Paroxetine

Encyclopedia : P : PA : PAR : Paroxetine

1. redirect [[Template:POV-check]]

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.

Paroxetine has been linked to suicidal ideation and attempts, particularly in children and young adults. It also has a demonstrated withdrawal syndrome, in which some users experience dizziness, electric shock-like sensations, and gastro-intestinal upset.

Trade Names

Paroxetine is marketed under the tradenames Paxil in the United States, Canada and Brazil; Seroxat in Austria, Greece, Poland, Portugal, the UK and China; Aropax in Australia, New Zealand, South Africa and Brazil; Pondera in Brazil; Deroxat in Switzerland and France; Paroxat in Germany, and Cebrilin in Latin America

Indications

Approved

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 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, Paxil CR was released after the patent expired for the original Paxil, which was seen as a ploy by GSK only to increase earnings, 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. In addition, the Paxil CR version is slightly less effective than the original and generic paroxetine, which is why the CR version is approved for fewer anxiety disorders.

Chemistry

Adverse effects

Recent studies have suggested that a small percentage of adolescents taking the drug are prone to becoming suicidal in the early stages of treatment.^{[[Citing sources citation needed]]} In May, 2006 a clinical analysis of trial data showed an increased frequency of suicide in young adults. Some psychologists believe that this is due to the way the drug begins to work in many patients.^{[[Citing sources citation needed]]} The first effect most patients notice is a decrease in the lethargy they experienced during their depression. This effect happens before the depression itself improves, so children may end up with enough "energy" and motivation to act on suicidal tendencies they may have already had.^{[[Citing sources citation needed]]}

Many adolescents who are prescribed paroxetine are suicidal to begin with. However most studies have compared suicide rates in patients using paroxetine against a control group of depressed individuals not being treated with paroxetine; the paroxetine group was reported to be twice as likely to commit suicide.^{[[Citing sources citation needed]]}

In June 2004, New York attorney general Eliot Spitzer began [civil proceedings] against GlaxoSmithKline over allegations that the company had suppressed five internal studies between 1998 and 2002 on the effects of the drug on both children and adults. The studies suggested that, in children, the drug had effects ranging from that of a placebo to inducing suicidal tendencies in its users. The company responded shortly later by making the results of the studies [publicly available].

In March 2005, the United States Food and Drug Administration ordered the [seizure] of millions of tablets of Paxil after 3 years of GlaxoSmithKline's unresolved manufacturing problems. These problems involved Paxil CR, a time-release version of the drug. Some capsules were found to break in two, potentially resulting in the user taking only the active element of the drug without the time-release portion, or vice versa.

In September 2005 the Therapeutic Goods Administration (TGA) of Australia issued a warning about the potential for increased birth defects in the babies of pregnant women taking the anti-depressant paroxetine. Early results from GlaxoSmithKline suggested an association between taking the drug in the first three months of pregnancy and birth defects. The risk of cardiovascular defects may double from 1 to 2 percent in babies of women taking paroxetine. A Dutch study suggested a 60 per cent increase in defects. The TGA urged women not to suddenly stop taking the SSRI as withdrawal may cause harmful side effects. In December 2005, the United States Food and Drug Administration issued a similar public health advisory [link]. In this report, the FDA decided to change paroxetine from pregnancy category C to D, indicating a higher degree of caution is warranted when using paroxetine in pregnant women.

-->

General 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:

• nausea
• drowsiness
• headache
• changes in weight and appetite
• changes in sexual behaviour
• increased feelings of depression and anxiety (initially)
• dry mouth
• constipation
• diarrhea
• rash
• restlessness or akathisia
• itch
• sodium depletion
• changes in urination
• sweating

• 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)

Addictive potential and withdrawal symptoms

The factual accuracy of this section is [Accuracy disputedisputed]. Please view the article's [talk page][[Template:Sectfact|.]]

Addictive potential

Withdrawal symptoms

Initially, the response of drug regulators (based eg on a report by Price et al, 1995) were that withdrawal symptoms (or 'discontinuation reactions' as SKB/GSK insisted) were generally mild and short-lived, an opinion that has been replaced by mounting concern. Now, it seems about a third of users have problems stopping paroxetine, and the symptoms are strikingly similar ('electric shock' paraesthesia, dizziness, flu-like symptoms, auditory hallucinations, etc). It is clear that what is under discussion is not psychological dependence.

Withdrawal symptom severity varies from individual to individual and can last from months to years. The most common and successful technique for protection against a difficult withdrawal experience is to lower dosage levels gradually over time. Symptoms arising from a dose change often don't fully appear for several weeks. Since paroxetine has a much shorter half life than other SSRIs like Prozac, people have occasionally sought to buffer their withdrawal plan with a liquid form of Prozac. In liquid form, dose diminishments of 1m.g. are easy to achieve.

Suicidal ideation is a frequently reported experience in those withdrawing from SSRIs like paroxetine. Never seek to withdraw from paroxetine or any other SSRI without supervision.

Lawsuits

External links

• [Paxil Information from Drugs.com]
• [Detailed Paroxetine Consumer Information: Uses, Precautions, Side Effects] from medlibrary.org
• [Seroxat must not be used for treatment of children], Royal College of Psychiatrists
• [The Secrets of Seroxat], BBC Panorama investigation
• [Antidepressant Use in Children Soars Despite Efficacy Doubts], Washington Post, April 18, 2004
• [Seroxat and Prozac 'can make people homicidal'], The Guardian
• [Paroxetine.com] - The official paroxetine site
• [Quitpaxil.org] - Information for persons suffering from Paxil withdrawal syndrome
• [Dependence on Antidepressants & Halting SSRIs - protocol for withdrawal]
• [NIH Expert Panel Report on the reproductive and developmental toxicology of Prozac (Fluoxetine)]
• [NIH Monograph on the potential human reproductive and developmental effects of Prozac (Fluoxetine)]
• ["Extroverted like me" A field report by Seth Stevenson]
• [Paxil Patient Information leaflet], Paxil Patient Information leaflet
• [Paxil CR Patient Information leaflet], Paxil CR Patient Information leaflet

References

Monoamine oxidase inhibitors (MAOI): Reversible Inhibitor of Monoamine oxidase A (RIMA): Dopamine Reuptake Inhibitor (DARI): Norepinephrine-dopamine reuptake inhibitors: Norepinephrine Reuptake Inhibitor (NRI) or (NARI): Serotonin-Norepinephrine Reuptake Inhibitor (SNRI): Selective Serotonin Reuptake Inhibitor (SSRI): Selective Serotonin Reuptake Enhancer (SSRE): Tricyclic antidepressants (TCA): Tetracyclic antidepressants: Noradrenergic and Specific Serotonergic Antidepressant (NaSSA):

From Wikipedia, the Free Encyclopedia. Original article here. Support Wikipedia by contributing or donating.
All text is available under the terms of the GNU Free Documentation License See Wikipedia Copyrights for details.