Paroxetine

Paroxetine or paroxetine hydrochloride is a selective serotonin reuptake inhibitor (SSRI) antidepressant. It was released in 1992 by the pharmaceutical company GlaxoSmithKline and has since become one of the most prescribed antidepressants on the market due to its efficacy in treating depression as well as a spectrum of anxiety disorders ranging from panic attacks to phobias.

Trade names

Paroxetine is marketed under several tradenames:

Aropax in Australia, New Zealand, South Africa, Argentina and Brazil

Cebrilin in Latin America

Deroxat in Switzerland and France

Paroxat in Germany and Hungary

Paxil or Paxil CR in the United States, Canada, Argentina and Brazil

Pondera in Brazil

Seroxat in Austria, Belgium, Greece, Israel, The Netherlands, Poland, Portugal, Singapore, Spain, Turkey, the UK and China.

Indications

Approved

Paroxetine is primarily used to treat the symptoms of depression, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, generalized anxiety disorder (GAD), social phobia/social anxiety disorder, and premenstrual dysphoric disorder (PMDD).

It was the first (and as of 2002, the only) antidepressant formally approved in the United States for the treatment of social anxiety disorder, causing it to be sometimes referred to (although inaccurately) as an anti-shyness drug.

Clinical Trials

Trials for Paxil CR have not lasted more than twelve months. The effectiveness of Paxil in major depressive disorders has been proven by two twelve week clinical trials in which the patients either had flexible doses or a placebo. Both of the studies concluded that Paxil is significantly more effective than the placebo control group. For another disorder, three 10-week studies were conducted to prove the effectiveness of Paxil CR on panic disorders. In the first and second studies, Paxil proved consistently better than the placebo. But the third trial Paxil CR failed to have any significant difference to the placebo. For social anxiety disorder, a 12-week trial for adult outpatients was conducted to show Paxil's effectiveness against the disease and prior information of Paxil's nature in the immediate release formulation. The study did not include adolescents with the disorder.

Unapproved/Off-label/Investigational

Paroxetine can also be used in the treatment of premature ejaculation, chronic headache, and bipolar disorder.

Paroxetine has been found to significantly reduce the symptoms of diabetic neuropathy.

There is also evidence that paroxetine may be effective in the treatment of compulsive gambling and hot flashes.

Pharmacology

Paroxetine is the most potent selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor (SSRI). 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.

Paroxetine controlled release (CR)

Paroxetine controlled release contains a GeomatrixT tablet that controls the absorption of the drug. Clinical studies show that controlled release tablet provides effective symptom relief with a lower number of patients stopping their treatment due to side effects.

However, the need for an extended release form of paroxetine has not been established, as the FDA indicated that the half-life for the original Paxil was ideal for once-daily dosing, and that a CR version was not needed.

Chemistry

Paroxetine hydrochloride is an odourless, off-white powder, having a melting point range of 120° to 138°C and a solubility of 5.4 mg/mL in water.

Formulations

Paxil / Seroxat (paroxetine) is available in 10, 20, 30, and 40 mg tablets.

Paxil CR (paroxetine extended release) is available in 12.5, 25, and 37.5 mg tablets.

Paxil, Seroxat and Paxil CR are manufactured by GlaxoSmithKline, however a generic is now available under the chemical name paroxetine.

Side effects

General side effects are mostly present during the first 1-4 weeks while the body adapts to the drug. 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 following side-effects, and most side-effects will disappear or lessen with continued treatment, though some may last throughout the duration.

Nausea

Drowsiness

Headache

Changes in weight and appetite

Changes in sexual behaviour

Increased feelings of depression and anxiety (initially)

Dry mouth

Constipation

diarrhoea

Aggressive behaviour (esp. in children)

Possible suicidal behaviour

Possible congenital malformations

Rash

Restlessness or Akathisia

Itch

Sodium depletion

Changes in urination

Sweating

Muscle weakness

Uncharacteristic levels of aggression

Inability to reach orgasm and other sexual side effects

Individuals experiencing any of the following symptoms should contact their doctor immediately:

Jaw, neck, and back muscle spasms

Fever, chills, sore throat, or flu-like symptoms

Yellowing of the skin or eyes

Black, tarry stools (this can indicate upper GI bleeding)

Despite these side effects, Paroxetine is effective and generally well-tolerated in adults. Paroxetine is a useful tool in treating major depression, particularly in adults who have not responded to other therapies.

Warnings

During the trials it was evident that there were major health risks involved such as possible suicide and major congenital malformations, the remedy was introduced despite those reasons. This is prompting a wave of litigation against the drug's manufacturer. One of the first litigation trials in America was set by the law firm of Robert Kwok & Associates, L.L.P. in Houston, TX.

Seroxat must not be used for treatment of children.

When reports came of suicide, the controversy about Paxil became public. The FDA continues to issue warnings regarding Paxil.

Paroxetine users should not discontinue and resume treatment with more than a few days' gap between dosings, as paroxetine decreases in effectiveness if it is stopped for a significant amount of time, and then resumed.

Discontinuation syndrome

While any psychoactive medication (from caffeine to anti-psychotics) can cause withdrawal symptoms upon discontinuation from acute administration, anecdotal evidence suggests that paroxetine has a higher incidence rate and severity of SSRI discontinuation syndrome than other SSRIs and psychoactive medications. For those experiencing extreme and unusual difficulty discontinuing paroxetine, it is recommended that an SSRI with a longer half-life, such as fluoxetine, be administered for approximately two weeks, then discontinued, to lessen symptoms.

Suicidal ideation is a frequently reported experience in those withdrawing from SSRIs. Withdrawal from paroxetine or any other SSRI should be medically supervised.

Source: wikipedia GFDL