US FDA The Food and Drug Administration is an agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, dietary supplements, drugs, vaccines, biological medical products, blood products, medical devices, radiation-emitting devices, veterinary products, and cosmetics. The FDA:link

D(US The United States of America is a federal constitutional republic comprising fifty states and a federal district. The country is situated mostly in central North America, where its forty-eight contiguous states and Washington, D.C., the capital district, lie between the Pacific and Atlantic Oceans, bordered by Canada to the north and Mexico to the)

℞ Prescription only

Paroxetine (trade names Seroxat, Paxil) is a selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. They are also typically effective and used in treating premature ejaculation problems as well as some cases of insomnia (SSRI) antidepressant An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia. Drugs including the monoamine oxidase inhibitors , tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). It was released in 1992 by the pharmaceutical company GlaxoSmithKline GlaxoSmithKline plc is a United Kingdom-based pharmaceutical, biological, and healthcare company. GSK is the world's third largest pharmaceutical company and a research-based company with a wide portfolio of pharmaceutical products covering anti-infectives, central nervous system, respiratory, gastro-intestinal/metabolic, oncology, and vaccines. It is used to treat major depression Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and loss of interest or pleasure in normally enjoyable activities. The term "major depressive disorder" was selected by the American Psychiatric Association to designate this symptom cluster as a mood disorder in, obsessive-compulsive Obsessive-compulsive disorder is a human anxiety disorder characterized by involuntary intrusive thoughts. When a sufferer begins to acknowledge these intrusive thoughts, the sufferer then develops anxiety based on the dread that something bad will happen. The sufferer feels compelled to voluntarily perform irrational, time-consuming behaviors to, panic Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks . Panic disorder is not the same as agoraphobia, although and social anxiety Social anxiety disorder , also known as social anxiety or social phobia is a diagnosis within psychiatry and other mental health professions referring to excessive social anxiety (anxiety in social situations) causing considerable distress and impaired ability to function in at least some areas of daily life. The diagnosis can be of a specific disorders in adult outpatients A patient is any person who receives medical attention, care, or treatment. The person is most often ill or injured and in need of treatment by a physician or other medical professional, although one who is visiting a physician for a routine check-up may also be viewed as a patient. It is also highly effective, as are other SSRIs in the treatment of severe premenstrual syndrome Premenstrual Syndrome (unlike PMT or Premenstrual Tension) is a collection of physical, psychological, and emotional symptoms related to a woman's menstrual cycle. While most women (about 80 percent) of child-bearing age have some symptoms of PMS, the official definition limits the scope to having symptoms of "sufficient severity to interfere^[1] and is considered a first-line agent in the treatment of generalised anxiety disorder as are several other SSRIs.^[2] Paroxetine is ranked 94th on the list of bestselling drugs, with over $1 billion in sales in 2007.

In adults, the efficacy of paroxetine for depression is comparable to that of older tricyclic antidepressants Tricyclic antidepressants are a class of antidepressant drugs first introduced in the 1950s. They are named after their molecular structure, which contains three rings of atoms. They are closely related to the tetracyclic antidepressants (TeCAs). In recent times, the TCAs have been largely replaced in clinical use in most parts of the world by 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 In medicine, a contraindication is a condition or factor that increases the risks involved in using a particular drug, carrying out a medical procedure, or engaging in a particular activity of other SSRIs, with high rates of nausea, somnolence, and sexual side effects. Unlike two other popular SSRI antidepressants fluoxetine EU EMEA:link, US FDA:link and sertraline Sertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It was introduced to the market by Pfizer in 1991. Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive–compulsive, panic, and social anxiety disorders in both adults and children. In 2007, it was, paroxetine is associated with a clinically significant weight gain^[5] and statistically significant increase in the risk of suicidality in adults.^[6] 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.^[7][8][9]

Stopping paroxetine is associated with a high risk of discontinuation or withdrawal syndrome.^[10][11] Due to the increased risk of birth defects, pregnant women or women planning to become pregnant are recommended to avoid or discontinue paroxetine use.^[12][13][14]

Indications

Paroxetine is primarily used to treat the symptoms of major depression Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and loss of interest or pleasure in normally enjoyable activities. The term "major depressive disorder" was selected by the American Psychiatric Association to designate this symptom cluster as a mood disorder in, obsessive-compulsive disorder Obsessive-compulsive disorder is a human anxiety disorder characterized by involuntary intrusive thoughts. When a sufferer begins to acknowledge these intrusive thoughts, the sufferer then develops anxiety based on the dread that something bad will happen. The sufferer feels compelled to voluntarily perform irrational, time-consuming behaviors to (OCD), post-traumatic stress disorder Posttraumatic stress disorder is an anxiety disorder that can develop after exposure to one or more traumatic events that threatened or caused great physical harm (PTSD), panic disorder Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks . Panic disorder is not the same as agoraphobia, although, generalized anxiety disorder Generalized anxiety disorder is an anxiety disorder that is characterized by excessive, uncontrollable and often irrational worry about everyday things that is disproportionate to the actual source of worry. This excessive worry often interferes with daily functioning, as individuals suffering GAD typically catastrophise, anticipate disaster, and (GAD),^[15] social phobia/social anxiety disorder Social anxiety disorder , also known as social anxiety or social phobia is a diagnosis within psychiatry and other mental health professions referring to excessive social anxiety (anxiety in social situations) causing considerable distress and impaired ability to function in at least some areas of daily life. The diagnosis can be of a specific,^[16] and premenstrual dysphoric disorder Premenstrual dysphoric disorder is a dramatic form of Premenstrual syndrome, afflicting 3% to 8% of women. It is a mental disorder associated with the luteal phase of the menstrual cycle (PMDD Premenstrual dysphoric disorder is a dramatic form of Premenstrual syndrome, afflicting 3% to 8% of women. It is a mental disorder associated with the luteal phase of the menstrual cycle).^[17] For some indications paroxetine has demonstrated high effectiveness for example in severe premenstrual syndrome Premenstrual Syndrome (unlike PMT or Premenstrual Tension) is a collection of physical, psychological, and emotional symptoms related to a woman's menstrual cycle. While most women (about 80 percent) of child-bearing age have some symptoms of PMS, the official definition limits the scope to having symptoms of "sufficient severity to interfere^[1] and is considered an evidence based Evidence-based medicine aims to apply evidence gained from the scientific method to certain parts of medical practice. It seeks to assess the quality of evidence relevant to the risks and benefits of treatments (including lack of treatment). According to the Centre for Evidence-Based Medicine, "Evidence-based medicine is the conscientious, 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 Dysthymia is a chronic mood disorder that falls within the depression spectrum. It is considered a chronic depression, but with less severity than major depressive disorder. This disorder tends to be a chronic, long-lasting illness although the evidence is conflicting. Dysthymia is a chronic disorder which involves depressive symptoms for most days of the year.^[18]

It was the first antidepressant formally approved in the United States for the treatment of panic attacks.^[19]

According to the prescribing information provided by the manufacturer of Paxil brand of paroxetine GlaxoSmithKline and approved by the FDA,^[20] 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.^[20] Similarly, three 12-week trials for adult outpatients with social anxiety disorder demonstrated better response to paroxetine than to placebo.^[20]

Unapproved/off-label/investigational

Moreover, studies have suggested that paroxetine can in fact be used in the treatment of premature ejaculation. In particular, intravaginal ejaculation latency time (IELT) was found to increase with a 6-13-fold, which was somewhat longer than the delay achieved by the treatment with other SSRIs (fluvoxamine, fluoxetine, sertraline and citalopram).^[21][22][23] 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 Clomipramine is a tricyclic antidepressant. It was developed in the 1960s by the Swiss drug manufacturer Geigy (now known as Novartis) and has been in clinical use worldwide for decades, which induced a fourfold delay.^[23]

There is also evidence that paroxetine may be effective in the treatment of compulsive gambling Problem gambling is an urge to gamble despite harmful negative consequences or a desire to stop. The term is preferred to compulsive gambling among many professionals[citation needed], as few people described by the term experience true compulsions in the clinical sense of the word.[citation needed] Problem gambling often is defined by whether^[24] and hot flashes Hot flashes, a common symptom of menopause and perimenopause, are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and may typically last from two to thirty minutes for each occurrence. The sensation of heat usually begins in the face or face and chest, although it may appear elsewhere such as the back of the.^[25]

In two double-blind studies of bipolar disorder patients, addition of paroxetine to a mood stabilizer had no advantages over addition of placebo.^[26][27] Benefits of paroxetine prescription for diabetic neuropathy Diabetic neuropathies are neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves . Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy; mononeuropathy;^[28] or chronic tension headache Tension headaches, which were renamed tension-type headaches by the International Headache Society in 1988, are the most common type of primary headaches. The pain can radiate from the neck, back, eyes, or other muscle groups in the body. Tension-type headaches account for nearly 90% of all headaches. Approximately 3% of the population suffers.^[29] 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 US FDA:link, and in adult women who are or may become pregnant US FDA:link. Paroxetine may also be contraindicated in many adult men due to sexual and reproductive side effects described below US FDA:link. In the United States, the Food and Drug Administration The Food and Drug Administration is an agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, dietary supplements, drugs, vaccines, biological medical products, blood products, medical devices, radiation-emitting devices, veterinary products, and cosmetics. The FDA requires this drug to carry a black box warning In the United States, a black box warning is a type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects. It is so named for the black border that usually surrounds the text of the warning, its "most serious type of warning in prescription drug labeling,"^[30] 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 The Medicines and Healthcare products Regulatory Agency is the UK government agency which is responsible for ensuring that medicines and medical devices work and are acceptably safe urging that paroxetine not be used in individuals younger than 18 years.^[31]

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 Nausea is the sensation of unease and discomfort in the stomach with an urge to vomit (26% on paroxetine vs 9% on placebo), somnolence Somnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods (c.f. hypersomnia). It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm. The disorder characterized by the latter (23% vs. 9% on placebo), ejaculatory disturbance (13% vs. 0% on placebo), other male genital disorders (10% vs. 0% on placebo), asthenia Asthenia is a medical term denoting symptoms of physical weakness and loss of strength (15% vs. 6% on placebo), sweating (11% vs. 2% on placebo), dizziness (13% vs. 6% on placebo), insomnia Insomnia is a symptom of any of several sleep disorders, characterized by persistent difficulty falling asleep or staying asleep despite the opportunity. Insomnia is a symptom, not a stand-alone diagnosis or a disease. By definition, insomnia is "difficulty initiating or maintaining sleep, or both" and it may be due to inadequate quality (13% vs. 6% on placebo), dry mouth (18% vs. 12% on placebo), constipation Constipation, costiveness, or irregularity is a condition of the digestive system in which a person experiences hard feces (faeces) that are difficult to expel. This usually happens because the colon absorbs too much water from the food. If the food moves through the gastro-intestinal tract too slowly, the colon may absorb too much water, (14% vs. 9% on placebo), and tremor A tremor is an unintentional, somewhat rhythmic, muscle movement involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, head, face, vocal cords, trunk, and legs. Most tremors occur in the hands. In some people, tremor is a symptom of another neurological disorder (8% vs. 2% on placebo).^[20] Other side effects include headache In medicine a headache or cephalalgia is a symptom of a number of different conditions of the head and sometimes neck. Some of the causes are benign while others are medical emergencies. It ranks among the most common pain complaints.[citation needed], agitation, weight gain Weight gain is an increase in body weight. This can be either an increase in muscle mass, fat deposits, or excess fluids such as water, impaired memory and paresthesia Paresthesia is a sensation of tingling, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb being "asleep" (although this is not directly related to the phenomenon of sleep). The manifestation of paresthesia may be.^[32]

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 Rebound effect is the tendency of a medication, when discontinued, to cause a return of the symptoms being treated more severe than before. Medications with a known rebound effect can be withdrawn gradually or in conjunction with another medication which does not exhibit a rebound effect. The symptom will be more pronounced after the medication is 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.^[20]

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 gave a warning to prescribers recommending close monitoring of adult patients at high risk of suicidal behaviour and/or suicidal thoughts. In other words, CHMP does not prohibit use of paroxetine with adults but stresses extreme caution in actual usage. Also withdrawal reactions upon stopping treatment is mentioned and therefore it is recommended to gradually reduce the dose over several weeks or months if decision of withdrawal is made.^[33]

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.^[7]

Cases of akathisia^[34][35] and activation syndrome^[36][37] have been observed during paroxetine treatment.

Rarely serotonin syndrome, a severe adverse effect may occur.^[38][39]

Paroxetine and other SSRIs have been shown to cause sexual side effects in most patients, both males and females.^[40] In males, paroxetine is also linked to sperm DNA fragmentation.^[41]

Mania or hypomania may occur as a serious side effect of paroxetine,^[42][43][44] 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.^[45]

Schmitt et al. (2001) suggested that paroxetine negatively affects cognition (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 and co-workers, however, did not account for significant differences in verbal recall at baseline between those receiving paroxetine and those receiving a placebo, differences which produced the significant finding. Furthermore, participants receiving paroxetine recalled as many words at baseline as they recalled on day 14. Accordingly, the conclusion that paroxetine affects verbal recall was unwarranted.^[46]

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.^[11][47] 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.^[48][49] 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][50][51]

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."^[52]

Paroxetine and pregnancy

The American College of Obstetricians and Gynecologists recommends that pregnant women and women planning to become pregnant should avoid using paroxetine.^[53] According to the prescribing information^[20] "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.^{[54][55][56][57][58]} 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".^[59] Other reviews vary on whether the teratogenic risks outweigh the risk of disease relapse if the drug is discontinued: some advocate discontinuation,^[54] while others suggest caution;^[56] even where the overview of antidepressants generally is favorable, paroxetine is singled out for specific risks.^[57]

Abrupt discontinuation of psychotropic drugs during pregnancy can also lead to serious adverse effects.^[60]

Counseling is effective in reassuring women to adhere to therapy,^[60] but neonatal paroxetine withdrawal symptoms described above have been documented from mothers taking Paxil during pregnancy.^[61]

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.^[62]

Pharmacology

Paroxetine is the most potent and one of the most specific selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRI).^[63] 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.^[64]

Controversy

For 10 years, GlaxoSmithKline's marketing of the drug stated falsely that it was not habit forming.^[47][65] In 2001, the BBC reported the World Health Organization had found paroxetine to have the hardest withdrawal problems of any antidepressant.^[66] In 2002, the Food and Drug Administration of the United States published a new product warning about the drug, and the International Federation of Pharmaceutical Manufacturers Associations found GSK guilty of misleading the public about paroxetine and breaching two of the Federation's codes of practice.^[11][67] 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."^[11] Paroxetine prescribing information posted at GlaxoSmithKline now acknowledges the occurrence of a discontinuation syndrome, including serious discontinuation symptoms.^[68]

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.^[69] 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^[65]

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.^[70][71]

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).^[72] 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"^[73].

On January 29, 2007, the BBC broadcast a fourth documentary in its Panorama series about the drug Seroxat.^[74] 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.

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, 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."^[75]

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^[76].

Sales

In 2006, paroxetine was the fifth-most prescribed antidepressant in the United States retail market, with more than 19.7 million prescriptions.^[77] In 2007, sales had dropped slightly to 18.1 million but paroxetine remained the fifth-most prescribed antidepressant in the U.S.^[78]

Footnotes

1. ^ ^{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. http://dx.doi.org/10.1002/14651858.CD001396.pub2.
2. ^ ^{a b} Katzman MA (2009). "Current considerations in the treatment of generalized anxiety disorder". CNS Drugs 23 (2): 103–20. PMID 19173371.
3. ^ Anderson IM (April 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. http://linkinghub.elsevier.com/retrieve/pii/S0165-0327(99)00092-0.
4. ^ http://cat.inist.fr/?aModele=afficheN&cpsidt=972015
5. ^ Papakostas GI (2008). "Tolerability of modern antidepressants". J Clin Psychiatry 69 Suppl E1: 8–13. PMID 18494538.
6. ^ Barbui C, Furukawa TA, Cipriani A (January 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. PMID 18227449.
7. ^ ^{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. 30. http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-10-TAB08-Hammads-Review.pdf. Retrieved on 2009-01-27.
8. ^ Hammad TA, Laughren T, Racoosin J (March 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.
9. ^ "Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitor antidepressants" (PDF). MHRA. 2004-12. http://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con019472.pdf. Retrieved on 2009-02-17.
10. ^ ^{a b} Haddad P (2001). "Antidepressant discontinuation syndromes". Drug Saf 24 (3): 183–97. doi:10.2165/00002018-200124030-00003. PMID 11347722.
11. ^ ^{a b c d} Tonks A (February 2002). "Withdrawal from paroxetine can be severe, warns FDA". BMJ 324 (7332): 260. doi:10.1136/bmj.324.7332.260. PMID 11823353. PMC: 1122195. http://bmj.com/cgi/pmidlookup?view=long&pmid=11823353.
12. ^ "ACOG Committee Opinion No. 354: Treatment with selective serotonin reuptake inhibitors during pregnancy". Obstet Gynecol 108 (6): 1601–3. December 2006. PMID 17138801.
13. ^ "FDA Public Health Advisory Paroxetine". Food and Drug Administration. http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm051731.htm. Retrieved on 05/02/2009.
14. ^ "Paroxetine and Pregnancy". GlaxoSmithKline. http://www.gsk.com/media/paroxetine_pregnancy.htm. Retrieved on 05/02/2009.
15. ^ 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.
16. ^ 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.
17. ^ 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.
18. ^ 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. PMID 19017592. http://www.annals.org/cgi/content/full/149/10/734.
19. ^ Turner, Francis Joseph (2005). Social Work Diagnosis in Contemporary Practice. Oxford University Press US. ISBN 019516878X.
20. ^ ^{a b c d e f} "PAXIL (paroxetine hydrochloride) Tablets and Oral Suspension: PRESCRIBING INFORMATION" (PDF). Research Triangle Park, NC: GlaxoSmithKline. August 2007. http://us.gsk.com/products/assets/us_paxil.pdf. Retrieved on 2007-08-14.
21. ^ 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.
22. ^ 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.
23. ^ ^{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.
24. ^ 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.
25. ^ 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.
26. ^ 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.
27. ^ 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.
28. ^ 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.
29. ^ 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.
30. ^ http://www.nimh.nih.gov/health/topics/child-and-adolescent-mental-health/antidepressant-medications-for-children-and-adolescents-information-for-parents-and-caregivers.shtml
31. ^ http://www.pharmacytimes.com/issues/articles/2008-05_002.asp
32. ^ 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.
33. ^ "Press release, CHMP meeting on Paroxetine and other SSRIs" (PDF). European Medicines Agency. 2004-12-09. http://www.emea.europa.eu/pdfs/human/press/pr/19257004en.pdf. Retrieved on 2007-08-24.
34. ^ Olivera AA (May 1996). "A case of paroxetine-induced akathisia". Biol. Psychiatry 39 (10): 910. doi:10.1016/0006-3223(96)84504-5. PMID 8860197. http://linkinghub.elsevier.com/retrieve/pii/0006-3223(96)84504-5.
35. ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0010-440X(96)90572-6.
36. ^ "Important Safety Information about Paxil CR" (HTML). GlaxoSmithKline. http://www.paxilcr.com/safety_information/important_safety_information.html.
37. ^ Nishida T, Wada M, Wada M, Ito H, Narabayashi M, Onishi H (June 2008). "Activation syndrome caused by paroxetine in a cancer patient". Palliat Support Care 6 (2): 183–5. doi:10.1017/S1478951508000278. PMID 18501054. http://journals.cambridge.org/abstract_S1478951508000278.
38. ^ Ochiai Y, Katsu H, Okino S, Wakutsu N, Nakayama K (2003). "[Case of prolonged recovery from serotonin syndrome caused by paroxetine]" (in Japanese). Seishin Shinkeigaku Zasshi 105 (12): 1532–8. PMID 15027311.
39. ^ Terao T, Hikichi T (January 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. http://linkinghub.elsevier.com/retrieve/pii/S0278-5846(06)00295-8.
40. ^ Clayton, A; Keller A, McGarvey EL. (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.
41. ^ http://findarticles.com/p/articles/mi_hb4365/is_1_42/ai_n31340240
42. ^ Vesely C, Fischer P, Goessler R, Kasper S (February 1997). "Mania associated with serotonin selective reuptake inhibitors". J Clin Psychiatry 58 (2): 88. PMID 9062382.
43. ^ Ramasubbu R (November 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. http://linkinghub.elsevier.com/retrieve/pii/S0278-5846(04)00141-1.
44. ^ Grubbs JH (April 1997). "SSRI-induced mania". J Am Acad Child Adolesc Psychiatry 36 (4): 445. doi:10.1097/00004583-199704000-00003. PMID 9100415.
45. ^ 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.
46. ^ Schmitt JA, Kruizinga MJ, Riedel WJ (September 2001). "Non-serotonergic pharmacological profiles and associated cognitive effects of serotonin reuptake inhibitors". J. Psychopharmacol. (Oxford) 15 (3): 173–9. PMID 11565624.
47. ^ ^{a b} BBC NEWS | Health | Anti-depressant addiction warning
48. ^ Skaehill, Penny A.; Welch, E.B. (October 1997). "Clinical Reviews: SSRI Withdrawal Syndrome". American Society of Consultant Pharmacists. http://www.ascp.com/publications/tcp/1997/oct/ssri.html. Retrieved on 2007-08-15.
49. ^ 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". Can J Clin Pharmacol 13 (1): e69–74. PMID 16456219. http://www.cjcp.ca/pdf/CJCP_04-032_e69.pdf.
50. ^ http://apt.rcpsych.org/cgi/content/full/13/6/447
51. ^ http://www.benzo.org.uk/healy.htm
52. ^ http://www.medscape.com/viewarticle/498763
53. ^ "ACOG Committee Opinion No. 354: Treatment with selective serotonin reuptake inhibitors during pregnancy". Obstet Gynecol 108 (6): 1601–3. December 2006. PMID 17138801.
54. ^ ^{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.
55. ^ Way CM (April 2007). "Safety of newer antidepressants in pregnancy". Pharmacotherapy 27 (4): 546–52. doi:10.1592/phco.27.4.546. PMID 17381382.
56. ^ ^{a b} Bellantuono C, Migliarese G, Gentile S (April 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.
57. ^ ^{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.
58. ^ Bar-Oz B, Einarson T, Einarson A, et al (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.
59. ^ 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.
60. ^ ^{a b} Einarson A, Selby P, Koren G (January 2001). "Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counselling". J Psychiatry Neurosci 26 (1): 44–8. PMID 11212593. PMC: 1408034. http://www.cma.ca/multimedia/staticContent/HTML/N0/l2/jpn/vol-26/issue-1/pdf/pg44.pdf.
61. ^ Haddad PM, Pal BR, Clarke P, Wieck A, Sridhiran S (September 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.
62. ^ http://us.gsk.com/products/assets/us_paxil.pdf
63. ^ Mellerup, Erling T.; Plenge, Per (July 1986). "High affinity binding of3H-paroxetine and3H-imipramine to rat neuronal membranes". Psychopharmacology (Springer Berlin / Heidelberg) 89 (4): 436–439. doi:10.1007/BF02412117. http://www.springerlink.com/content/5888x32v705t336r/.
64. ^ 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.
65. ^ ^{a b} USATODAY.com - Judge: Paxil ads can't say it isn't habit-forming
66. ^ http://news.bbc.co.uk/2/hi/health/1382551.stm
67. ^ http://findarticles.com/p/articles/mi_qa4070/is_200206/ai_n9121579
68. ^ Paxil (paroxetine hydrochloride) prescribing information
69. ^ 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. http://www.drugscope.org.uk/Resources/Drugscope/Documents/PDF/Appgotcreport.pdf. Retrieved on 21 January 2009.
70. ^ "The Chemistry of Happiness". The Guardian. http://society.guardian.co.uk/mentalhealth/story/0,,707016,00.html. Retrieved on 2007-09-09.
71. ^ Stayton, Jonathan (2008-01-22). "Punk rocker sues over anti-depressant". The Argus. http://www.theargus.co.uk/news/generalnews/display.var.1984445.0.punk_rocker_sues_over_antidepressant.php. Retrieved on 2008-01-23.
72. ^ Angell, Marcia (2009), "Drug Companies & Doctors: A Story of Corruption", New York Review of Books, Vol 56, No 1; 15 January 2009.
73. ^ 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. PMID 14993169. PMC: 343848. http://www.cmaj.ca/cgi/pmidlookup?view=long&pmid=14993169.
74. ^ "Secrets of the drug trials". BBC. 2007-01-29. http://news.bbc.co.uk/1/hi/programmes/panorama/6291773.stm. Retrieved on 2007-08-15.
75. ^ Kurt Sammson (December 2008). "SENATE PROBE SEEKS INDUSTRY PAYMENT DATA ON INDIVIDUAL ACADEMIC RESEARCHERS". Annals of neurology: A7.
76. ^ Bass, Alison (2008), Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial, Algonquin Books of Chapel Hill.
77. ^ 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. http://www.drugtopics.com/drugtopics/article/articleDetail.jsp?id=407652. Retrieved on 2007-04-08.
78. ^ 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. http://drugtopics.modernmedicine.com/drugtopics/Top200Drugs/ArticleStandard/article/detail/491194. Retrieved on 2008-10-23. "Top 200 brand drugs by units in 2007.". Drug Topics, Feb 18, 2008. http://drugtopics.modernmedicine.com/drugtopics/PharmacyFactsAndFigures/ArticleStandard/article/detail/491210. Retrieved on 2008-10-23.

External links

• 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

Categories: Selective serotonin reuptake inhibitors

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