The great majority of data on the efficacy of putative mood stabilizers in bipolar disorder is derived from monotherapy studies, while in actual treatment settings, most patients receive more than one medication. Academic psychiatry, unlike the rest of medicine, has traditionally referred to combined treatment as“polypharmacy,” a term often viewed as derogatory. The research community's preference for monotherapy trials (they are methodologically “cleaner”) is shared by the pharmaceutical industry (the source of most support for clinical trials in psychopharmacology) for an additional reason-FDA policy in the neuropharmacology division has strongly favored monotherapy trials.
This presentation will focus on new data on the effects of mood stabilizers (particularly lithium and the anticonvulsants) involving the postsynaptic signal transduction cascade, which suggests that lithium and the anticonvulsant divalproex may act synergistically in their beneficial effects. If so, this would further suggest that the lithium-divalproex combination might be effective at doses of each drug well below the usual monotherapy dose. Viewed in this light, the recent report that compliance is greater with the combination of lithium plus divalproex, rather than with either monotherapy, is not counter-intuitive.