Paroxetine , also known by trade names including Paxil and Seroxat , among others, are antidepressants of the selective serotonin reuptake inhibitor class (SSRI). It is used to treat major depressive disorders, obsessive-compulsive disorder, social anxiety disorder, panic disorder, post traumatic stress disorder, general anxiety disorder and premenstrual dysphoric disorder. It has also been used in the treatment of hot flashes and night sweats associated with menopause.
It has the same tolerability profile as other SSRIs. Common side effects include drowsiness, dry mouth, loss of appetite, sweating, sleeplessness and delayed ejaculation. It may also be associated with a slightly increased risk of birth defects. Levels of withdrawal symptoms in young people may be higher with paroxetine and venlafaxine than SSRIs and other SNRIs. Several studies have linked paroxetine with suicidal thoughts and behaviors in children and adolescents.
Drug marketing began in 1992 by pharmaceutical company SmithKline Beecham, known since 2000 as GlaxoSmithKline. Generic formulations have been available since 2003 when the patent expires. The United States Department of Justice fined GlaxoSmithKline $ 3 billion in 2012, including the amount to withhold data on paroxetine, promote it illegally for under 18s and prepare articles, following one of its clinical trials, study 329, misleadingly reporting the drug is effective in treat teen depression.
Video Paroxetine
Medical use
Paroxetine is primarily used to treat major depressive disorders, obsessive-compulsive disorder, post-traumatic stress disorder, social anxiety disorder, panic disorder, generalized anxiety disorder, premenstrual dysphoric disorder and menopausal hot flashes.
Depression
Various meta-analyzes have been performed to evaluate the effectiveness of paroxetine in depression. They have concluded that paroxetine is superior or equal to placebo and is equivalent or inferior to other antidepressants. Nevertheless, there is no clear evidence that paroxetine is better or worse than other antidepressants in an increased response to treatment at any point in time.
Panic disorder
Paroxetine is the first antidepressant officially 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.
Social anxiety disorder
Paroxetine has demonstrated efficacy for the treatment of social anxiety disorders in adults and children. There was a significant increase in scores on the Liebowitz Social Anxiety Scale and Social Phobia Inventory compared with placebo. It is also beneficial for people with social anxiety disorders and alcohol use disorders.
Obsessive-compulsive disorder
Paroxetine is used in the treatment of obsessive-compulsive disorder. Comparative efficacy of paroxetine is equivalent to clomipramine and venlafaxine. Paroxetine is also effective for children with obsessive-compulsive disorder.
Menopausal hot flash
On June 28, 2013, the US Food and Drug Administration approved low-dose paroxetine for the treatment of moderate-to-severe vasomotor symptoms such as hot flashes and night sweats associated with menopause. At low doses used for menopausal hot flash, side effects similar to placebo and dose reduction are not required for termination.
Maps Paroxetine
Adverse effects
Paroxetine shares many of the common adverse effects of SSRIs, including (with appropriate levels seen in people treated with placebo in parentheses): nausea 26% (9%), diarrhea 12% (8%), 14% constipation (9%) , dry mouth 18% (12%), somnolen 23% (9%), insomnia 13% (6%), headache 18% (17%), hypomania 1% (0.3%), blurred vision 4% 1%), loss of appetite 6% (2%), anxiety 5% (3%), parestesia 4% (2%), dizziness 13% (6%), astenia (weakness, 15% (6%)), tremor 8% (2%), 11% sweating (2%), and sexual dysfunction (> = 10% incident). Most of these side effects are temporary and disappear with continued treatment. 5-HT 3 middle and peripheral receptor stimulation is believed to cause gastrointestinal effects observed with SSRI treatment. Compared with other SSRIs, it has a lower incidence of diarrhea, higher incidence of anticholinergic effects (eg dry mouth, constipation, blurred vision, etc.), sedation/somnolence/drowsiness, sexual side effects, and weight gain.
Due to an adverse reactions report of withdrawal at the end of treatment, the Committee for Drugs for Human Use (CHMP) at the European Drug Agency recommends gradually reducing for weeks or months if the decision to resign is made. See also the withdrawal syndrome.
Mania or hypomania can occur in 1% of patients with depression and up to 12% of patients with bipolar disorder. These side effects can occur in individuals without a history of mania but may be more likely to occur in those with bipolar or with a family history of mania.
Suicide
Like other antidepressants, paroxetine may increase the risk of suicidal thinking and behavior in children and adolescents. The FDA performed a statistical analysis of paroxetine clinical trials in children and adolescents in 2004 and found an increase in suicide and ideation compared with placebo, which was observed in trials for both depression and anxiety disorders. In 2015 a paper published in The BMJ that repeated the original case note argued that in Study 329, assessing paroxetine and imipramine against placebo in adolescents with depression, the incidence of suicidal behavior has been reported and excessive efficacy for paroxetine.
Sex Sexual dysfunction
Sexual dysfunction, including loss of libido, anorgasmia, lack of vaginal lubrication, and erectile dysfunction, is one of the most common side effects of treatment with paroxetine and other SSRIs. While preliminary clinical trials show relatively low levels of sexual dysfunction, newer studies in which researchers are actively inquiring about sexual problems show that the incidence is higher than 70%. The symptoms of sexual dysfunction have been reported to persist after stopping the SSRI, although this is considered occasionally.
Pregnancy
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 becomes individualized and the use of paroxetine among pregnant women or women planning to become pregnant is avoided, if allow ". According to the prescribed information, "epidemiological studies have shown that infants born to women with first-trimester paroxetine exposure have an increased risk of cardiovascular malformation, particularly ventricular and atrium (VSD and ASD) septal defects.In general, septal defects range from symptomatic and may require surgery for those who are asymptomatic and may disappear spontaneously. If a patient becomes pregnant while taking paroxetine, he should be informed of the potential harm to the fetus. Unless the paroxetine benefits to the mother justify continuing the treatment, consideration should be given either to discontinue paroxetine therapy or switch to other antidepressants. "This conclusion is supported by several systematic reviews and meta-analyzes that found that, on average, the use of paroxetine during pregnancy was associated with an increase of about 1.5 to 1.7-fold in congenital birth defects, in particular, heart defects.
Termination syndrome
Many psychoactive drugs may cause withdrawal symptoms when discontinuation of administration. Evidence suggests that paroxetine has the highest incidence rate and severity of any drug withdrawal syndrome in its class. Common withdrawal symptoms for paroxetine include nausea, dizziness, dizziness and vertigo; insomnia, nightmares, and clear dreams; feelings of electricity in the body, and crying and anxiety. Paroxetine fluid formulations are available and allow a very gradual dose reduction, which can prevent the termination syndrome. Another recommendation is to temporarily switch to fluoxetine, which has a longer half-life and thus reduces the severity of the termination syndrome.
Overdose
Acute overdose is often manifested by emesis, lethargy, ataxia, tachycardia, and seizures. Plasma, serum, or paroxetine blood concentrations can be measured to monitor therapeutic administration, confirm the diagnosis of poisoning in hospitalized patients or to assist in medical investigations into death. Plasma paroxetine concentrations are generally in the range of 40-400 μg/L in people receiving daily therapeutic doses and 200-2,000 μg/L in poisoned patients. Postmortem blood levels ranged from 1-4Ã, mg/L in a deadly acute overdose situation. Together with other SSRIs, sertraline and fluoxetine, paroxetine is considered a low-risk drug in case of overdose.
Interactions
Interactions with other drugs working on the serotonin system or impairing serotonin metabolism may increase the risk of Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS) -as a reaction. Such reactions have been observed with SNRI and SSRI alone, but especially with the use of triptans, MAO inhibitors, antipsychotics, or other dopamine antagonists simultaneously.
Paroxetine may interact with statins, resulting in elevated blood glucose levels. This is shown in small retrospective studies and needs confirmation in prospective studies.
The prescribed information states that paroxetine should be "not used in combination with MAOI (including linezolid, an antibiotic which is a reversible non-selectively MAOI), or within 14 days after stopping treatment with MAOI", and should not be used in combination with pimozide, thioridazine , tryptophan, or warfarin.
Paroxetine interacts with the following P450 cytochrome enzymes:
- CYP2D6 which is a substrate and a potential inhibitor.
- CYP2B6 (strong ) inhibitor.
- CYP3A4 ( weak ) inhibitor.
- CYP1A2 ( weak ) inhibitor.
- CYP2C9 ( weak ) inhibitor.
- CYP2C19 ( weak ) inhibitor.
Pharmacology
Pharmacodynamics
Paroxetine is the most powerful and one of the most specific selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor (SSRI). It also binds to the allosteric sites of serotonin transporters, similar, but less powerful, than escitalopram. Paroxetine also inhibits the reuptake of norepinephrine to lower levels (& lt; 50 nmol/L). Based on evidence from four weeks of administration in mice, the equivalent of 20 mg of paroxetine taken once daily accounts for about 88% of serotonin transporters in the prefrontal cortex.
Pharmacokinetics
Paroxetine is well absorbed after oral administration. It has an absolute bioavailability of about 50%, with evidence of a saturated first-pass effect. When taken orally, it reaches maximum concentration in about 6-10 hours and reaches steady state in 7-14 days. Paroxetine shows significant interindividual variation in volume distribution and clearance. Less than 2% of the oral dose excreted in the urine is unchanged.
Paroxetine is a CYP2D6-based inhibitor mechanism.
Society and culture
GlaxoSmithKline has paid substantial fines, paid payments in class action lawsuits, and is the subject of some very critical books about paroxetine marketing, particularly off-label marketing of paroxetine for children, the suppression of negative research results related to use in children, and allegations that it failed to warn consumers about the substantial withdrawal effects associated with drug use.
Withdrawal symptoms
In 2002, the US FDA issued warnings about symptoms of "severe" termination among those who discontinued paroxetine treatment, including paresthesias, nightmares, and dizziness. The agency also warned case reports depicting agitation, sweating, and nausea. In connection with a Glaxo spokesperson statement that the withdrawal reaction occurred in only 0.2% of patients and "mild and short-lived", the Federation of International Pharmaceutical Producers Association said GSK had violated two Federation practice codes.
Paroxetine prescribes information posted on GlaxoSmithKline now recognizes the occurrence of the termination syndrome, including serious termination symptoms.
Unlabeled marketing
In early 2004, GSK agreed to settle consumer fraud charges of $ 2.5 million. The process of legal discovery also reveals evidence of systematic and deliberate suppression of unfavorable results of Paxil's research. One of GSK's internal documents reads, "It is commercially unacceptable to include statements that efficacy [in children] has not been proven, as this will damage the profile of paroxetine".
In 2012 the US Justice Department announced that GSK has agreed to plead guilty and pay a $ 3 billion fine, in part to promote the use of Paxil for children.
Marketing
On February 12, 2016, the British Competition and the Market Authority imposed a record fine of £ 45 million on companies found to have violated European Union and United Kingdom Competition laws by signing an agreement to delay the entry of the generic version of the drug market in UK. GlaxoSmithKline received most of the fine, fined Ã, Â £ 37,600,757. Another company, which produces generic drugs, is issued a penalty that collectively amounts to £ 7,384,146. The UK public health service is likely to claim damages for being overcharged in the period in which the generic version of the drug is illegally blocked from the market, since the generic is more than 70% cheaper. GlaxoSmithKline can also deal with the actions of other generic manufacturers who incur losses as a result of anticompetitive behavior. On April 18, 2016, an appeal was filed to the Competition Appeals Court by a fined company.
Sales
In 2007, paroxetine was ranked 94th in the list of best-selling drugs, with more than $ 1 billion in sales. In 2006, paroxetine was the most widely prescribed antidepressant in the US retail market, with over 19.7 million prescriptions. In 2007, sales dropped slightly to 18.1 million, but paroxetine remains the most widely prescribed antidepressant drug in the US.
Trade name
Trade names include Aropax, Brisdelle, Deroxat, Paxil, Pexeva, Paxtine, Paxetin, Paroxat, Paraxyl, Sereupin, and Seroxat.
Research
Several studies have shown that paroxetine can be used in the treatment of premature ejaculation. In particular, the time of intravaginal ejaculatory latency (IELT) was found to increase by 6-13-fold, which is somewhat longer than the delay achieved by treatment with other SSRIs (fluvoxamine, fluoxetine, sertraline, and citalopram). However, paroxetine taken acutely ("on demand") 3-10 hours before coitus only resulted in a clinically incomplete and less sexually satisfying ejaculation delay and lower than clomipramine, which led to a fourfold delay.
There is also evidence that paroxetine may be effective in the treatment of compulsive gambling and hot flashes.
The benefits of a paroxetine prescription for diabetic neuropathy or a chronic tension headache are uncertain.
Although the evidence is contradictory, paroxetine may be effective for the treatment of dysthymia, a chronic disorder involving depressive symptoms for most days of the year.
References
External links
- List of international brand names for paroxetine
- Paroxetine Consumer Information Details: Use, Precautions, Side Effects from medlibrary.org
Source of the article : Wikipedia
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