September 23, 2008 (Toronto, ON) — Patients with both heart failure and clinical depression who received the selective serotonin reuptake inhibitor (SSRI) sertraline (Zoloft/Lustral, Pfizer) for three months and those who received placebo showed about the same improvements in their depression and similar clinical outcomes, in a randomized trial that explored the long-intriguing question of whether treating the psychiatric condition would also improve the clinical disorder .
Although the 469-patient trial didn't have anything conclusive to say about that question, it did suggest--to its investigators and to some observers, at least--that a unique nonpharmacologic intervention aimed at both depression and heart failure might have been more powerful against depression than the SSRI. Patients in both randomization groups of the Safety and Efficacy of Sertraline for Depression in Patients with Congestive Heart Failure (SADHART-CHF) trial, presented this week here at the Heart Failure Society of America 2008 Scientific Meeting, were closely managed by heart-failure nurses with special training in psychiatric evaluation and follow-up.
When presenting the study, Dr Christopher M O'Connor (Duke University, Durham, NC) said the "nurse-facilitated supportive intervention," as the special program was called, "resulted in equal reduction in short-term depression scores and similar rates of short-term cardiovascular outcomes." The nurse intervention program was apparently so successful, as evidenced by dramatic improvements in depression scores in both randomization arms over the trial's first few weeks, that it "may have allowed a strong response in both groups, limiting the ability to distinguish the effects of sertraline alone."
Patients in both groups also fared about as well on a second primary end point: whether they worsened, stayed the same, or improved with respect to a composite end point that included death, CV hospitalization, and "going off double-blind medications" due to worsening CV disease, according to O'Connor. Sertraline-treated patients had slightly fewer HF hospitalizations, but the difference didn't reach significance.
"SADHART-CHF raises the really intriguing possibility that nonpharmacologic therapy may be more effective [for depression] than pharmacologic therapy in patients with heart failure," according to Dr Douglas L Mann (Baylor College of Medicine, Houston, TX), the assigned discussant for O'Connor's presentation. "I would submit that in a disease as poorly understood as depression, the benefits of the nursing-facilitated support may trump the benefits of pharmacologic intervention, particularly for people who have as many comorbidities and significant heart failure as the patients in [SADHART-CHF]."
Then Mann added, only half tongue-in-cheek, "I think the trial that really needs to be done is nursing intervention vs usual care. Forget about the SSRIs! If we had better nursing care for these patients who are very significantly depressed, we might have a beneficial outcome."
There had been reason to believe that SSRIs might have extra benefits for patients with clinical depression and CV disease, O'Connor explained heartwire . Some evidence suggests that the drugs may influence platelet and endothelial activation pathways and may otherwise reduce the risk of myocardial ischemia and heart failure, he said. And in the previously published SADHART trial , according to O'Connor, SSRIs in a post-MI population may have improved CV risk, although it was only a nonsignificant trend.
About 70% of the SADHART-CHF patients had ischemic disease, "so we thought there might be a signal on the chest-pain admissions, MIs, things like that." Given the trial's small size and relatively short follow-up, he speculated, such a signal could have been "buried in the heart failure." The trial wasn't longer, he said, because "in depression trials, you can't ethically go with a [SSRI] placebo for more than 12 weeks," at least when the depression is as severe as it was in SADHART-CHF.
In his presentation, O'Connor said antidepressants might also improve heart-failure status by "restoring autonomic nervous system control that is poorly regulated in the setting of depression or by modulating the immune system and proinflammatory activation."
SADHART-CHF randomized patients at least 45 years old with chronic heart failure of NYHA functional class 2–4, an LVEF <45%, and a "structured psychiatric diagnosis of a major depressive disorder," who scored >10 on the Beck Depression Inventory (BDI), a standard instrument for assessing depression severity, to receive sertraline at 50 mg/day initially, then titrated to a maximum of 200 mg/day (n=234), or placebo (n=235) for 12 weeks, both in conjunction with the nurse-facilitated supportive intervention program.
The program was conducted by "nurse clinicians with psychiatric training, backed up by a psychiatrist and cardiologist" and called for telephone contact with patients at weeks 1, 2, 4, 8, and 10 and visits in person at weeks 6 and 12. During the contacts, the nurses evaluated the patients' depression using the Hamilton Depression Rating Scale (HDRS) and other tools. Those found with "significant depression," O'Connor said, "received a home visit and possible psychiatric referral."
HDRS scores plunged in both groups over the first two to four weeks of the study and were maintained in the range of 7 to 10, suggesting significant alleviation of depression in both groups. But, O'Connor noted, scores >7 still indicate the presence of depression; about half the patients in the trial still had depressive symptoms by the trial's end.
Throughout the trial, there were significant improvements in scores for most domains on the Kansas City Cardiomyopathy Questionnaire (KCCQ), including quality of life, self-efficacy, symptom stability, physical limitation, functional status, and "clinical summary" in both groups, but with no significant differences between them. Nor was there a significant difference in change in NYHA class. And there were few fatal or nonfatal CV events, with no differences at 12 weeks in rates of CV death, MI, arrhythmias, stroke, HF exacerbation, or unstable angina.
The rates of HF hospitalization were 8.1% in the sertraline group and 12.8% among controls (p=0.1), "perhaps a trend suggesting a 33% reduction," O'Connor said, noting, however, that the trial wasn't nearly powered for such clinical end points.
The unusual nursing intervention impressed members of the audience, including Dr Barry H Greenberg (University of California San Diego Medical Center), who commented, "The enormous impact that the nurse facilitators had on this patient population and the reduction in the [Hamilton] scale within a two-week period of about 40%, from a very high level, was just extraordinary and points out what simply seeing these patients, the laying-on of hands, will do for these depressed heart-failure patients. It's really quite striking."
To heartwire , Mann observed that elements of the trial's nursing intervention could potentially be incorporated into contemporary care of heart-failure patients with depression, but it would take further study. "We don't know the components of care that were essential for improving outcomes, so it may be that if we could better understand [those], we could make it simpler for distillation into clinical practice." Mann emphasized that SADHART-CHF, as a short and underpowered trial, can be no more than hypothesis-generating.
The trial was funded by the National Institute of Mental Health; Pfizer supplied the sertraline.
O'Connor CM. Safety and Efficacy of Sertraline for Depression in Patients with Congestive Heart Failure (SADHART-CHF). Heart Failure Society of America 2008 Scientific Meeting; September 22, 2008; Toronto, ON. Late Breaking Clinical Trials I.
Heartwire from Medscape © 2008 Medscape
Cite this: Steve Stiles. SADHART-CHF: Nurse Intervention Impresses for Depression in Heart Failure, SSRI Doesn't - Medscape - Sep 23, 2008.