The induction of mania. A natural history study with controls

Previous reports have indicated that tricyclic antidepressants (TCAs) induce mania, but the studies suffer from lack of control groups. This study included 137 unipolar and 157 bipolar patients, all having two or more admissions to the same hospital. In many cases, the same patients were treated at one time with TCAs and at another time with no somatic therapy at all. Most patients who switched (20/23) were bipolar. Twenty-seven bipolar patients receiving no treatment had a 41% switch rate (rate/person). They had 32 admissions, and the rate of switch while receiving no treatment was 34% (rate/admission). Twenty-six patients receiving tricyclics had a 28% switch rate; for these, there were 30 admissions and the switch rate was 23%. Thus, it appears that the rate of induction of mania by TCAs is not greater than what one would expect from the natural history of the illness itself. Validity of these findings is attested to by the fact that lithium carbonate and neuroleptic treatment, as expected, significantly prevented the induction of mania.