Post-stroke depression: Rapid action helps restore lost function

Antidepressants in other classes—such as venlafaxine, bupropion, and mirtazapine—have not been studied in patients with PSD.

Without strong evidence to guide the initial antidepressant choice, a pragmatic approach is to start with one or two agents with which you are most familiar. Consider side effects, potential drug-drug interactions, cost, and available formulations. A patient with post-stroke swallowing difficulties, for example, may benefit from a liquid form.

We do not have good data regarding the optimum starting dose and duration of therapy for any antidepressants in PSD. To minimize side effects, I recommend starting with low dosages, such as:

• fluoxetine, 10 mg/d
• sertraline, 25 to 50 mg/d
• nortriptyline, 10 to 25 mg/d.

Increase dosages gradually, watching for side effects and symptom improvement.

If treatment is effective, continue the antidepressant for at least 1 year. In patients with a history of depression, continue treatment longer to prevent depressive relapse.

Small, double-blind, controlled trials have used citalopram, fluoxetine, nortriptyline, or sertraline to treat post-stroke emotional lability.¹⁴ Compared with placebo, these agents all significantly reduced post-stroke emotionalism.

Psychostimulants such as methylphenidate and dextroamphetamine might be an effective alternative to antidepressants.¹⁵ They have a morerapid onset of action, better tolerability, and may be more effective in alleviating post-stroke apathy. Disadvantages include risks for tolerance, dependence, and psychiatric side effects.

As with antidepressants, start low and go slow to minimize side effects. You could start methylphenidate at 5 mg in the morning and increase to 20 to 30 mg/d before you decide—based on response—to continue or discontinue. After the dosage is stabilized, you could switch to a controlled-release formulation.

ECT. Although no controlled trials of electroconvulsive therapy for PSD have been reported, ECT can be an effective option for patients with treatment-resistant depression. Some retrospective studies¹⁶ have shown a good response among patients with PSD, although ECT may worsen stroke-related cognitive deficits.

rTMS. University of Iowa researchers recently completed a double-blind controlled trial evaluating the efficacy of repetitive transcranial magnetic stimulation (rTMS) in PSD. R.G. Robinson, MD (personal communication, 2003), reported that preliminary results are encouraging.

Psychotherapy. Cognitive-behavioral therapy—used alone patients or combined with medication—has yielded good results in some PSD studies. Controlled trials^17,18 have shown that individual counseling, occupational therapy, leisure activities, and social work improve all aspects of PSD except mood.

Can be prevented?

Many patients who are not depressed during an initial post-stroke evaluation develop depression within 2 years.¹⁹ This raises the question: Can PSD be prevented by treating stroke patients prophylactically?

In a 12-week, randomized, double-blind trial,²⁰ 48 nondepressed post-stroke patients were treated with nortriptyline, fluoxetine, or placebo. Dosages were:

• nortriptyline—25 mg/d in week 1; 50 mg/d in weeks 2 and 3; 75 mg/d in weeks 4 to 6, and 100 mg/d in weeks 7 to 12
• fluoxetine—10 mg/d in weeks 1 to 3; 20 mg/d in weeks 4 to 6; 30 mg/d in weeks 7 to 9, and 40 mg/d in weeks 10 to 12.

After 3 months, the two antidepressants appeared comparable in efficacy and significantly more effective than placebo in preventing depression. Patients who had taken nortriptyline were more likely to develop depression during the subsequent 6 months than were patients in the other two groups, and their symptoms were more severe. However, the authors noted many study limitations, including small sample size and loss of some patients to follow-up.

In a randomized, double-blind study, prophylaxis with mianserin (not available in the United States) did not prevent post-stroke depression.²¹ For 1 year, 100 patients presenting with acute ischemic stroke received mianserin, 60 mg/d, or placebo. Monitoring at 2, 6, 12, and 18 months found no differences between the two groups with respect to PSD onset.

Recommendation. As with most aspects of PSD treatment, the issue of prophylaxis remains unsettled. I do not routinely start antidepressants in nondepressed stroke patients because evidence of benefit is lacking and any added medications increase the risk of side effects and drug-drug interactions.

Related resources

• National Institute of Neurological Disorders and Stroke. Stroke information page www.ninds.nih.gov/health_and_medical/disorders/stroke.htm
• Robinson RG. The clinical neuropsychiatry of stroke: cognitive, behavioral, and emotional disorders following vascular brain injury. New York: Cambridge University Press, 1998.

Drug brand names

• Bupropion • Wellbutrin
• Citalopram • Celexa
• Desipramine • Norpramin
• Dextroamphetamine • Dexedrin
• Fluoxetine • Prozac
• Imipramine • Tofranil
• Methylphenidate • Concerta, Ritalin
• Mirtazapine • Remeron
• Nortriptyline • Aventyl, Pamelor
• Paroxetine • Paxil
• Sertraline • Zoloft
• Trazodone • Desyrel
• Venlafaxine • Effexor

Disclosure

Dr. Fozdar is a speaker for Eli Lilly and Company.