Multicenter, placebo-controlled, fixed-dose study of citalopram in moderate-to-severe depression

Background: Citalopram, the most selective serotonin reuptake inhibitor (SS RI), is a bicyclic phthalane derivative with a chemical structure that is u nrelated to that of Ether SSRIs and available antidepressants. The drug is approved for use in 69 countries. This 6-week, fixed-dose, placebo-controll ed, parallel-arm, multicenter trial was performed to confirm its efficacy a nd safety in treatment of outpatients with major depression in the United S tates. Method: Six hundred and fifty adult outpatients with moderate-to-severe maj or depression (DSM-III-R) were randomly assigned to receive citalopram at d oses of 10 mg (N = 131), 20 mg (N = 130), 40 mg (N = 131), or 60 mg (N = 12 9) or placebo (N = 129) once daily. Outcome assessments were the 21-item Ha milton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depressio n Rating Scale (MADRS), and the Clinical Global Impressions scale. Results: Between-group comparisons of the change from baseline to endpoint revealed significantly greater improvement in the citalopram patients relat ive to the placebo patients on all 3 efficacy measures. Patients randomly a ssigned to 40 mg/day and 60 mg/day of citalopram showed significantly great er improvement than placebo on all efficacy measures, as well as on the HAM -D symptom clusters measuring depressed mood, melancholia, cognitive distur bance, and psychomotor retardation Patients who received 10 mg/day and 20 m g/day of citalopram also showed consistent improvement relative to placebo on all efficacy ratings, with statistical significance demonstrated in the MADRS response rate, the HAM-D depressed mood item, and the HAM-D melanchol ia subscale. Citalopram was well tolerated, with only 15% of patients disco ntinuing for adverse events. The side effects most commonly associated with citalopram treatment were nausea, dry mouth, somnolence, insomnia, and inc reased sweating. Conclusion: Citalopram was significantly more effective than placebo in the treatment of moderate-to-severe major depression, especially symptoms of d epressed mood and melancholia, with particularly robust effects shown at do ses of 40 and 60 mg/day. Citalopram was well tolerated in spite of forced u pward titration to fixed-dose levels, with a low incidence of anxiety, agit ation, and nervousness.