Research Updates in Psychiatry

Research Updates in Psychiatry


Zoloft Ineffective for Depression in Heart Failure

As we reviewed in the July/August 2009 issue of TCPR (Vol 7, Issue 7), cardiac disease leads to major depression, and, conversely, depression is a risk factor for developing cardiac disease. In that issue, we reviewed studies of antidepressants in patients with recent MIs or acute chest pain, finding that while the results were mixed, both antidepressants and cognitive behavioral therapy are helpful for depressive symptoms, with some suggestion that antidepressants might improve cardiac symptoms.

The most recent study, the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial, tested an antidepressant for a slightly different population—cardiac patients with heart failure. In the trial, 469 patients with heart failure and major depression were randomized to either placebo (234 patients) or Zoloft 50 to 200 mg per day (235 patients) for 12 weeks. The final average dose of Zoloft was 65 mg/day.

The mean improvement in Hamilton Depression Rating Scale scores at the end of the trial was -7.1 for the Zoloft group and -6.8 for the placebo group. Improvements in cardiovascular status were seen in 40.6% of the Zoloft group and 43.8% of the placebo group. Worsening of cardiovascular status was seen in 29.9% of the Zoloft group and 31.1% of the placebo group. The between-group differences were not statistically significant.

Only 290 patients (62%) completed the full 12-week trial (138 patients in the Zoloft group and 152 in the placebo group). The most common reasons for dropout in both groups included withdrawal by the clinical team (for reasons unspecified by the authors) and noncompliance. A significantly higher number of patients withdrew from the Zoloft group (27 participants or 11.5%) than from the placebo group (14 participants or 6%), because of side effects. The most common of these were nausea and dizziness (O’Connor CM et al., J Am Coll Cardiol 2010;56(9):692–699).

TCPR’s Take: Why didn’t Zoloft beat placebo? The investigators point out that all patients in the study had unusually intensive nursing care, which may have increased the placebo response, blunting the additive effect of Zoloft. Perhaps the dose of Zoloft (65 mg/day) was not high enough. Or perhaps there is something about depression in patients with heart failure that makes them unresponsive to standard antidepressants. At any rate, this large study should diminish our enthusiasm for using antidepressants in this population.


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SAMe May be Effective Augmentation for Antidepressants

SAMe, long a favorite of Italian psychiatrists, has hopped the pond and installed itself as a “natural” remedy for depression in the U.S. The research supporting its effectiveness, however, has been limited to small studies, most of which were done with the IV version of SAMe. This may explain why a recent study has generated such enthusiasm and press coverage.

In this six-week trial, researchers enrolled 73 patients with depression who had not responded to four weeks of SSRIs, and divided them into two groups. One group was given SAMe augmentation (N=39) and the other group was given placebo augmentation (N=34). Patients continued to receive their stable dose of SSRI throughout the trial. SAMe dosage started at 400 mg twice a day, and was increased to 800 mg twice a day after the second week.

Fifty-five patients completed the six week trial, 24 from the placebo group and 31 from the SAMe group. SAMe augmentation yielded a response rate of 36.1%, significantly more than the 17.6% response rate of those on placebo. The most common side effects in the SAMe group were gastrointestinal—diarrhea and stomach upset. SAMe did not cause sexual side effects or weight gain (Papakostas GI et al., Am J Psychiatry 2010;167(8):942–948).

TCPR’s Take: This should not really be a practice-changing study, since it is a preliminary result that needs to be replicated with a much larger number of patients. But because of the understandable thirst for new remedies for depression (especially those with few side effects), small and merely suggestive studies of natural agents are often trumpeted if the results are positive. To give you an idea of the numbers expected of prescription medications, a recent review of atypical antipsychotics for augmentation of antidepressants analyzed 16 placebo-controlled trials comprising 3,480 patients—nearly 50 times larger than the sample size of this study. (For a review of this complicated and controversial data, see TCPR, March 2009 and November 2009.) So should you try SAMe for treatment-resistant patients? Perhaps so, but warn them that the cost will be high—up to $142 per month, according to the editorial accompanying this article (Nelson JC, Am J Psychiatry 2010;167(8):889–891), which is much more than most prescription medication co-pays.

Research Updates in Psychiatry

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This article was published in print 10/2010 in Volume:Issue 8:10.

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APA Reference
Psychiatry Report, T. (2013). Research Updates in Psychiatry. Psych Central. Retrieved on September 18, 2020, from


Scientifically Reviewed
Last updated: 30 Sep 2013
Last reviewed: By John M. Grohol, Psy.D. on 30 Sep 2013
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