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Paroxetine


See also Selective serotonin re-uptake inhibitors (SSRIs)

General information

Paroxetine is a phenylpiperidine derivative and a selective serotonin reuptake inhibitor (SSRI).

Pharmacokinetics

The half-life of paroxetine is about 17–22 hours and about 95% of it is bound to plasma proteins. Its metabolites have no more than 1/50 of the potency of the parent compound in inhibiting serotonin re-uptake. The metabolism of paroxetine is accomplished in part by CYP2D6, saturation of which at therapeutic doses appears to account for the non-linearity of paroxetine kinetics at higher doses and increasing durations of treatment.

General adverse effects and adverse reactions

The adverse effects of paroxetine and adverse reactions to it are those of the SSRIs in general. Commonly observed adverse events in placebo-controlled clinical trials were weakness, sweating, nausea, reduced appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders. Paroxetine seems to have a higher incidence of withdrawal symptoms than other SSRIs.

Organs and systems

Cardiovascular

Electrocardiographic changes, with a prolonged QT c interval and bradycardia, have been reported with paroxetine [ ].

Nervous system

Serotonin syndrome

The serotonin syndrome is a recognized complication of SSRI treatment. Usually it occurs as part of a drug–drug interaction, when the serotonergic effects of SSRIs are augmented by medications that also have serotonin-potentiating properties [ ]. Occasionally, however, the serotonin syndrome can occur after SSRI monotherapy.

  • A 23-year-old Japanese woman with major depression took a single dose of paroxetine (20 mg) and 1 hour later had agitation, myoclonus, mild hyperthermia (37.5 °C), sweating, and diarrhea, symptoms that meet the criteria for the serotonin syndrome; she recovered with supportive treatment over 3 days [ ].

Blood concentrations of paroxetine were not obtained, but the authors reported that the patient was homozygous for the 10* form of the CYP2D6 allele, which is associated with low CYP2D6 activity in vivo. While this is an interesting observation, it is unlikely by itself to explain the patient’s sensitivity to paroxetine, because this genotype is not uncommon in the Japanese population, and if a lot of Japanese have this genotype, the serotonin syndrome with SSRI monotherapy would be quite common, given the widespread prescription of SSRIs. However, it reinforces clinical advice that in patients new to SSRI treatment it is advisable to start therapy with half the standard dose.

Dystonias

Acute dystonia has been described during the first days of paroxetine treatment [ ].

Paroxetine-induced akathisia has been described in an 81-year-old man with bipolar depression. The akathisia began one week after paroxetine treatment (20 mg/day) and remitted within 6 days of withdrawal [ ].

The authors pointed out that it is important to recognize SSRI-induced akathisia, because increasing agitation and restlessness early in treatment can be mistaken for worsening depression. In addition, case reports have suggested that akathisia can be associated with suicidal impulses.

Sensory systems

Tricyclic antidepressants can precipitate acute glaucoma through their anticholinergic effects. There are also reports that paroxetine can cause acute glaucoma, presumably by pupillary dilatation.

  • An 84-year-old woman developed acute closed-angle glaucoma after taking paroxetine for 6 days [ ].

  • A 70-year-old woman taking paroxetine developed acute closed-angle glaucoma [ ].

  • A 91-year-old developed bilateral acute closed-angle glaucoma after taking paroxetine [ ].

Three patients taking paroxetine for interferon-alpha-induced depression developed retinal hemorrhages, including one with irreversible loss of vision [ ].

Psychiatric

For the risk of suicide, see the monograph on Selective serotonin reuptake inhibitors.

In three children (two aged 9 years and one aged 10 years) who took paroxetine 10–20 mg/day for the treatment of childhood obsessive–compulsive disorder, symptoms of mania, including overactivity, pressure of speech, irritability, and antisocial behavior, occurred within 3 weeks of starting paroxetine and remitted after paroxetine withdrawal or dosage reduction [ ]. Symptoms of mania are rare in childhood, suggesting that the elevated mood in these cases was a direct effect of the paroxetine.

Psychomotor retardation with semistupor has been reported in one patient taking paroxetine; however, she was also taking antipsychotic drugs, which may have contributed [ ].

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