Paroxetine 61869-08-7

Indications

Paroxetine is primarily used to treat the symptoms of major 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 . Paroxetine was the first antidepressant formally approved in the United States for the treatment of panic attacks. According to the prescribing information provided by the manufacturer of the Paxil brand of paroxetine (GlaxoSmithKline) and approved by the U. S. Food and Drug Administration (FDA),

Unapproved/off-label/investigational

Several studies have suggested that paroxetine can be used in the treatment of premature ejaculation. 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). However, paroxetine taken acutely ("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. ; however, paroxetine is contraindicated in women who may become pregnant due to its teratogenicity and its high risk of withdrawal syndrome in both adults and neonates. See Paroxetine and pregnancy. There is also evidence that paroxetine may be effective in the treatment of compulsive gambling and hot flashes. In two double-blind studies of bipolar disorder patients, addition of paroxetine to a mood stabilizer had no advantages over addition of placebo. Benefits of paroxetine prescription for diabetic neuropathy or chronic tension headache. are uncertain. Emerging evidence shows that antipsychotics can be used as a supplement or alternative to paroxetine in patients with generalised anxiety disorder.

Contraindications

Paroxetine is contraindicated in all patients under 18, in all patients taking any of the drugs listed in the interactions section below, and in adult women who are or may become pregnant. Paroxetine may also be contraindicated in many adult men due to sexual and reproductive side effects described below. In the United States, the Food and Drug Administration requires this drug to carry a black box warning, its "most serious type of warning in prescription drug labeling,"

Side effects

Among the common adverse effects associated with paroxetine treatment of depression and listed in the prescribing information, those with the greatest difference from placebo are nausea (26% on paroxetine vs 9% on placebo), somnolence (23% vs. 9% on placebo), ejaculatory disturbance (13% vs. 0% on placebo), other male genital disorders (10% vs. 0% on placebo), asthenia (15% vs. 6% on placebo), sweating (11% vs. 2% on placebo), dizziness (13% vs. 6% on placebo), insomnia (13% vs. 6% on placebo), dry mouth (18% vs. 12% on placebo), constipation (14% vs. 9% on placebo), and tremor (8% vs. 2% on placebo). General side effects are mostly present during the first 1–4 weeks while the body acquires a tolerance to the drug, although once this happens, withdrawal can cause a rebound effect with symptoms re-emerging in an exaggerated form for very long periods of time. 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 listed 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/or more severe symptoms being reported at higher dosages. Increases or changes in dosage may also cause symptoms to reappear or worsen. On 9 December 2004, the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) informed patients, prescribers, and parents that paroxetine should not be prescribed to children. CHMP also gave a warning to prescribers recommending close monitoring of adult patients at high risk of suicidal behaviour and/or suicidal thoughts. CHMP does not prohibit use of paroxetine with high risk adults but urges extreme caution. Due to reports of adverse withdrawal reactions upon terminating treatment, CHMP recommends to reduce gradually over several weeks or months if the decision to withdraw is made. See also Discontinuation syndrome (withdrawal). The FDA conducted a statistical analysis of paroxetine clinical trials in children and adolescents in 2004, finding a statistically significant 2. 7-fold raise in suicide behavior and ideation as compared to placebo; the trend for increased suicidality was observed in both trials for depression and for anxiety disorders. A University of North Carolina review of SSRIs found the average risk of suicide among adolescents was 4%, versus 2% on placebo, and among all patients "the greatest risk of self-harm was among paroxetine users. "Cases of akathisia have been observed during paroxetine treatment. Rarely serotonin syndrome, a severe adverse effect may occur. Paroxetine and other SSRIs have been shown to cause sexual side effects in most patients, both males and females. In males, paroxetine is also linked to sperm DNA fragmentation. Mania or hypomania may occur as a serious side effect of paroxetine, affecting up to 8% of psychiatric patients treated. This side effect can occur in individuals with no history of mania but it is more likely to occur in those with bipolar or with a family history of mania. Schmitt et al. (2001) suggested that paroxetine negatively affects memory (i. e. , IQ). In their study, healthy participants given paroxetine for 14 days (20 mg for days 1–7 and 40 mg days 8–14) showed poorer recall of words on day 14 compared to those receiving a placebo. Schmitt et al. did not take into account a significant difference in verbal recall at baseline between the paroxetine and placebo groups, however, and this difference may have been the source of the significant group difference on day 14. Moreover, participants receiving paroxetine recalled as many words at baseline as they recalled on day 14, which is not consistent with the conclusion that paroxetine negatively affects verbal recall.

Discontinuation syndrome (withdrawal)

{{See also

SSRI discontinuation syndrome