Interaction between disulfiram and antidepressant drugs.

Fråga: Interaction between disulfiram and antidepressant drugs.

Sammanfattning: Seller et al (1) state that disulfiram should not be used with antidepressant drugs (tricyclic or monoamine oxidase inhibitors). It does appear, however, that the combination can be used without adverse effects, but that patients should be closely monitored because of the risk of serious toxicity. But the therapeutic objectives in using both types of drug should be carefully assessed for each patient.

Svar: The unpleasant symptoms experienced after drinking alcohol when taking disulfiram are considered to be due to the accumulation of acetaldehyde, whose oxidation by liver aldehyde dehydrogenase is blocked by disulfiram (1). Disulfiram also inhibits other enzymes, giving it the potential to interact with antidepressant drugs. It inhibits dopamine-beta-hydroxylase, causing increased levels of dopamine and decreased noradrenaline (1). It has also been shown to inhibit monoamine oxidase in rat liver mitochondria (2). Therefore, one might expect interactions between disulfiram and antidepressants, whose actions are believed to depend on alterations in brain amine activity. Disulfiram is also known to decrease the oxidative metabolism of several drugs (1) and may also inhibit antidepressant elimination although there are no direct data on this.

Maany et al (3) reported two cases of acute organic brain syndrome which were apparently related to the combined use of disulfiram and amitriptyline. These conditions developed one and four weeks after amitriptyline was added to disulfiram therapy, and improved rapidly on discontinuing either amitriptyline or both drugs. In one case the drug levels in blood were determined, and were found to be below the normal range.

On the other hand, in a trial treatment of depression in disulfiram taking alcoholics, chlordiazepoxide (40 mg) and imipramine (150 mg) were given daily to 15 patients for one month without adverse effects (4 and comment in 3). MacCallum (5) noted a clinical impression that amitriptyline (25 mg tds) potentiates the disulfiram-alcohol reaction without interacting with disulfiram alone.

Another consideration is that depression is associated with alcohol abuse, and may be exacerbated by disulfiram and that antidepressants should be used only for endogenous depression (1). That is, there may be a risk of using antidepressants to treat the side effects of disulfiram. 1 Sellers EM, Naranjo CA, Peachey JE: Drugs to decrease alcohol consumption. N Engl J Med 1981; 305: 1255-1262 2 Schurr A, Ho BT, Schoolar JC: The effects of disulfiram on rat liver mitchondrial monoamine oxidase. Life Sci 1978; 22: 1979-1984 3 Maany I, Hayashida M, Pfeffer SL, Kron RE: Possible toxic interaction between disulfiram and amitriptyline. Arch Gen Psychiatry 1982; 39: 743-744 4 Shaw JA, Donley P, Morgan DW, Robinson JA: Treatment of depression in alcoholics. Am J psychiatry 1975; 132: 641-643 5 MacCallum WAG: Drug interactions in alcoholism treatment. Lancet 1969; I: 313