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Influence of Sertraline and Mood Improvement

Alexander H. Glassman, MD; J. Thomas Bigger, MD; Michael Gaffney, PhD; Louis T. Van Zyl, MB, ChB, MMed (Psych)

Arch Gen Psychiatry. 2007;64(9):1025-1031.

Context  Major depressive disorder (MDD) associated with acute coronary syndrome (ACS) increases the risk of mortality. Decreased heart rate variability (HRV), also a predictor of mortality, is reduced in patients with MDD after ACS, and has been suggested to be a mediator of MDD mortality after ACS. Although selective serotonin reuptake inhibitors may reduce mortality post-ACS, little is known about their effects on HRV.

Objective  To examine the influence of both sertraline and improvement in mood on HRV.

Methods  The Sertraline Antidepressant Heart Attack Randomized Trial assessed HRV from 24-hour Holter electrocardiogram recordings at baseline in 290 patients and from a second recording in 258 of these patients 16 weeks after randomization to sertraline or placebo. Frequency domain measures of HRV included high-frequency power, low-frequency power, very low–frequency power, ultra low–frequency power, and total power. Depression severity was measured by the Hamilton Rating Scale for Depression. Clinical response was measured with the Clinical Global Impressions Improvement scale.

Results  At baseline, prior episodes of MDD were associated with lower HRV. Sertraline significantly increased ultra low–frequency power, while improvement in mood was associated with higher low-frequency power independent of treatment. However, the expected recovery in HRV following ACS was not observed in patients with MDD. Higher ultra low–frequency during sertraline treatment and higher low-frequency power in patients whose mood improved resulted primarily from these measures decreasing in their comparison groups.

Conclusions  Heart rate variability recovery is impaired in depressed patients after ACS. Previously reported differences in baseline HRV between patients with and without depression after ACS grew larger in the 16 weeks following a coronary event. Both sertraline treatment and symptomatic recovery from depression were associated with increased HRV compared with placebo-treated and nonrecovered post-ACS control groups, respectively, but this results primarily from decreased HRV in the comparison groups.

Author Affiliations: Departments of Psychiatry (Dr Glassman) and Medicine (Dr Bigger), Columbia University College of Physicians and Surgeons, New York, New York; Pfizer Inc, New York, New York (Dr Gaffney); and Department of Psychiatry, Queens University, Kingston, Ontario, Canada (Dr Van Zyl).

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