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Milnacipran and pindolol: a randomized trial of reduction of antidepressant latency
Michael T Isaac1, Maria B Isaac, Fidel Gallo
1South London and Maudsley NHS Trust, Psychopharmacology Evaluation Unit, Ladywell Building, University Hospital Lewisham, London SE13 6LH, UK. misaac@stekel.demon.ac.uk
Background:
New, 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.
Aims:
The 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.
Method:
Randomized, double-blind, placebo-controlled study over 42 days.
Setting:
Inner city London community mental health teams.
Participants:
80 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.
Intervention:
All 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 Measures:
The 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).
Results:
Improvement 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%).
Conclusion:
The 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.
Insights
Adding pindolol to milnacipran significantly accelerated antidepressant response in patients with major depression. This combination demonstrated improved efficacy and safety, offering a faster treatment option.
Area of Science:
- Psychiatry and Pharmacology
- Clinical Neuroscience
Background:
- Current antidepressant treatments for depression have a delayed onset of action (3-4 weeks), negatively impacting patient compliance.
- There is a need for faster-acting and better-tolerated depression therapies.
Purpose of the Study:
- To evaluate the effect of pindolol on the speed of antidepressant response to milnacipran.
- To compare the efficacy and safety of milnacipran combined with pindolol versus milnacipran with placebo.
Main Methods:
- A randomized, double-blind, placebo-controlled study was conducted over 42 days.
- 80 patients with major depression were enrolled from inner-city London community mental health teams.
- Patients received either milnacipran (100 mg/day) plus pindolol (2.5 mg three times daily) or milnacipran plus placebo.
Main Results:
- The milnacipran-pindolol group showed significantly greater improvement in Montgomery-Asberg Depression Rating Scale (MADRS) scores from day 7 compared to placebo (p=0.03).
- Responder rates for clinical global impression were substantially higher in the pindolol group (97.2%) versus the placebo group (60.6%).
- The combination therapy was well-tolerated, with manageable side effects.
Conclusions:
- The combination of milnacipran and pindolol is a safe, well-tolerated, and effective treatment for major depression.
- This combination strategy may accelerate or enhance antidepressant action, addressing the need for faster treatment onset.
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