Paroxetine
Paroxetine, sold under the brand name Paxil among others, is an antidepressant medication of the selective serotonin reuptake inhibitor class used to treat major depressive disorder, obsessive–compulsive disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder, generalized anxiety disorder, and premenstrual dysphoric disorder. It has also been used in the treatment of premature ejaculation, and hot flashes due to menopause. It is taken orally.
Common side effects include drowsiness, dry mouth, loss of appetite, sweating, trouble sleeping, and sexual dysfunction. Serious side effects may include suicidal thoughts in those under the age of 25, serotonin syndrome, and mania. While the rate of side effects appears similar compared to other SSRIs and SNRIs, antidepressant discontinuation syndrome may occur more often. Use in pregnancy is not recommended, while use during breastfeeding is relatively safe. It is believed to work by blocking the reuptake of the chemical serotonin by neurons in the brain.
Paroxetine was approved for medical use in the United States in 1992 and initially sold by GlaxoSmithKline. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2023, it was the 72nd most commonly prescribed medication in the United States, with more than 9million prescriptions. In 2018, it was in the top 10 of most prescribed antidepressants in the United States.
Medical uses
Paroxetine is primarily used to treat major depressive disorder, obsessive–compulsive disorder, post-traumatic stress disorder, social anxiety disorder, and panic disorder. It is also occasionally used for agoraphobia, generalized anxiety disorder, premenstrual dysphoric disorder, and menopausal hot flashes.Depression
A variety of meta-analyses have been conducted to evaluate the efficacy of paroxetine in depression. They have variously concluded that paroxetine is superior to placebo and that it is equivalent to other antidepressants. Despite this, there was no clear evidence that paroxetine was better or worse compared with other antidepressants at increasing response to treatment at any point in time.Anxiety disorders
Paroxetine was the first antidepressant 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.Paroxetine has demonstrated efficacy for the treatment of social anxiety disorder in adults and children. It is also beneficial for people with co-occurring social anxiety disorder and alcohol use disorder. It appears to be similar to a number of other SSRIs.
Paroxetine is used in the treatment of obsessive-compulsive disorder. Comparative efficacy of paroxetine is equivalent to that of clomipramine and venlafaxine. Paroxetine is also effective for children with obsessive-compulsive disorder.
Paroxetine is approved for the treatment of PTSD in the United States, Japan, and Europe. In the United States, it is approved for short-term use.
Paroxetine is also FDA-approved for generalized anxiety disorder.
Menopausal hot flashes
In 2013, low-dose paroxetine was approved in the US for the treatment of moderate-to-severe vasomotor symptoms such as hot flashes and night sweats associated with menopause. At the low dose used for menopausal hot flashes, side effects are similar to placebo and dose tapering is not required for discontinuation.Fibromyalgia
Studies have also shown paroxetine "appears to be well-tolerated and improve the overall symptomatology in patients with fibromyalgia", but is less robust in helping with the pain involved.Adverse effects
Common side effects include drowsiness, dry mouth, loss of appetite, sweating, insomnia, and sexual dysfunction. Serious side effects may include suicide in those under the age of 25, serotonin syndrome, and mania. While the rate of side effects appears similar compared to other SSRIs and SNRIs, antidepressant discontinuation syndromes may occur more often. Use in pregnancy is not recommended, while use during breastfeeding is relatively safe.The Federal Aviation Administration, the U.S. agency responsible for regulating civil aviation, considers paroxetine to be an antidepressant medication that is ineligible for an FAA Authorization of Special Issuance or Special Consideration of a medical certificate.
Paroxetine shares many of the common adverse effects of SSRIs, including :
- nausea 26%
- somnolence 23%
- dry mouth 18%
- headache 18%
- asthenia 15%
- constipation 14%
- dizziness 13%
- insomnia 13%
- diarrhea 12%
- sweating 11%
- tremor 8%
- loss of appetite 6%
- nervousness 5%
- blurred vision 4%
- paraesthesia 4%
- hypomania 1%
- sexual dysfunction.
Due to reports of adverse withdrawal reactions upon terminating treatment, the Committee for Medicinal Products for Human Use at the European Medicines Agency recommends gradually reducing over several weeks or months if the decision to withdraw is made. See also Discontinuation syndrome.
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 disorder or with a family history of mania.
Paroxetine is described as a 'hepatoxic agent' and has been associated with hepatoxicity and jaundice.
Suicide
Like other antidepressants, paroxetine may increase the risk of suicidal thinking and behaviour in people under the age of 25. The FDA conducted a statistical analysis of paroxetine clinical trials in children and adolescents in 2004 and found an increase in suicidality and ideation as compared to placebo, which was observed in trials for both depression and anxiety disorders. 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 the efficacy exaggerated for paroxetine.Sexual dysfunction
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. 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 higher than 70%. Symptoms of sexual dysfunction have been reported to persist after discontinuing SSRIs, although this is thought to be occasional.Pregnancy
Antidepressant exposure is associated with shorter duration of pregnancy, increased risk of preterm delivery, lower birth weight, and lower Apgar scores. The American College of Obstetricians and Gynecologists recommends that for pregnant women and women planning to become pregnant, paroxetine "be avoided, if possible", as it may be associated with increased risk of birth defects.Babies born to women who used paroxetine during the first trimester have an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects. Unless the benefits of paroxetine justify continuing treatment, consideration should be given to stopping or switching to another antidepressant. Paroxetine use during pregnancy is associated with about 1.5– to 1.7-fold increase in congenital birth defects, in particular, heart defects, cleft lip and palate, clubbed feet, or any birth defects.
Discontinuation syndrome
Many psychoactive medications can cause withdrawal symptoms upon discontinuation from administration. Paroxetine has among the highest incidence rates and severity of withdrawal syndrome of any medication of its class. 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 rebound depression and anxiety. A liquid formulation of paroxetine is available and allows a very gradual decrease of the dose, which may prevent discontinuation syndrome. Another recommendation is to temporarily switch to fluoxetine, which has a longer half-life and thus decreases the severity of discontinuation syndrome.In 2002, the U.S. FDA published a warning regarding "severe" discontinuation symptoms among those terminating paroxetine treatment, including paraesthesia, nightmares, and dizziness. 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.
Paroxetine prescribing information posted at GlaxoSmithKline has been updated related to the occurrence of a discontinuation syndrome, including serious discontinuation symptoms.