SUBCHRONIC ANTIDEPRESSANT TREATMENT WITH VENLAFAXINE OR IMIPRAMINE AND EFFECTS ON BLOOD-PRESSURE AND HEART-RATE - ASSESSMENT BY AUTOMATIC 24-HOUR MONITORING

Venlafaxine is a new nontricyclic antidepressant inhibiting the reupta ke of serotonin, noradrenaline, and, to a lesser extent, dopamine with out antagonizing cholinergic, histaminergic, or noradrenergic receptor s. Significantly, in a first placebo-controlled safety and efficacy st udy, high doses of venlafaxine increased blood pressure in some study subjects. In order to investigate further the effect of subchronic ant idepressant drug treatment on blood pressure and heart rate, the effec ts of a conventional tricyclic (imipramine) and a structurally differe nt phenethylamine antidepressant (venlafaxine) were compared. Sixteen inpatients with major depression (melancholic type) were treated for s ix weeks with imipramine or venlafaxine in a randomized parallel doubl e-blind design. Blood pressure was monitored for 24 hours before treat ment and at days 14 and 28 by means of a portable, automatic blood-pre ssure monitoring system. Both compounds lowered systolic blood pressur e by about 5 % on average, while diastolic pressure was influenced nei ther by imipramine nor by venlafaxine. Imipramine treatment resulted i n a significant 15 % increase in heart rate on both day 14 and day 28, whereas heart rate tended to decrease under venlafaxine. When the dat a of individual patients were evaluated, a clinically significant incr ease in blood pressure was apparent in one venlafaxine-treated patient ; a marked increase in blood pressure in one patient treated with imip ramine proved to be reversible with continued treatment. Due to the re latively small sample sizes, the present data do not allow a definitiv e judgement as to whether venlafaxine may cause differential blood pre ssure alterations in comparison with imipramine. However, our results demonstrate that the blood pressure-increasing effect reported for ven lafaxine from first clinical studies might be clinically significant i n individual patients. Furthermore, our study shows that 24-hour monit oring of blood pressure and heart rate is a powerful tool in safety ev aluations of new drugs, even in relatively small samples.