Psychiatric side effects associated with the ten most commonly dispensed prescription drugs: a review

Journal of Family Practice, August, 1991 by John R. Hubbard, James L. Levenson, Graham A. Patrick

Zantac, Tagamet

GENERIC-RANITIDINE; CIMETIDINE

General Information. Ranitidine is commonly administered in one 150-mg dose every 12 hours, while cimetidine is administered in a 300-mg dose 3 to 4 times per day.[7,11] These drugs are used in the therapy of duodenal (and some gastric) ulcers, Zollinger-Ellison syndrome, and for prophylaxis of stress ulcers (eg, after surgery, bums, and trauma).[2,11] Ranitidine and cimetidine decrease the concentration and volume of acid secreted by gastric parietal cells by acting as histamine [H.sub.2]-receptor antagonists. Cimetidine (more than ranitidine) is also known to inhibit hepatic cytochrome P-450 and P-448 mixed-function oxidase (MFO) enzyme systems, thereby altering the metabolism of certain drugs.[7]

POTENTIAL PSYCHIATRIC SIDE EFFECTS

** Mania and aggressiveness

** Sexual dysfunction including decreased

libido

(******) Confusion, delirium, or psychosis

* Depression

Discussion. There are many reports (mostly case reports) of [H.sub.2]-receptor antagonists having adverse psychiatric side effects. The elderly and those with serious medical illness appear to be at highest risk. Mania, including aggressive behavior, has been particularly noted[43-49] a few days after initiating treatment, with return of adverse symptoms with drug rechallenge.[43,48] A few cases of depression have also been noted, although no drug rechallenge results have been reported to help confirm this possible effect.[50-53]

Confusion, delirium, and psychosis secondary to use of these [H.sub.2]-receptor antagonists have also been reported. Case studies have noted confusion with ranitidine[45,54-57] and cimetidine[53,56-63] especially in the elderly.[57] In a small placebo-controlled trial, no instances of confusion were noted with ranitidine use,[64] but negative results are not surprising given the low incidence of this adverse effect. Psychosis with auditory and visual hallucinations with use of these drugs has also been reported.53-66] For example, a 72-year-old woman reported visual hallucinations when ranitidine therapy was initiated.[65] Supportive evidence was provided when symptoms, including both auditory and visual hallucinations, returned with drug rechallenge. Psychosis can also occur in younger patients, as with a 14-year-old girl with no history of a psychiatric disorder or drug abuse who had hallucinations 3 days after cimetidine treatment was started.[66] The effect was reversed within 24 hours of discontinuing the drug.

Sexual dysfunction with decreased libido, as well as impotence and gynecomastia, have been noted in several cases with cimetidine use.[68-70] This effect appears to be dose related. Rechallenge leads to recurrence of sexual dysfunction.[70] While doses used to treat duodenal ulcers do not appear to cause impotence, in a study of 22 men on high dose cimetidine (3.5 times the amount used in duodenal ulcer therapy), about 50% subjectively reported sexual problems secondary to drug therapy even though only three men had abnormal nocturnal penile tumescence.[68]