Effects of treating depression and low perceived social support on clinical events after myocardial infarction.
The Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial Writing Committee;
Commented by , 28 Jul 2003
Background
Depression and low perceived social support (LPSS) predict morbidity and mortality following myocardial infarction (MI).
Purpose
Determine whether early post-MI treatment of depression and LPSS with cognitive behaviour therapy (CBT), supplemented with a selective serotonin reuptake inhibitor (SSRI) when indicated, reduces recurrent infarction and mortality.
Methods
In an American multisite randomized trial, 2841 post-MI patients (1084 women, 1397 men) were enrolled: 39% depressed, 26% LPSS and 34% had both. Major or minor depression was diagnosed using a semistructured interview as per modified DSM-IV criteria, including the 17-item Hamilton Rating Scale for Depression (HSRD); LPSS was determined by the ENRICHD Social Support Instrument (ESSI). Randomization was to usual care or CBT intervention.
Individual CBT commenced at a median 17 days post-MI for a median 11 sessions over 6 months, plus 12 weeks of group CBT when feasible. Intervention group patients with HSRD > 24 or < 50% reduction in the Beck Depression Inventory (BDI) after 5 weeks were started on an SSRI.
Follow-up visits occurred at 6-month intervals for a mean 29 months. Primary outcome was death or recurrent MI; secondary outcomes were change in 6-month HSRD or ESSI scores. Kaplan-Meier survival curves were generated, using intention-to-treat, accounting for potential baseline confounders. Post-hoc analyses assessed the independent effect of antidepressants.
Results
Four-year survival curves revealed no significant difference between treatments in recurrence of MI or death. The intervention yielded significant but small differences in secondary outcomes: mean HSRD change of –10.1 and –8.4 in the depressed intervention and usual care groups, respectively; mean ESSI change of 5.1 and 3.4 in the LPSS intervention and usual care groups, respectively.
13.4% of usual care patients and 20.5% in the intervention arm were on antidepressants at 6 months. Antidepressant use was associated with a lower risk of the primary outcome with a crude hazard ratio for death or MI of 0.67 (95% CI; 0.49-0.92), but paradoxically not depression outcome.
Discussion
ENRICHD is the first study to evaluate the impact of treating depression and LPSS post-MI on survival, and is the largest controlled psychotherapy trial to date. The study demonstrates that multiple treatment providers across disciplines and sites can successfully collaborate in a trial of this size and complexity.
The modest improvements in depression and LPSS with treatment did not translate into improvements in cardiac health, highlighting the elusive nature of the mechanisms linking these psychosocial parameters to cardiac morbidity.
In addition, several limitations may underscore the negative findings. The short median interval of 6 days from index MI to enrollment raises the likelihood of a sampling bias. Specifically, about 50% of “depressions” in the acute post-MI setting rapidly remit (1); thus patients enrolled as depressed may have rather been experiencing an adjustment disorder.
As suggested by the post-hoc analyses, the large number of patients in the control group on antidepressants may have confounded the survival outcomes, as SSRIs have been associated with reduced cardiac morbidity (2), perhaps related to their inhibitory effects on platelets (3).
The authors relied upon a new untested form of CBT to target LPSS. While tailored to strengthen social ties, this is not at the core of the CBT model. In contrast, the thrust of interpersonal psychotherapy (IPT) is to target interpersonal conflicts and social isolation, and in so forth may be helpful in this population.
The ENRICHD trial has set an important benchmark. The optimal timing and nature of intervention in post-MI depression bear further exploration.
References
1. Schleifer SJ, Macari-Hinson MM, Coyle DA et al. The nature and course of depression following myocardial infarction. Archives of Internal Medicine 1989; 149; 1785-1789
2. Sauer WH, Berlin JA, Kimmel SE. Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 2001; 104; 1894-1898
3. Serebruany VL, Gurbel PA, O'Connor CM. Platelet Inhibition by Sertraline and N-Desmethylsertraline: A Possible Missing Link Between Depression, Coronary Events, and Mortality Benefits of Selective Serotonin Reuptake Inhibitors. Pharmacological Research 2001; 43 (5); 453-462