last1 = Kelly | first1 = S. P. | last2 = Gomez-Ramirez | first2 = M. | last3 = Montesi | first3 = J. L. | last4 = Foxe | first4 = J. J. | title = L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance | journal = The Journal of Nutrition | volume = 138 | issue = 8 | pages = 1572S–1577S | year = 2008 | pmid = 18641209}}</ref><ref>{{Cite journal | last1 = Park | first1 = S. K. | last2 = Jung | first2 = I. C. | last3 = Lee | first3 = W. K. | last4 = Lee | first4 = Y. S. | last5 = Park | first5 = H. K. | last6 = Go | first6 = H. J. | last7 = Kim | first7 = K. | last8 = Lim | first8 = N. K. | last9 = Hong | first9 = J. T. | last10 = Ly | first10 = S. Y. | last11 = Rho | first11 = S. S. | doi = 10.1089/jmf.2009.1374 | title = A Combination of Green Tea Extract andl-Theanine Improves Memory and Attention in Subjects with Mild Cognitive Impairment: A Double-Blind Placebo-Controlled Study | journal = Journal of Medicinal Food | volume = 14 | issue = 4 | pages = 334–343 | year = 2011 | pmid =  21303262| pmc = }}</ref><ref>{{Cite journal | last1 = Foxe | first1 = J. J. | last2 = Morie | first2 = K. P. | last3 = Laud | first3 = P. J. | last4 = Rowson | first4 = M. J. | last5 = De Bruin | first5 = E. A. | last6 = Kelly | first6 = S. P. | doi = 10.1016/j.neuropharm.2012.01.020 | title = Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task | journal = Neuropharmacology | volume = 62 | issue = 7 | pages = 2320–2327 | year = 2012 | pmid =  22326943| pmc = }}</ref><ref>{{Cite journal | last1 = Nobre | first1 = A. C. | last2 = Rao | first2 = A. | last3 = Owen | first3 = G. N. | title = L-theanine, a natural constituent in tea, and its effect on mental state | journal = Asia Pacific Journal of Clinical Nutrition | volume = 17 Suppl 1 | pages = 167–168 | year = 2008 | pmid = 18296328}}</ref> Research suggests that theanime has a regulatory effect on the nicotine acetylcholine receptor-dopamine reward pathway, and was shown to reduced dopamine production in the midbrain of mice.<ref>{{Cite journal | last1 = Di | first1 = X. | last2 = Yan | first2 = J. | last3 = Zhao | first3 = Y. | last4 = Chang | first4 = Y. | last5 = Zhao | first5 = B. | title = L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway | doi = 10.1007/s11427-012-4401-0 | journal = Science China Life Sciences | volume = 55 | issue = 12 | pages = 1064–1074 | year = 2012 | pmid =  23233221| pmc = }}</ref>
+| [[L-Theanine]]<ref>{{Cite journal | last1 = Ritsner | first1 = M. S. | last2 = Miodownik | first2 = C. | last3 = Ratner | first3 = Y. | last4 = Shleifer | first4 = T. | last5 = Mar | first5 = M. | last6 = Pintov | first6 = L. | last7 = Lerner | first7 = V. | doi = 10.4088/JCP.09m05324gre | title = L-Theanine Relieves Positive, Activation, and Anxiety Symptoms in Patients with Schizophrenia and Schizoaffective Disorder | journal = The Journal of Clinical Psychiatry | volume = 72 | issue = 1 | pages = 34–42 | year = 2011 | pmid =  21208586| pmc = }}</ref><ref>{{Cite journal | last1 = Miodownik | first1 = C. | last2 = Maayan | first2 = R. | last3 = Ratner | first3 = Y. | last4 = Lerner | first4 = V. | last5 = Pintov | first5 = L. | last6 = Mar | first6 = M. | last7 = Weizman | first7 = A. | last8 = Ritsner | first8 = M. S. | doi = 10.1097/WNF.0b013e318220d8c6 | title = Serum Levels of Brain-Derived Neurotrophic Factor and Cortisol to Sulfate of Dehydroepiandrosterone Molar Ratio Associated with Clinical Response to l-Theanine as Augmentation of Antipsychotic Therapy in Schizophrenia and Schizoaffective Disorder Patients | journal = Clinical Neuropharmacology | volume = 34 | issue = 4 | pages = 155–160 | year = 2011 | pmid =  21617527| pmc = }}</ref><ref>{{Cite journal | last1 = Lardner | first1 = A. L. | title = Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders | doi = 10.1179/1476830513Y.0000000079 | journal = Nutritional Neuroscience | pages = 145-155 | year = 2013 | pmid =  23883567| pmc = | volume=17| issue = 4 }}</ref> || Positive, activation, and anxiety symptoms || Well-tolerated || 2 DB-RPCTs || 40 ||  [[Glutamic acid]] analog. Primary study noted reduction in positive, activation, and anxiety symptoms. Additional studies have noted improvements in attention.<ref>{{Cite journal | last1 = Kelly | first1 = S. P. | last2 = Gomez-Ramirez | first2 = M. | last3 = Montesi | first3 = J. L. | last4 = Foxe | first4 = J. J. | title = L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance | journal = The Journal of Nutrition | volume = 138 | issue = 8 | pages = 1572S–1577S | year = 2008 | pmid = 18641209| doi = 10.1093/jn/138.8.1572S }}</ref><ref>{{Cite journal | last1 = Park | first1 = S. K. | last2 = Jung | first2 = I. C. | last3 = Lee | first3 = W. K. | last4 = Lee | first4 = Y. S. | last5 = Park | first5 = H. K. | last6 = Go | first6 = H. J. | last7 = Kim | first7 = K. | last8 = Lim | first8 = N. K. | last9 = Hong | first9 = J. T. | last10 = Ly | first10 = S. Y. | last11 = Rho | first11 = S. S. | doi = 10.1089/jmf.2009.1374 | title = A Combination of Green Tea Extract andl-Theanine Improves Memory and Attention in Subjects with Mild Cognitive Impairment: A Double-Blind Placebo-Controlled Study | journal = Journal of Medicinal Food | volume = 14 | issue = 4 | pages = 334–343 | year = 2011 | pmid =  21303262| pmc = }}</ref><ref>{{Cite journal | last1 = Foxe | first1 = J. J. | last2 = Morie | first2 = K. P. | last3 = Laud | first3 = P. J. | last4 = Rowson | first4 = M. J. | last5 = De Bruin | first5 = E. A. | last6 = Kelly | first6 = S. P. | doi = 10.1016/j.neuropharm.2012.01.020 | title = Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task | journal = Neuropharmacology | volume = 62 | issue = 7 | pages = 2320–2327 | year = 2012 | pmid =  22326943| pmc = }}</ref><ref>{{Cite journal | last1 = Nobre | first1 = A. C. | last2 = Rao | first2 = A. | last3 = Owen | first3 = G. N. | title = L-theanine, a natural constituent in tea, and its effect on mental state | journal = Asia Pacific Journal of Clinical Nutrition | volume = 17 Suppl 1 | pages = 167–168 | year = 2008 | pmid = 18296328}}</ref> Research suggests that theanime has a regulatory effect on the nicotine acetylcholine receptor-dopamine reward pathway, and was shown to reduced dopamine production in the midbrain of mice.<ref>{{Cite journal | last1 = Di | first1 = X. | last2 = Yan | first2 = J. | last3 = Zhao | first3 = Y. | last4 = Chang | first4 = Y. | last5 = Zhao | first5 = B. | title = L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway | doi = 10.1007/s11427-012-4401-0 | journal = Science China Life Sciences | volume = 55 | issue = 12 | pages = 1064–1074 | year = 2012 | pmid =  23233221| pmc = }}</ref>
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 | [[Famotidine]]†<ref>{{cite journal|last=Meskanen|first=K|author2=Ekelund, H |author3=Laitinenm, J |author4=Neuvonen, PJ |author5=Haukka, J |author6=Panula P |author7= Ekelund, J |title=A randomized clinical trial of histamine 2 receptor antagonism in treatment-resistant schizophrenia|journal=Journal of Clinical Psychopharmacology|date=August 2013|volume=33|issue=4|pages=472–478|doi=10.1097/JCP.0b013e3182970490|pmid=23764683}}</ref> || Global || Well-tolerated || 1 DB-RPCT || 30 || May reduce the absorption of vitamin B12 from the stomach. Might also increase susceptibility to food poisoning.
 |-
-| [[Ginkgo biloba]] ||  Tardive dyskinesia, positive symptoms || Well-tolerated || 4 DB-RPCTs || 157 || Atmaca 2005,<ref>{{Cite journal | last1 = Atmaca | first1 = M. | last2 = Tezcan | first2 = E. | last3 = Kuloglu | first3 = M. | last4 = Ustundag | first4 = B. | last5 = Kirtas | first5 = O. | title = The effect of extract of ginkgo biloba addition to olanzapine on therapeutic effect and antioxidant enzyme levels in patients with schizophrenia | doi = 10.1111/j.1440-1819.2005.01432.x | journal = Psychiatry and Clinical Neurosciences | volume = 59 | issue = 6 | pages = 652–656 | year = 2005 | pmid = 16401239 | pmc = }}</ref> Doruk 2008,<ref>{{Cite journal | last1 = Doruk | first1 = A. | last2 = Uzun | first2 = Ö. | last3 = Ozşahin | first3 = A. | doi = 10.1097/YIC.0b013e3282fcff2f | title = A placebo-controlled study of extract of ginkgo biloba added to clozapine in patients with treatment-resistant schizophrenia | journal = International Clinical Psychopharmacology | volume = 23 | issue = 4 | pages = 223–227 | year = 2008 | pmid =  18545061| pmc = }}</ref> Zhang 2001,<ref>{{Cite journal | doi = 10.1097/00004714-200102000-00015 | last1 = Zhang | first1 = X. Y. | last2 = Zhou | first2 = D. F. | last3 = Su | first3 = J. M. | last4 = Zhang | first4 = P. Y. | title = The effect of extract of ginkgo biloba added to haloperidol on superoxide dismutase in inpatients with chronic schizophrenia | journal = Journal of Clinical Psychopharmacology | volume = 21 | issue = 1 | pages = 85–88 | year = 2001 | pmid = 11199954}}</ref> Zhang 2001,<ref>{{Cite journal | doi = 10.4088/JCP.v62n1107 | last1 = Zhang | first1 = X. Y. | last2 = Zhou | first2 = D. F. | last3 = Zhang | first3 = P. Y. | last4 = Wu | first4 = G. Y. | last5 = Su | first5 = J. M. | last6 = Cao | first6 = L. Y. | title = A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia | journal = The Journal of Clinical Psychiatry | volume = 62 | issue = 11 | pages = 878–883 | year = 2001 | pmid = 11775047}}</ref> Zhang 2006,<ref>{{Cite journal | last1 = Zhang | first1 = X. Y. | last2 = Zhou | first2 = D. F. | last3 = Cao | first3 = L. Y. | last4 = Wu | first4 = G. Y. | title = The effects of Ginkgo biloba extract added to haloperidol on peripheral T cell subsets in drug-free schizophrenia: A double-blind, placebo-controlled trial | doi = 10.1007/s00213-006-0476-2 | journal = Psychopharmacology | volume = 188 | issue = 1 | pages = 12–17 | year = 2006 | pmid = 16906395 | pmc = }}</ref> Zhang 2011,<ref>{{Cite journal | last1 = Zhang | first1 = W. F. | last2 = Tan | first2 = Y. L. | last3 = Zhang | first3 = X. Y. | last4 = Chan | first4 = R. C. K. | last5 = Wu | first5 = H. R. | last6 = Zhou | first6 = D. F. | doi = 10.4088/JCP.09m05125yel | title = Extract ofGinkgo bilobaTreatment for Tardive Dyskinesia in Schizophrenia | journal = The Journal of Clinical Psychiatry | volume = 72 | issue = 5 | pages = 615–621 | year = 2011 | pmid =  20868638| pmc = }}</ref> Zhou 1999<ref>{{Cite journal | last1 = Zhou | first1 = D. | last2 = Zhang | first2 = X. | last3 = Su | first3 = J. | last4 = Nan | first4 = Z. | last5 = Cui | first5 = Y. | last6 = Liu | first6 = J. | last7 = Guan | first7 = Z. | last8 = Zhang | first8 = P. | last9 = Shen | first9 = Y. | title = The effects of classic antipsychotic haloperidol plus the extract of ginkgo biloba on superoxide dismutase in patients with chronic refractory schizophrenia | journal = Chinese medical journal | volume = 112 | issue = 12 | pages = 1093–1096 | year = 1999 | pmid = 11721446}}</ref>
+| [[Ginkgo biloba]] ||  Tardive dyskinesia, positive symptoms || Well-tolerated || 4 DB-RPCTs || 157 || Atmaca 2005,<ref>{{Cite journal | last1 = Atmaca | first1 = M. | last2 = Tezcan | first2 = E. | last3 = Kuloglu | first3 = M. | last4 = Ustundag | first4 = B. | last5 = Kirtas | first5 = O. | title = The effect of extract of ginkgo biloba addition to olanzapine on therapeutic effect and antioxidant enzyme levels in patients with schizophrenia | doi = 10.1111/j.1440-1819.2005.01432.x | journal = Psychiatry and Clinical Neurosciences | volume = 59 | issue = 6 | pages = 652–656 | year = 2005 | pmid = 16401239 | pmc = }}</ref> Doruk 2008,<ref>{{Cite journal | last1 = Doruk | first1 = A. | last2 = Uzun | first2 = Ö. | last3 = Ozşahin | first3 = A. | doi = 10.1097/YIC.0b013e3282fcff2f | title = A placebo-controlled study of extract of ginkgo biloba added to clozapine in patients with treatment-resistant schizophrenia | journal = International Clinical Psychopharmacology | volume = 23 | issue = 4 | pages = 223–227 | year = 2008 | pmid =  18545061| pmc = }}</ref> Zhang 2001,<ref>{{Cite journal | doi = 10.1097/00004714-200102000-00015 | last1 = Zhang | first1 = X. Y. | last2 = Zhou | first2 = D. F. | last3 = Su | first3 = J. M. | last4 = Zhang | first4 = P. Y. | title = The effect of extract of ginkgo biloba added to haloperidol on superoxide dismutase in inpatients with chronic schizophrenia | journal = Journal of Clinical Psychopharmacology | volume = 21 | issue = 1 | pages = 85–88 | year = 2001 | pmid = 11199954}}</ref> Zhang 2001,<ref>{{Cite journal | doi = 10.4088/JCP.v62n1107 | last1 = Zhang | first1 = X. Y. | last2 = Zhou | first2 = D. F. | last3 = Zhang | first3 = P. Y. | last4 = Wu | first4 = G. Y. | last5 = Su | first5 = J. M. | last6 = Cao | first6 = L. Y. | title = A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia | journal = The Journal of Clinical Psychiatry | volume = 62 | issue = 11 | pages = 878–883 | year = 2001 | pmid = 11775047}}</ref> Zhang 2006,<ref>{{Cite journal | last1 = Zhang | first1 = X. Y. | last2 = Zhou | first2 = D. F. | last3 = Cao | first3 = L. Y. | last4 = Wu | first4 = G. Y. | title = The effects of Ginkgo biloba extract added to haloperidol on peripheral T cell subsets in drug-free schizophrenia: A double-blind, placebo-controlled trial | doi = 10.1007/s00213-006-0476-2 | journal = Psychopharmacology | volume = 188 | issue = 1 | pages = 12–17 | year = 2006 | pmid = 16906395 | pmc = }}</ref> Zhang 2011,<ref>{{Cite journal | last1 = Zhang | first1 = W. F. | last2 = Tan | first2 = Y. L. | last3 = Zhang | first3 = X. Y. | last4 = Chan | first4 = R. C. K. | last5 = Wu | first5 = H. R. | last6 = Zhou | first6 = D. F. | doi = 10.4088/JCP.09m05125yel | title = Extract ofGinkgo bilobaTreatment for Tardive Dyskinesia in Schizophrenia | journal = The Journal of Clinical Psychiatry | volume = 72 | issue = 5 | pages = 615–621 | year = 2011 | pmid =  20868638| pmc = }}</ref> Zhou 1999<ref>{{Cite journal | last1 = Zhou | first1 = D. | last2 = Zhang | first2 = X. | last3 = Su | first3 = J. | last4 = Nan | first4 = Z. | last5 = Cui | first5 = Y. | last6 = Liu | first6 = J. | last7 = Guan | first7 = Z. | last8 = Zhang | first8 = P. | last9 = Shen | first9 = Y. | title = The effects of classic antipsychotic haloperidol plus the extract of ginkgo biloba on superoxide dismutase in patients with chronic refractory schizophrenia | journal = Chinese Medical Journal | volume = 112 | issue = 12 | pages = 1093–1096 | year = 1999 | pmid = 11721446}}</ref>
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 | [[Ondansetron]]<ref>{{cite journal|last=Bennett|first=AC|author2=Vila, TM|title=The role of ondansetron in the treatment of schizophrenia|journal=Annals of Pharmacotherapy|date=July–August 2010|volume=44|issue=7–8|pages=1301–1306|doi=10.1345/aph.1P008|pmid=20516364}}</ref> || Negative and cognitive symptoms || Well-tolerated || 3 DB-RPCTs || 151 || [[5-HT3 antagonist|5-HT<sub>3</sub> antagonist]]. May prolong the QT interval. Expensive (>$4 AUD/tablet).
@@ Line 144: / Line 144: @@
 [[Psychotherapy]] is also widely recommended, though not widely used in the treatment of schizophrenia, due to reimbursement problems or lack of training. As a result, treatment is often confined to psychiatric medication.<ref>{{cite journal | author=Moran M |url=http://pn.psychiatryonline.org/cgi/content/full/40/22/24-b |title=Psychosocial Treatment Often Missing From Schizophrenia Regimens | journal=Psychiatr News|date=18 November 2005|volume=40 | issue=22|pages=24–37|accessdate= 2007-05-17 | doi=10.1176/pn.40.22.0024b}}</ref>
-[[Cognitive behavioral therapy]] (CBT) is used to target specific symptoms and improve related issues such as [[self-esteem]] and social functioning.  Although the results of early trials were inconclusive<ref>{{Cite journal|last=Jones|first=C.|last2=Cormac|first2=I.|last3=Silveira da Mota Neto|first3=J. I.|last4=Campbell|first4=C.|date=2004-10-18|title=Cognitive behaviour therapy for schizophrenia|journal=The Cochrane Database of Systematic Reviews|issue=4|pages=CD000524|doi=10.1002/14651858.CD000524.pub2|issn=1469-493X|pmid=15495000}}</ref> as the therapy advanced from its initial applications in the mid-1990s, meta-analytic reviews suggested CBT to be an effective treatment for the psychotic symptoms of schizophrenia.<ref>{{cite journal |vauthors=Wykes T, Steel C, Everitt B, Tarrier N |title=Cognitive behavior therapy for schizophrenia: effect sizes, clinical models, and methodological rigor |journal=Schizophr Bull |volume=34 |issue=3 |pages=523–37 |date=May 2008 |pmid=17962231 |doi=10.1093/schbul/sbm114 |url= |pmc=2632426}}</ref><ref name="fn_39">{{cite journal |vauthors=Zimmermann G, Favrod J, Trieu VH, Pomini V |title=The effect of cognitive behavioral treatment on the positive symptoms of schizophrenia spectrum disorders: a meta-analysis |journal=Schizophrenia Research |volume=77 |issue=1 |pages=1–9 |date=September 2005 |pmid=16005380 |doi=10.1016/j.schres.2005.02.018 |url=http://linkinghub.elsevier.com/retrieve/pii/S0920-9964(05)00084-8|accessdate=2008-07-03}}</ref> Nonetheless, more recent meta analyses have cast doubt upon the utility of CBT as a treatment for the symptoms of psychosis<ref>{{cite journal |author1=Lynch D. |author2=Laws K. R. |author3=McKenna P. J. | year = 2010 | title = Cognitive behavioural therapy for major psychiatric disorder: does it really work? A meta-analytical review of well-controlled trials | url = | journal = Psychological Medicine | volume = 40 | issue = 01| pages = 9–24 | doi=10.1017/s003329170900590x | pmid=19476688}}</ref><ref>Newton‐Howes, Giles and Rebecca Wood. "Cognitive behavioural therapy and the psychopathology of schizophrenia: Systematic review and meta‐analysis." Psychology and Psychotherapy: Theory, Research and Practice (2011).</ref><ref>{{cite journal | author = Jones Christopher | year = 2011 | title = Cognitive behaviour therapy versus other psychosocial treatments for schizophrenia | doi = 10.1002/14651858.cd000524.pub3 | journal = The Cochrane Library | volume =  | issue = | page =  |display-authors=etal}}</ref>
+[[Cognitive behavioral therapy]] (CBT) is used to target specific symptoms and improve related issues such as [[self-esteem]] and social functioning.  Although the results of early trials were inconclusive<ref>{{Cite journal|last=Jones|first=C.|last2=Cormac|first2=I.|last3=Silveira da Mota Neto|first3=J. I.|last4=Campbell|first4=C.|date=2004-10-18|title=Cognitive behaviour therapy for schizophrenia|journal=The Cochrane Database of Systematic Reviews|issue=4|pages=CD000524|doi=10.1002/14651858.CD000524.pub2|issn=1469-493X|pmid=15495000}}</ref> as the therapy advanced from its initial applications in the mid-1990s, meta-analytic reviews suggested CBT to be an effective treatment for the psychotic symptoms of schizophrenia.<ref>{{cite journal |vauthors=Wykes T, Steel C, Everitt B, Tarrier N |title=Cognitive behavior therapy for schizophrenia: effect sizes, clinical models, and methodological rigor |journal=Schizophr Bull |volume=34 |issue=3 |pages=523–37 |date=May 2008 |pmid=17962231 |doi=10.1093/schbul/sbm114 |url= |pmc=2632426}}</ref><ref name="fn_39">{{cite journal |vauthors=Zimmermann G, Favrod J, Trieu VH, Pomini V |title=The effect of cognitive behavioral treatment on the positive symptoms of schizophrenia spectrum disorders: a meta-analysis |journal=Schizophrenia Research |volume=77 |issue=1 |pages=1–9 |date=September 2005 |pmid=16005380 |doi=10.1016/j.schres.2005.02.018 |url=http://linkinghub.elsevier.com/retrieve/pii/S0920-9964(05)00084-8|accessdate=2008-07-03}}</ref> Nonetheless, more recent meta analyses have cast doubt upon the utility of CBT as a treatment for the symptoms of psychosis<ref>{{cite journal |author1=Lynch D. |author2=Laws K. R. |author3=McKenna P. J. | year = 2010 | title = Cognitive behavioural therapy for major psychiatric disorder: does it really work? A meta-analytical review of well-controlled trials | url = | journal = Psychological Medicine | volume = 40 | issue = 1| pages = 9–24 | doi=10.1017/s003329170900590x | pmid=19476688}}</ref><ref>Newton‐Howes, Giles and Rebecca Wood. "Cognitive behavioural therapy and the psychopathology of schizophrenia: Systematic review and meta‐analysis." Psychology and Psychotherapy: Theory, Research and Practice (2011).</ref><ref>{{cite journal | author = Jones Christopher | year = 2011 | title = Cognitive behaviour therapy versus other psychosocial treatments for schizophrenia | doi = 10.1002/14651858.cd000524.pub3 | pmid = 21491377 | journal = The Cochrane Library | volume =  | issue = 4| pages = CD000524 |display-authors=etal}}</ref>
-Another approach is cognitive remediation therapy, a technique aimed at remediating the [[neurocognitive deficit]]s sometimes present in schizophrenia. Based on techniques of [[neuropsychological rehabilitation]], early evidence has shown it to be cognitively effective, resulting in the improvement of previous deficits in psychomotor speed, verbal memory, nonverbal memory, and executive function, such improvements being related to measurable changes in brain activation as measured by [[fMRI]].<ref name="fn_40">{{cite journal  |vauthors=Wykes T, Brammer M, Mellers J, etal | year = 2002 | title = Effects on the brain of a psychological treatment: cognitive remediation therapy: functional magnetic resonance imaging in schizophrenia | doi = 10.1192/bjp.181.2.144 | journal = [[British Journal of Psychiatry]] | volume = 181 | issue = | pages = 144–52 | pmid = 12151286 }}</ref>
+Another approach is cognitive remediation therapy, a technique aimed at remediating the [[neurocognitive deficit]]s sometimes present in schizophrenia. Based on techniques of [[neuropsychological rehabilitation]], early evidence has shown it to be cognitively effective, resulting in the improvement of previous deficits in psychomotor speed, verbal memory, nonverbal memory, and executive function, such improvements being related to measurable changes in brain activation as measured by [[fMRI]].<ref name="fn_40">{{cite journal  |vauthors=Wykes T, Brammer M, Mellers J, etal | year = 2002 | title = Effects on the brain of a psychological treatment: cognitive remediation therapy: functional magnetic resonance imaging in schizophrenia | doi = 10.1192/bjp.181.2.144 | journal = [[British Journal of Psychiatry]] | volume = 181 | issue = | pages = 144–52 | pmid = 12151286 | doi-broken-date = 2018-09-07 }}</ref>
-Metacognitive training: In view of many empirical findings <ref name="Moritz1">{{cite journal | doi = 10.1097/YCO.0b013e3282f0b8ed |vauthors=Moritz S, Woodward TS | year = 2007 | title = Metacognitive training in schizophrenia: from basic research to knowledge translation and intervention | url = | journal = Current Opinion in Psychiatry | volume = 20 | issue = | pages = 619–625 }}</ref> suggesting deficits of metacognition (thinking about one’s thinking, reflecting upon one’s cognitive process) in patients with schizophrenia, metacognitive training (MCT) <ref name="Moritz1" /><ref name="Moritz2">{{cite journal |vauthors=Moritz S, Woodward TS, Burlon M |year=2005|title=Metacognitive skill training for patients with schizophrenia (MCT) | publisher= VanHam Campus|location= Hamburg | url=http://www3.telus.net/Todd_S_Woodward/MKT_Manual_%28eng%29_18_4_06.pdf| format=PDF | accessdate=1 April 2011 }}</ref> is increasingly adopted as a complementary treatment approach. MCT aims at sharpening the awareness of patients for a variety of cognitive biases (e.g. jumping to conclusions, attributional biases, over-confidence in errors), which are implicated in the formation and maintenance of schizophrenia positive symptoms (especially delusions),<ref>{{cite journal | doi = 10.1016/j.tics.2006.03.004 |vauthors=Bell V, Halligan PW, Ellis HD | year = 2006 | title = Explaining delusions: a cognitive perspective | url = | journal = Trends in Cognitive Sciences | volume = 10 | issue = 5| pages = 219–226 | pmid = 16600666 }}</ref> and to ultimately replace these biases with functional cognitive strategies.
+Metacognitive training: In view of many empirical findings <ref name="Moritz1">{{cite journal | doi = 10.1097/YCO.0b013e3282f0b8ed |pmid=17921766 |vauthors=Moritz S, Woodward TS | year = 2007 | title = Metacognitive training in schizophrenia: from basic research to knowledge translation and intervention | url = | journal = Current Opinion in Psychiatry | volume = 20 | issue = 6| pages = 619–625 }}</ref> suggesting deficits of metacognition (thinking about one’s thinking, reflecting upon one’s cognitive process) in patients with schizophrenia, metacognitive training (MCT) <ref name="Moritz1" /><ref name="Moritz2">{{cite journal |vauthors=Moritz S, Woodward TS, Burlon M |year=2005|title=Metacognitive skill training for patients with schizophrenia (MCT) | publisher= VanHam Campus|location= Hamburg | url=http://www3.telus.net/Todd_S_Woodward/MKT_Manual_%28eng%29_18_4_06.pdf| format=PDF | accessdate=1 April 2011 }}</ref> is increasingly adopted as a complementary treatment approach. MCT aims at sharpening the awareness of patients for a variety of cognitive biases (e.g. jumping to conclusions, attributional biases, over-confidence in errors), which are implicated in the formation and maintenance of schizophrenia positive symptoms (especially delusions),<ref>{{cite journal | doi = 10.1016/j.tics.2006.03.004 |vauthors=Bell V, Halligan PW, Ellis HD | year = 2006 | title = Explaining delusions: a cognitive perspective | url = | journal = Trends in Cognitive Sciences | volume = 10 | issue = 5| pages = 219–226 | pmid = 16600666 }}</ref> and to ultimately replace these biases with functional cognitive strategies.
 The training consists of 8 modules and can be obtained cost-free from the internet in 15 languages.<ref name="Moritz1" /><ref name="Moritz2" /> Studies confirm the feasibility <ref>{{cite journal |vauthors=Moritz S, Woodward TS | year = 2007 | title = Metacognitive training for schizophrenia patients (MCT): A pilot study on feasibility, treatment adherence, and subjective efficacy | url =http://www.gjpsy.uni-goettingen.de/gjp-article-moritz3.pdf | format=PDF | journal = German Journal of Psychiatry | volume = 10 | issue = | pages = 69–78 }}</ref> and lend preliminary support to the efficacy <ref name="Moritz1" /><ref>{{cite journal |vauthors=Aghotor J, Pfueller U, Moritz S, Weisbrod M, Roesch-Ely D |title=Metacognitive training for patients with schizophrenia (MCT): feasibility and preliminary evidence for its efficacy |journal=J Behav Ther Exp Psychiatry |volume=41 |issue=3 |pages=207–11 |date=September 2010 |pmid=20167306 |doi=10.1016/j.jbtep.2010.01.004 |url=}}</ref><ref>{{cite journal |vauthors=Ross K, Freeman D, Dunn G, Garety P |title=A randomized experimental investigation of reasoning training for people with delusions |journal=Schizophr Bull |volume=37 |issue=2 |pages=324–33 |date=March 2011 |pmid=19520745 |pmc=3044626 |doi=10.1093/schbul/sbn165 |url=}}</ref> of the intervention. Recently, an individualized format has been developed which combines the metacognitive approach with methods derived from cognitive-behavioral therapy.<ref>Moritz S, Veckenstedt R, Randjbar S, Vitzthum F (in press). "Individualized metacognitive therapy for people with schizophrenia psychosis (MCT+)", Springer, Heidelberg. {{clarify|date=April 2011|<!-- several recent papers from https://www.ncbi.nlm.nih.gov/pubmed?term=Moritz[Author]%20Vitzthum[Author] -->}}</ref>
-Family Therapy or Education, which addresses the whole family system of an individual with a diagnosis of schizophrenia, may be beneficial, at least if the duration of intervention is longer-term.<ref>{{cite journal | doi = 10.1111/j.1752-0606.2003.tb01202.x | pmid = 12728780 | volume=29 | issue=2 | journal = Journal of marital and family therapy |date=April 2003 | title = Family psychoeducation and schizophrenia: a review of the literature.  | pages=223–45 |vauthors=McFarlane WR, Dixon L, Lukens E, Lucksted A }}</ref><ref>{{cite journal | pmid = 17187495 | doi=10.1586/14737175.7.1.33 | volume=7 | issue=1 | journal = Expert Review of Neurotherapeutics |date=January 2007 | title = New challenges in family interventions for schizophrenia  | pages=33–43 |vauthors=Glynn SM, Cohen AN, Niv N }}</ref><ref name=":0">{{Cite journal|last=Pharoah|first=Fiona|last2=Mari|first2=Jair|last3=Rathbone|first3=John|last4=Wong|first4=Winson|date=2010-12-08|title=Family intervention for schizophrenia|journal=The Cochrane Database of Systematic Reviews|issue=12|pages=CD000088|doi=10.1002/14651858.CD000088.pub2|issn=1469-493X|pmc=4204509|pmid=21154340}}</ref> A 2010 Cochrane review concluded that many of the clinical trials that studied the effectiveness of family interventions were poorly designed, and may over estimate the effectiveness of the therapy. High-quality randomized controlled trials in this area are required.<ref name=":0" /> Aside from therapy, the impact of schizophrenia on families and the burden on careers has been recognized, with the increasing availability of self-help books on the subject.<ref>{{cite book | author = Jones, S., Hayward, P. | title = Coping with Schizophrenia: A Guide for Patients, Families and Caregivers | publisher = Oneworld Pub. | year = 2004 | location = Oxford, England | isbn = 1-85168-344-5}}</ref><ref>{{cite book | last = Torrey | first = EF | authorlink = E. Fuller Torrey | title = Surviving Schizophrenia: A Manual for Families, Consumers, and Providers (5th Edition) | publisher = HarperCollins | year = 2006 | isbn = 0-06-084259-8}}</ref> There is also some evidence for benefits from social skills training, although there have also been significant negative findings.<ref>{{cite journal |vauthors=Kopelowicz A, Liberman RP, Zarate R |date=Oct 2006 | title = Recent advances in social skills training for schizophrenia | url = | journal = [[Schizophrenia Bulletin]] | volume = 32 | issue = Suppl 1| pages = S12–23 | pmid = 16885207 | pmc = 2632540 | doi=10.1093/schbul/sbl023}}</ref><ref>American Psychiatric Association (2004) Practice Guideline for the Treatment of Patients With Schizophrenia. Second Edition.</ref> Some studies have explored the possible benefits of music therapy and other creative therapies.<ref>{{cite journal | url = http://bjp.rcpsych.org/cgi/content/abstract/189/5/405 | pmid = 17077429 | journal = The British Journal of Psychiatry | doi=10.1192/bjp.bp.105.015073 | volume=189 | title = Music therapy for in-patients with schizophrenia: Exploratory randomised controlled trial |date=November 2006 | pages=405–9 |vauthors=Talwar N, Crawford MJ, Maratos A, Nur U, McDermott O, Procter S | issue=5}}</ref><ref>{{cite journal |author=Ruddy R, Milnes D |editor1-last=Ruddy |editor1-first=Rachel |title=Art therapy for schizophrenia or schizophrenia-like illnesses |journal=Cochrane Database of Systematic Reviews |volume= |issue=4 |pages=CD003728 |year=2005 |pmid=16235338 |doi=10.1002/14651858.CD003728.pub2 |url=}}</ref><ref>{{cite journal |author=Ruddy RA, Dent-Brown K |editor1-last=Ruddy |editor1-first=Rachel |title=Drama therapy for schizophrenia or schizophrenia-like illnesses |journal=Cochrane Database of Systematic Reviews |volume= |issue=1 |pages=CD005378 |year=2007 |pmid=17253555 |doi=10.1002/14651858.CD005378.pub2 |url=}}</ref>
+Family Therapy or Education, which addresses the whole family system of an individual with a diagnosis of schizophrenia, may be beneficial, at least if the duration of intervention is longer-term.<ref>{{cite journal | doi = 10.1111/j.1752-0606.2003.tb01202.x | pmid = 12728780 | volume=29 | issue=2 | journal = Journal of Marital and Family Therapy |date=April 2003 | title = Family psychoeducation and schizophrenia: a review of the literature  | pages=223–45 |vauthors=McFarlane WR, Dixon L, Lukens E, Lucksted A }}</ref><ref>{{cite journal | pmid = 17187495 | doi=10.1586/14737175.7.1.33 | volume=7 | issue=1 | journal = Expert Review of Neurotherapeutics |date=January 2007 | title = New challenges in family interventions for schizophrenia  | pages=33–43 |vauthors=Glynn SM, Cohen AN, Niv N }}</ref><ref name=":0">{{Cite journal|last=Pharoah|first=Fiona|last2=Mari|first2=Jair|last3=Rathbone|first3=John|last4=Wong|first4=Winson|date=2010-12-08|title=Family intervention for schizophrenia|journal=The Cochrane Database of Systematic Reviews|issue=12|pages=CD000088|doi=10.1002/14651858.CD000088.pub2|issn=1469-493X|pmc=4204509|pmid=21154340}}</ref> A 2010 Cochrane review concluded that many of the clinical trials that studied the effectiveness of family interventions were poorly designed, and may over estimate the effectiveness of the therapy. High-quality randomized controlled trials in this area are required.<ref name=":0" /> Aside from therapy, the impact of schizophrenia on families and the burden on careers has been recognized, with the increasing availability of self-help books on the subject.<ref>{{cite book | author = Jones, S., Hayward, P. | title = Coping with Schizophrenia: A Guide for Patients, Families and Caregivers | publisher = Oneworld Pub. | year = 2004 | location = Oxford, England | isbn = 978-1-85168-344-4}}</ref><ref>{{cite book | last = Torrey | first = EF | authorlink = E. Fuller Torrey | title = Surviving Schizophrenia: A Manual for Families, Consumers, and Providers (5th Edition) | publisher = HarperCollins | year = 2006 | isbn = 978-0-06-084259-8}}</ref> There is also some evidence for benefits from social skills training, although there have also been significant negative findings.<ref>{{cite journal |vauthors=Kopelowicz A, Liberman RP, Zarate R |date=Oct 2006 | title = Recent advances in social skills training for schizophrenia | url = | journal = [[Schizophrenia Bulletin]] | volume = 32 | issue = Suppl 1| pages = S12–23 | pmid = 16885207 | pmc = 2632540 | doi=10.1093/schbul/sbl023}}</ref><ref>American Psychiatric Association (2004) Practice Guideline for the Treatment of Patients With Schizophrenia. Second Edition.</ref> Some studies have explored the possible benefits of music therapy and other creative therapies.<ref>{{cite journal | url = http://bjp.rcpsych.org/cgi/content/abstract/189/5/405 | pmid = 17077429 | journal = The British Journal of Psychiatry | doi=10.1192/bjp.bp.105.015073 | volume=189 | title = Music therapy for in-patients with schizophrenia: Exploratory randomised controlled trial |date=November 2006 | pages=405–9 |vauthors=Talwar N, Crawford MJ, Maratos A, Nur U, McDermott O, Procter S | issue=5}}</ref><ref>{{cite journal |author=Ruddy R, Milnes D |editor1-last=Ruddy |editor1-first=Rachel |title=Art therapy for schizophrenia or schizophrenia-like illnesses |journal=Cochrane Database of Systematic Reviews |volume= |issue=4 |pages=CD003728 |year=2005 |pmid=16235338 |doi=10.1002/14651858.CD003728.pub2 |url=}}</ref><ref>{{cite journal |author=Ruddy RA, Dent-Brown K |editor1-last=Ruddy |editor1-first=Rachel |title=Drama therapy for schizophrenia or schizophrenia-like illnesses |journal=Cochrane Database of Systematic Reviews |volume= |issue=1 |pages=CD005378 |year=2007 |pmid=17253555 |doi=10.1002/14651858.CD005378.pub2 |url=}}</ref>
 The [[Soteria (psychiatric treatment)|Soteria]] model is alternative to inpatient hospitalization using full non professional care and a minimal medication approach.<ref name="mosh99">{{vcite journal |author=Mosher LR |title=Soteria and other alternatives to acute psychiatric hospitalization: a personal and professional review |journal=[[Journal of Nervous and Mental Disease]] |volume=187 |issue=3 |pages=142–9 |year=1999 |month=March |pmid=10086470 |doi=10.1097/00005053-199903000-00003}}</ref> Although evidence is limited, a review found the programme equally as effective as treatment with medications but due to the limited evidence did not recommend it as a standard treatment.<ref name="Calton_et_al_2008">{{vcite journal |author=Calton T, Ferriter M, Huband N, Spandler H |title=A systematic review of the Soteria paradigm for the treatment of people diagnosed with schizophrenia |journal=[[Schizophrenia Bulletin]] |volume=34 |issue=1 |pages=181–92 |year=2008 |month=January |pmid=17573357 |doi=10.1093/schbul/sbm047 |url=http://schizophreniabulletin.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=17573357|accessdate=2008-07-03 |pmc=2632384}}</ref> Training in the detection of subtle facial expressions has been used to improve facial emotional recognition.<ref>{{cite book|last=Bartholomeusz|first=Call|title=Handbook of Schizophrenia Spectrum Disorders, Volume III: Therapeutic Approaches, Comorbidity, and Outcomes|year=2011|publisher=Springer|isbn=9789400708341|page=189|url=https://books.google.com/books?id=SJLrIa7yFBgC&pg=PA189}}</ref>
@@ Line 163: / Line 163: @@
 ==Other==
-A 2015 Cochrane review found unclear evidence regarding if [[transcranial magnetic stimulation]] (TMS) is useful for schizophrenia.<ref>{{cite journal |last1=Dougall |first1=N |last2=Maayan |first2=N |last3=Soares-Weiser |first3=K |last4=McDermott |first4=LM |last5=McIntosh |first5=A |title=Transcranial magnetic stimulation (TMS) for schizophrenia. |journal=The Cochrane Database of Systematic Reviews |date=20 August 2015 |issue=8 |pages=CD006081 |doi=10.1002/14651858.CD006081.pub2 |pmid=26289586}}</ref>
+A 2015 Cochrane review found unclear evidence regarding if [[transcranial magnetic stimulation]] (TMS) is useful for schizophrenia.<ref>{{cite journal |last1=Dougall |first1=N |last2=Maayan |first2=N |last3=Soares-Weiser |first3=K |last4=McDermott |first4=LM |last5=McIntosh |first5=A |title=Transcranial magnetic stimulation (TMS) for schizophrenia |journal=The Cochrane Database of Systematic Reviews |date=20 August 2015 |issue=8 |pages=CD006081 |doi=10.1002/14651858.CD006081.pub2 |pmid=26289586}}</ref>
-[[Electroconvulsive therapy]] is not considered a [[first-line treatment]] but may be prescribed in cases where other treatments have failed. It is more effective where symptoms of catatonia are present,<ref>{{cite journal |vauthors=Greenhalgh J, Knight C, Hind D, Beverley C, Walters S |date=March 2005 |title= Clinical and cost-effectiveness of electroconvulsive therapy for depressive illness, schizophrenia, catatonia and mania: systematic reviews and economic modeling studies.|journal= Health Technol Assess.|volume= 9|issue=9 |pages=1–156 |pmid=15774232 |doi=10.3310/hta9090}}</ref> and is recommended for use under [[National Institute for Health and Clinical Excellence|NICE]] guidelines in the UK for catatonia if previously effective, though there is no recommendation for use for schizophrenia otherwise.<ref>{{cite web |url=http://www.nice.org.uk/page.aspx?o=TA059 |title= The clinical effectiveness and cost effectiveness of electroconvulsive Therapy (ECT) for depressive illness, schizophrenia, catatonia and mania.|accessdate=2007-06-17 |author= National Institute for Health and Clinical Excellence|date=April 2003 |publisher= National Institute for Health and Clinical Excellence}}</ref> [[Psychosurgery]] has now become a rare procedure and is not a recommended treatment for schizophrenia.<ref name="Mashour_et_al_2005">{{cite journal |vauthors=Mashour GA, Walker EE, Martuza RL | year = 2005 | title = Psychosurgery: past, present, and future | url = | journal = Brain Research. Brain Research Reviews | volume = 48 | issue = 3| pages = 409–19 | pmid = 15914249 | doi=10.1016/j.brainresrev.2004.09.002}}</ref>
+[[Electroconvulsive therapy]] is not considered a [[first-line treatment]] but may be prescribed in cases where other treatments have failed. It is more effective where symptoms of catatonia are present,<ref>{{cite journal |vauthors=Greenhalgh J, Knight C, Hind D, Beverley C, Walters S |date=March 2005 |title= Clinical and cost-effectiveness of electroconvulsive therapy for depressive illness, schizophrenia, catatonia and mania: systematic reviews and economic modeling studies|journal= Health Technol Assess.|volume= 9|issue=9 |pages=1–156 |pmid=15774232 |doi=10.3310/hta9090}}</ref> and is recommended for use under [[National Institute for Health and Clinical Excellence|NICE]] guidelines in the UK for catatonia if previously effective, though there is no recommendation for use for schizophrenia otherwise.<ref>{{cite web |url=http://www.nice.org.uk/page.aspx?o=TA059 |title= The clinical effectiveness and cost effectiveness of electroconvulsive Therapy (ECT) for depressive illness, schizophrenia, catatonia and mania|accessdate=2007-06-17 |author= National Institute for Health and Clinical Excellence|date=April 2003 |publisher= National Institute for Health and Clinical Excellence}}</ref> [[Psychosurgery]] has now become a rare procedure and is not a recommended treatment for schizophrenia.<ref name="Mashour_et_al_2005">{{cite journal |vauthors=Mashour GA, Walker EE, Martuza RL | year = 2005 | title = Psychosurgery: past, present, and future | url = | journal = Brain Research. Brain Research Reviews | volume = 48 | issue = 3| pages = 409–19 | pmid = 15914249 | doi=10.1016/j.brainresrev.2004.09.002}}</ref>
 A study in 2014 conducted by an Australian researcher indicated that the [[Fruit anatomy#Pericarp layers|pericarp]] powder of ''[[Purple mangosteen|Garcinia mangostana L.]]'' have the ability to reduce [[oxidative stress]] as an effective treatment for [[schizophrenia]] by increasing [[glutathione S-transferase]] levels which enhances [[mitochondria]]l activity over a period of 180 days under a sustained intake of 1000&nbsp;mg/day.<ref name="Laupu 2014">{{cite journal|last1=Laupu|first1=Wendy Kay|title=The efficacy of Garcinia mangostana L. (mangosteen) pericarp as an adjunctive to second-generation antipsychotics for the treatment of schizophrenia: a double blind, randomised, placebo-controlled trial|date=2014|url=https://researchonline.jcu.edu.au/40097/|accessdate=April 24, 2017|publisher=James Cook University|id=40097}}</ref><ref name="Laupu 2016">{{cite journal|last1=Laupu|first1=W|title=Interpreting outcomes from the supplementation of mangosteen rind powder capsules in schizophrenia and schizoaffective disorders|journal=British Journal of Medical and Health Research|date=September 2016|volume=3|issue=9|url=http://www.bjmhr.com/show_author_index_script.php?volume=3&issue=9&month=September&user=334#|accessdate=April 24, 2017}}</ref>
-There may be some benefit in trying several treatment modalities at the same time, especially those that could be classed as lifestyle interventions.<ref name="Helman_2018">{{cite journal|vauthors=Helman DS|year=2018|title=Recovery from schizophrenia: An autoethnography|url=http://www.tandfonline.com/doi/full/10.1080/01639625.2017.1286174|journal=Deviant Behavior|volume=39|issue=3|pages=380–399|doi=10.1080/01639625.2017.1286174}}</ref>
+There may be some benefit in trying several treatment modalities at the same time, especially those that could be classed as lifestyle interventions.<ref name="Helman_2018">{{cite journal|vauthors=Helman DS|year=2018|title=Recovery from schizophrenia: An autoethnography|journal=Deviant Behavior|volume=39|issue=3|pages=380–399|doi=10.1080/01639625.2017.1286174}}</ref>
 ==References==