Adverse reactions to five new antidepressants.

Postmarketing adverse drug reaction reports for amoxapine, maprotiline hydrochloride, and trazodone hydrochloride and premarketing adverse drug reaction data for bupropion hydrochloride and nomifensine maleate are reviewed, and the role of the new agents in the management of depressive illness is discussed. Nomifensine was withdrawn from markets worldwide because of reports of serious hypersensitivity reactions, especially hemolytic anemia, and marketing of bupropion in the United States was delayed after seizures occurred in bulimic patients in clinical trials. Amoxapine and maprotiline, when taken in overdose attempts, are more toxic and cause more serious central nervous system reactions than the standard tricyclics. Acute renal failure and an increased mortality rate are associated with amoxapine overdose. Amoxapine causes several acute and chronic untoward neurologic and endocrine reactions not commonly associated with the standard tricyclics. For maprotiline and bupropion, maximum doses have been established because of dose-related seizures. Trazodone has minimal effect on cardiac conduction; its main cardiovascular effects are hypotension, orthostasis, and dizziness. The trazodone package insert has been revised to warn of priapism; patients with prolonged or inappropriate penile erections are instructed to discontinue the drug and notify the physician. Serious cardiovascular and neurologic toxicities are rare with trazodone overdose. Of the newly marketed antidepressants, only trazodone offers some advantages over the tricyclic and tetracyclic agents in the areas of side effects and toxicities. The number and type of patients exposed to a new drug during clinical trials is too small for detection of rare but potentially serious adverse effects.

Effect of ibuprofen on lithium plasma and red blood cell concentrations.

The effect of ibuprofen on steady-state lithium plasma and red blood cell concentrations was studied in 11 normal volunteers. During the seven-day control phase, sustained-release lithium carbonate 450 mg was administered every 12 hours. Lithium plasma and red blood cell concentrations were determined on days 5, 6, and 7. During the treatment phase (days 7-15), ibuprofen 400 mg was administered four times a day concurrently with lithium. Lithium plasma and red blood cell concentrations were obtained on days 14, 15, and 16. Multiple blood samples were obtained over a 12-hour period on days 6 and 15. Urine samples were collected from six subjects. The mean minimum lithium concentration increased 15% when ibuprofen was added. Mean maximum lithium concentration, area under the curve, red blood cell concentrations, and the lithium red blood cell to plasma ratio were significantly higher during the treatment phase. Mean lithium total body and renal clearance values were significantly lower during the treatment with ibuprofen. The administration of ibuprofen can increase steady-state plasma lithium concentrations and decrease lithium clearance.