Paxil's neural mechanisms, efficacy, and adverse effects

Paxil

BOON or BANE?

History and Neural Mechanisms

Paxil is the brand name of an orally administered psychotropic drug, Paroxetine hydrochloride, manufactured by Glaxo Smith Kline (GlaxoSmithKline 2007). The effectiveness of paroxetine in treating major depressive disorder, social anxiety disorder, obsessive compulsive disorder, panic disorder, generalized anxiety disorder and posttraumatic stress disorder has been the focus of studies, which linked the chemical combination to central nervous system activities involved in the disorders. These studies showed that sufficient doses of the drug block neuronal uptake of serotonin into human platelets. Animal studies also suggested that paroxetine strongly and selectively inhibit reuptake and has negligible allergic, sedative and cardiovascular effects as do other psychotropic drugs (GlaxoSmithKline).

Adverse Effects

Studies on Paxil CR as treatment for menopausal hot flashes implied long-term risks of hormone replacement therapy (Nursing 2003). These divided 165 menopausal women respondents into groups who took three regimens of Paxil CR 12.5 mg per day, Paxil Cr 25 mg per day and a placebo for six weeks. Results showed that 60% of those on either dose of Paxil experienced reduced symptoms of hot flashes in number and intensity. Those taking placebo had 38% reduced symptoms. Treatment of hot flashes, however, was not included in FDA-approved indication list for the drug (Nursing).

From its own analytical findings, Paxil manufacturer GlaxoSmithKline warned doctors in writing that the drug could increase the risk of suicide attempts in some young adults (Carey and Harris 2006). It informed the doctors that the finding was indicated on the drug's labels. Its clinical analysis of 15,000 respondents revealed that suicide attempts were more common in those who took the drug for depression than those on placebo. The company, however, reported only one suicide in the trials. It reasoned that the number is so negligible to pose any significant risk. In response, the FDA issued a strong warning on antidepressant labels. Critics believed that this confession by the manufacturer itself suggested that the risk is not only real but not confined to minors only. FDA said that it was still evaluating the data but went ahead and recommended caution in the use of antidepressants. It warned about the worsening of depression and increased suicidal thinking and behavior and sudden discontinuation of the drug. It asked psychiatric drug manufacturers to review their data on the side effects of such drugs on adults. The objective was to establish the link between suicide attempts and any of the antidepressants. Since then, FDA required a label, warning the use of the drugs by children and adolescents. It also believed that the public should treat Glaxo's findings with caution. Its antidepressant trials were not aimed at evaluating suicide dangers, thus did not establish that the drug was not the cause of the behavioral disorder. Glaxo voluntarily issued the warnings while maintaining that the drug's benefits outweighed the risks. It also said that it had advised doctors to monitor their patients to make sure the symptoms do not get worse during the entire treatment. Earlier researches implied that the highest risk of suicidal thinking or behavior occurred in the first few weeks of treatment. This was when patients stopped the medication. A British review on antidepressant trials conducted in the previous year said that patients on Paxil and similar drugs, like Prozac, reported suicide attempts more frequently (Carey and Harris).

The Glaxo study involved 8,958 takers of Paxil and 5,953 of placebo (Carey and Harris 2006). Their ages ranged from 18 to 64 and took the drug for one of the indicated disorders. The study found that 11 of the total of 3,455 patients reported suicide attempts, compared with only one in 1,978 on placebo. Most of those who attempted suicide were adults whose ages ranged from 18 to 30, Glaxo said. From the results, Glaxo concluded no increased risk in adults over 30 years old. Doctors felt that the warning should trigger more careful supervision when the drug entered the market (Carey and Harris).

The U.S. Food and Drug Administration took up from the stance of the British food and drug agency in warning against the use of Paxil by children (Healthfacts 2003). The brand name of the British drug was Seroxat. Seroxat was suspected as the causing suicidal tendencies and other abnormal or dangerous behavioral reactions to those under 18 in the UK. Paxil manufacturer Glaxo, on the other hand, was suspected to hide negative results of a similar kind. The UK Medicines and Healthcare Products Regulatory Agency demanded access to Glaxo's files, data and studies on Paxil or Seroxat, with the release of new data on the drug. These data compared with those on children who were given a placebo. Findings revealed an increase in suicide, aggressive behavior and other forms of psychosis in the children subjects taking the drug. The agency was quoted as saying that Glaxo could be subjected to criminal charges if found withholding earlier studies with these or similar findings (Healthfacts).

Paxil has been approved by the U.S. FDA for adults with established mental conditions, but not for children (Healthfacts 2003). Some American physicians, however, prescribe it to some children. The FDA website publishes three well-controlled trials on children with major depression. They failed to prove that Paxil does better than a placebo. It now requires manufacturers to present two trials, which would prove that antidepressants did better than placebos. Drug companies had to conduct several trials just to come up with two with the required positive results (Healthfacts).

Paxil's medication guide includes information on antidepressants, depression and other serious mental disorders and suicidal thoughts or actions (GlaxoSmithKline 2007). It states that these medicines could induce or produce suicidal tendencies in young adults, teenagers and children within the first few months of treatment. Depression and other serious mental disorders are the most frequent causes of suicidal thoughts or actions. Certain groups of people are at a higher risk of this tendency than others. These can be prevented by watching out for symptoms like changes in mood and behavior. These symptoms include thoughts about suicide or dying; attempts to commit suicide; new or greater depression; new or greater anxiety; strong agitation or restlessness; panic attacks; insomnia; extreme irritability; aggressiveness or violent behavior; impulsiveness; manias; and other unusual behavioral or mood changes. It reminds patients never to stop a Paxil regimen without first notifying a healthcare provider. Antidepressants are medicines intended to treat depression and other serious mental illnesses. They have side effects. They can interact with other medicines. And not all medicines prescribed for children are not approved for children by the FDA (GlaxoSmithKline).