A group of 480 patients, aged 19-78 with an HRSD score of at least 17 and who met DSM-III criteria for major depressive disorder were studied. Patients were given placebo for a one-week single-blind run-in period, after which sertraline was administered for eight weeks. This was followed by 44 weeks in which patients received sertraline or placebo on a double-blind, randomised basis. Patients were assessed periodically using the 17-item HRSD and the Clinical Global Impression scales. During the entire double-blind period 24 (13.0%) sertraline patients relapsed compared with 48 (45.7%) placebo patients (P less than 0.001). The protective effect of sertraline was maintained throughout the 44 weeks. The study provides evidence that sertraline prevents relapse of the index episode of depression as well as recurrence of further episodes and has few side-effects.

The percentage occupation of striatal dopamine D2 receptors has been evaluated in 25 patients using 76Br-bromospiperone positron emission tomography (PET) and prolactin plasma levels (PRL) during oral neuroleptic treatment (11 studies), 1-90 days following discontinuation of such treatment (16 studies), and 1-120 days after last intramuscular administration of depot neuroleptics (nine studies). The PET-estimated occupation was highly significantly correlated in a sigmoid-like fashion to the logarithm of the chlorpromazine-equivalent dose of oral neuroleptics (suggesting a strict dose-occupation relationship during oral neuroleptic treatment and supporting the D2-mediated hypothesis of neuroleptic action), while PRL was weakly related to daily dosage. Following withdrawal, return to normal receptor availability, as estimated by PET, occurred within 5-15 days (suggesting that protracted effects of neuroleptics after withdrawal are not due to sustained D2 receptor occupation), but PRL values fell even more rapidly. Efficient treatment with depot neuroleptics resulted in marked PET-estimated D2 receptor occupation, stable over the whole 4-week drug-administration interval, suggesting that longer intervals could be appropriate; PRL values bore no relationship to PET-estimated occupation, indicating variable intersubject tolerance to neuro-endocrine dopamine blockade. Overall, PET was much more sensitive than PRL to estimate striatal D2 receptor occupation in vivo.

Among remitted patients with a history of multiple depressive episodes, sertraline at a dose of either 50 or 100 mg/day prevented recurrences significantly more than did placebo.

The clinical profile of reboxetine, a selective noradrenaline reuptake inhibitor, was compared with that of the selective serotonin reuptake inhibitor fluoxetine and placebo in a double-blind, multicenter, parallel-group clinical trial of patients with major depression. Among the 381 patients treated with reboxetine 8 to 10 mg/day, fluoxetine 20 to 40 mg/day, or placebo for up to 8 weeks, a statistically significant greater reduction in the mean Hamilton Rating Scale for Depression (21-item HAM-D) total score (the primary efficacy variable) was seen for both active treatment groups compared with placebo (p < 0.024). A significantly greater proportion of patients treated with either reboxetine or fluoxetine also achieved a response (>or=50% reduction in HAM-D) or remission (HAM-D