Paroxetine: Difference between revisions
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'''Paroxetine''' (trade names '''Seroxat''', '''Paxil''') is a [[selective serotonin reuptake inhibitor]] (SSRI) [[antidepressant]]. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline [[Beecham (pharmaceutical company)|Beecham]], now [[GlaxoSmithKline]]. Paroxetine is used to treat [[major depressive disorder|major depression]], [[obsessive-compulsive disorder|obsessive-compulsive]], [[panic disorder|panic]], [[social phobia|social anxiety]], and [[generalised anxiety disorder|generalised anxiety]]<ref name="pmid19173371">{{cite journal |author=Katzman MA |title=Current considerations in the treatment of generalized anxiety disorder |journal=CNS Drugs |volume=23 |issue=2 |pages=103–20 |year=2009 |pmid=19173371 |doi= |url=}}</ref> disorders in adult [[Patient#Outpatient vs inpatient|outpatients]]. |
'''Paroxetine''' (trade names '''Seroxat''', '''Paxil''') is a [[selective serotonin reuptake inhibitor]] (SSRI) [[antidepressant]]. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline [[Beecham (pharmaceutical company)|Beecham]], now [[GlaxoSmithKline]]. Paroxetine is used to treat [[major depressive disorder|major depression]], [[obsessive-compulsive disorder|obsessive-compulsive]], [[panic disorder|panic]], [[social phobia|social anxiety]], and [[generalised anxiety disorder|generalised anxiety]]<ref name="pmid19173371">{{cite journal |author=Katzman MA |title=Current considerations in the treatment of generalized anxiety disorder |journal=CNS Drugs |volume=23 |issue=2 |pages=103–20 |year=2009 |pmid=19173371 |doi= |url=}}</ref> disorders in adult [[Patient#Outpatient vs inpatient|outpatients]]. |
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In adults, the efficacy of paroxetine for depression is comparable to that of older [[tricyclic antidepressant]]s, with fewer side effects and lower toxicity.<ref name="pmid10760555">{{cite journal |author=Anderson IM |title=Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability |journal=J Affect Disord |volume=58 |issue=1 |pages=19–36 |year=2000 |month=April |pmid=10760555 |doi= 10.1016/S0165-0327(99)00092-0|url=http://linkinghub.elsevier.com/retrieve/pii/S0165-0327(99)00092-0}}</ref><ref>http://cat.inist.fr/?aModele=afficheN&cpsidt=972015 </ref> Differences with newer antidepressants are subtler and mostly confined to side effects. It shares the common side effects and [[contraindication]]s of other SSRIs, with high rates of nausea, somnolence, and sexual side effects. Unlike two other popular SSRI antidepressants, [[fluoxetine]] and [[sertraline]], paroxetine is associated with clinically significant weight gain<ref name="pmid18494538">{{cite journal |author=Papakostas GI |title=Tolerability of modern antidepressants |journal=J Clin Psychiatry |volume=69 Suppl E1 |issue= |pages=8–13 |year=2008 |pmid=18494538 |doi= |url=}}</ref> and statistically significant increase in the risk of suicidality in adults,<ref name="pmid18227449">{{cite journal |author=Barbui C, Furukawa TA, Cipriani A |title=Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials |journal=CMAJ |volume=178 |issue=3 |pages=296–305 |year=2008 |month=January |pmid=18227449 |pmc=2211353 |doi=10.1503/cmaj.070693 |url=}}</ref> Pediatric trials of paroxetine for depression did not demonstrate efficacy and showed an increase in the risk of harmful outcomes, including episodes of self-harm and potentially suicidal behavior.<ref name=FDA1/><ref name="pmid16520440">{{cite journal |author=Hammad TA, Laughren T, Racoosin J |title=Suicidality in pediatric patients treated with antidepressant drugs |journal=Arch. Gen. Psychiatry |volume=63 |issue=3 |pages=332–9 |year=2006 |month=March |pmid=16520440 |doi=10.1001/archpsyc.63.3.332 |url=}}</ref><ref>{{cite web|url=http://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con019472.pdf |title=Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitor antidepressants|accessdate=2009-02-17 |date=2004-12 |format=PDF |publisher=MHRA }}</ref> |
In adults, the efficacy of paroxetine for depression is comparable to that of older [[tricyclic antidepressant]]s, with fewer side effects and lower toxicity.<ref name="pmid10760555">{{cite journal |author=Anderson IM |title=Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability |journal=J Affect Disord |volume=58 |issue=1 |pages=19–36 |year=2000 |month=April |pmid=10760555 |doi= 10.1016/S0165-0327(99)00092-0|url=http://linkinghub.elsevier.com/retrieve/pii/S0165-0327(99)00092-0}}</ref><ref>http://cat.inist.fr/?aModele=afficheN&cpsidt=972015 </ref> Differences with newer antidepressants are subtler and mostly confined to side effects. It shares the common side effects and [[contraindication]]s of other SSRIs, with high rates of nausea, somnolence, and sexual side effects. Unlike two other popular SSRI antidepressants, [[fluoxetine]] and [[sertraline]], paroxetine is associated with clinically significant weight gain<ref name="pmid18494538">{{cite journal |author=Papakostas GI |title=Tolerability of modern antidepressants |journal=J Clin Psychiatry |volume=69 Suppl E1 |issue= |pages=8–13 |year=2008 |pmid=18494538 |doi= |url=}}</ref> and statistically significant increase in the risk of suicidality in adults,<ref name="pmid18227449">{{cite journal |author=Barbui C, Furukawa TA, Cipriani A |title=Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials |journal=CMAJ |volume=178 |issue=3 |pages=296–305 |year=2008 |month=January |pmid=18227449 |pmc=2211353 |doi=10.1503/cmaj.070693 |url=}}</ref> although no causal relationship with actual suicide.<ref>http://www3.interscience.wiley.com/journal/118002942/abstract?CRETRY=1&SRETRY=0</ref> Pediatric trials of paroxetine for depression did not demonstrate efficacy and showed an increase in the risk of harmful outcomes, including episodes of self-harm and potentially suicidal behavior.<ref name=FDA1/><ref name="pmid16520440">{{cite journal |author=Hammad TA, Laughren T, Racoosin J |title=Suicidality in pediatric patients treated with antidepressant drugs |journal=Arch. Gen. Psychiatry |volume=63 |issue=3 |pages=332–9 |year=2006 |month=March |pmid=16520440 |doi=10.1001/archpsyc.63.3.332 |url=}}</ref><ref>{{cite web|url=http://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con019472.pdf |title=Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitor antidepressants|accessdate=2009-02-17 |date=2004-12 |format=PDF |publisher=MHRA }}</ref> |
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Discontinuing paroxetine is associated with a high risk of discontinuation or withdrawal syndrome.<ref name="Drug Saf2001-Haddad">{{cite journal | author = Haddad P | title = Antidepressant discontinuation syndromes | journal = Drug Saf | volume = 24 | issue = 3 | pages = 183–97 | year = 2001 | pmid = 11347722 | doi = 10.2165/00002018-200124030-00003}}</ref><ref name="pmid11823353">{{cite journal |author=Tonks A |title=Withdrawal from paroxetine can be severe, warns FDA |journal=BMJ |volume=324 |issue=7332 |pages=260 |year=2002 |month=February |pmid=11823353 |pmc=1122195 |doi=10.1136/bmj.324.7332.260 |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=11823353}}</ref> Due to the increased risk of birth defects, pregnant women or women planning to become pregnant are recommended to avoid or discontinue paroxetine use.<ref name="ReferenceA">{{cite journal |author= |title=ACOG Committee Opinion No. 354: Treatment with selective serotonin reuptake inhibitors during pregnancy |journal=Obstet Gynecol |volume=108 |issue=6 |pages=1601–3 |year=2006 |month=December |pmid=17138801 |doi= |url=}}</ref><ref>{{cite web|title=FDA Public Health Advisory Paroxetine|publisher=[[Food and Drug Administration]]|url=http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm051731.htm|accessdate=05/02/2009}}</ref><ref>{{cite web|title=Paroxetine and Pregnancy|publisher=[[GlaxoSmithKline]]|url=http://www.gsk.com/media/paroxetine_pregnancy.htm|accessdate=05/02/2009}}</ref> |
Discontinuing paroxetine is associated with a high risk of discontinuation or withdrawal syndrome.<ref name="Drug Saf2001-Haddad">{{cite journal | author = Haddad P | title = Antidepressant discontinuation syndromes | journal = Drug Saf | volume = 24 | issue = 3 | pages = 183–97 | year = 2001 | pmid = 11347722 | doi = 10.2165/00002018-200124030-00003}}</ref><ref name="pmid11823353">{{cite journal |author=Tonks A |title=Withdrawal from paroxetine can be severe, warns FDA |journal=BMJ |volume=324 |issue=7332 |pages=260 |year=2002 |month=February |pmid=11823353 |pmc=1122195 |doi=10.1136/bmj.324.7332.260 |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=11823353}}</ref> Due to the increased risk of birth defects, pregnant women or women planning to become pregnant are recommended to avoid or discontinue paroxetine use.<ref name="ReferenceA">{{cite journal |author= |title=ACOG Committee Opinion No. 354: Treatment with selective serotonin reuptake inhibitors during pregnancy |journal=Obstet Gynecol |volume=108 |issue=6 |pages=1601–3 |year=2006 |month=December |pmid=17138801 |doi= |url=}}</ref><ref>{{cite web|title=FDA Public Health Advisory Paroxetine|publisher=[[Food and Drug Administration]]|url=http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm051731.htm|accessdate=05/02/2009}}</ref><ref>{{cite web|title=Paroxetine and Pregnancy|publisher=[[GlaxoSmithKline]]|url=http://www.gsk.com/media/paroxetine_pregnancy.htm|accessdate=05/02/2009}}</ref> |
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General side effects are mostly present during the first 1–4 weeks while the body acquires a tolerance to the drug, although once this happens, withdrawal can cause a [[rebound effect]] with symptoms re-emerging in an exaggerated form for very long periods of time. Almost all SSRIs are known to cause either one or more of these symptoms. A person receiving paroxetine treatment may experience a few, all, or none of the listed side-effects, and most side-effects will disappear or lessen with continued treatment, though some may last throughout the duration. Side effects are also often dose-dependent, with fewer and/or less severe symptoms being reported at lower dosages, and/or more severe symptoms being reported at higher dosages. Increases or changes in dosage may also cause symptoms to reappear or worsen.<ref name="gsk-paxil">{{cite web|url=http://us.gsk.com/products/assets/us_paxil.pdf|format=PDF|title=PAXIL (paroxetine hydrochloride) Tablets and Oral Suspension: PRESCRIBING INFORMATION|year=2007|month=August|accessdate=2007-08-14|publisher=[[GlaxoSmithKline]]|location=Research Triangle Park, NC}}</ref> |
General side effects are mostly present during the first 1–4 weeks while the body acquires a tolerance to the drug, although once this happens, withdrawal can cause a [[rebound effect]] with symptoms re-emerging in an exaggerated form for very long periods of time. Almost all SSRIs are known to cause either one or more of these symptoms. A person receiving paroxetine treatment may experience a few, all, or none of the listed side-effects, and most side-effects will disappear or lessen with continued treatment, though some may last throughout the duration. Side effects are also often dose-dependent, with fewer and/or less severe symptoms being reported at lower dosages, and/or more severe symptoms being reported at higher dosages. Increases or changes in dosage may also cause symptoms to reappear or worsen.<ref name="gsk-paxil">{{cite web|url=http://us.gsk.com/products/assets/us_paxil.pdf|format=PDF|title=PAXIL (paroxetine hydrochloride) Tablets and Oral Suspension: PRESCRIBING INFORMATION|year=2007|month=August|accessdate=2007-08-14|publisher=[[GlaxoSmithKline]]|location=Research Triangle Park, NC}}</ref> |
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There is no statistical proof of a causal relationship between paroxetine and suicide, but there is a relationship between depression, anxiety and suicide.<ref>http://www3.interscience.wiley.com/journal/118002942/abstract?CRETRY=1&SRETRY=0</ref> |
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On 9 December 2004, the [[European Medicines Agency]]'s (EMEA) Committee for Medicinal Products for Human Use (CHMP) informed patients, prescribers, and parents that paroxetine should not be prescribed to children. CHMP also gave a warning to prescribers recommending close monitoring of adult patients at high risk of suicidal behaviour and/or suicidal thoughts. CHMP does not prohibit use of paroxetine with high risk adults but urges extreme caution. Due to reports of adverse withdrawal reactions upon terminating treatment, CHMP recommends to reduce gradually over several weeks or months if the decision to withdraw is made.<ref>{{cite web|url=http://www.emea.europa.eu/pdfs/human/press/pr/19257004en.pdf|format=PDF|publisher=European Medicines Agency|title=Press release, CHMP meeting on Paroxetine and other SSRIs|date=2004-12-09|accessdate=2007-08-24}}</ref> See also [[Paroxetine#Discontinuation syndrome (withdrawal)|Discontinuation syndrome (withdrawal)]]. |
On 9 December 2004, the [[European Medicines Agency]]'s (EMEA) Committee for Medicinal Products for Human Use (CHMP) informed patients, prescribers, and parents that paroxetine should not be prescribed to children. CHMP also gave a warning to prescribers recommending close monitoring of adult patients at high risk of suicidal behaviour and/or suicidal thoughts. CHMP does not prohibit use of paroxetine with high risk adults but urges extreme caution. Due to reports of adverse withdrawal reactions upon terminating treatment, CHMP recommends to reduce gradually over several weeks or months if the decision to withdraw is made.<ref>{{cite web|url=http://www.emea.europa.eu/pdfs/human/press/pr/19257004en.pdf|format=PDF|publisher=European Medicines Agency|title=Press release, CHMP meeting on Paroxetine and other SSRIs|date=2004-12-09|accessdate=2007-08-24}}</ref> See also [[Paroxetine#Discontinuation syndrome (withdrawal)|Discontinuation syndrome (withdrawal)]]. |
Revision as of 08:58, 28 August 2009
File:Paroxetine.svg | |
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Clinical data | |
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License data |
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Routes of administration | Oral |
ATC code | |
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Pharmacokinetic data | |
Bioavailability | Completely absorbed from GI, but extensive first-pass metabolism in the liver; Tmax 4.9 (with meals) to 6.4 hours (fasting) |
Protein binding | 93–95% |
Metabolism | Extensive, hepatic (mostly CYP2D6-mediated) |
Elimination half-life | 24 hours (range 3–65 hours) |
Excretion | 64% in urine, 36% in bile |
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CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.112.096 |
Chemical and physical data | |
Formula | C19H20FNO3 |
Molar mass | 329.3 g·mol−1 |
3D model (JSmol) | |
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Paroxetine (trade names Seroxat, Paxil) is a selective serotonin reuptake inhibitor (SSRI) antidepressant. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline. Paroxetine is used to treat major depression, obsessive-compulsive, panic, social anxiety, and generalised anxiety[2] disorders in adult outpatients.
In adults, the efficacy of paroxetine for depression is comparable to that of older tricyclic antidepressants, with fewer side effects and lower toxicity.[3][4] Differences with newer antidepressants are subtler and mostly confined to side effects. It shares the common side effects and contraindications of other SSRIs, with high rates of nausea, somnolence, and sexual side effects. Unlike two other popular SSRI antidepressants, fluoxetine and sertraline, paroxetine is associated with clinically significant weight gain[5] and statistically significant increase in the risk of suicidality in adults,[6] although no causal relationship with actual suicide.[7] Pediatric trials of paroxetine for depression did not demonstrate efficacy and showed an increase in the risk of harmful outcomes, including episodes of self-harm and potentially suicidal behavior.[8][9][10]
Discontinuing paroxetine is associated with a high risk of discontinuation or withdrawal syndrome.[11][12] Due to the increased risk of birth defects, pregnant women or women planning to become pregnant are recommended to avoid or discontinue paroxetine use.[13][14][15]
Indications
Paroxetine is primarily used to treat the symptoms of major depression, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, generalized anxiety disorder (GAD),[16] social phobia/social anxiety disorder,[17] and premenstrual dysphoric disorder (PMDD).[18] For some indications paroxetine has demonstrated high effectiveness for example in severe premenstrual syndrome[19] and is considered an evidence based first line agent in the treatment of generalised anxiety disorder in a review of the literature. Other SSRIs are also effective and considered first line treatment agents. Side effects may limit its effectiveness and as with many drugs not everyone has an effective response. Emerging evidence shows that antipsychotics can be used as an alternative in such individuals.[2] Paroxetine may be effective for the treatment of dysthymia although the evidence is conflicting. Dysthymia is a chronic disorder which involves depressive symptoms for most days of the year.[20]
Paroxetine was the first antidepressant formally approved in the United States for the treatment of panic attacks.[21]
According to the prescribing information provided by the manufacturer of the Paxil brand of paroxetine (GlaxoSmithKline) and approved by the U.S. Food and Drug Administration (FDA),[22] the effectiveness of paroxetine in major depressive disorder has been proven by six placebo-controlled clinical trials. For panic disorder, three 10-12-week studies indicated paroxetine superiority to placebo.[22] Similarly, three 12-week trials for adult outpatients with social anxiety disorder demonstrated better response to paroxetine than to placebo.[22]
Unapproved/off-label/investigational
Several studies have suggested that paroxetine can be used in the treatment of premature ejaculation. In particular, intravaginal ejaculation latency time (IELT) was found to increase with 6-13-fold, which was somewhat longer than the delay achieved by the treatment with other SSRIs (fluvoxamine, fluoxetine, sertraline, and citalopram).[23][24][25] However, paroxetine taken acutely ("on demand") 3–10 hours before coitus resulted only in a "clinically irrelevant and sexually unsatisfactory" 1.5-fold delay of ejaculation and was inferior to clomipramine, which induced a fourfold delay.[25]
SSRIs are also highly effective in the treatment of severe premenstrual syndrome[19]; however, paroxetine is contraindicated in women who may become pregnant due to its teratogenicity and its high risk of withdrawal syndrome in both adults and neonates. See Paroxetine and pregnancy.
There is also evidence that paroxetine may be effective in the treatment of compulsive gambling[26] and hot flashes.[27]
In two double-blind studies of bipolar disorder patients, addition of paroxetine to a mood stabilizer had no advantages over addition of placebo.[28][29] Benefits of paroxetine prescription for diabetic neuropathy[30] or chronic tension headache.[31] are uncertain.
Contraindications
Paroxetine is contraindicated in all patients under 18, in all patients taking any of the drugs listed in the interactions section below, and in adult women who are or may become pregnant. Paroxetine may also be contraindicated in many adult men due to sexual and reproductive side effects described below. In the United States, the Food and Drug Administration requires this drug to carry a black box warning, its "most serious type of warning in prescription drug labeling,"[32] due to increased risk of suicidal ideation and behavior. The warning also applies to other SSRIs, but the concern began with reports of suicidal behavior in paroxetine trials, as well as recommendations from the United Kingdom Medicines and Healthcare products Regulatory Agency urging that paroxetine not be used in individuals younger than 18 years.[33]
Side effects
Among the common adverse effects associated with paroxetine treatment of depression and listed in the prescribing information, those with the greatest difference from placebo are nausea (26% on paroxetine vs 9% on placebo), somnolence (23% vs. 9% on placebo), ejaculatory disturbance (13% vs. 0% on placebo), other male genital disorders (10% vs. 0% on placebo), asthenia (15% vs. 6% on placebo), sweating (11% vs. 2% on placebo), dizziness (13% vs. 6% on placebo), insomnia (13% vs. 6% on placebo), dry mouth (18% vs. 12% on placebo), constipation (14% vs. 9% on placebo), and tremor (8% vs. 2% on placebo).[22] Other side effects include headache, agitation, weight gain, impaired memory and paresthesia.[34]
General side effects are mostly present during the first 1–4 weeks while the body acquires a tolerance to the drug, although once this happens, withdrawal can cause a rebound effect with symptoms re-emerging in an exaggerated form for very long periods of time. Almost all SSRIs are known to cause either one or more of these symptoms. A person receiving paroxetine treatment may experience a few, all, or none of the listed side-effects, and most side-effects will disappear or lessen with continued treatment, though some may last throughout the duration. Side effects are also often dose-dependent, with fewer and/or less severe symptoms being reported at lower dosages, and/or more severe symptoms being reported at higher dosages. Increases or changes in dosage may also cause symptoms to reappear or worsen.[22]
There is no statistical proof of a causal relationship between paroxetine and suicide, but there is a relationship between depression, anxiety and suicide.[35]
On 9 December 2004, the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) informed patients, prescribers, and parents that paroxetine should not be prescribed to children. CHMP also gave a warning to prescribers recommending close monitoring of adult patients at high risk of suicidal behaviour and/or suicidal thoughts. CHMP does not prohibit use of paroxetine with high risk adults but urges extreme caution. Due to reports of adverse withdrawal reactions upon terminating treatment, CHMP recommends to reduce gradually over several weeks or months if the decision to withdraw is made.[36] See also Discontinuation syndrome (withdrawal).
A statistical analysis of paroxetine clinical trials in children and adolescents was conducted by the FDA in 2004. It indicated a statistically significant 2.7-fold raise in suicide behavior and ideation as compared to placebo. The trend for increased suicidality was observed in both trials for depression and for anxiety disorders.[8]
Cases of akathisia[37][38] and activation syndrome[39][40] have been observed during paroxetine treatment.
Rarely serotonin syndrome, a severe adverse effect may occur.[41][42]
Paroxetine and other SSRIs have been shown to cause sexual side effects in most patients, both males and females.[43] In males, paroxetine is also linked to sperm DNA fragmentation.[44]
Mania or hypomania may occur as a serious side effect of paroxetine,[45][46][47] affecting up to 8% of psychiatric patients treated. This side effect can occur in individuals with no history of mania but it is more likely to occur in those with bipolar or with a family history of mania.[48]
Schmitt et al. (2001) suggested that paroxetine negatively affects memory (i.e., IQ). In their study, healthy participants given paroxetine for 14 days (20 mg for days 1–7 and 40 mg days 8–14) showed poorer recall of words on day 14 compared to those receiving a placebo. Schmitt et al. did not take into account a significant difference in verbal recall at baseline between the paroxetine and placebo groups, however, and this difference may have been the source of the significant group difference on day 14. Moreover, participants receiving paroxetine recalled as many words at baseline as they recalled on day 14, which is not consistent with the conclusion that paroxetine negatively affects verbal recall.[49]
Discontinuation syndrome (withdrawal)
Many psychoactive medications can cause withdrawal symptoms upon discontinuation from administration. Evidence has shown that paroxetine has among the highest incidence rates and severity of withdrawal syndrome of any medication of its class.[12][50] Common withdrawal symptoms for paroxetine include nausea, dizziness, lightheadedness and vertigo; insomnia, nightmares and vivid dreams; feelings of electricity in the body, as well as crying and anxiety.[51][52] Liquid formulation of paroxetine is available and allows a very gradual decrease of the dose, which may prevent discontinuation syndrome. Another recommendation is to temporarily switch to fluoxetine, which has a longer half-life and thus decreases the severity of discontinuation syndrome.[11][53][54]
In addition, The Lancet published an analysis of World Health Organization data showing SSRIs taken during pregnancy may cause withdrawal symptoms, including convulsions, in newborn children: among "93 suspected cases of SSRI-induced neonatal withdrawal syndrome...64 were associated with paroxetine, 14 with fluoxetine, nine with sertraline, and seven with citalopram."[55]
Paroxetine and pregnancy
The American College of Obstetricians and Gynecologists recommends that pregnant women and women planning to become pregnant should avoid using paroxetine.[13] According to the prescribing information[22] "epidemiological studies have shown that infants born to women who had first trimester paroxetine exposure had an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects (VSDs and ASDs). In general, septal defects range from those that are symptomatic and may require surgery to those that are asymptomatic and may resolve spontaneously. If a patient becomes pregnant while taking paroxetine, she should be advised of the potential harm to the fetus. Unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant. For women who intend to become pregnant or are in their first trimester of pregnancy, paroxetine should only be initiated after consideration of the other available treatment options." These conclusions are supported by multiple systematic reviews and meta-analyses that found that, on average, the use of paroxetine during pregnancy is associated with about 1.5-1.7-fold increase in congenital birth defects, in particular, heart defects.[56][57][58][59][60] A recent non-systematic review in the Journal of Clinical Psychiatry, with the lead author, Salvatore Gentile, reporting to have received material or financial support from GSK, came to a different conclusion: "the teratogenic potential of paroxetine that has been reported in some studies remains unproven." Gentile called for large, epidemiologic, prospective, controlled studies on "mothers who accept taking paroxetine during pregnancy".[61] Other reviews vary on whether the teratogenic risks outweigh the risk of disease relapse if the drug is discontinued: some advocate discontinuation,[56] while others suggest caution;[58] even where the overview of antidepressants generally is favorable, paroxetine is singled out for specific risks.[59]
Abrupt discontinuation of psychotropic drugs during pregnancy can also lead to serious adverse effects.[62]
Counseling is effective in reassuring women to adhere to therapy,[62] but neonatal paroxetine withdrawal symptoms described above have been documented from mothers taking Paxil during pregnancy.[63]
Paroxetine interactions with other drugs
GlaxoSmithKline cautions that drug interactions may create or increase specific risks, including Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions:
- The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including treatment with PAXIL, but particularly with concomitant use of serotonergic drugs (including triptans) with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists.
The prescribing information states that paroxetine should "not be used in combination with an MAOI (including linezolid, an antibiotic which is a reversible non-selective MAOI), or within 14 days of discontinuing treatment with an MAOI," and should not be used in combination with pimozide, thioridazine, tryptophan, or warfarin.[64]
Pharmacology
Paroxetine is the most potent and one of the most specific selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRI).[65] This activity of the drug on brain neurons is thought to be responsible for its antidepressant effects.
Paroxetine is a phenylpiperidine derivative which is chemically unrelated to the tricyclic or tetracyclic antidepressants. In receptor binding studies, paroxetine did not exhibit significant affinity for the adrenergic (α1, α2, β), dopaminergic, serotonergic (5HT1, 5HT2), or histamine receptors of rat brain membrane. A weak affinity for the muscarinic acetylcholine and noradrenaline receptors was evident. The predominant metabolites of paroxetine are essentially inactive as 5-HT reuptake inhibitors.
Formulations
Paroxetine CR (controlled release) was shown to be associated with a lower rate of nausea during the first week of treatment than paroxetine immediate release. However, the rate of treatment discontinuation due to nausea was not significantly different.[66]
Controversy
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For 10 years, GlaxoSmithKline's marketing of the drug stated that it was "not habit forming," which numerous experts and at least one court found to be incorrect.[50][67][68][69] In 2001, the BBC reported the World Health Organization had ranked paroxetine as the most difficult antidepressant to withdraw from.[70][71][72] In 2002, the U.S. FDA published a new product warning about the drug, and the International Federation of Pharmaceutical Manufacturers Associations said GSK had misled the public about paroxetine and breached two of the Federation's codes of practice.[12][73] The British Medical Journal quoted Charles Medawar, head of Social Audit: "This drug has been promoted for years as safe and easy to discontinue.... The fact that it can cause intolerable withdrawal symptoms of the kind that could lead to dependence is enormously important to patients, doctors, investors, and the company. GlaxoSmithKline has evaded the issue since it was granted a license for paroxetine over 10 years ago, and the drug has become a blockbuster for them, generating about a tenth of their entire revenue. The company has been promoting paroxetine directly to consumers as 'non-habit forming' for far too long."[12] Paroxetine prescribing information posted at GlaxoSmithKline now acknowledges the occurrence of a discontinuation syndrome, including serious discontinuation symptoms.[74]
A British Government parliamentary inquiry into a number of prescription and over the counter drugs noted problems with SSRI antidepressants including withdrawal, suicidal thoughts, and other adverse effects. The inquiry found that paroxetine (Paxil, Seroxat) has, more commonly than other SSRI antidepressants, a very devastating impact on some users' lives.[75] Since the FDA approved paroxetine in 1992, approximately 5,000 U.S. citizens have sued GSK. Most of these people feel they were not sufficiently warned in advance of the drug's side effects—particularly the withdrawal syndrome discussed above, after GSK had specifically advertised the drug as non-habit forming[67]
In the UK, since 2001 lawsuits have been filed representing people who have been prescribed Seroxat. They allege that the drug has serious side effects, which GlaxoSmithKline downplayed in patient information.[76][77]
In early 2004, GSK agreed to settle charges of consumer fraud for $2.5 million (a tiny fraction of the over $2.7 billion in yearly Paxil sales at that time).[78] The legal discovery process also uncovered evidence of deliberate, systematic suppression of unfavorable Paxil research results. One of GSK's internal documents had said, "It would be commercially unacceptable to include a statement that efficacy [in children] had not been demonstrated, as this would undermine the profile of paroxetine"[79].
In June 2004, FDA published a violation letter to GSK in response to a "false or misleading" TV ad for Paxil CR; FDA stated, "This ad is concerning from a public health perspective because it broadens the use of Paxil CR [beyond the conditions it was approved for] while also minimizing the serious risks associated with the drug."[80] GSK claimed the ad had been previously reviewed by FDA, but said the ad would not run again.[81]
On January 29, 2007, the BBC broadcast a fourth documentary in its Panorama series about the drug Seroxat.[82] This programme, entitled Secrets of the Drug Trials, focused on three GSK paediatric clinical trials on depressed children and adolescents. Data from the trials show that Seroxat could not be proven to work for teenagers. Also, one clinical trial indicated that adolescents were six times more likely to become suicidal after taking it. Results from Study 329, one of the trials, were reported [83] in a way which misled readers about paroxetine's safety and efficacy, and contributed to repeated distortions in the assessment of the drug's value in paediatric depression in the scientific literature.[84]
The court documents released as a result of one of the lawsuits in October 2008 indicated that GSK "and/or researchers may have suppressed or obscured suicide risk data during clinical trials" of paroxetine. One of the investigators, "Charles Nemeroff, former chairman of the Department of Psychiatry at Emory University, was the first big name 'outed' ...In early October 2008, Nemeroff stepped down as department chair amid revelations that he had received over $960,000 from GSK in 2006, yet reported less than $35,000 to the school. Subsequent investigations revealed payments totaling more than $2.5 million from drug companies between 2000 and 2006, yet only a fraction was disclosed."[85]
The suppression of unfavorable research findings on Paxil by GSK — and the legal discovery process that uncovered it — is the subject of Alison Bass's 2008 book Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial[86].
Sales
In 2007, paroxetine was ranked 94th on the list of bestselling drugs, with over $1 billion in sales. In 2006, paroxetine was the fifth-most prescribed antidepressant in the United States retail market, with more than 19.7 million prescriptions.[87] In 2007, sales had dropped slightly to 18.1 million but paroxetine remained the fifth-most prescribed antidepressant in the U.S.[88]
Footnotes
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
- ^ a b Katzman MA (2009). "Current considerations in the treatment of generalized anxiety disorder". CNS Drugs. 23 (2): 103–20. PMID 19173371.
- ^ Anderson IM (2000). "Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability". J Affect Disord. 58 (1): 19–36. doi:10.1016/S0165-0327(99)00092-0. PMID 10760555.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ http://cat.inist.fr/?aModele=afficheN&cpsidt=972015
- ^ Papakostas GI (2008). "Tolerability of modern antidepressants". J Clin Psychiatry. 69 Suppl E1: 8–13. PMID 18494538.
- ^ Barbui C, Furukawa TA, Cipriani A (2008). "Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials". CMAJ. 178 (3): 296–305. doi:10.1503/cmaj.070693. PMC 2211353. PMID 18227449.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ http://www3.interscience.wiley.com/journal/118002942/abstract?CRETRY=1&SRETRY=0
- ^ a b Hammad TA (2004-08-16). "Review and evaluation of clinical data: relationship between psychotropic drugs and pediatric suicidality" (PDF). Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and Pediatric Advisory Committee. September 13 - 14, 2004. Briefing Information. FDA. p. 30. Retrieved 2009-01-27.
- ^ Hammad TA, Laughren T, Racoosin J (2006). "Suicidality in pediatric patients treated with antidepressant drugs". Arch. Gen. Psychiatry. 63 (3): 332–9. doi:10.1001/archpsyc.63.3.332. PMID 16520440.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ "Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitor antidepressants" (PDF). MHRA. 2004-12. Retrieved 2009-02-17.
{{cite web}}
: Check date values in:|date=
(help) - ^ a b Haddad P (2001). "Antidepressant discontinuation syndromes". Drug Saf. 24 (3): 183–97. doi:10.2165/00002018-200124030-00003. PMID 11347722.
- ^ a b c d Tonks A (2002). "Withdrawal from paroxetine can be severe, warns FDA". BMJ. 324 (7332): 260. doi:10.1136/bmj.324.7332.260. PMC 1122195. PMID 11823353.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ a b "ACOG Committee Opinion No. 354: Treatment with selective serotonin reuptake inhibitors during pregnancy". Obstet Gynecol. 108 (6): 1601–3. 2006. PMID 17138801.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ "FDA Public Health Advisory Paroxetine". Food and Drug Administration. Retrieved 05/02/2009.
{{cite web}}
: Check date values in:|accessdate=
(help) - ^ "Paroxetine and Pregnancy". GlaxoSmithKline. Retrieved 05/02/2009.
{{cite web}}
: Check date values in:|accessdate=
(help) - ^ Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Scott J, Wittchen HU (2005). "Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology". Journal of Psychopharmacology. 19 (6): 567–596. doi:10.1177/0269881105059253. PMID 16272179.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ D Baldwin, J Bobes, DJ Stein, I Scharwachter and M Faure (1999). "Paroxetine in social phobia/social anxiety disorder. Randomised, double-blind, placebo-controlled study. Paroxetine Study Group". The British Journal of Psychiatry. 175: 120–126. doi:10.1192/bjp.175.2.120. PMID 10627793.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Yonkers KA, Gullion C, Williams A, Novak K, Rush AJ. (1996). "Paroxetine as a treatment for premenstrual dysphoric disorder". Journal of Clinical Psychopharmacology. 16 (1): 3–8. doi:10.1097/00004714-199602000-00002. PMID 8834412.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Brown J, O' Brien PM, Marjoribanks J, Wyatt K (2009). "Selective serotonin reuptake inhibitors for premenstrual syndrome". Cochrane Database Syst Rev (2): CD001396. doi:10.1002/14651858.CD001396.pub2. PMID 19370564.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Gartlehner G, Gaynes BN, Hansen RA; et al. (2008). "Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians". Ann. Intern. Med. 149 (10): 734–50. PMID 19017592.
{{cite journal}}
: Explicit use of et al. in:|author=
(help); Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Turner, Francis Joseph (2005). Social Work Diagnosis in Contemporary Practice. Oxford University Press US. ISBN 019516878X.
- ^ a b c d e f "PAXIL (paroxetine hydrochloride) Tablets and Oral Suspension: PRESCRIBING INFORMATION" (PDF). Research Triangle Park, NC: GlaxoSmithKline. 2007. Retrieved 2007-08-14.
{{cite web}}
: Unknown parameter|month=
ignored (help) - ^ Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B (1998). "Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline". Journal of clinical psychopharmacology. 18 (4): 274–81. doi:10.1097/00004714-199808000-00004. PMID 9690692.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Waldinger MD, Zwinderman AH, Olivier B (2001). "SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram". Journal of clinical psychopharmacology. 21 (6): 556–60. doi:10.1097/00004714-200112000-00003. PMID 11763001.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Waldinger MD, Zwinderman AH, Olivier B (2004). "On-demand treatment of premature ejaculation with clomipramine and paroxetine: a randomized, double-blind fixed-dose study with stopwatch assessment". Eur. Urol. 46 (4): 510–5, discussion 516. doi:10.1016/j.eururo.2004.05.005. PMID 15363569.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Kim SW, Grant JE, Adson DE, Shin YC, Zaninelli R (2002). "A double-blind placebo-controlled study of the efficacy and safety of paroxetine in the treatment of pathological gambling". Journal of Clinical Psychiatry. 63 (6): 501–507. PMID 12088161.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Weitzner MA, Moncello J, Jacobsen PB, Minton S. (2002). "A pilot trial of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer". Journal of Pain and Symptom Management. 23 (4): 337–345. doi:10.1016/S0885-3924(02)00379-2. PMID 11997203.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Nemeroff CB, Evans DL, Gyulai L, Sachs GS, Bowden CL, Gergel IP, Oakes R, Pitts CD (2001). "Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression". The American journal of psychiatry. 158 (6): 906–12. PMID 11384898.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Sachs GS, Nierenberg AA, Calabrese JR, Marangell LB, Wisniewski SR, Gyulai L, Friedman ES, Bowden CL, Fossey MD, Ostacher MJ, Ketter TA, Patel J, Hauser P, Rapport D, Martinez JM, Allen MH, Miklowitz DJ, Otto MW, Dennehy EB, Thase ME (2007). "Effectiveness of adjunctive antidepressant treatment for bipolar depression". N. Engl. J. Med. 356 (17): 1711–22. doi:10.1056/NEJMoa064135. PMID 17392295.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Vieta E, Martinez-Aran A, Goikolea JM, Torrent C, Colom F, Benabarre A, Reinares M (1999). "The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms". Pain. 42 (2): 135–144. doi:10.1016/0304-3959(90)91157-E. PMID 2147235.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Langemark M, Olesen J (1994). "Sulpiride and paroxetine in the treatment of chronic tension-type headache. An explanatory double-blind trial". Headache. 34 (1): 20–4. doi:10.1111/j.1526-4610.1994.hed3401020.x. PMID 8132436.
- ^ http://www.nimh.nih.gov/health/topics/child-and-adolescent-mental-health/antidepressant-medications-for-children-and-adolescents-information-for-parents-and-caregivers.shtml
- ^ http://www.pharmacytimes.com/issues/articles/2008-05_002.asp
- ^ Masand PS, Gupta S (1999). "Selective serotonin-reuptake inhibitors: an update". Harv Rev Psychiatry. 7 (2): 69–84. doi:10.1093/hrp/7.2.69. PMID 10471245.
- ^ http://www3.interscience.wiley.com/journal/118002942/abstract?CRETRY=1&SRETRY=0
- ^ "Press release, CHMP meeting on Paroxetine and other SSRIs" (PDF). European Medicines Agency. 2004-12-09. Retrieved 2007-08-24.
- ^ Olivera AA (1996). "A case of paroxetine-induced akathisia". Biol. Psychiatry. 39 (10): 910. doi:10.1016/0006-3223(96)84504-5. PMID 8860197.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Baldassano CF, Truman CJ, Nierenberg A, Ghaemi SN, Sachs GS (1996). "Akathisia: a review and case report following paroxetine treatment". Compr Psychiatry. 37 (2): 122–4. doi:10.1016/S0010-440X(96)90572-6. PMID 8654061.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ "Important Safety Information about Paxil CR". GlaxoSmithKline.
- ^ Nishida T, Wada M, Wada M, Ito H, Narabayashi M, Onishi H (2008). "Activation syndrome caused by paroxetine in a cancer patient". Palliat Support Care. 6 (2): 183–5. doi:10.1017/S1478951508000278. PMID 18501054.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Ochiai Y, Katsu H, Okino S, Wakutsu N, Nakayama K (2003). "[Case of prolonged recovery from serotonin syndrome caused by paroxetine]". Seishin Shinkeigaku Zasshi (in Japanese). 105 (12): 1532–8. PMID 15027311.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Terao T, Hikichi T (2007). "Serotonin syndrome in a case of depression with various somatic symptoms: the difficulty in differential diagnosis". Prog. Neuropsychopharmacol. Biol. Psychiatry. 31 (1): 295–6. doi:10.1016/j.pnpbp.2006.07.007. PMID 16916568.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Clayton, A (2006). "Burden of phase-specific sexual dysfunction with SSRIs". Journal of Affective Disorders. 91: 27–32. doi:10.1016/j.jad.2005.12.007. PMID 16430968.
{{cite journal}}
: Unknown parameter|coauthors=
ignored (|author=
suggested) (help) - ^ http://findarticles.com/p/articles/mi_hb4365/is_1_42/ai_n31340240
- ^ Vesely C, Fischer P, Goessler R, Kasper S (1997). "Mania associated with serotonin selective reuptake inhibitors". J Clin Psychiatry. 58 (2): 88. PMID 9062382.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Ramasubbu R (2004). "Antidepressant treatment-associated behavioural expression of hypomania: a case series". Prog. Neuropsychopharmacol. Biol. Psychiatry. 28 (7): 1201–7. doi:10.1016/j.pnpbp.2004.06.015. PMID 15610935.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Grubbs JH (1997). "SSRI-induced mania". J Am Acad Child Adolesc Psychiatry. 36 (4): 445. doi:10.1097/00004583-199704000-00003. PMID 9100415.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Morishita S, Arita S (2003). "Induction of mania in depression by paroxetine". Hum Psychopharmacol. 18 (7): 565–8. doi:10.1002/hup.531. PMID 14533140.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Schmitt JA, Kruizinga MJ, Riedel WJ (2001). "Non-serotonergic pharmacological profiles and associated cognitive effects of serotonin reuptake inhibitors". J. Psychopharmacol. (Oxford). 15 (3): 173–9. PMID 11565624.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b BBC NEWS | Health | Anti-depressant addiction warning
- ^ Skaehill, Penny A. (1997). "Clinical Reviews: SSRI Withdrawal Syndrome". American Society of Consultant Pharmacists. Retrieved 2007-08-15.
{{cite web}}
: Unknown parameter|coauthors=
ignored (|author=
suggested) (help); Unknown parameter|month=
ignored (help) - ^ Bhanji NH, Chouinard G, Kolivakis T, Margolese HC (2006). "Persistent tardive rebound panic disorder, rebound anxiety and insomnia following paroxetine withdrawal: a review of rebound-withdrawal phenomena" (PDF). Can J Clin Pharmacol. 13 (1): e69–74. PMID 16456219.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ http://apt.rcpsych.org/cgi/content/full/13/6/447
- ^ http://www.benzo.org.uk/healy.htm
- ^ http://www.medscape.com/viewarticle/498763
- ^ a b Thormahlen GM (2006). "Paroxetine use during pregnancy: is it safe?". Ann Pharmacother. 40 (10): 1834–7. doi:10.1345/aph.1H116. PMID 16926304.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Way CM (2007). "Safety of newer antidepressants in pregnancy". Pharmacotherapy. 27 (4): 546–52. doi:10.1592/phco.27.4.546. PMID 17381382.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ a b Bellantuono C, Migliarese G, Gentile S (2007). "Serotonin reuptake inhibitors in pregnancy and the risk of major malformations: a systematic review". Hum Psychopharmacol. 22 (3): 121–8. doi:10.1002/hup.836. PMID 17397101.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Källén B (2007). "The safety of antidepressant drugs during pregnancy". Expert Opin Drug Saf. 6 (4): 357–70. doi:10.1517/14740338.6.4.357. PMID 17688379.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Bar-Oz B, Einarson T, Einarson A; et al. (2007). "Paroxetine and congenital malformations: meta-Analysis and consideration of potential confounding factors". Clin Ther. 29 (5): 918–26. doi:10.1016/j.clinthera.2007.05.003. PMID 17697910.
{{cite journal}}
: Explicit use of et al. in:|author=
(help); Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Gentile S, Bellantuono C (2009). "Selective serotonin reuptake inhibitor exposure during early pregnancy and the risk of fetal major malformations: focus on paroxetine". J Clin Psychiatry. 70 (3): 414–22. doi:10.4088/JCP.08r04468. PMID 19254517.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ a b Einarson A, Selby P, Koren G (2001). "Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counselling" (PDF). J Psychiatry Neurosci. 26 (1): 44–8. PMC 1408034. PMID 11212593.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Haddad PM, Pal BR, Clarke P, Wieck A, Sridhiran S (2005). "Neonatal symptoms following maternal paroxetine treatment: serotonin toxicity or paroxetine discontinuation syndrome?". J. Psychopharmacol. (Oxford). 19 (5): 554–7. doi:10.1177/0269881105056554. PMID 16166193.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ http://us.gsk.com/products/assets/us_paxil.pdf
- ^ Mellerup, Erling T. (1986). "High affinity binding of3H-paroxetine and3H-imipramine to rat neuronal membranes". Psychopharmacology. 89 (4). Springer Berlin / Heidelberg: 436–439. doi:10.1007/BF02412117.
{{cite journal}}
: Unknown parameter|coauthors=
ignored (|author=
suggested) (help); Unknown parameter|month=
ignored (help) - ^ Golden RN, Nemeroff CB, McSorley P, Pitts CD, Dube EM. (2002). "Efficacy and tolerability of controlled-release and immediate-release paroxetine in the treatment of depression". Journal of Clinical Psychiatry. 63 (7): 577–584. PMID 12143913.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b USATODAY.com - Judge: Paxil ads can't say it isn't habit-forming
- ^ http://www.socialaudit.org.uk/4606-BAUM%20HEDLUND.htm
- ^ http://www.citypages.com/2002-10-16/news/paxil-is-forever/
- ^ http://news.bbc.co.uk/2/hi/health/1382551.stm
- ^ [1]
- ^ [2]
- ^ http://findarticles.com/p/articles/mi_qa4070/is_200206/ai_n9121579
- ^ Paxil (paroxetine hydrochloride) prescribing information
- ^ DrugScope (2007 - 2008). "All-Party Parliamentary Drugs Misuse Group - An Inquiry into Physical Dependence and Addiction to Prescription and Over-the-Counter Medication" (PDF). UK: DrugScope.org.uk. Retrieved 21 January 2009.
{{cite web}}
: Check date values in:|year=
(help); Cite has empty unknown parameter:|month=
(help); Unknown parameter|coauthors=
ignored (|author=
suggested) (help); Unknown parameter|dateformat=
ignored (help)CS1 maint: year (link) - ^ "The Chemistry of Happiness". The Guardian. Retrieved 2007-09-09.
- ^ Stayton, Jonathan (2008-01-22). "Punk rocker sues over anti-depressant". The Argus. Retrieved 2008-01-23.
- ^ Angell, Marcia (2009), "Drug Companies & Doctors: A Story of Corruption", New York Review of Books, Vol 56, No 1; 15 January 2009.
- ^ Kondro W, Sibbald B (2004). "Drug company experts advised staff to withhold data about SSRI use in children". CMAJ. 170 (5): 783. doi:10.1503/cmaj.1040213. PMC 343848. PMID 14993169.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/ucm055293.pdf
- ^ http://www.nytimes.com/2004/06/12/business/company-news-fda-asks-glaxosmithkline-to-stop-running-a-paxil-ad.html
- ^ "Secrets of the drug trials". BBC. 2007-01-29. Retrieved 2007-08-15.
- ^ Keller MB; et al. (2001). "Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial". J Am Acad Child Adolesc Psychiatry. 40 (7): 762–72. PMID 11437014.
{{cite journal}}
: Explicit use of et al. in:|author=
(help); Unknown parameter|month=
ignored (help) - ^ http://healthyskepticism.org/documents/PaxilStudy329.php
- ^ Kurt Sammson (2008). "SENATE PROBE SEEKS INDUSTRY PAYMENT DATA ON INDIVIDUAL ACADEMIC RESEARCHERS". Annals of neurology: A7.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Bass, Alison (2008), Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial, Algonquin Books of Chapel Hill.
- ^ The paroxetine prescriptions were calculated as a total of prescriptions for Paxil CR and generic paroxetine using data from the charts for generic and brand-name drugs."Top 200 generic drugs by units in 2006. Top 200 brand-name drugs by units". Drug Topics, Mar 5, 2007. Retrieved 2007-04-08.
- ^ The paroxetine prescriptions were calculated as a total of prescriptions for Paxil CR and generic paroxetine using data from the charts for generic and brand-name drugs."Top 200 generic drugs by units in 2007". Drug Topics, Feb 18, 2008. Retrieved 2008-10-23. "Top 200 brand drugs by units in 2007". Drug Topics, Feb 18, 2008. Retrieved 2008-10-23.
External links
![](http://upload.wikimedia.org/wikipedia/en/thumb/4/4a/Commons-logo.svg/30px-Commons-logo.svg.png)
- List of international brand names for paroxetine
- Detailed Paroxetine Consumer Information: Uses, Precautions, Side Effects from medlibrary.org
- The Secrets of Seroxat, BBC Panorama investigation
- Antidepressant Use in Children Soars Despite Efficacy Doubts, Washington Post, April 18, 2004
- One Bad Day, Hartford Advocate, Sept 11, 2008
- Healthy Skepticism's repository and analysis of GSK documents related to Study 329