Treatment of Pathologic Laughing and Weeping with Amitriptyline

Patients with bilateral forebrain disease may commonly manifest the syndrome of pathologic laughing and weeping. We investigated the efficacy of low-dose amitriptyline in 12 patients in whom this syndrome was a consequence of multiple sclerosis. In a double-blind crossover study comparing amitriptyline with placebo, eight patients experienced dramatic and significant improvement with amitriptyline (P = 0.02). The mean dose of amitriptyline was 57.8 mg per day and did not exceed 75 mg per day in any patient. Concurrent measurements of depression showed no change during the study. We conclude that amitriptyline is effective in the treatment of this disturbance of affective expression, and that this effect is distinct from the antidepressant effect of the medication. (N Engl J Med 1985; 312:1480–2.) Neurologic diseases that damage subcortical forebrain structures can disinhibit the motor systems for emotional expression, producing the syndrome of pathologic laughing and weeping. 1 2 3 4 5 Affected patients are contorted by paroxysms of involuntary facial expressions, such as laughing, weeping, and grimacing. 6 The emotional outbursts cannot be initiated or inhibited voluntarily. They may be triggered by relatively minor environmental events, and they correlate poorly with the underlying mood. Persons with this syndrome may be socially disabled because of disruption of an important mechanism for emotional communication. There are few reports of pharmacologic therapy for this behavioral syndrome. In patients with stroke, levodopa and . . .