Selective serotonin reuptake inhibitors modify the effect of beta-blockers on long-term survival of patients with end-stage heart failure and major depression.
BACKGROUND
Major depression (MD) is a key feature in heart failure (HF), and it is unclear whether common antidepressive medications interact with cardiovascular drugs used for the treatment of patients with MD and HF, affecting their efficacy. We examined the impact of MD on long-term survival of patients with end-stage severe HF. We also evaluated the interaction between antidepressive medication and beta-blockers on the clinical outcome of these patients.


RESULTS
The study population consisted of 250 patients with end-stage severe HF. Sixty-one percent of these patients suffered MD and were receiving selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCA). All patients were followed prospectively for 18 months. The primary end point was cardiovascular death. At baseline, patients with severe MD had higher serum interleukin 6 (P < .05) and soluble vascular cell adhesion molecule (P < .01). During the follow-up, 167 cardiovascular deaths were reported, and MD was 1 of the major predictors of cardiovascular death (P = .031), whereas treatment with angiotensin receptor inhibitors and statins were also important negative predictors of mortality (P = .036 and P = .039, respectively). Although beta-blockers had a borderline nonsignificant effect on cardiovascular mortality in the overall population, they had a striking beneficial effect among those patients with major depression receiving SSRIs (P = .006), whereas they had a negative effect on mortality in those patients receiving SNRIs/TCAs (P = .025).


CONCLUSIONS
MD is an independent predictor of cardiovascular death in patients with end-stage HF. beta-blockers are associated with lower cardiovascular mortality in patients with end-stage HF and depression only when they are combined with SSRIs.
Tousoulis
Dimitris
D
1st Cardiology Department, Athens University Medical School, Athens, Greece.
Antoniades
Charalambos
C
Drolias
Apostolos
A
Stefanadi
Elli
E
Marinou
Kyriakoyla
K
Vasiliadou
Carmen
C
Tsioufis
Costas
C
Toutouzas
Kostas
K
Latsios
George
G
Stefanadis
Christodoulos
C
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015996:Survival Rate / Q000639:trends; D013995:Time; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D017367:Selective Serotonin Reuptake Inhibitors