Depression and Congestive Heart Failure

Thomas P. Guck, PhD, Gary N. Elsasser, PharmD, Michael G. Kavan, PhD, Eugene J. Barone, MD

CHF. 2003;9(3) 

In This Article

Pharmacologic Treatment

When choosing an antidepressant for the CHF patient, the physician must take into consideration efficacy and adverse effects. A consistent finding in the literature is that there are few differences with respect to effectiveness, not only among antidepressant agents within a particular class but also among classes of agents. In addition, no differences have been found in the treatment of mild to moderate depression.[20,21] Consequently, efficacy issues may be a secondary concern, while the side effect profile of these agents and their potential for significant drug interactions become of prime importance. This is particularly true in CHF patients, as they are more likely to be elderly and suffering from other comorbidities. In addition, the routine treatment of CHF requires the use of multiple medications. Therefore, polypharmacy often is advocated rather than avoided. All of these factors increase the likelihood of an antidepressant-related side effect or drug-drug interaction.[22]

Hypotension is one of the most notable adverse effects associated with the antidepressants. The -adrenergic blocking activity of the tricyclic antidepressants (TCAs) can have a direct blood pressure-lowering effect.[23] Differences exist with both the propensity and the magnitude for hypotension among the TCAs, with nortriptyline having the least effect. The cardiac effects of the TCAs and other selected antidepressants are presented in Table III . In a study by Glassman et al.[24] of 15 heart failure patients treated with imipramine, seven developed severe orthostatic hypotension. Furthermore, the potential for significant orthostatic blood pressure changes is exaggerated by agents frequently employed to treat CHF. These episodes of hypotension may, in turn, predispose the elderly CHF patient to falls and a higher frequency of hip fractures. In the previously mentioned study, six of the seven patients fell as a result of an orthostatic drop in blood pressure. The atypical antidepressant trazodone has also been noted to produce hypotension, while the selective serotonin reuptake inhibitors (SSRIs) have minimal influence on blood pressure. Bupropion likewise does not significantly lower blood pressure. However, bupropion and venlafaxine have been associated with the development of treatment-emergent hypertension in approximately 6% and 3% of patients, respectively.[25,26]

Cardiac conduction has also been problematic in patients taking TCAs. Conduction is delayed and this can lead to significant morbidity in the presence of a pre-existing conduction disturbance. Eighteen percent of patients with a pre-existing bundle branch block treated with therapeutic concentrations of imipramine developed a worsening of their condition, either as 2:1 atrioventricular block or a 25% increase in QRS duration.[27] Alteration in cardiac conduction with the SSRIs, even in the event of overdose, is negligible. Symptomatic bradycardia has been reported in patients taking fluoxetine but has not been substantiated in clinical trials.[28] There was no evidence of QRS widening or conduction delays in 234 cases of fluoxetine overdose reported to poison control centers.[29]

The occurrence of life-threatening arrhythmias has long been noted as a complication of TCA overdose, and their proarrhythmic potential has been well documented elsewhere. Atypical antidepressants, such as trazodone and bupropion, as well as the SSRIs, have not been noted to produce arrhythmias when taken alone, even in the case of overdose.

Of particular importance to the patient with CHF is the effect of an antidepressant on myocardial contractility. The small number of trials involving human subjects has not demonstrated a significant detriment to left ventricular function with antidepressants as a whole.[24,30,31,32]

With the addition of each medication, the clinician must be cognizant of the potential for significant drug interactions. Table IV highlights some of the more common interactions with respect to antidepressants and drugs commonly utilized in patients with CHF. Interference with drug metabolism through an interaction with the cytochrome P450 system is a common mechanism. Not all antidepressants are equal with respect to their involvement with the CYP450 system. Fluvoxamine has the greatest potential for drug interactions, as it interacts with all of the major P450 isoenzymes. Fluoxetine and paroxetine are potent inhibitors of the 2D6 isoenzyme. This isoenzyme is intimately involved in the metabolism of a number of important drugs and its inhibition can result in delays in metabolism, higher drug serum concentrations, and possible toxicity of 2D6 substrates. Citalopram, sertraline, and venlafaxine appear to have the least potential for significant P450 mediated interactions.

Despite the plethora of available agents for treatment of depression, the presence of CHF and other cardiovascular diseases complicates selection. Given the frequency of TCA-related side effects, the SSRIs should be considered as preferred therapy. Further consideration should be given to an agent with the least potential for significant interactions with drugs commonly used in the treatment of CHF and other concomitant illnesses.

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