There is some evidence that the hypothalamic-pituitary-thyroid axis plays a role in the pathophysiology of affective illness, particularly in patients with rapid cycling forms of manic- depressive illness, who have a very high incidence of lithium- induced hypothyroidism. Rapid cycling patients are often refractory to standard types of mood-stabilizing treatments. Since the 1930s there have been three reports that hypermetabolic doses of thyroxine suppress rapid cycling. These reports were based on uncontrolled studies. We treated seven rapid cycling patients with suppressive and hypermetabolic doses of thyroxine in a placebo controlled, double- blind study. No patient improved on suppressive doses. Two patients remitted completely on hypermetabolic doses, but both eventually relapsed after many months of treatment. This result is interesting from a theoretical point of view, but does not seem to offer any new approach to treatment for refractory rapid cycling patients. Therefore, the project has been terminated.
