The better the quality of the research, the more likely it is to show that antidepressants work. This rule held up in a major study of medication and psychotherapy to prevent depression in stroke victims.
Depression is a frequent complication of strokes, and it is a dangerous one, associated with an increased risk of death. The randomized controlled trial, headed by Robert G. Robinson of the University of Iowa and showcased in the current issue of JAMA, demonstrated that Lexapro given in the year following a stroke greatly reduces the risk of depression. Subjects on placebo were 4.5 times as likely to contract depression as subjects on medication.
A psychotherapy designed for the elderly (“problem-solving therapy”) also seemed to prevent stroke, although it failed statistically in the strictest analysis.
The interventions appeared to have no negative effects although, strangely, impaired sex drive was observed a good deal more often in the patients given psychotherapy. The patients on antidepressant may have had an incidental positive effect: they had fewer subsequent cardiac events.
The overall finding is a landmark in preventive psychiatry. Epidemiologists recognize three levels of prevention for people in a given category, in this case, those who have just had a stroke: indicated (intervening with patients who have early signs of the disease in question — here, depression), selective (intervening with patients at high risk for the disease in question), and universal (intervening for all patients). The Iowa study suggests that antidepressants may be a universal preventive for depression in acute stroke victims.
The medication doses were reasonably low: ten milligrams of Lexapro for patients under age 65, and five milligrams for patients 65 or older. One problem with some prior studies is that the antidepressant doses were high in an elderly population. The most successful prior trial used the equivalent of these modest doses.
To give a sense of the power of the result: to prevent the onset of depression in one patient, you would need to give 7.2 stroke victims medication for a year. This “needed to treat” figure may sound high — unless you consider that when administering a cholesterol-lowering drug, you have to treat 40 men for five years to prevent one heart attack.
This study has its limitations. It could only admit patients with uncomplicated strokes and without prior ongoing depression. But what is impressive is how straightforward the research was.
The study was announced in advance, in a government registry. It was conducted by the leading expert in the field. Robinson has been studying post-stroke depression for years and is chair of psychiatry at Iowa. The study was funded by the National Institute of Mental Health and written and vouched for by the lead author. The eminence of the research team and the reasonable sample size, 176 subjects, guaranteed that the research would be published, no matter what the result.
And then there is the question of admission criteria. I have written that many outcome trials are weakened by researchers’ haste to admit subjects – so that people who do not really suffer depression are enrolled, and then placebo response rates are high. Of course, in this study, no such damaging incentive exists. Initially, none of the subjects had depression.
So in research that has none of the problems that lead to criticism of outcome trials, antidepressants worked — not perfectly, but decisively. If you have an uncomplicated stroke, you probably should take antidepressants for a year.
The question of stroke and psychotherapy is interesting. Cognitive-behavioral therapy seems not to work; it failed a prior trial, and Robinson chose not to re-test it. The new, specially designed therapy did work, except in the most rigorous analysis, which assumed that every subject who dropped out of treatment got depression. (Lexapro succeeded even in this demanding "intention-to-treat" analysis.) Using more standard calculations, it looked as if giving 9.1 acute stroke patients 12 sessions of therapy would prevent one case of depression — again, not a bad investment.
Another take-home lesson from this research is the one I have reiterated in these postings. Antidepressants work. The better the study, and the tougher the population under study, the clearer the demonstration of efficacy.
