The tolerability and safety of treatment with paroxetine have been assessed by analysis of a clinical trial database that extends to 4126 patients treated with paroxetine, 1954 patients on active control, and 625 placebo patients. A total of 451 patients were exposed to paroxetine for periods of 1 or more years. Paroxetine was generally better tolerated than active control and was associated with a lower frequency of manic reactions in bipolar patients and fewer seizures than active control. Paroxetine appears to offer a differential advantage in reducing suicidal thoughts; the number of suicides and attempted suicides per patient exposure year were lower for paroxetine than for other antidepressants or placebo.

Depression is commonly associated with suicidal thoughts and behaviour. The effect of the antidepressant, paroxetine, on suicidality in depressed patients has been assessed by retrospective analysis of the worldwide database of short-term clinical trials. Data were analysed on 2963 patients treated with paroxetine. 554 placebo patients, and 1151 patients treated with an active control. The results clearly demonstrate the beneficial effect of antidepressant therapy on suicidal ideation. Paroxetine was not associated with the emergence of suicidality, which appears to be a feature of depressive disorder unrelated to antidepressant therapy.

Long-term treatment with antidepressants is now an accepted strategy in the management of depression. The demonstration of efficacy in this setting requires specific placebo-controlled trials of patients with recurrent depression studied after an adequate period of euthymia and for a long period of follow-up. This review examines the evidence for the prophylactic efficacy of antidepressant therapy with particular emphasis on the selective serotonin reuptake inhibitor, paroxetine.

Meta-analyses of 417 patients diagnosed either prospectively (316 US patients) or retrospectively (101 European patients) as suffering from melancholia according to DSM III criteria have shown that paroxetine was significantly better than placebo with respect to all outcome measures. There was no significant difference between active control and placebo in these analyses. In a group of 216 severely depressed hospitalised patients with a HAMD score of 25 or more, paroxetine was as effective as active control.

Paroxetine is a highly potent and selective inhibitor of serotonin reuptake, with in vitro potency greater than that of fluoxetine, fluvoxamine, and sertraline. It has little affinity for a wide variety of neurotransmitter receptors, including catecholaminergic or histaminergic systems, in marked contrast to the tricyclic antidepressants. Paroxetine undergoes first-pass metabolism that is partially saturable to give metabolites that are pharmacologically inactive in vivo, unlike those of fluoxetine or sertraline.

The effect of paroxetine on symptoms of anxiety associated with depression were assessed by meta-analysis of data on the use of paroxetine (n = 2963), active control (n = 1151), and placebo (n = 554) in six-week clinical trials. Paroxetine significantly reduced psychic anxiety by comparison with placebo from week 1 and was more effective than active control from week 2. Paroxetine improved somatic anxiety from week 4 of treatment. There was no association between antidepressant therapy and the emergence of anxiety symptoms in patients with little or no baseline anxiety. Paroxetine resolved baseline symptoms of agitation from week 1 of treatment, and both paroxetine and active control prevented the emergence of agitation. There was no difference between placebo and antidepressant therapy in the frequency of adverse events indicative of increased arousal. The results indicate the utility of paroxetine in depressed patients presenting with associated anxiety symptoms.