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

Abstract

BACKGROUND:

Citalopram, the most selective serotonin reuptake inhibitor (SSRI), is a bicyclic phthalane derivative with a chemical structure that is unrelated to that of other SSRIs and available antidepressants. The drug is approved for use in 69 countries. This 6-week, fixed-dose, placebo-controlled, parallel-arm, multicenter trial was performed to confirm its efficacy and safety in treatment of outpatients with major depression in the United States.

METHOD:

Six hundred and fifty adult outpatients with moderate-to-severe major depression (DSM-III-R) were randomly assigned to receive citalopram at doses of 10 mg (N = 131), 20 mg (N = 130), 40 mg (N = 131), or 60 mg (N = 129) or placebo (N = 129) once daily. Outcome assessments were the 21-item Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression 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 relative to the placebo patients on all 3 efficacy measures. Patients randomly assigned to 40 mg/day and 60 mg/day of citalopram showed significantly greater improvement than placebo on all efficacy measures, as well as on the HAM-D symptom clusters measuring depressed mood, melancholia, cognitive disturbance, and psychomotor retardation. Patients who received 10 mg/day and 20 mg/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 melancholia subscale. Citalopram was well tolerated, with only 15% of patients discontinuing for adverse events. The side effects most commonly associated with citalopram treatment were nausea, dry mouth, somnolence, insomnia, and increased sweating.

CONCLUSION:

Citalopram was significantly more effective than placebo in the treatment of moderate-to-severe major depression, especially symptoms of depressed mood and melancholia, with particularly robust effects shown at doses of 40 and 60 mg/day. Citalopram was well tolerated in spite of forced upward titration to fixed-dose levels, with a low incidence of anxiety, agitation, and nervousness.

• Authors: J P Feighner, K Overø
• Journal: The Journal of clinical psychiatry (J Clin Psychiatry) Vol. 60 Issue 12 Pg. 824-30 (Dec 1999) ISSN: 0160-6689 [Print] United States
• PMID: 10665628 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Placebos
• Serotonin Uptake Inhibitors
• Citalopram

Topics

• Administration, Oral
• Adult
• Ambulatory Care
• Citalopram (administration & dosage, adverse effects, therapeutic use)
• Depressive Disorder (drug therapy, psychology)
• Drug Administration Schedule
• Female
• Headache (chemically induced)
• Humans
• Male
• Nausea (chemically induced)
• Placebos
• Psychiatric Status Rating Scales
• Selective Serotonin Reuptake Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Severity of Illness Index
• Sleep Initiation and Maintenance Disorders (chemically induced)
• Treatment Outcome