Seroxat is a selective serotonin reuptake inhibitor (SSRI) antidepressant. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline. Seroxat is used to treat major depression, obsessive-compulsive, panic, social anxiety, and generalised anxiety disorders in adult outpatients.
In adults, the efficacy of Seroxat for depression is comparable to that of older tricyclic antidepressants, with fewer side effects and lower toxicity. Differences with newer antidepressants are subtler and mostly confined to side effects. It shares the common side effects and contraindications of other SSRIs, with high rates of nausea, somnolence, and sexual side effects. Unlike two other popular SSRI antidepressants, fluoxetine and sertraline, Seroxat is associated with clinically significant weight gain and statistically significant increase in the risk of suicidality in adults. Pediatric trials of Seroxat for depression did not demonstrate efficacy and showed an increase in the risk of harmful outcomes, including episodes of self-harm and potentially suicidal behaviour.
Discontinuing Seroxat is associated with a high risk of discontinuation or withdrawal syndrome. Due to the increased risk of birth defects, pregnant women or women planning to become pregnant are recommended to avoid or discontinue Seroxat use.
Seroxat is primarily used to treat the symptoms of major depression, obsessive-compulsive disorder (OCD), (PTSD), panic disorder, generalized anxiety disorder (GAD), social phobia/social anxiety disorder, and premenstrual dysphoric disorder (PMDD).
Seroxat was the first antidepressant formally approved in the United States for the treatment of panic attacks.
According to the prescribing information provided by the manufacturer of the Paxil brand of Seroxat (GlaxoSmithKline) and approved by the U.S. Food and Drug Administration (FDA) the effectiveness of Seroxat in major depressive disorder has been proven by six placebo-controlled clinical trials. For panic disorder, three 10-12 week studies indicated Seroxat superiority to placebo. Similarly, three 12-week trials for adult outpatients with social anxiety disorder demonstrated better response to Seroxat than to placebo. Additional studies show patients are 10-20% more likely to benefit compared to placebo.
Among the common adverse effects associated with Seroxat treatment of depression and listed in the prescribing information, those with the greatest difference from placebo are nausea (26% on paroxetine vs 9% on placebo), somnolence (23% vs. 9% on placebo), ejaculatory disturbance (13% vs. 0% on placebo), other male genital disorders (10% vs. 0% on placebo), asthenia (15% vs. 6% on placebo), sweating (11% vs. 2% on placebo), dizziness (13% vs. 6% on placebo), insomnia (13% vs. 6% on placebo), dry mouth (18% vs. 12% on placebo), constipation (14% vs. 9% on placebo), and tremor (8% vs. 2% on placebo). Other side effects include headache, agitation, weight gain, impaired memory and paresthesia.
General side effects are mostly present during the first 1–4 weeks while the body acquires a tolerance to the drug, although once this happens, withdrawal can cause a rebound effect with symptoms re-emerging in an exaggerated form for very long periods of time. Almost all SSRIs are known to cause either one or more of these symptoms. A person receiving Seeroxat 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.
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 Seroxat 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.
The FDA conducted a statistical analysis of Seroxat clinical trials in children and adolescents in 2004, finding 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. 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 Seroxat users. Cases of akathisia and activation syndrome have been observed during Seroxat treatment. Rarely serotonin syndrome, a severe adverse effect may occur.
Seroxat and other SSRIs have been shown to cause sexual side effects in most patients, both males and females. In males, Seroxat is also linked to sperm DNA fragmentation.
Mania or hypomania may occur as a serious side effect of Seroxat 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.
Schmitt et al. (2001) suggested that Seroxat negatively affects memory (i.e., IQ). In their study, healthy participants given Seroxat for 14 days (20 mg for days 1–7 and 40 mg days 8–14) showed poorer recall of words on day 14 compared to those receiving a placebo Schmitt et al. did not take into account a significant difference in verbal recall at baseline between the Seroxat and placebo groups, however, and this difference may have been the source of the significant group difference on day 14. Moreover, participants receiving seroxat scandal recalled as many words at baseline as they recalled on day 14, which is not consistent with the conclusion that Seroxat negatively affects verbal recall.
For 10 years, GlaxoSmithKline (GSK) stated that it was “not habit forming,” which numerous experts and at least one court found to be incorrect. In 2001, the BBC reported the World Health Organization had ranked Seroxat as the most difficult antidepressant to withdraw from. In 2002, the U.S. FDA published a new product warning about the drug, and the International Federation of Pharmaceutical Manufacturers Associations said GSK had misled the public about Seroxat and breached two of the Federation’s codes of practice. 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 Seroxat 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 Seroxat directly to consumers as ‘non-habit forming’ for far too long. Seroxat prescribing information posted at GlaxoSmithKline now acknowledges the occurrence of a discontinuation syndrome, including serious discontinuation symptoms.
Since the FDA approved Seroxat 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.
In 2001, GSK increased its American TV advertising of Paxil after the September 11 attacks; in October 2001, GSK spent nearly twice as much as in October 2000. The difficulty of withdrawal from Seroxat, and GSK’s concealment of it, was later reported on ABC.
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.
In early 2004, GSK agreed to settle charges of consumer fraud for $2.5 million. 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 Seroxat.
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. GSK claimed the ad had been previously reviewed by FDA, but said the ad would not run again.
On January 29, 2007, the BBC broadcast a fourth documentary in its Panorama series about the drug Seroxat. 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 in a way which misled readers about paroxetine’s safety and efficacy, and contributed to repeated distortions in the assessment of the drug’s value in paediatric depression in the scientific literature.
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 Seroxat. 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”.
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.
In 2007, Seroxat was ranked 94th on the list of bestselling drugs, with over $1 billion in sales. In 2006, Seroxat was the fifth-most prescribed antidepressant in the United States retail market, with more than 19.7 million prescriptions. In 2007, sales had dropped slightly to 18.1 million but Seroxat remained the fifth-most prescribed antidepressant in the U.S.
With all the controversy surrounding the use of Seroxat, do you think that Seroxat should be on sale?
Do you think that the benefits out way the risks associated with Seroxat?