Paroxetine. A review of its pharmacology, therapeutic use in depression and therapeutic potential in diabetic neuropathy.

Paroxetine is a selective serotonin reuptake inhibitor effective in a once-daily administration regimen in the treatment of depression. In elderly patients (aged > or = 60 years) with major depression, short term (6 weeks) treatment with paroxetine produces clinical improvements significantly superior to those seen with placebo and similar to those with tricyclic antidepressant agents, mianserin and fluoxetine. There is evidence that paroxetine has positive effects on co-existing anxiety and does not precipitate agitation. Paroxetine has also shown potential in the symptomatic treatment of diabetic neuropathy; however, further clinical experience is needed to confirm this preliminary result. Short term paroxetine therapy is associated with fewer anticholinergic and CNS adverse effects, but generally more gastrointestinal disturbances, than tricyclic antidepressants and mianserin. Unlike the tricyclic agents, paroxetine does not significantly affect cardiovascular function or impair psychomotor performance. This tolerability profile should be particularly beneficial in elderly patients, who are generally more susceptible than younger patients to the anticholinergic and CNS adverse events associated with tricyclic antidepressant drugs, and in whom there is a higher prevalence of pre-existing cardiovascular disease. It also suggests an important potential advantage over tricyclic antidepressants in the setting of overdosage. Thus, primarily because of its better tolerability profile and potentially lower toxicity in overdosage and in patients with cardiovascular disease, paroxetine appears to be a more attractive option than tricyclic antidepressants for the treatment of depression in late life. Future research should attempt to define more fully the efficacy of paroxetine as long term prophylactic therapy for recurrent depression and to assess how its overall therapeutic profile compares with other selective serotonin reuptake inhibitors in the elderly.