Effects of Venlafaxine on Blood Pressure
aBSTRACT & COMMENTARY
Synopsis: This large meta-analysis reports that, overall, venlafaxine and imipramine slightly increased supine diastolic blood pressure compared to placebo. The magnitude of the change in blood pressure from venlafaxine is statistically significant, but likely clinically insignificant at doses less than 300 mg per day.
Source: Thase ME. Effects of venlafaxine on blood pressure: A meta-analysis of original data from 3744 depressed patients. J Clin Psychiatry 1998;59:502-508.
Venlafaxine (effexor) is the only commonly used psychotropic agent associated with a significant incidence of induced hypertension. Similar to the tricyclic class of antidepressants, venlafaxine inhibits the reuptake of norepinephrine and serotonin, yet lacks affinity at the receptors commonly associated with tricyclic side effects, such as histamine1, muscarinic acetylcholine, and alpha1-adrenergic. Venlafaxine’s hypertensive effect may be due to relative overactivity of adrenergic neurotransmission without the possible compensatory hypotensive effect of alpha1-adrenergic blockade. In this thorough meta-analysis, Thase examined the incidence and characteristics of venlafaxine-associated hypertension in a large data set derived from phase 2 and 3 clinical trials provided by the manufacturer. This meta-analysis examined blood pressure changes in 2817 subjects treated with venlafaxine, 320 subjects treated with imipramine, and 607 subjects treated with placebo in 27 separate double-blind trials at 180 different study sites, all lasting at least six weeks. Blood pressure measurements were performed in a standardized and uniform fashion across studies. Thase used recently developed and appropriate statistical methods to minimize the effects of study "drop-outs." Continuous variables (blood pressure measurements) were examined with the random-effects model with repeated measures. Categorical data (hypertension or not) were analyzed using survival analysis (with the Cox proportional hazards model to account for key covariates, such as age and sex), with drop-outs censored at the time of attrition from the study. The results showed that, overall, venlafaxine and imipramine slightly increased supine diastolic blood pressure compared to placebo. However, as Thase points out, overall, the magnitude of the change in blood pressure from venlafaxine is statistically significant, but likely clinically insignificant (mean increase in diastolic blood pressure with venlafaxine was approximately 1 mmHg). Looking at the data in a slightly different way, 11.5% of venlafaxine-treated subjects had a supine diastolic blood pressure higher than 90 mmHg at the study end point, compared to 7.9% for imipramine and 5.7% for placebo. This venlafaxine-associated elevation in diastolic blood pressure appeared to persist in 50% of subjects continuing to receive venlafaxine for long-term treatment. Subjects with pre-existing hypertension (on stable dosages of antihypertensives) were slightly more likely than nonhypertensive subjects to experience venlafaxine-associated high blood pressure. Men and elderly subjects were also more likely to experience high blood pressure during venlafaxine therapy. Overall, the venlafaxine dosages varied widely, and there was a statistically and clinically relevant relationship between venlafaxine dosage and increased supine diastolic blood pressure. Only the group of subjects receiving more than 300 mg/d of venlafaxine experienced a significantly increased frequency of sustained elevated diastolic blood pressure.
COMMENT BY ANDREW L. STOLL, MD
This meta-analysis of the risk of high blood pressure during venlafaxine therapy was well designed and represents the largest series of blood pressure measurements in depressed subjects receiving antidepressants. The results support the notion that clinically significant elevated blood pressure during venlafaxine therapy is generally present only at high dosages (> 300 mg/d). Several risk factors exist for developing high blood pressure during venlafaxine therapy (age, sex, pre-existing hypertension, and high-dose venlafaxine). One limitation of the study is that systolic blood pressure measurements were not analyzed. Clinically, one sees elevations in systolic and diastolic blood pressure during venlafaxine therapy, and the only modest elevations in diastolic blood pressure observed in this study may not be representative of any systolic blood pressure effects of venlafaxine. Overall, these results imply that venlafaxine is a first-line antidepressant drug and that it is not necessary to restrict venlafaxine to refractory patients. However, prudence dictates that regular blood pressure monitoring be performed on any patient receiving venlafaxine. This is because, rarely, a patient may develop high blood pressure during venlafaxine therapy.
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