Paxil

Paxil, or paroxetine, is a selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor (SSRI) antidepressant, working primarily on the brain neurons. The pharmaceutical company, GlaxoSmithKline, released Paxil in 1992, and by 2006, it had become the one of the most prescribed antidepressants in the United States.

Paxil is a phenylpiperidine derivative, chemically unrelated to tricyclic or tetracyclic antidepressants. In research studies, paroxetine did not show any significant affinity for adrenergic (α1, α2, β), dopaminergic, serotonergic (5HT1, 5HT2), or histamine receptors of rat brain membrane, though a faint affinity for muscarinic acetylcholine and noradrenaline receptors was found.

According to the chemical properties, paroxetine hydrochloride is an odorless, off-white powder, with a melting point range of 120°C−138°C and a solubility of 5.4 mg/ml in water. The predominant metabolites of this drug are inactive as 5−HT reuptake inhibitors.

Paxil is most commonly used to treat social anxiety disorders, panic disorders, depression, and pre-menstrual dysphoric disorders (PMDD). Social anxiety disorder is a common treatable medical condition, under which a person experiences persistent and overwhelming fear of performances and social situations, to the extent of deliberately avoiding them. This disorder is generally noticed in human beings from childhood or early adolescence. Panic disorder refers to the state where an individual suffers panic attacks with symptoms like chest pains, pounding heart, and a shortness of breath. A continuous state of severe depression over a number of days is referred to as the major depressive disorder. PMDD symptoms include intense irritability, severe depression, and a feeling of being bloated during the days before one’s period.

Some of the other disorders treated with paroxetine include obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Paxil was the first antidepressant formally approved by the United States government to treat panic attacks. Six placebo-controlled clinical trials have proved the effectiveness of paroxetine in controlling the symptoms of major depressive disorder. Similarly, 3 12-week trials have indicated the superiority of paroxetine in the treatment of both panic disorders and social anxiety disorders.

In addition to these, studies have proved that Paxil can be used for the treatment of premature ejaculation, and intravaginal ejaculation. The intravaginal ejaculation latency time (IELT) was, in particular, found to increase by a 6-13 fold, which was a marked improvement from the previous medication available for this problem. However, paroxetine had only a “clinically irrelevant and sexually unsatisfactory” delay of ejaculation when consumed 3-10 hours before coitus.

Studies regarding the effect of Paxil in the treatment of bipolar disorder patients, and its advantages over the addition of placebo as a mood stabilizer in such patients have remained inconclusive. On the contrary, when used in the treatment of compulsive gambling and hot flashes, paroxetine has proved to be effective.

For the treatment of most of the disorders, a single dose of Paxil should be administered in the morning on an empty stomach. The initial dose should be around 20 mg/ day, but this depends largely on the needs and requirements of the patient. As is the case with most of drugs used to treat these disorders, the full effect of paroxetine may be delayed. Doses are generally changed in the interval of one week.

Paxil is available in both tablet and liquid form. The pills generally come in compositions of 10mg, 20mg, 30mg, and 40mg. The tablets come in various colors like yellow, pink, blue and green, and are usually oval shaped and coated with a film to make for easier swallowing. The liquid is generally orange in color and flavor. A 5 ml dose of the liquid is equivalent to a 10 mg pill. It should ideally be stored below 77°F (25°C) and should be shaken well before use.

It cannot be conclusively stated how long a patient being treated with Paxil needs to remain on it. Several months may be required to treat acute disorders through sustained pharmacologic therapy. Systematic evaluations have shown that the efficacy of this drug is sustained for periods of up to 1 year. However, whether the dose required to induce remission is the same as the dose needed to maintain euthymia is not known yet.

Generally, the side effects of this drug become evident during the first 4 week of its use. This is the time when the body starts adapting to the drug. Certain side effects are dependant on the dosage, with more or severe side effects being reported only in cases of high dosages. It is often observed that an increase or a change in the dosage may cause the side effects to reappear or worsen.
The European Medicines Agency (EMEA) has declared paroxetine unfit to be used on children. Also, adults have been advised to exercise caution while undergoing a course of paroxetine as it presents risks of suicidal behavior. Some of the more common side effects experienced while having Paxil include fluctuations in weight, headache, nausea, increased sweating, drowsiness and insomnia, constipation, diarrhea, erectile dysfunction, partial or complete loss of libido, failure to achieve orgasm, and vertigo and motion sickness.

Some of the other side effects patients complain of include an initial feeling of depression or anxiety, nocturnal salivation and bruxism, asthenia or muscle weakness, pruritis, rashes, and frequent nightmares. In pregnant women, consumption of Paxil may lead to teratologic conditions like fetal heart defects. Neonates exposed to this drug have also developed complications that required respiratory support and tube feeding. Paroxetine is also known have negative effects on cognition, particularly worsening dementia in patients suffering from cognitive impairments.

Patients using Paxil are known to suffer withdrawal symptoms. According to reports, among all medication of its class, paroxetine has one of the highest incidence rates of SSRI discontinuation syndrome. Some of the common withdrawal symptoms are repeated electrical shock sensations in the brain and body, hot flashes, vertigo, and suicidal tendencies. For over a decade, paroxetine had been promoted as a drug that was “not habit forming”. This changed with the FDA publishing a new product warning in 2002 which clearly stated that patients could develop a dependency on this drug, and that there could be acute withdrawal symptoms. Fluoxetine has been medically prescribed to lessen the symptoms in patients suffering from withdrawal.

A number of lawsuits have been brought by individuals against the GlaxoSmithKline company for holding back information regarding the use of Paxil, and deeming it fit to be prescribed to minors and adolescents. Patients were also not warned of the side effects of this drug. Patients, particularly children, developed suicidal thoughts post the consumption of this drug and this has led the FDA to order a “black box warning” to be placed on this drug. This is a type of warning whereby a package insert for prescription drugs informs users of the serious adverse effects of the consumption of that particular drug. The BBC has also broadcast a number of programmes on the pediatric clinical trials on depressed children and adolescents. It was proved in these trials that children had a six-fold more susceptibility to suicidal tendencies and depression after taking paroxetine.