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.

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.

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 Geomatrix™ 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 odorless, 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
 * Diarrhea
 * Aggressive behavior (esp. in children)
 * Possible suicidal behavior
 * Possible congenital malformations
 * Rash
 * Restlessness or Akathisia
 * Itch
 * Sodium depletion
 * Changes in urination
 * Sweating
 * Muscle weakness
 * Uncharacteristic levels of aggression

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.