Plasma, serum or blood concentrations of paroxetine may be measured to monitor therapeutic administration, confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. Acute overdosage is often manifested by emesis, lethargy, ataxia, tachycardia and seizures. Postmortem blood levels have ranged from 1–4 mg/L in acute lethal overdose situations. It is usually considered, along with the other SSRIs, sertraline and fluoxetine to be a low-risk drug in cases of overdose. Plasma paroxetine concentrations are generally in a range of 40–400 μg/L in persons receiving daily therapeutic doses and 200–2000 μg/L in poisoned patients.
At the low dose used for menopausal hot flashes side effects are similar to placebo and dose tapering is not required for discontinuation. hot flashes and night sweats) associated with menopause. Randomized controlled trials have shown modest relief in such cases. FDA approved low dose paroxetine for the treatment of moderate-to-severe vasomotor symptoms (e.g. On June 28, 2013 U.S.
While early clinical trials suggested a relatively low rate of sexual dysfunction, more recent studies in which the investigator actively inquires about sexual problems suggest that the incidence is >70%. Sexual dysfunction, including loss of libido, anorgasmia, lack of vaginal lubrication, and erectile dysfunction, is one of the most commonly encountered adverse effects of treatment with paroxetine and other SSRIs. Symptoms of sexual dysfunction have been reported to persist after discontinuing SSRIs, although this is thought to be occasional.
Mania or hypomania may occur in 1% of patients with depression and up to 12% of patients with bipolar disorder. This side effect can occur in individuals with no history of mania but it may be more likely to occur in those with bipolar or with a family history of mania.
GlaxoSmithKline may also face actions from other generics manufacturers who incurred loss as a result of the anticompetitive conduct. On 18 April 2016, appeals were lodged with the Competition Appeal Tribunal by the companies which were fined. UK public health services are likely to claim damages for being overcharged in the period where the generic versions of the drug were illegally blocked from the market, as the generics are over 70% less expensive. GlaxoSmithKline received the bulk of the fines, being fined £37,600,757. Other companies, which produce generics, were issued fines which collectively total £7,384,146. On 12 February 2016, the UK Competition and Markets Authority imposed record fines of £45,000,000 on companies which were found to have infringed European Union and UK Competition law by entering into agreements to delay the market entry of generic versions of the drug in the United Kingdom.
Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, known since 2000 as GlaxoSmithKline. The United States Department of Justice fined GlaxoSmithKline $3 billion in 2012, including a sum for withholding data on paroxetine, unlawfully promoting it for under-18s and preparing an article, following one of its clinical trials, study 329, that misleadingly reported the drug was effective in treating adolescent depression. Generic formulations have been available since 2003 when the patent expired.
Such reactions have been observed with SNRIs and SSRIs alone, but particularly with concurrent use of triptans, MAO inhibitors, antipsychotics or other dopamine antagonists. Interactions with other drugs acting on the serotonin system or impairing the metabolism of serotonin may increase the risk of Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reaction.
Justice Department announced that GSK had agreed to plead guilty and pay a $3 billion fine, in part for promoting the use of Paxil for children. In 2012 the U.S.
The legal discovery process also uncovered evidence of deliberate, systematic suppression of unfavorable Paxil research results. One of GSK's internal documents had said, "It would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine". In early 2004, GSK agreed to settle charges of consumer fraud for $2.5 million.
There is also evidence that paroxetine may be effective in the treatment of compulsive gambling and hot flashes.
GlaxoSmithKline has paid substantial fines, paid settlements in class action lawsuits, and become the subject of several highly critical books in relation to its marketing of paroxetine, in particular the off-label marketing of paroxetine for children, the suppression of negative research results relating to its use in children, and allegations that it failed to warn consumers of substantial withdrawal effects associated with use of the drug.
Paroxetine also inhibits the reuptake of norepinephrine to a lesser extent (<50 nmol/L). It also binds to the allosteric site of the serotonin transporter, similarly, but less potently than escitalopram. Paroxetine is the most potent and one of the most specific selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs). This activity of the drug on brain neurons is thought to be responsible for its antidepressant effects.
Benefits of paroxetine prescription for diabetic neuropathy or chronic tension headache are uncertain.
In particular, intravaginal ejaculation latency time (IELT) was found to increase with 6–13-fold, which was somewhat longer than the delay achieved by the treatment with other SSRIs (fluvoxamine, fluoxetine, sertraline, and citalopram). Several studies have suggested that paroxetine can be used in the treatment of premature ejaculation. However, paroxetine taken acuy ("on demand") 3–10 hours before coitus resulted only in a "clinically irrelevant and sexually unsatisfactory" 1.5-fold delay of ejaculation and was inferior to clomipramine, which induced a fourfold delay.
Paroxetine prescribing information posted at GlaxoSmithKline now acknowledges the occurrence of a discontinuation syndrome, including serious discontinuation symptoms.
If a patient becomes pregnant while taking paroxetine, she should be advised of the potential harm to the fetus. In general, septal defects range from those that are symptomatic and may require surgery to those that are asymptomatic and may resolve spontaneously. The American College of Obstetricians and Gynecologists recommends that for pregnant women and women planning to become pregnant, "treatment with all SSRIs or selective norepinephrine reuptake inhibitors or both during pregnancy be individualized and paroxetine use among pregnant women or women planning to become pregnant be avoided, if possible." According to the prescribing information "epidemiological studies have shown that infants born to women who had first trimester paroxetine exposure had an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects (VSDs and ASDs). Unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant." These conclusions are supported by multiple systematic reviews and meta-analyses that found that, on average, the use of paroxetine during pregnancy is associated with about 1.5–1.7-fold increase in congenital birth defects, in particular, heart defects.
It is used to treat major depressive disorder, obsessive-compulsive disorder, social anxiety disorder, panic disorder, posttraumatic stress disorder, generalized anxiety disorder and premenstrual dysphoric disorder. Paroxetine, also known by the trade names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It has also been used in the treatment of hot flashes and night sweats associated with menopause.
Paroxetine interacts with the following cytochrome P450 enzymes:
Paroxetine might interact with statins resulting in increased blood glucose levels; this was demonstrated in a small retrospective study and needs confirmation in a prospective study.
Like other antidepressants, paroxetine may increase the risk of suicidal thinking and behaviour in children and adolescents. In 2015 a paper published in the BMJ that reanalysed the original case notes, argued that in Study 329, assessing paroxetine and imipramine against placebo in adolescents with depression, the incidence of suicidal behavior had been under-reported and efficacy exaggerated for paroxetine. The FDA conducted a statistical analysis of paroxetine clinical trials in children and adolescents in 2004, finding an increase in "suicidality" and ideation as compared to placebo; the trend for increased "suicidality" was observed in both trials for depression and for anxiety disorders.
Paroxetine is also effective for children with obsessive-compulsive disorder. Paroxetine is used in the treatment of obsessive-compulsive disorder. Comparative efficacy of paroxetine is equivalent to that of clomipramine and venlaine.
Paroxetine is primarily used to treat major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder, social anxiety disorder, panic disorder, generalized anxiety disorder, premenstrual dysphoric disorder and menopausal hot flashes.
The Agency also warned of case reports describing agitation, sweating, and nausea. In connection with a Glaxo spokesperson's statement that withdrawal reactions occur only in 0.2% of patients and are "mild and short-lived", the International Federation of Pharmaceutical Manufacturers Associations said GSK had breached two of the Federation's codes of practice. FDA published a warning regarding "severe" discontinuation symptoms among those terminating paroxetine treatment, including paraesthesia, bad dreams, and dizziness. In 2002 the U.S.
Several studies have associated paroxetine with suicidal thinking and behavior in children and adolescents. It has a similar tolerability profile to other SSRIs. It may also be associated with a slightly increased risk of birth defects. The rate of withdrawal symptoms in young people may be higher with paroxetine and venlaine than other SSRIs and SNRIs. The common side effects include drowsiness, dry mouth, loss of appetite, sweating, trouble sleeping and delayed ejaculation.
Most of these adverse effects are transient and go away with continued treatment. Paroxetine shares many of the common adverse effects of SSRIs, including (with the corresponding rates seen in people treated with placebo in parentheses): nausea 26% (9%), diarrhea 12% (8%), constipation 14% (9%), dry mouth 18% (12%), somnolence 23% (9%), insomnia 13% (6%), headache 18% (17%), hypomania 1% (0.3%), blurred vision 4%(1%), loss of appetite 6% (2%), nervousness 5% (3%), paraesthesia 4% (2%), dizziness 13% (6%), asthenia (weakness; 15% (6%)), tremor 8% (2%), sweating 11% (2%) and sexual dysfunction (≥10% incidence). Central and peripheral 5-HT 3 receptor stimulation is believed to result in the gastrointestinal effects observed with SSRI treatment. dry mouth, constipation, blurred vision, etc.), sedation/somnolence/drowsiness, sexual side effects and weight gain. Compared to other SSRIs it has a lower incidence of diarrhea, a higher incidence of anticholinergic effects (e.g.
They have variously concluded that paroxetine is superior or equivalent to placebo and that it is equivalent or inferior to other antidepressants. A variety of meta analyses have been conducted to evaluate the efficacy of paroxetine in depression. Despite this, there was no clear evidence that paroxetine was better or worse compared with other antidepressants at increasing response to treatment at any time point.
Trade names include Aropax, Brisdelle, Deroxat, Paxil, Pexeva, Paxtine, Paxetin, Paroxat, Paraxyl, Sereupin, and Seroxat.
Paroxetine was the first antidepressant formally approved in the United States for the treatment of panic disorder. Several studies have concluded that paroxetine is superior to placebo in the treatment of panic disorder.
See also Discontinuation syndrome (withdrawal). Due to reports of adverse withdrawal reactions upon terminating treatment, the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency recommends to reduce gradually over several weeks or months if the decision to withdraw is made.
Boseley, Sarah. "Seroxat study under-reported harmful effects on young people, say scientists", The Guardian, 16 September 2015.
Common withdrawal symptoms for paroxetine include nausea, dizziness, lightheadedness and vertigo; insomnia, nightmares and vivid dreams; feelings of electricity in the body, as well as crying and anxiety. Many psychoactive medications can cause withdrawal symptoms upon discontinuation from administration. Liquid formulation of paroxetine is available and allows a very gradual decrease of the dose, which may prevent discontinuation syndrome. Evidence has shown that paroxetine has among the highest incidence rates and severity of withdrawal syndrome of any medication of its class. Another recommendation is to temporarily switch to fluoxetine, which has a longer half-life and thus decreases the severity of discontinuation syndrome.
Although the evidence is conflicting, paroxetine may be effective for the treatment of dysthymia, a chronic disorder involving depressive symptoms for most days of the year.
In 2007, sales had dropped slightly to 18.1 million but paroxetine remained the fifth-most prescribed antidepressant in the U.S. In 2006, paroxetine was the fifth-most prescribed antidepressant in the United States retail market, with more than 19.7 million prescriptions. In 2007, paroxetine was ranked 94th on the list of bestselling drugs, with over $1 billion in sales.
The prescribing information states that paroxetine should "not be used in combination with an MAOI (including linezolid, an antibiotic which is a reversible non-selective MAOI), or within 14 days of discontinuing treatment with an MAOI", and should not be used in combination with pimozide, thioridazine, tryptophan, or warfarin.
Paroxetine has demonstrated efficacy for the treatment of social anxiety in adults and children. It is also beneficial for people with co-occurring social anxiety disorder and alcohol use disorder. There was a significant improvement in scores on the Liebowitz Social Anxiety Scale and Social Phobia Inventory compared with placebo.Paroxetine