Is recurrent atrial fibrillation a contraindication for treatment with venlafaxine (Efexor) bearing

Fråga: Is recurrent atrial fibrillation a contraindication for treatment with venlafaxine (Efexor) bearing in mind that tachychardia is listed as a common adverse effect to venlafaxin in FASS 2001? Should another antidepressant drug be preferred? A 79-year-old man with recurrent atrial fibrillation has been treated with Efexor, 75 mg daily, for the last year. The patient has had no negative effects from the treatment.

Sammanfattning: Venlafaxine is not contraindicated in patients with stable cardiovascular disease. The drug has not been associated with causing serious arrhythmia, significant prolongation of cardiac conduction, or clinically significant orthostatic hypotension. However, venlafaxine has not been studied specifically in patients with underlying cardiovascular disease and SSRI may be a safer choice in such patients. However, in this specific case, when the patient has been treated with venlafaxine for a long time and had had no adverse effect, there is no need for changing the antidepressant treatment.

Svar: Venlafaxine (a serotonin and noradrenaline reuptake inhibitor) is not contraindicated in patients with stable cardiovascular disease (1,2,3). In patients without cardiovascular disease, venlafaxine is not associated with causing serious arrhythmia, significant prolongation of cardiac conduction, or clinically significant orthostatic hypotension (4). However, the drug has not been studied specifically in patients with underlying cardiovascular disease, such as arrhythmia or conduction abnormalities. In the Swedish register on adverse side effects (Swedis), there are totally 23 reports on venlafaxine circulatory adverse effects, most of which include alterations in blood pressure and tachychardia, but there are no reports on atrial fibrillation (5). In the international WHO-database on adverse drug reactions (Intdis) there are totally 83 reports on heart rate and rhythm disorders in patients treated with venlafaxine, six of which concern atrial fibrillation (6). The manufacturer has not received any alarming reports on patients with atrial fibrillation (2).

In animal models, venlafaxine has been shown to increase arterial pressure and heart rate, an effect that was consistent with blockade of noradrenaline reuptake (4). There are some clinical trials on the effect of venlafaxine on blood pressure. In placebo-controlled clinical studies increases (increase in diastolic blood pressure of >15 mmHg and to >105 mmHg from baseline) in blood pressure were observed in 5.5 percent of patients at doses above 200 mg daily. The increase in blood pressure can probably be attributed to venlafaxine´s central inhibition of noradrenergic reuptake. At a dose of 75 mg daily, clinically significant increase in blood pressure is uncommon with venlafaxine (4). In a study of cardiovascular safety of venlafaxine in young (age, 13 to 56 years) versus old (age, 65 to 86 years) patients with comorbid medical disorders, venlafaxin was not associated with significant, sustained changes in blood pressure in any patient receiving doses of 50 to 250 mg daily (7).

The choice of antidepressant agent to patients with underlying cardiovascular disease has been discussed in several publications (4, 8-13). Tricyclic antidepressants (TCAs) or monoaminie oxidase inhibitors are known to cause adverse cardiovascular effects, mainly orthostatic hypotension and cardiac conduction abnormalities. TCAs may cause arrhythmia due to their antiarrhythmic properties. Studies have shown that selective serotonin reuptake inhibitors (SSRIs) have much less electrophysiological effects and orthostatic reflexes than TCA and are therefore considered as a safer choice than TCAs in patients with cardiovascular diseases. The data on venlafaxine and other substances acting with blockade of both noradrenaline and serotonin reuptake in treatment of patients with underlying cardiovascular disease is scarce. Therefore, SSRI, so far, should be the first drug of choice if antidepressant treatment is considered in a patient with underlying heart disease.

In this specific case, when the patient has been treated with venlafaxine for a long time and had had no adverse effect, there is no need for changing the antidepressant treatment. Although there is limited data on venlafaxine-treatment in patients with underlying cardiac disease, a dose of 75 mg daily could be regarded as safe as long as the patient´s heart disease is under control and he has no complications from the treatment.