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Treatment-resistant depression

From Wikipedia, the free encyclopedia
Treatment-resistant depression
Other namesTreatment-refractory depression
SpecialtyPsychiatry
SymptomsDepressive mood, anhedonia, low energy
ComplicationsSelf-harm, suicide

Treatment-resistant depression (TRD) is major depressive disorder in which an affected person does not respond adequately to at least two different antidepressant medications at an adequate dose and for an adequate duration.[1] Inadequate response has most commonly been defined as less than 25% reduction in depressive symptoms following treatment with an antidepressant.[2] Many clinicians and researchers question the construct validity and clinical utility of treatment-resistant depression as currently conceptualized.[3][4]

Other factors that may contribute to inadequate treatment are: a history of repeated or severe adverse childhood experiences, early discontinuation of treatment, failure to consider psychotherapy and other psychosocial interventions, patient noncompliance, misdiagnosis, cognitive impairment, low income and other social determinants, and concurrent medical conditions, including comorbid psychiatric disorders.[2] Cases of treatment-resistant depression may also be referred to by which medications people are resistant to (e.g.: SSRI-resistant).[5] Adding further treatments such as aripiprazole or quetiapine is weakly supported as of 2022.[6]

Risk factors

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Comorbid psychiatric disorders

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Comorbid psychiatric disorders commonly go undetected in the treatment of depression. If left untreated, the symptoms of these disorders can interfere with both evaluation and treatment. Anxiety disorders are one of the most common disorder types associated with treatment-resistant depression. The two disorders commonly co-exist, and have some similar symptoms. Some studies have shown that patients with both major depressive disorder and panic disorder are the most likely to be nonresponsive to treatment. Substance abuse may also be a predictor of treatment-resistant depression. It may cause depressed patients to be noncompliant in their treatment, and the effects of certain substances can worsen the effects of depression. Other psychiatric disorders that may predict treatment-resistant depression include attention deficit hyperactivity disorder,[7] personality disorders, obsessive compulsive disorder, and eating disorders.[8]

Comorbid medical disorders

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Some people who are diagnosed with treatment-resistant depression may have an underlying undiagnosed health condition that is causing or contributing to their depression. Endocrine disorders like hypothyroidism, Cushing's disease, and Addison's disease are among the most commonly identified as contributing to depression. Others include diabetes, coronary artery disease, cancer, HIV, and Parkinson's disease. Another factor is that medications used to treat comorbid medical disorders may lessen the effectiveness of antidepressants or cause depression symptoms.[8]

Features of depression

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People with depression who also display psychotic symptoms such as delusions or hallucinations are more likely to be treatment resistant. Another depressive feature that has been associated with poor response to treatment is longer duration of depressive episodes.[5] Finally, people with more severe depression and those who are suicidal are more likely to be nonresponsive to antidepressant treatment.[9]

Treatment

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See also: Management of depression

There are three basic categories of drug treatment that can be used when a medication course is found to be ineffective. One option is to switch the patient to a different medication. Another option is to add a medication to the patient's current treatment. This can include combination therapy: the combination of two different types of antidepressants, or augmentation therapy: the addition of a non-antidepressant medication that may increase the effectiveness of the antidepressant.[10]

Medication

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Antidepressants

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Dose increase
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Increasing the dosage of an antidepressant is a common strategy to treat depression that does not respond after adequate treatment duration. Practitioners who use this strategy will usually increase the dose until the person reports intolerable side effects, symptoms are eliminated, or the dose is increased to the limit of what is considered safe.[11]

Switching antidepressants
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Studies have shown a wide variability in the effectiveness of switching antidepressants, with anywhere from 25 to 70% of people responding to a different antidepressant.[12] There is support for the effectiveness of switching people to a different SSRI; 50% of people that were non-responsive after taking one SSRI were responsive after taking a second type. Switching people with treatment-resistant depression to a different class of antidepressants may also be effective. People who are non-responsive after taking an SSRI may respond to moclobemide or tricyclic antidepressants, bupropion or an MAOI.[11]

Some off label antidepressants are low dose ketamine and highly serotonergic catecholamines (including very controlled use of MDMA in the treatment of PTSD and crippling depression/anxiety).[citation needed] For lethargic syndromes, dysthymia, or caffeine-resistant amotivation, a dopaminergic stimulant such as methylphenidate, or even dextroamphetamine or methamphetamine can be helpful.[citation needed]

Primarily dopaminergic or norepinephrine releasing stimulants, in low doses, have been used especially in the past, or in conjunction with a multidisciplinary therapy approach, although more targeted and "mild" agents, including modafinil and atomoxetine are considered first line[by whom?] for both childhood and adult lethargy and inattention disorders, due to their virtually nonexistent abuse potential (limited to one or two cases per 10 000), and higher selectivity, safety, and thus slightly broader therapeutic index. When depression is related or co-morbid to an inattention disorder, often ADHD, then both can be carefully managed with the same first line stimulant medication, typically both methylphenidate and lisdexamfetamine.[13]

Other medications

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Medications that have been shown to be effective in people with treatment-resistant depression include lithium, liothyronine, benzodiazepines, atypical antipsychotics, and stimulants. Adding lithium may be effective for people taking some types of antidepressants including SSRIs or SNRIs. Lithium augmentation therapy was associated with a 41.2% remission rate of unipolar depression compared to 14.4% with placebo.[14][15] Liothyronine (synthetic T3) is a type of thyroid hormone and has been associated with improvement in mood and depression symptoms. Benzodiazepines may improve treatment-resistant depression by decreasing the adverse side effects caused by some antidepressants and therefore increasing patient compliance.[16]

Atypical antipsychotics such as aripiprazole, quetiapine or olanzapine can be added to anti-depressants as part of augmentation of treatment.[15] Eli Lilly, the company that sells both olanzapine and fluoxetine individually, has also released a combination formulation which contains olanzapine and fluoxetine in a single capsule. Some low to moderate quality evidence points to success in the short term (8–12 weeks) using mianserin (or antipsychotics cariprazine, olanzapine, quetiapine or ziprasidone) to augment antidepressant medications.[17] These have shown promise in treating refractory depression but come with serious side effects.[18] Stimulants such as amphetamines and methylphenidate have also been tested with positive results but have potential for abuse. However, stimulants have been shown to be effective for the unyielding depressed combined lacking addictive personality traits or heart problems.[19][20][21]

Ketamine has been tested as a rapid-acting antidepressant[22] for treatment-resistant depression in bipolar disorder, and major depressive disorder.[23] Spravato, a nasal spray form of esketamine, was approved by the FDA in 2019 for use in treatment-resistant depression when combined with an oral antidepressant.[24][25]

Research
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A 2016 placebo randomized controlled trial evaluated the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression with positive outcome.[26][27]

In 2018, the United States Food and Drug Administration (FDA) granted breakthrough therapy designation for psilocybin-assisted therapy for treatment-resistant depression.[28][29] A systematic review published in 2021 found that the use of psilocybin as a pharmaceutical substance was associated with reduced intensity of depression symptoms.[30]

Physical psychiatric treatments

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Electroconvulsive therapy

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Electroconvulsive therapy is generally only considered as a treatment option in severe cases of treatment-resistant depression. It is used when medication has repeatedly failed to improve symptoms, and usually when the patient's symptoms are so severe that they have been hospitalized. Electroconvulsive therapy has been found to reduce thoughts of suicide and relieve depressive symptoms.[31] It is associated with an increase in glial cell line derived neurotrophic factor.[32]

rTMS

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rTMS (repetitive transcranial magnetic stimulation) is gradually becoming recognised as a valuable therapeutic option in treatment-resistant depression. A number of randomised placebo-controlled trials have compared real versus sham rTMS. These trials have consistently demonstrated the efficacy of this treatment against major depression. There have also been a number of meta-analyses of RCTs[33] confirming the efficacy of rTMS in treatment-resistant major depression, as well as naturalistic studies showing its effectiveness in "real world" clinical settings.[34][35]

dTMS

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dTMS (deep transcranial magnetic stimulation) is a continuation of the same idea as rTMS, but with the hope that deeper stimulation of subcortical areas of the brain leads to increased effect.[36] A 2015 systematic review and health technology assessment found lacking evidence in order to recommend the method over either ECT or rTMS because so few studies had been published.[36]

Vagus Nerve Stimulation

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Vagus nerve stimulation has also been used for treatment-resistant depression.[37]

Deep Brain Stimulation

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Deep brain stimulation has been used in a small number of clinical trials to treat people with severe treatment-resistant depression.[38]

Magnetic seizure therapy

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Magnetic seizure therapy is currently being investigated for treating refractory depression.

Transcranial direct-current stimulation

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Transcranial direct-current stimulation is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head.

Psychotherapy

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There is sparse evidence on the effectiveness of psychotherapy in cases of treatment-resistant depression.[9] However, a review of the literature suggests that it may be an effective treatment option.[39] Psychotherapy may be effective in people with treatment-resistant depression because it can help relieve stress that may contribute to depressive symptoms.[40]

A Cochrane systematic review has shown that psychological therapies (including cognitive behavioural therapy, dialectical behavior therapy, interpersonal therapy and intensive short-term dynamic psychotherapy) added to usual care (with antidepressants) can be beneficial for depressive symptoms and for response and remission rates over the short term (up to six months) for patients with treatment-resistant depression. Medium- (7–12 months) and long‐term (longer than 12 months) effects seem similarly beneficial. Psychological therapies, including cognitive behavioral therapy, added to usual care (antidepressants) seem as acceptable as usual care alone and may be used as a first line treatment for mild to moderate treatment resistant depression.[41][15]

Outcomes

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Treatment-resistant depression is associated with more instances of relapse than depression that is responsive to treatment. One study showed that as many as 80% of people with treatment-resistant depression who needed more than one course of treatment relapsed within a year. Treatment-resistant depression has also been associated with lower long-term quality of life.[42][clarification needed]

Another study saw just 8 of 124 patients in remission after two years of standard depression treatment.[43]

References

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  1. ^ Wijeratne C, Sachdev P (September 2008). "Treatment-resistant depression: critique of current approaches". The Australian and New Zealand Journal of Psychiatry. 42 (9): 751–762. doi:10.1080/00048670802277206. PMID 18696279. S2CID 2848646.
  2. ^ a b Sforzini L, Worrell C, Kose M, Anderson IM, Aouizerate B, Arolt V, et al. (March 2022). "A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials". Molecular Psychiatry. 27 (3): 1286–1299. doi:10.1038/s41380-021-01381-x. PMC 9095475. PMID 34907394.
  3. ^ Malhi, Gin S.; Das, Pritha; Mannie, Zola; Irwin, Lauren (2019). "Treatment-resistant depression: problematic illness or a problem in our approach?". British Journal of Psychiatry. 214 (1): 1–3. doi:10.1192/bjp.2018.246. ISSN 0007-1250. failure to respond is often the result of administering inappropriate treatment, which occurs principally because of paradigm failure
  4. ^ Rost, Felicitas; Booker, Thomas; Gonsard, Aneliya; de Felice, Giulio; Asseburg, Lorena; Malda-Castillo, Javier; Koutoufa, Iakovina; Ridsdale, Hannah; Johnson, Rebecca; Taylor, David; Fonagy, Peter (2024). "The complexity of treatment-resistant depression: A data-driven approach". Journal of Affective Disorders. 358: 292–301. doi:10.1016/j.jad.2024.04.093. Our findings reveal a complex and multifaceted condition and call for an urgent reconceptualization of TRD, which encompasses many interdependent variables and experiences.
  5. ^ a b Berman RM, Narasimhan M, Charney DS (1997). "Treatment-refractory depression: definitions and characteristics". Depression and Anxiety. 5 (4): 154–164. doi:10.1002/(sici)1520-6394(1997)5:4<154::aid-da2>3.0.co;2-d. PMID 9338108. S2CID 33974050.
  6. ^ Nuñez, Nicolas A; Joseph, Boney; Pahwa, Mehak; Kumar, Rakesh; Resendez, Manuel Gardea; Prokop, Larry J; Veldic, Marin; Seshadri, Ashok; Biernacka, Joanna M; Frye, Mark A; Wang, Zhen; Singh, Balwinder (January 2022). "Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis". Journal of Affective Disorders. 302: 385–400. doi:10.1016/j.jad.2021.12.134. PMC 9328668. PMID 34986373.
  7. ^ Sternat T, Katzman MA (2016-08-25). "Neurobiology of hedonic tone: the relationship between treatment-resistant depression, attention-deficit hyperactivity disorder, and substance abuse". Neuropsychiatric Disease and Treatment. 12: 2149–2164. doi:10.2147/NDT.S111818. PMC 5003599. PMID 27601909.
  8. ^ a b Kornstein SG, Schneider RK (2001). "Clinical features of treatment-resistant depression". The Journal of Clinical Psychiatry. 62 (Suppl 16): 18–25. PMID 11480880.
  9. ^ a b Thase ME, Kasper S, Montgomery S (2013). Treatment-resistant Depression - The Role of Psychotherapy in the Management of Treatment-resistant Depression. pp. 183–208. doi:10.1002/9781118556719. ISBN 9781118556719.
  10. ^ Andrews LW (2010). Encyclopedia of depression. Santa Barbara, Calif: Greenwood Press. [page needed]
  11. ^ a b Shelton RC, Osuntokun O, Heinloth AN, Corya SA (February 2010). "Therapeutic options for treatment-resistant depression". CNS Drugs. 24 (2): 131–161. doi:10.2165/11530280-000000000-00000. PMID 20088620. S2CID 32936223.
  12. ^ Friedman ES, Anderson IM (2011). Managing depression in clinical practice. London: Springer. page 81
  13. ^ Ruhé HG, Huyser J, Swinkels JA, Schene AH (December 2006). "Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review". The Journal of Clinical Psychiatry. 67 (12): 1836–1855. doi:10.4088/JCP.v67n1203. PMID 17194261. S2CID 9758110.
  14. ^ Crossley, Nicolas Andres; Bauer, Michael (15 June 2007). "Acceleration and Augmentation of Antidepressants With Lithium for Depressive Disorders: Two Meta-Analyses of Randomized, Placebo-Controlled Trials". The Journal of Clinical Psychiatry. 68 (06): 935–940. doi:10.4088/jcp.v68n0617.
  15. ^ a b c Steffens, David C. (15 February 2024). "Treatment-Resistant Depression in Older Adults". New England Journal of Medicine. 390 (7): 630–639. doi:10.1056/NEJMcp2305428. PMC 10885705.
  16. ^ Carvalho AF, Cavalcante JL, Castelo MS, Lima MC (October 2007). "Augmentation strategies for treatment-resistant depression: a literature review". Journal of Clinical Pharmacy and Therapeutics. 32 (5): 415–428. doi:10.1111/j.1365-2710.2007.00846.x. PMID 17875106.
  17. ^ Davies P, Ijaz S, Williams CJ, Kessler D, Lewis G, Wiles N (December 2019). "Pharmacological interventions for treatment-resistant depression in adults". The Cochrane Database of Systematic Reviews. 12 (12): CD010557. doi:10.1002/14651858.CD010557.pub2. PMC 6916711. PMID 31846068.
  18. ^ Stead LG, Stead SM, Kaufman MS, Melin GJ (2005). First aid for the psychiatry clerkship: a student-to-student guide. New York: McGraw-Hill. p. 140. ISBN 978-0-07-144872-7.
  19. ^ Parker G, Brotchie H (April 2010). "Do the old psychostimulant drugs have a role in managing treatment-resistant depression?". Acta Psychiatrica Scandinavica. 121 (4): 308–314. doi:10.1111/j.1600-0447.2009.01434.x. PMID 19594481. S2CID 11417490.
  20. ^ Satel SL, Nelson JC (July 1989). "Stimulants in the treatment of depression: a critical overview". The Journal of Clinical Psychiatry. 50 (7): 241–249. PMID 2567730.
  21. ^ Warneke L (February 1990). "Psychostimulants in psychiatry". Canadian Journal of Psychiatry. 35 (1): 3–10. doi:10.1177/070674379003500102. PMID 2180548. S2CID 35020426.
  22. ^ Abdallah CG, Sanacora G, Duman RS, Krystal JH (2015). "Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics". Annual Review of Medicine. 66: 509–523. doi:10.1146/annurev-med-053013-062946. PMC 4428310. PMID 25341010.
  23. ^ Serafini G, Howland RH, Rovedi F, Girardi P, Amore M (September 2014). "The role of ketamine in treatment-resistant depression: a systematic review". Current Neuropharmacology. 12 (5): 444–461. doi:10.2174/1570159X12666140619204251. PMC 4243034. PMID 25426012.
  24. ^ McIntyre RS, Rosenblat JD, Nemeroff CB, Sanacora G, Murrough JW, Berk M, et al. (May 2021). "Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation". The American Journal of Psychiatry. 178 (5). American Psychiatric Association Publishing: 383–399. doi:10.1176/appi.ajp.2020.20081251. PMC 9635017. PMID 33726522.
  25. ^ Bahr R, Lopez A, Rey JA (June 2019). "Intranasal Esketamine (Spravato) for Use in Treatment-Resistant Depression In Conjunction With an Oral Antidepressant". P & T. 44 (6): 340–375. PMC 6534172. PMID 31160868.
  26. ^ Palhano-Fontes F, Barreto D, Onias H, Andrade KC, Novaes MM, Pessoa JA, et al. (March 2019). "Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial". Psychological Medicine. 49 (4): 655–663. doi:10.1017/S0033291718001356. PMC 6378413. PMID 29903051.
  27. ^ Barros de Araujo D (15 February 2017). "Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  28. ^ "COMPASS Pathways Receives FDA Breakthrough Therapy Designation for Psilocybin Therapy for Treatment-resistant Depression". Compass Pathways. Archived from the original on December 4, 2018. Retrieved 2018-12-03.
  29. ^ Richard Staines (2 December 2019). "FDA tags psilocybin drug as clinical depression Breakthrough Therapy". Pharmaphorum. Archived from the original on September 7, 2021. Retrieved 7 September 2021.
  30. ^ Więckiewicz G, Stokłosa I, Piegza M, Gorczyca P, Pudlo R (August 2021). "Lysergic Acid Diethylamide, Psilocybin and Dimethyltryptamine in Depression Treatment: A Systematic Review". Pharmaceuticals. 14 (8): 793. doi:10.3390/ph14080793. PMC 8399008. PMID 34451890.
  31. ^ Fink M (2009). Electroconvulsive therapy: A guide for professionals and their patients. Oxford: Oxford University Press. [page needed]
  32. ^ Zhang X, Zhang Z, Sha W, Xie C, Xi G, Zhou H, Zhang Y (December 2009). "Electroconvulsive therapy increases glial cell-line derived neurotrophic factor (GDNF) serum levels in patients with drug-resistant depression". Psychiatry Research. 170 (2–3): 273–275. doi:10.1016/j.psychres.2009.01.011. PMID 19896212. S2CID 3392108.
  33. ^ Hovington CL, McGirr A, Lepage M, Berlim MT (June 2013). "Repetitive transcranial magnetic stimulation (rTMS) for treating major depression and schizophrenia: a systematic review of recent meta-analyses". Annals of Medicine. 45 (4): 308–321. doi:10.3109/07853890.2013.783993. PMID 23687987. S2CID 46443378.
  34. ^ Carpenter LL, Janicak PG, Aaronson ST, Boyadjis T, Brock DG, Cook IA, et al. (July 2012). "Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice". Depression and Anxiety. 29 (7): 587–596. doi:10.1002/da.21969. PMID 22689344. S2CID 22968810.
  35. ^ Euba R, Panihhidina I, Zamar A (2015). "Treatment-resistant depression: the experience of the first rTMS Clinic in the UK". Future Neurology. 10 (3): 211–215. doi:10.2217/fnl.15.8.
  36. ^ a b "Effekter av djup transkraniell magnetstimulering med H-spole". Statens beredning för medicinsk och social utvärdering (SBU) [Swedish Agency for Health Technology Assessment and Assessment of Social Services] (in Swedish). October 2015. Retrieved 2017-06-02.
  37. ^ Carreno FR, Frazer A (July 2017). "Vagal Nerve Stimulation for Treatment-Resistant Depression". Neurotherapeutics. 14 (3): 716–727. doi:10.1007/s13311-017-0537-8. PMC 5509631. PMID 28585221.
  38. ^ Anderson RJ, Frye MA, Abulseoud OA, Lee KH, McGillivray JA, Berk M, Tye SJ (September 2012). "Deep brain stimulation for treatment-resistant depression: efficacy, safety and mechanisms of action". Neuroscience and Biobehavioral Reviews. 36 (8): 1920–1933. doi:10.1016/j.neubiorev.2012.06.001. PMID 22721950. S2CID 207089716.
  39. ^ Trivedi RB, Nieuwsma JA, Williams JW (June 2011). "Examination of the utility of psychotherapy for patients with treatment resistant depression: a systematic review". Journal of General Internal Medicine. 26 (6): 643–650. doi:10.1007/s11606-010-1608-2. PMC 3101965. PMID 21184287.
  40. ^ Greden J, Riba M, McInnis M (2011). Treatment resistant depression: A roadmap for effective care. Arlington, VA: American Psychiatric Publishing. [page needed]
  41. ^ Ijaz S, Davies P, Williams CJ, Kessler D, Lewis G, Wiles N (May 2018). "Psychological therapies for treatment-resistant depression in adults". The Cochrane Database of Systematic Reviews. 5 (5): CD010558. doi:10.1002/14651858.CD010558.pub2. PMC 6494651. PMID 29761488.
  42. ^ Fekadu A, Wooderson SC, Markopoulo K, Donaldson C, Papadopoulos A, Cleare AJ (July 2009). "What happens to patients with treatment-resistant depression? A systematic review of medium to long term outcome studies". Journal of Affective Disorders. 116 (1–2): 4–11. doi:10.1016/j.jad.2008.10.014. PMID 19007996.
  43. ^ "APA PsycNet".
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