Bipolar disorder is prevalent, with high risks of disability, substance abuse and premature
mortality. Treatment responses typically are incomplete, especially for depressive components, so that
many cases can be considered “treatment resistant.” We reviewed reports on experimental treatments
for such patients: there is a striking paucity of such research, mainly involving small incompletely
controlled trials of add-on treatment, and findings remain preliminary. Encouraging results have been reported by adding
aripiprazole, bupropion, clozapine, ketamine, memantine, pramipexole, pregabalin, and perhaps tri-iodothyronine in
resistant manic or depressive phases. The urgency of incomplete responses in such a severe illness underscores the need
for more systematic, simpler, and better controlled studies in more homogeneous samples of patients.