Depression associated with cimetidine

Over the past three years we have seen twelve patients who have become depressed while taking cimetidine. Clinically the depression is similar to that seen in a Primary Affective Disorder. Two representative cases are presented. It is suggested that cimetidine has precipitated a depressive reaction in vulnerable patients. Tricyclic antidepressants are effective in relieving the depression. It is postulated that cimetidine, by blocking H2 receptors in the CNS, produces an imbalance between1 and H2. This imbalance may be an etiological factor in precipitating the depression. Tricyclic antidepressants have little effect on H2 but are potent H1 receptor blockers. This H1 blockade could restore the balance between H1 and H2, thereby relieving the depression.