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 apparent efficacy in treating depression as well as a spectrum of anxiety disorders ranging from panic attacks to phobias. The prescription of this drug is currently controversial because of legal proceedings against the manufacturer (see controversy below).
Trade names
Paroxetine is marketed under several tradenames:
Aropax or Oxetine in Australia, New Zealand, South Africa, Argentina, Mexico and Brazil,
Aroxat or Aroxat CR in Chile,
Bectam in Chile,
Benepax in Brazil,
Cebrilin in Latin America,
Deroxat 4528 in Switzerland and France,
Loxamine as generic replacement for Aropax in New Zealand,
Motivan and Paroxetina in Spain,Italy,
Optipar in Finland,
Pamax in Chile,
Paroxat in Germany and Hungary,
Psicoasten in Argentina,
Paxera in Turkey,
Paxil or Paxil CR in the United States, Canada, Mexico, Argentina, Brazil, Japan, Venezuela, Honduras, and Peru
Paradise CR in India,
Pexot, Paraxyle and Plasare in Pakistan,
Pondera in Brazil,
Posivyl in Chile,
Remood in Czech Republic, Slovakia,
Rexetin in Poland,
Sereupin in Italy,
Seretran in Chile,
Seroxat in Austria, Belgium, Saudi Arabia, Egypt, Estonia, Finland, Iceland, Sweden, Norway, Greece, Israel, Latvia, The Netherlands, Poland, Portugal, Singapore, Spain, Turkey, the UK & Ireland, China and South Korea,
Traviata in Chile,
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 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
GlaxoSmithKline, the manufacturer of the brand name Paxil conducted clinical trials on the drug paroxetine hydrochloride. Results from these tests are published in the prescribing information on GSK's website.[4] The following is a summary of the effectiveness of paroxetine hydrochloride on a variety of psychological disorders.
Trials for Paxil 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 on panic disorders. In the first and second studies, Paxil proved consistently better than the placebo. But the third trial Paxil 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 not 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 and one of the most specific selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (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
Remood (paroxetine) is available in 20 mg tablets.
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 (though not yet for the extended release) 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. Side effects are also often dose-dependent, with fewer and/or less severe symptoms being reported at lower dosages, and more and/or more severe symptoms being reported at higher dosages. Increases or changes in dosage may also cause symptoms to reappear or worsen.
Most common
Weight loss or gain (most often gain rather than loss)
Headache
Nausea
Dry mouth
Increased sweating
Drowsiness/Somnolence or Insomnia
Increased or decreased appetite
Constipation or diarrhea
Inability to achieve orgasm
Partial or complete loss of libido (sexual desire)
Erectile dysfunction
Tremor
Vertigo/Dizziness/Motion sickness
Less common
Check with your doctor if these continue or are bothersome.
Increased feelings of depression and anxiety (initially)
Apathy
Loss of empathy
Flattening of emotional response
Nocturnal salivation
Nocturnal bruxism (teeth grinding)
Pupil dilation
Asthenia or muscle weakness
Muscle ache
Pruritis
Rash
Nightmares or change in dreams
Change in sense of taste
Rare
See your doctor if you have any of these symptoms.
Myoclonus (involuntary muscle twitching)
Sodium depletion
Severe restlessness or akathisia
Uncharacteristic levels of aggression (especially in children and teens)
Uncharacteristic risk taking
Very rare but serious
Suicidal ideation and Suicide
Serotonin syndrome
Bipolar mania or hypomania
Schizophrenia (unverified)
Jaw, neck, and back muscle spasms
Fever, chills, sore throat, or flu-like symptoms
Yellowing of the skin or eyes (Jaundice)
Black, tarry stools (this can indicate upper GI bleeding)
Other
Teratogenicity: Pregnant women are advised not to take the drug due to possible fetal heart defects.
The patient information leaflet for Paroxetine seems to differ from country to country The Tauraso Medical Clinic.
Paroxetine and other SSRIs have been shown to cause sexual side effects in most patients, both males and females. Although usually reversible, these sexual side effects can sometimes last for months, years or possibly indefinitely even after the drug has been completely withdrawn. This disorder is known as Post SSRI Sexual Dysfunction.
Withdrawal syndrome
Many psychoactive medications can cause withdrawal symptoms upon discontinuation from administration. Substantial evidence has shown that paroxetine has the highest incidence rate and severity of SSRI discontinuation syndrome of any medication of its class. Repeated electrical shock sensations of the brain and body (see "brain zaps"), vertigo and hot flashes being prevalent. 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 closely medically supervised by the prescribing physician.
Warning for pregnant women
Pregnant women and those who might become pregnant should avoid taking the antidepressant Paxil because of a high risk of birth defects, according to a committee of obstetricians who published their opinion in the December issue of the journal Obstetrics & Gynecology.
The obstetric practice committee of the American College of Obstetricians and Gynecologists said pregnant women should not take Paxil because two previous studies found that the drug posed up to double the risk of heart defects in fetuses.
Nearly a year ago, the U.S. Food and Drug Administration (FDA) and GlaxoSmithKline -- which makes Paxil -- changed the warnings on the drug to include the results of the studies. The FDA then advised pregnant women to merely switch from Paxil to another SSRI drug, such as Prozac or Zoloft.
The FDA's enhanced warning on Paxil followed the results of a review of Sweden's birth registry that found pregnant women who took Paxil were 1.5 to 2 times more likely to give birth to a baby with heart defects than women who took other SSRIs or who did not take antidepressants at all.
Neonatal withdrawal symptoms from Paxil have also been documented from mothers taking Paxil during pregnancy.
Controversy
On October 6, 2006, a US court preliminarily approved a settlement in a class action lawsuit brought on behalf of everyone in the United States who purchased Paxil(R) or Paxil CR(TM) prescribed for consumption by a minor child. The lawsuit alleges that GlaxoSmithKline promoted Paxil(R) or Paxil CR(TM) for prescription to children and adolescents while withholding and concealing material information about the medication's safety and effectiveness for minors. GSK denies all claims. If approved, the Proposed Settlement will provide $63.8 million to pay consumers, who submit valid Claim Forms, cash for the total amount they paid for Paxil(R) or Paxil CR(TM). Eligible Class Members can get up to 100% of the amount paid for Paxil(R) or Paxil CR(TM).
The Court will hold a Final Approval Hearing on March 9, 2007. At that time, the Court will consider whether to approve the Proposed Settlement and award attorneys' fees and costs.
Update to aforementioned settlement: This class action settlement (Hoormann v. SmithKline Beecham Corporation) was approved in May 2007. Although a settlement was reached in October 2006, that settlement was dramatically improved at a recent hearing (after Public Citizen Litigation Group got involved). Under the terms of the revised settlement, if you ever purchased Paxil or Paxil CR for your child or ward, you are entitled to recover up to 100% of your documented out-of-pocket expenses. If you are unable to find documentation of your Paxil purchases, you can still recover up to $100. To receive a refund for the money you spent buying Paxil or Paxil CR, you must submit a claim ; the claim forms must be received by August 31, 2007.
In March 2004 the FDA placed a black box warning on SSRI and other antidepressants, warning of the risk for potential suicidal thinking in children and adolescents. ABC News reported that the prescribing of these medications to children subsequently dropped by 20 percent. According to the Center for Disease Control and Prevention's Annual Summary of Vital Statistics, the suicide rate rose more than 18 percent in those 1 to 19 years old, from 2.2 per 100,000 in 2003 to 2.6 per 100,000 in 2004. In those 15 to 19 years old, the figures reflected a more than 12 percent rise in suicide, from 7.3 per 100,000 in 2003 to 8.2 per 100,000 in 2004. This led many experts to conclude that the warning, and subsequent reduction in the use of antidepressants, led to an increased suicide rate in this age group. The finding is consistent with an earlier finding, reported to the 2003 FDA Advisory Committee by Dr David Shaffer, that suicide rates in the United States fell during the 1990s, in line with the introduction of SSRIs.
Since the FDA approved paroxetine in 1992, approximately 5,000 U.S. citizens have sued GSK. Most of these people feel they were not sufficiently warned in advance of the drug's side effects.
According to the Paxil Protest website, hundreds more lawsuits have been filed against GSK. The Paxil Protest website was launched August 8, 2005 to offer both information about the protest and information on Paxil previously unavailable to the public. Just three weeks after its launch, the site received more than a quarter of a million hits. The original Paxil Protest website was removed from the internet in 2006. It is understood that the action to remove the site from the internet was undertaken as part of a confidentiality agreement or 'gagging order' which the owner of the site entered into as part of a settlement of his action against GlaxoSmithKline. (However, in March 2007, the website Seroxat Secrets discovered that an archive of Paxil Protest site was still available on the internet via Archive.org) Gagging orders are common in such cases and can extend to documents that defendants wish to remain hidden from the public. However in some cases, such documents can become public at a later date, such as those made public by Dr. Peter Breggin in February of 2006.
In January 2007, according to the Seroxat Secrets website, the national group litigation in the United Kingdom, on behalf of several hundred people who allege withdrawal reactions through their use of the drug Seroxat, against GlaxoSmithKline plc, moved a step closer to the High Court in London, with the confirmation that Public Funding had been reinstated following a decision by the Public Interest Appeal Panel. The issue at the heart of this particular action claims Seroxat is a defective drug in that it has a propensity to cause a withdrawal reaction. Hugh James Solicitors have confirmed this news.
On January 29 2007, the BBC in the UK broadcast a fourth documentary in its 'Panorama' series about the drug Seroxat. This programme, entitled Secrets of the Drug Trials, focused on three GSK paediatric clinical trials on depressed children and adolescents. Data from the trials show that Seroxat could not be proven to work for teenagers. Not only that, one clinical trial indicated that they were six times more likely to become suicidal after taking it. In the programme, Panorama revealed the secret trail of internal emails which show how GlaxoSmithKline manipulated the results of the trials for its own commercial gain. Access to the documents has been gained as GlaxoSmithKline fights a fraud trial in the US.
What cannot be denied is that the release into the public domain of previously secret Glaxo documents,[30] can only serve to stimulate discussion and debate regarding the way certain companies choose to market their products.
On the 12th Of February 2007, according to The Sun newspaper (and news organisations around the world) singer Robbie Williams checked himself into rehab to kick his addiction to Seroxat.
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