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Paroxetine

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Paroxetine
Clinical data
Trade namesPaxil, Pexeva, Brisdelle, Rexetin
AHFS/Drugs.comMonograph
MedlinePlusa698032
License data
Pregnancy
category
  • AU: D
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityExtensively absorbed from the GI tract, but extensive first-pass metabolism in the liver[2][3][4][5]
Protein binding93–95%[2][3][4]
MetabolismExtensive, hepatic (mostly CYP2D6-mediated)[2][3][4]
Elimination half-life21 hours[2][3][4]
ExcretionRenal (64%; 2% unchanged and 62% as metabolites), Faecal (36%; <1% unchanged)[2][3][4]
Identifiers
  • (3S,4R)-3-[(2H-1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.112.096 Edit this at Wikidata
Chemical and physical data
FormulaC19H20FNO3
Molar mass329.3 g·mol−1
3D model (JSmol)
  • c1cc(ccc1[C@@H]2CCNC[C@H]2COc3ccc4c(c3)OCO4)F
  • InChI=1S/C19H20FNO3/c20-15-3-1-13(2-4-15)17-7-8-21-10-14(17)11-22-16-5-6-18-19(9-16)24-12-23-18/h1-6,9,14,17,21H,7-8,10-12H2/t14-,17-/m0/s1 checkY
  • Key:AHOUBRCZNHFOSL-YOEHRIQHSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Paroxetine (also known by the trade name Paxil among others) is an antidepressant drug of the SSRI type. Paroxetine is used to treat major depression, obsessive-compulsive disorder, panic disorder, social anxiety, posttraumatic stress disorder, generalized anxiety disorder and vasomotor symptoms (e.g. hot flashes and night sweats) associated with menopause[6][7] in adult outpatients.

Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline. Generic formulations have been available since 2003 when the patent expired.[8] As with all antidepressants there may be an increased risk of suicidality in patients receiving paroxetine, although the only solid evidence regarding this is with regard to children and young adults under the age of 25.[3]

Differences between newer antidepressants are usually fairly subtle and mostly confined to side effects. It shares the common side effects and contraindications of other SSRIs, with high rates of nausea, sleepiness, and sexual side effects. Paroxetine is associated with weight gain.[9] Discontinuing paroxetine is associated with a high risk of withdrawal syndrome.[10][11] Paroxetine is the only SSRI proven to be associated with an increased risk of birth defects.[12]

Medical uses

Paroxetine is primarily used to treat major depression, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, generalized anxiety disorder (GAD),[13] social phobia/social anxiety disorder,[14] premenstrual dysphoric disorder (PMDD)[15] and menopausal hot flashes.

Paroxetine was the first antidepressant formally approved in the United States for the treatment of panic attacks.[16]

Depression

A variety of meta analyses have been conducted to evaluate the efficacy of paroxetine in depression. They have variously concluded that paroxetine is superior[17][18][19] or equivalent[20] to placebo and that it is equivalent to[21][22] or inferior[23] to other antidepressants.

Menopausal hot flashes

On June 28, 2013 U.S. FDA approved low dose paroxetine – for the treatment of moderate-to-severe vasomotor symptoms (e.g. hot flashes and night sweats) associated with menopause.[24] Randomized controlled trials have shown modest relief in such cases.[25] Side effect such as nausea and weakness are however relatively common.[26]

Pregnancy

The American College of Obstetricians and Gynecologists recommends that for pregnant women and women planning to become pregnant, "treatment with all SSRIs or selective norepinephrine reuptake inhibitors or both during pregnancy be individualized and paroxetine use among pregnant women or women planning to become pregnant be avoided, if possible."[12] According to the prescribing information[27] "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.[28][29][30][31][32] A recent non-systematic review, reporting to have received support from GSK, came to a different conclusion: "the teratogenic potential of paroxetine that has been reported in some studies remains unproven".[33] Other reviews vary on whether the teratogenic risks outweigh the risk of disease relapse if the drug is discontinued: some advocate discontinuation,[28] while others suggest caution;[30] even where the overview of antidepressants generally is favorable, paroxetine is singled out for specific risks.[31] Paroxetine use during pregnancy increases the risk of spontaneous abortion.[34][35]

A large 2010 study — using the Swedish Medical Birth Register (MBR) from 1 July 1995 up to 2007 identified women who reported the use of antidepressants in early pregnancy or were prescribed antidepressants during pregnancy by antenatal care — found a specific association between Paxil use and infant cardiovascular defects.[36] A strong association between Paxil and hypospadias was also concluded in this study, though the researchers concluded that it is not clear if these effects were due to drug use or underlying pathology.[36]

Contraindications

Paroxetine is contraindicated in all patients under 18 and in adult women who are or may become pregnant.

Adverse effects

See also: List of adverse effects of paroxetine

Paroxetine shares many of the common adverse effects of SSRIs, including (with the corresponding rates seen in people treated with placebo in parentheses): nausea 26%(9%), diarrhoea 12% (8%), constipation 14% (9%), dry mouth 18% (12%), somnolence 23% (9%), insomnia 13% (6%), headache 18% (17%), hypomania 1% (0.3%), blurred vision 4%(1%), loss of appetite 6% (2%), nervousness 5% (3%), paraesthesia 4% (2%), dizziness 13% (6%), asthenia (weakness; 15% (6%)), tremor 8% (2%), sweating 11% (2%) and sexual dysfunction (≥10% incidence).[5] Most of these adverse effects are transient and go away with continued treatment. Excess 5-HT2 receptor stimulation in the brain results in the increased anxiety, insomnia, reduced libido and irritability.[37] Excess 5-HT2receptor stimulation in the spinal cord results in the physical (as opposed to psychological, namely reductions in libido) aspects of sexual dysfunction such as erectile dysfunction, ejaculatory delay and anorgasmia (trouble achieving orgasm).[38] Central and peripheral 5-HT3 receptor stimulation is believed to result in the gastrointestinal effects observed with SSRI treatment.[37] Compared to other SSRIs it has a lower incidence of diarrhoea, a higher incidence of anticholinergic effects (e.g. dry mouth, constipation, blurred vision, etc.), sedation/somnolence/drowsiness, sexual side effects and weight gain.[39]

Sexual side effects often include difficulty becoming aroused, lack of interest in sex, and anorgasmia. Genital anaesthesia,[40] loss of or decreased response to sexual stimuli, and ejaculatory anhedonia are also possible. Although usually reversible, these sexual side effects can last for months or years after the drug has been completely withdrawn.[41]

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.[42] See also Discontinuation syndrome (withdrawal).

Mania or hypomania may occur in 1% of patients with depression and up to 12% of patients with bipolar disorder. [43]This side effect can occur in individuals with no history of mania but it may be more likely to occur in those with bipolar or with a family history of mania.[44] Cases of akathisia[45][46] and activation syndrome[47][48] have been observed during paroxetine treatment. Rarely serotonin syndrome, a severe adverse effect may occur.[49][50] Paroxetine is associated with an increased risk of hyperacusis as compared with some similar medications.[51]

Suicide

Paroxetine may increase the risk of suicidal ideation and suicidal behaviour in children and adolescents. Because suicide is rare, it is difficult to test its relationship with the use of paroxetine. Some studies instead analyze suicidality, which generally refers to suicidal ideation and suicidal behaviour. The FDA conducted a statistical analysis of paroxetine clinical trials in children and adolescents in 2004, finding an increase in "suicidality" and ideation as compared to placebo; the trend for increased "suicidality" was observed in both trials for depression and for anxiety disorders.[52] A University of North Carolina review of SSRIs found the average risk of suicide among adolescents was 4%, versus 2% on placebo, and among all patients "the greatest risk of self-harm was among paroxetine users."[53]

Discontinuation syndrome

See also: SSRI discontinuation syndrome

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.[54] 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.[55][56] 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.[10][57][58]

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."[59]

Overdose

Acute overdosage is often manifested by emesis, lethargy, ataxia, tachycardia and seizures. Plasma, serum or blood concentrations of paroxetine may be measured to monitor therapeutic administration, confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. Plasma paroxetine concentrations are generally in a range of 40–400 μg/L in persons receiving daily therapeutic doses and 200–2000 μg/L in poisoned patients. Postmortem blood levels have ranged from 1–4 mg/L in acute lethal overdose situations.[60][61] It is usually considered, along with the other SSRIs, sertraline and fluoxetine to be a low-risk drug in cases of overdose.[62]

Interactions

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 that 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.[27]

Paroxetine interacts with the following cytochrome P450 enzymes:[39]

  • CYP2D6 for which it is both a substrate and a potent inhibitor.[2][39] Its interaction with the CYP2D6 substrate (which is activated by CYP2D6 into its pharmacologically active form) and breast cancer medication, tamoxifen, is so great that the risk of mortality from breast cancer is increased by 24–91% (depending on the time and extent of coexposure) in patients coadministered paroxetine during tamoxifen treatment.[63]
  • CYP2B6 (strong) inhibitor.
  • CYP3A4 (weak) inhibitor.
  • CYP1A2 (weak) inhibitor.
  • CYP2C9 (weak) inhibitor.
  • CYP2C19 (weak) inhibitor.

Pharmacology

Paroxetine is the most potent and one of the most specific selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRI).[64] It also binds to the allosteric site of the serotonin transporter, similarly, but less potently than escitalopram.[65] This activity of the drug on brain neurons is thought to be responsible for its antidepressant effects. Paroxetine inhibits the reuptake of norepinephrine more than the other SSRIs, just as sertraline inhibits the reuptake of dopamine more than the other SSRIs.[39]

Its affinities are as follows:[66][37]

Paroxetine has been shown to have antimicrobial activity against several groups of microorganisms, mainly Gram positive microorganisms. It also shows synergistic activity when combined with some antibiotics against several bacteria.[67] Additionally, paroxetine has demonstrated antifungal activity, being most potent against the hypersusceptible Candida albicans strain DSY1204.[68]

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.[69]

Society and culture

GlaxoSmithKline has paid substantial fines, paid settlements in class action lawsuits, and become the subject of several highly critical books in relation to its marketing of paroxetine, in particular the off-label marketing of paroxetine to children, the suppression of negative research results relating to its use in children, and allegations that it failed to warn consumers of substantial withdrawal effects associated with use of the drug.

Withdrawal symptoms

In 2002 the U.S. FDA published a warning regarding "severe" discontinuation symptoms among those terminating paroxetine treatment, including paraesthesia, bad dreams, and dizziness. The Agency also warned of case reports describing agitation, sweating, and nausea.[70] In connection with a Glaxo spokesperson's statement that withdrawal reactions occur only in 0.2% of patients and are "mild and short-lived", the International Federation of Pharmaceutical Manufacturers Associations said GSK had breached two of the Federation's codes of practice.[citation needed]

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.

Paroxetine prescribing information posted at GlaxoSmithKline now acknowledges the occurrence of a discontinuation syndrome, including serious discontinuation symptoms.[27]

Violence

Treatment guidelines published by the American Psychiatric Association and by the National Institute for Health and Clinical Excellence describe the propensity for violence as an aspect of the depressive state in some patients, rather than as a side effect of anti-depressant treatment.[71][72] Nonetheless, in 2001 a jury in a lawsuit against SmithKline Beacham concerning a 60-year-old man who killed his wife, daughter, infant granddaughter, and himself within 48 hours of being prescribed Paxil for anxiety, found for the plaintiff and awarded $6.4 million.[73]

Off-label marketing to children

In early 2004, GSK agreed to settle charges of consumer fraud for $2.5 million.[74] 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".[75]

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."[76] GSK claimed the ad had been previously reviewed by FDA, but said the ad would not run again.[77]

On January 29, 2007, the BBC broadcast a fourth documentary in its Panorama series about the drug Seroxat.[78] 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[79] in a way that 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.[80][unreliable source?]

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."[81]

In 2012 the U.S. Justice Department announced that GSK had agreed to plead guilty and pay a $3 billion fine, in part for promoting the use of Paxil for children.[82]

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.[83] In 2007, sales had dropped slightly to 18.1 million but paroxetine remained the fifth-most prescribed antidepressant in the U.S.[84][85]

Trade names

Aropax, Brisdelle, Deroxat, Paxil,[86] Pexeva, Paxtine, Seroxat,[87] and Sereupin.

In 1999 paroxetine was the second SSRI (after fluvoxamine) to be approved in Japan.[88] Paroxetine became the first and non-hormonal prescription therapy for menopausal hot flashes approved by FDA.[24]

Research

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).[89][90][91] 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.[91] The reason it causes a delay in ejaculation is because it greatly reduces sex drive, in some cases, causing an inability to gain an erection or ejaculate. SSRIs are also effective in the treatment of severe premenstrual syndrome;[92] 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[93] and hot flashes.[94]

Benefits of paroxetine prescription for diabetic neuropathy[95] or chronic tension headache.[96] are uncertain.

Emerging evidence shows that antipsychotics can be used as a supplement or alternative to paroxetine in patients with generalised anxiety disorder.[6]

Although the evidence is conflicting, paroxetine may be effective for the treatment of dysthymia, a chronic disorder involving depressive symptoms for most days of the year.[97]

References

  1. ^ "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.
  2. ^ a b c d e f "PRODUCT INFORMATION PAROXETINE SANDOZ 20mg FILM-COATED TABLETS" (PDF). TGA eBusiness Services. Sandoz Pty Ltd. 18 January 2012. Retrieved 22 November 2013.
  3. ^ a b c d e f "PAROXETINE (paroxetine hydrochloride hemihydrate) tablet, film coated [Mylan Institutional Inc.]". DailyMed. Mylan Institutional Inc. January 2012. Retrieved 22 November 2013.
  4. ^ a b c d e "Paroxetine 20 mg Tablets – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Sandoz Limited. 21 March 2013. Retrieved 22 November 2013.
  5. ^ a b "Paxil, Paxil CR (paroxetine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 22 November 2013.
  6. ^ a b Katzman MA (2009). "Current considerations in the treatment of generalized anxiety disorder". CNS Drugs. 23 (2): 103–20. doi:10.2165/00023210-200923020-00002. PMID 19173371.
  7. ^ Food and Drug Administration (June 28, 2013). "FDA NEWS RELEASE: FDA approves the first non-hormonal treatment for hot flashes associated with menopause".
  8. ^ Smith, Aaron (May 11, 2005). "New profit twist for drugmakers". CNN Money.
  9. ^ Papakostas GI (2008). "Tolerability of modern antidepressants". J Clin Psychiatry. 69 (Suppl E1): 8–13. PMID 18494538.
  10. ^ a b Haddad PM (2001). "Antidepressant discontinuation syndromes". Drug Saf. 24 (3): 183–97. doi:10.2165/00002018-200124030-00003. PMID 11347722.
  11. ^ Tonks A (February 2002). "Withdrawal from paroxetine can be severe, warns FDA". BMJ. 324 (7332): 260. doi:10.1136/bmj.324.7332.260. PMC 1122195. PMID 11823353.
  12. ^ a b "ACOG Committee Opinion No. 354: Treatment with selective serotonin reuptake inhibitors during pregnancy". Obstet Gynecol. 108 (6): 1601–3. 2006. doi:10.1097/00006250-200612000-00058. PMID 17138801.
  13. ^ 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)
  14. ^ Baldwin D, Bobes J, Stein DJ, Scharwächter I, Faure M (1999). "Paroxetine in social phobia/social anxiety disorder. Randomised, double-blind, placebo-controlled study. Paroxetine Study Group". The British Journal of Psychiatry. 175 (2): 120–6. doi:10.1192/bjp.175.2.120. PMID 10627793.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ 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)
  16. ^ Turner, Francis Joseph (2005). Social Work Diagnosis in Contemporary Practice. Oxford University Press US. ISBN 0-19-516878-X.
  17. ^ Hansen R, Gaynes B, Thieda P; et al. (October 2008). "Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants". Psychiatr Serv. 59 (10): 1121–30. doi:10.1176/appi.ps.59.10.1121. PMC 2840386. PMID 18832497. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  18. ^ Dunner DL, Lipschitz A, Pitts CD, Davies JT (December 2005). "Efficacy and tolerability of controlled-release paroxetine in the treatment of severe depression: post hoc analysis of pooled data from a subset of subjects in four double-blind clinical trials". Clin Ther. 27 (12): 1901–11. doi:10.1016/j.clinthera.2005.12.013. PMID 16507376.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ Carpenter DJ, Fong R, Kraus JE, Davies JT, Moore C, Thase ME (November 2011). "Meta-analysis of efficacy and treatment-emergent suicidality in adults by psychiatric indication and age subgroup following initiation of paroxetine therapy: a complete set of randomized placebo-controlled trials". J Clin Psychiatry. 72 (11): 1503–14. doi:10.4088/JCP.08m04927blu. PMID 21367354.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ Barbui C, Furukawa TA, Cipriani A (Jan 29, 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 : Canadian Medical Association journal = journal de l'Association medicale canadienne. 178 (3): 296–305. doi:10.1503/cmaj.070693. PMC 2211353. PMID 18227449. {{cite journal}}: Missing pipe in: |journal= (help)CS1 maint: multiple names: authors list (link)
  21. ^ Tignol J, Stoker MJ, Dunbar GC (November 1992). "Paroxetine in the treatment of melancholia and severe depression". Int Clin Psychopharmacol. 7 (2): 91–4. doi:10.1097/00004850-199207020-00005. PMID 1487627.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ Gartlehner G, Gaynes BN, Hansen RA; et al. (November 2008). "Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians". Ann. Intern. Med. 149 (10): 734–50. doi:10.7326/0003-4819-149-10-200811180-00008. PMID 19017592. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  23. ^ Cipriani A, Furukawa TA, Salanti G; et al. (February 2009). "Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis". Lancet. 373 (9665): 746–58. doi:10.1016/S0140-6736(09)60046-5. PMID 19185342. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  24. ^ a b FDA NEWS RELEASE: FDA approves the first non-hormonal treatment for hot flashes associated with menopause, Jun. 28, 2013http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm359030.htm
  25. ^ Orleans, Ronald J.; Li, Li; Kim, Myong-Jin; Guo, Jia; Sobhan, Mahboob; Soule, Lisa; Joffe, Hylton V. (2014). "FDA Approval of Paroxetine for Menopausal Hot Flushes". New England Journal of Medicine. 370 (19): 1777–1779. doi:10.1056/NEJMp1402080. ISSN 0028-4793.
  26. ^ Marjoribanks J, Brown J, O'Brien PM, Wyatt K (Jun 7, 2013). "Selective serotonin reuptake inhibitors for premenstrual syndrome". The Cochrane database of systematic reviews. 6: CD001396. doi:10.1002/14651858.CD001396.pub3. PMID 23744611.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ a b c "PAXIL (paroxetine hydrochloride) Tablets and Oral Suspension: PRESCRIBING INFORMATION". Research Triangle Park, NC: GlaxoSmithKline. August 2007. Archived from the original (PDF) on 2011-08-25. Retrieved 2007-08-14.
  28. ^ a b Thormahlen GM (October 2006). "Paroxetine use during pregnancy: is it safe?". Ann Pharmacother. 40 (10): 1834–7. doi:10.1345/aph.1H116. PMID 16926304.
  29. ^ Way CM (2007). "Safety of newer antidepressants in pregnancy". Pharmacotherapy. 27 (4): 546–52. doi:10.1592/phco.27.4.546. PMID 17381382.
  30. ^ 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}}: CS1 maint: multiple names: authors list (link)
  31. ^ a b Källén B (July 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.
  32. ^ Bar-Oz B, Einarson T, Einarson A, Boskovic R, O'Brien L, Malm H, Bérard A, Koren G (May 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}}: CS1 maint: multiple names: authors list (link)
  33. ^ Gentile S, Bellantuono C (March 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.
  34. ^ Broy P, Bérard A (2010). "Gestational exposure to antidepressants and the risk of spontaneous abortion: A review". Current drug delivery. 7 (1): 76–92. doi:10.2174/156720110790396508. PMID 19863482.
  35. ^ Nakhai-Pour HR, Broy P, Bérard A (2010). "Use of antidepressants during pregnancy and the risk of spontaneous abortion". Canadian Medical Association Journal. 182 (10): 1031–1037. doi:10.1503/cmaj.091208. PMC 2900326. PMID 20513781. {{cite journal}}: Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
  36. ^ a b Reis M, Källén B (2010). "Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data". Psychological Medicine. 40 (10): 1723–33. doi:10.1017/S0033291709992194. PMID 20047705.
  37. ^ a b c Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.{{cite book}}: CS1 maint: multiple names: authors list (link)
  38. ^ "www.accessdata.fda.gov" (PDF).
  39. ^ a b c d Ciraulo, DA; Shader, RI, ed. (2011). Pharmacotherapy of Depression (2nd ed.). New York, NY: Humana Press. doi:10.1007/978-1-60327-435-7. ISBN 978-1-60327-434-0. {{cite book}}: |work= ignored (help)CS1 maint: multiple names: editors list (link)
  40. ^ Bolton JM, Sareen J, Reiss JP (2006). "Genital anaesthesia persisting six years after sertraline discontinuation". J Sex Marital Ther. 32 (4): 327–30. doi:10.1080/00926230600666410. PMID 16709553.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  41. ^ Csoka AB, Csoka A, Bahrick A, Mehtonen OP (2008). "Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors (SSRIs)". J Sex Med. 5 (1): 227–33. doi:10.1111/j.1743-6109.2007.00630.x. PMID 18173768.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  42. ^ "Press release, CHMP meeting on Paroxetine and other SSRIs" (PDF). European Medicines Agency. 2004-12-09. Retrieved 2007-08-24.[dead link‍]
  43. ^ "www.accessdata.fda.gov" (PDF).
  44. ^ Morishita S, Arita S (October 2003). "Induction of mania in depression by paroxetine". Hum Psychopharmacol. 18 (7): 565–8. doi:10.1002/hup.531. PMID 14533140.
  45. ^ Olivera AA (1996). "A case of paroxetine-induced akathisia". Biol. Psychiatry. 39 (10): 910. doi:10.1016/0006-3223(96)84504-5. PMID 8860197.
  46. ^ 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)
  47. ^ "Important Safety Information about Paxil CR". GlaxoSmithKline. Archived from the original on 2007-07-15.
  48. ^ 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}}: CS1 maint: multiple names: authors list (link)
  49. ^ 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)
  50. ^ 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.
  51. ^ Tabachnick, Barbara (September 1998). "Sound Sensitivity" (PDF). Tinnitus Today. Retrieved 2013-10-30.
  52. ^ 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.
  53. ^ Gartlehner G, Hansen RA, Kahwati L, Lohr KN, Gaynes B, Carey T (March 2006). "Drug Class Review on Second Generation Antidepressants: Final Report". Drug Class Reviews. Portland OR: Oregon Health & Science University. PMID 20480925. NBK10326.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  54. ^ "Anti-depressant addiction warning". BBC News. 2001-06-11. Retrieved 2010-05-21.
  55. ^ Skaehill, Penny A.; Welch, E.B. (October 1997). "Clinical Reviews: SSRI Withdrawal Syndrome". American Society of Consultant Pharmacists. Archived from the original on 2006-05-03. Retrieved 2007-08-15.
  56. ^ 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)
  57. ^ Haddad PM, Anderson IM (November 2007). "Recognising and managing antidepressant discontinuation symptoms". Advances in Psychiatric Treatment. 13 (6): 447–457. doi:10.1192/apt.bp.105.001966.
  58. ^ on Antidepressants & Halting SSRIs by Dr David Healy MD, FRCPsych[dead link‍]. benzo.org.uk. Retrieved on 2013-04-23.
  59. ^ SSRIs Given During Pregnancy May Cause Withdrawal Symptoms in the Neonate. Medscape.com (2005-02-03). Retrieved on 2013-04-23.
  60. ^ Goeringer KE, Raymon L, Christian GD, Logan BK (May 2000). "Postmortem forensic toxicology of selective serotonin reuptake inhibitors: a review of pharmacology and report of 168 cases". J. Forensic Sci. 45 (3): 633–48. PMID 10855970.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  61. ^ R. Baselt,Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1190–1193.
  62. ^ White N, Litovitz T, Clancy C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type". Journal of Medical Toxicology. 4 (4): 238–250. doi:10.1007/BF03161207. PMC 3550116. PMID 19031375.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  63. ^ Kelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, Paszat LF (2010). "Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study". BMJ. 340: c693. doi:10.1136/bmj.c693. PMC 2817754. PMID 20142325.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  64. ^ Mellerup ET, Plenge P (July 1986). "High affinity binding of3H-paroxetine and3H-imipramine to rat neuronal membranes". Psychopharmacology. 89 (4): 436–9. doi:10.1007/BF02412117. PMID 2944152.
  65. ^ Mansari ME, Wiborg O, Mnie-Filali O, Benturquia N, Sánchez C, Haddjeri N (February 2007). "Allosteric modulation of the effect of escitalopram, paroxetine and fluoxetine: in-vitro and in-vivo studies". The International Journal of Neuropsychopharmacology. 10 (1): 31–40. doi:10.1017/S1461145705006462. PMID 16448580.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  66. ^ Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 22 November 2013.{{cite web}}: CS1 maint: multiple names: authors list (link)
  67. ^ Munoz-Bellido JL, Munoz-Criado S, Garcìa-Rodrìguez JA (2000). "Antimicrobial activity of psychotropic drugs: selective serotonin reuptake inhibitors". Int. J. Antimicrob. Agents. 14 (3): 177–80. doi:10.1016/S0924-8579(99)00154-5. PMID 10773485.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  68. ^ Young TJ, Oliver GP, Pryde D, Perros M, Parkinson T (2003). "Antifungal activity of selective serotonin reuptake inhibitors attributed to non-specific cytotoxicity". J. Antimicrob. Chemother. 51 (4): 1045–7. doi:10.1093/jac/dkg184. PMID 12654745.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  69. ^ Golden RN, Nemeroff CB, McSorley P, Pitts CD, Dubé 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. doi:10.4088/JCP.v63n0707. PMID 12143913.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  70. ^ "Withdrawal from paroxetine can be severe, warns FDA | BMJ".
  71. ^ "Depression in adults (update)".
  72. ^ "PsychiatryOnline | Guidelines".
  73. ^ Philip J. Hilts (June 8, 2001). "Jury Awards $6.4 Million in Killings Tied to Drug". The New York Times.
  74. ^ Angell M (15 January 2009). "Drug Companies & Doctors: A Story of Corruption". New York Review of Books. Vol. 56, no. 1.
  75. ^ Kondro W, Sibbald B (March 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.
  76. ^ to P. Kaia Agarwal. fda.gov. Retrieved on 2013-04-23.
  77. ^ "Company News; F.D.A. Asks Glaxosmithkline To Stop Running A Paxil Ad". The New York Times. 2004-06-12. Retrieved 2010-03-27.
  78. ^ "Secrets of the drug trials". BBC. 2007-01-29. Retrieved 2007-08-15.
  79. ^ Keller MB, Ryan ND, Strober M, Klein RG, Kutcher SP, Birmaher B, Hagino OR, Koplewicz H, Carlson GA, Clarke GN, Emslie GJ, Feinberg D, Geller B, Kusumakar V, Papatheodorou G, Sack WH, Sweeney M, Wagner KD, Weller EB, Winters NC, Oakes R, McCafferty JP (July 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. doi:10.1097/00004583-200107000-00010. PMID 11437014.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  80. ^ Paxil Study 329: Paroxetine vs Imipramine vs Placebo in Adolescents, Healthy Skepticism International News, January 2010
  81. ^ Samson K (December 2008). "Senate probe seeks industry payment data on individual academic researchers". Ann. Neurol. 64 (6): A7–9. doi:10.1002/ana.21271. PMID 19107985.
  82. ^ Thomas, Katie; Schmidt, Michael S. (July 2, 2012). "Glaxo Agrees to Pay $3 Billion in Fraud Settlement". The New York Times.
  83. ^ 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.
  84. ^ 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. February 18, 2008. Archived from the original on 2009-07-18. Retrieved 2008-10-23.
  85. ^ "Top 200 brand drugs by units in 2007". Drug Topics, Feb 18, 2008. Archived from the original on 2009-06-29. Retrieved 2008-10-23.
  86. ^ Coleman, Andrew (2006). Dictionary of Psychology (Second Edition). Oxford University Press. p. 552.
  87. ^ Coleman, Andrew (2006). Dictionary of Psychology (Second Edition). Oxford University Press. p. 161.
  88. ^ Higuchi T, Briley M (February 2007). "Japanese experience with milnacipran, the first serotonin and norepinephrine reuptake inhibitor in Japan". Neuropsychiatric Disease and Treatment. 3 (1): 41–58. PMC 2654524. PMID 19300537.
  89. ^ Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B (August 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)
  90. ^ 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)
  91. ^ 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)
  92. ^ Brown J, O' Brien PM, Marjoribanks J, Wyatt K (2009). Brown, Julie (ed.). "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)
  93. ^ 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): 501–7. doi:10.4088/JCP.v63n0606. PMID 12088161.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  94. ^ 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)
  95. ^ Sindrup SH, Gram LF, Brøsen K, Eshøj O, Mogensen EF (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)
  96. ^ 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.
  97. ^ Gartlehner G, Gaynes BN, Hansen RA, Thieda P, DeVeaugh-Geiss A, Krebs EE, Moore CG, Morgan L, Lohr KN (November 2008). "Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians". Ann. Intern. Med. 149 (10): 734–50. doi:10.7326/0003-4819-149-10-200811180-00008. PMID 19017592.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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