Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Citalopram was effective in alleviating post-stroke depression

ACP J Club. 1994 Nov-Dec;121:67. doi:10.7326/ACPJC-1994-121-3-067


Source Citation

Andersen G, Vestergaard K, Lauritzen L. Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram. Stroke. 1994 Jun;25:1099-104.


Abstract

Objective

To determine the safety and efficacy of the selective serotonin reuptake inhibitor citalopram compared with placebo in patients with post-stroke depression (PSD).

Design

6-week randomized, double-blind, placebo-controlled trial.

Setting

2 hospitals in Denmark.

Patients

Of 320 consecutive patients admitted with acute stroke, 66 (mean age 67 y, 61% women) were diagnosed with PSD based on a Hamilton Depression Scale (HDS) score ≥ 13. Exclusion criteria were subarachnoid hemorrhage, Binswanger disease, previous degenerative or expansive neurologic diseases, or psychiatric illness. Follow-up was 86%.

Intervention

Patients were randomly allocated to receive citalopram, 20 mg/d, for patients < 66 years and 10 mg/d, for patients ≥ 66 years (n = 33) or placebo (n = 33). The citalopram dose was doubled after 3 weeks if patients did not respond to treatment. After 6 weeks, patients with an HDS score < 13 (responders) continued treatment for 10 more weeks, and patients with an HDS score ≥ 13 (nonresponders) were offered nortriptyline, mianserin, or a combination of the 2.

Main outcome measures

HDS and melancholia scale (MES) scores, and side effects.

Main results

At 6 weeks, an intention-to-treat analysis showed lower mean HDS scores for patients receiving citalopram when compared with placebo recipients (11.4 vs 14.1, {95% CI for the 2.7 difference 0.3 to 5.1}*). Patients receiving citalopram improved to a greater extent than did those receiving placebo (P < 0.05). Excluding early withdrawals, mean HDS and MES scores were lower in the citalopram group when compared with the placebo group (10.3 vs 14.0, {CI for the 3.7 difference 1.2 to 6.2}* and 9.6 vs 12.8, {CI for the 3.2 difference 0.7 to 5.7}*, respectively). The citalopram group had a decrease in HDS and MES scores almost twice that of the placebo group (P < 0.005). Among responders at 16 weeks, a greater decrease in HDS scores was maintained by the citalopram group when compared with the placebo group (P < 0.05). During the first week, a greater incidence of side effects existed (nausea, vomiting, asthenia, lassitude, and fatigue) with citalopram treatment (P < 0.05).

Conclusion

Citalopram was safe and effective when compared with placebo for treating patients with post-stroke depression.

Sources of funding: Lundbeck Foundation; Medical Research Foundation for North Jutland County; Aalborg Diocese Research Foundation; Consultant Otorhinolaryngologist Kopp's Foundation; Stine and Martinus Sørensen's Foundation, Aalborg.

For article reprint: Dr. G. Andersen, University Hospital of Aarhus, Aarhus Kommunehospital, Department of Neurology, DK-8000, Aarhus,Denmark. Fax 45-99-32-1927.

*Numbers calculated from data in article.


Commentary

Andersen and colleagues report that the serotonin reuptake inhibitor citalopram is effective for patients who have PSD. In a 6-week, randomized, double-blind, placebo-controlled trial, citalopram significantly improved depressive symptoms, as measured by 2 mood scales. The authors cite relevant work showing the responsiveness of PSD to other antidepressants and emphasize the biological basis for the disorder. They re-emphasize the notion that many, if not most, depressive disorders after a stroke appear to be caused by an underlying biological process rather than by a psychological reaction. They extend previous studies in PSD by confirming that the newer class of antidepressant drugs, serotonin reuptake inhibitors, also work for these disorders.

This study applies to persons who have become acutely depressed after a stroke. Because the study did not include an active treatment group, it is unclear whether citalopram is more effective than other agents. For example, tricyclic antidepressants are effective for PSD (1).

This study emphasizes that PSD should be treated as a neurobehavioral disorder because it will respond to appropriate biological interventions, such as citalopram. Simple clinical tools, such as the HDS, can identify persons who will benefit from treatment. Citalopram appears to have few important adverse effects and is well tolerated.

John Absher, MD
Bowman Gray School of MedicineWinston-Salem, North Carolina, USA


Reference

1. Lipsey JR, Robinson RG, Pearlson GD, Rao K, Price TR. Nortriptyline treatment of post-stroke depression: a double-blind study. Lancet. 1984;1:297-300.