Prophylaxis of Bipolar Affective Disorders

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Abstract
While lithium carbonate remains the treatment of choice for bipolar affective disorders, there is increasing recognition that a substantial proportion of patients do not show a complete response. Although unimodal antidepressants and neuroleptics were used almost exclusively a decade ago for respective breakthrough episodes of depression and mania occurring during lithium prophylaxis, a new series of treatment alternatives, particularly the anticonvulsants, has become available. Increasing evidence suggests that carbamazepine, when used either adjunctively or, in some instances, alone, may provide adequate prophylaxis for the lithium non-responder. Preliminary evidence indicates that some variables that are highly associated with lithium non-response (such as rapid cycling) may be associated with a good response to carbamazepine or valproate. Response to one anticonvulsant agent does not appear to predict response to another, and we have observed some patients who responded to carbamazepine and not valproate, and vice versa. There are relatively few data on clinical and biological markers of response to lithium compared with the anticonvulsants, and virtually no data indicating responsivity among the anticonvulsants or marking those patients who require combination therapy. Preliminary data suggest that novel strategies such as thyroid potentiation with suppressive doses or use of calcium channel blockers may also be of clinical utility in the treatment of the refractory bipolar patient. The author emphasizes the recurrent and, at times, malignantly progressive nature of manic-depressive illness and the need for early recognition and prophylaxis in the hope of halting this progression. Two preclinical models, those of behavioral sensitization to psychomotor stimulants and electrophysiological kindling, are presented for their heuristic value in assessing possible principles underlying the progressive evolution of psychopathological and neuropathological syndromes. These data further suggest the importance of early intervention as well as the possibility that pharmacotherapeutic responsiveness may vary as a function of when in the stage of evolution of an illness one intervenes. A series of possible explanations for loss of efficacy to drugs that were initially effective in the treatment of manic-depressive illness is also discussed.