• Michael T Isaac, Maria B Isaac, Fidel Gallo, and Alan Tournoux.
• South London and Maudsley NHS Trust, Psychopharmacology Evaluation Unit, Ladywell Building, University Hospital Lewisham, London SE13 6LH, UK. misaac@stekel.demon.ac.uk
• Hum Psychopharmacol. 2003 Dec 1;18(8):595-601.

BackgroundNew, better tolerated and faster treatments for depression are needed. Patients are understandably unhappy with having to wait 3 to 4 weeks for a response to an antidepressant, while experiencing side effects almost immediately. This frequently has an adverse effect on compliance and engagement with treatment.AimsThe primary objective was to assess the activity of pindolol on the onset of antidepressive response of milnacipran. The secondary objective was to assess the number of responders among the patients who received milnacipran and pindolol versus patients who received milnacipran and placebo. The tertiary objective was to evaluate the safety of milnacipran and pindolol versus milnacipran and placebo.MethodRandomized, double-blind, placebo-controlled study over 42 days.SettingInner city London community mental health teams.Participants80 patients were selected and gave written consent to treatment, 78 were randomized (39 in each group) and evaluated for safety (intention-to-treat, ITT, safety data set), 77 (ITT efficacy data set), and 64 (per protocol, PP, data set) were evaluated for efficacy. The mean age was 31.9 for the pindolol group and 32.3 for the placebo.InterventionAll patients received milnacipran 50 mg twice a day plus either pindolol 2.5 mg (the 'pindolol group') or matching placebo (the 'placebo group') three times a day.Outcome MeasuresThe main efficacy variable was the Montgomery-Asberg depression rating scale (MADRS) score at days 0, 4, 7, 10, 14, 21, 28, 42 on PP data set in an observation carried (OC) approach. Secondary efficacy variables were clinical global impression (global improvement) and Hamilton depression rating scale (HDRS).ResultsImprovement in MADRS total score was greater in the pindolol group than in the placebo group from day 7 (p=0.03). Responder rates in the clinical global impression were 97.2% for the pindolol group and 60.6% for the placebo group. The treatment was well tolerated with the most common side effects being nausea (28.2%; 35.9%), vomiting (7.7%; 23.1%), hot flushes (15.4%; 5.1%) and sweating (12.8%; 12.8%).ConclusionThe milnacipran and pindolol combination is safe, well tolerated and efficacious in major depression, and represents a rational strategy for the possible acceleration or potentiation of antidepressant action.Copyright 2003 John Wiley & Sons, Ltd.

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