Addition of monoamine oxidase inhibitors to carbamazepine: preliminary evidence of safety and antidepressant efficacy in treatment-resistant depression.

BACKGROUND: Depression is often resistant to treatment with mood stabilizers. The antidepressant effects of carbamazepine can be potentiated by lithium supplementation, but some patients fail to respond to the combination. Although monoamine oxidase inhibitors (MAOIs) appear useful in atypical and bipolar depressions, concerns have been raised regarding safety and pharmacokinetic interactions when they are combined with carbamazepine.
METHOD: Ten inpatients (7 bipolar, 3 unipolar) with refractory DSM-III-R major depression, also resistant to double-blind treatment with carbamazepine, plus lithium augmentation in 8, received double-blind MAOI augmentation (phenelzine in 4, tranylcypromine in 6).
RESULTS: All 10 patients tolerated the addition of an MAOI well, and mean self-rated side effect scores did not change significantly. Four of 10 patients improved substantially and became euthymic, allowing discharge from hospital on the carbamazepine +/- lithium plus MAOI combination. These 4 patients improved in spite of prior inadequate responses to the same MAOI without carbamazepine and carbamazepine without an MAOI.
CONCLUSION: This preliminary evidence suggests that the addition of MAOIs to carbamazepine +/- lithium may be well tolerated, may not affect carbamazepine and lithium pharmacokinetics, and may provide relief of refractory depressive symptoms in some patients. Further studies are needed to establish the safety and efficacy of combining carbamazepine with MAOIs.