Forty-seven studies with a total of 3,318 participants were included in the MOC meta-analysis. Nine studies with a total of 527 were included in the BRO meta-analysis.
Brofaromine (BRO). BRO versus active comparator (6 studies): there were differences of 4.8% (standard deviation, SD=5.3) and 0.2% (SD=17.6) in the ITT and AT samples, respectively, which favoured BRO.
Safety.
BRO was significantly better tolerated than imipramine in 2 studies, and tranylcypromine in 2 studies. Three other studies showed no differences in the tolerability. BRO was generally better tolerated than the combination of maprotiline and lithium, although complaints about sleep problems were higher in the BRO group.
Moclobemide (MOC).
MOC versus active comparator (47 studies): there was a difference of 3.2% (SD=1.9) in the ITT sample, which favoured MOC.
MOC versus active comparator (39 studies): there was a difference of 1.7% (SD=1.3) in the AT sample, which favoured MOC.
MOC versus placebo (12 studies): there was a difference of 15.8% (SD=6.1) in the ITT sample, which favoured MOC.
MOC versus placebo (11 studies): there was a difference of 24.2% (SD=5.6) in the AT sample, which favoured MOC.
Out-patient studies.
MOC versus active comparator (16 studies): there was a difference of 2.6% (SD=2.5) in the ITT sample, which favoured MOC.
MOC versus active comparator (13 studies): there was a difference of 24.2% (SD=3.7) in the AT sample, which favoured MOC.
In-patient studies.
MOC versus active comparator (5 studies): there were differences of 2.7% (SD=6.2) and 0.7% (SD=5.2) in the ITT and AT samples, respectively, which favoured MOC; these differences were not significant.
MOC versus selective SSRIs (8 studies): there were differences of 6.4% (SD=3.9) and 4.8% (SD=4.1) in the ITT and AT samples, respectively, which favoured MOC.
MOC versus older monoamine oxidase inhibitors (MAOIs) (3 studies): there was a difference of -5.8% (SD=8.4) in the ITT sample, which favoured the older MAOIs.
MOC versus older MAOIs (2 studies): there was a difference of -13.3% (SD=6.8) in AT sample, which favoured the older MAOIs.
MOC versus tricyclic antidepressants (28 studies): there was a difference of 1.8% (SD=2.3) in the ITT sample, which favoured MOC.
MOC versus tricyclic antidepressants (23 studies): there was a difference of -1.2% (SD=2.0) in the AT sample, which favoured the tricyclics.
Elderly patients.
MOC versus active comparator (5 studies): there were differences of 1.3% (SD=7.6) and 6.3% (SD=8.4) in the ITT and AT samples, respectively, which favoured MOC.
Safety.
During acute phase therapy there were no significant differences between MOC and placebo for any of the serious adverse events. The most frequent and (relative to placebo) significantly greater reported adverse events were dizziness, nausea and insomnia. MOC was generally better tolerated than tricyclic antidepressants, except for the increased incidence of nausea and insomnia; MOC therapy resulted in significantly more complaints of headaches and insomnia.
During continuation or maintenance therapy, 3 studies showed that MOC was associated with sustained response rates that would have definitely surpassed those observed in placebo-controlled discontinuation designs. Although prophylaxis against recurrent depression has not been established empirically, the favourable tolerability of MOC observed during continuation phase therapy was promising when compared with longer-term studies of older MAOIs.