A male patient has been treated with Nardil (phenelzine), with a special license, for some years. T

Fråga: A male patient has been treated with Nardil (phenelzine), with a special license, for some years. The patient was hypertensive before the treatment and is still hypertensive. The physician does not think that this could be a side-effect. Plans have been made to treat the patient´s hypertension with a calcium channel blocker (verapamil or nifedipine). Are there any interactions between these drugs?

Sammanfattning: Very limited experience regarding verapamil-phenelzine interaction is available, but concomitant treatment with both drugs seems to be possible.

Svar: MAO-inhibitors, such as phenelzine, were withdrawn from the market in Sweden many years ago due to the number and severity of the side-effects. One of the most common is a hypertensive crisis, which is infrequent if the treatment is well-controlled and the patient follows diet recommendations (1,2,3).

There is a lack of information about interactions between MAO-inhibitors and new drugs (1), and no references about kinetic or clinical interactions between calcium channel blockers and MAO-inhibitors (4,5) have been found.

In 1985 Dubovsky (6) published a case report of a severely depressed woman, who did not respond to tricyclic antidepressants, and was treated with phenelzine. She developed hypomania even with low doses. Manic symptoms abated when the antidepressant was discontinued, but the patient remained depressed. The patient was treated with verapamil (400 mg/day) or placebo (in a double-blind manner) in combination with phenelzine. During treatment with verapamil and phenelzine the patient´s condition improved without any manic symptoms, whereas during the placebo treatment psychiatric test scores worsened. No side-effects developed during the eight month period of control, although depression did not resolve fully until verapamil and phenelzine were administered for a total of 2.5 months.

Antimanic effects have been described with verapamil but not with other calcium-antagonists (diltiazem, nifedipine). There are some case-reports of depression associated to calciumantagonists reported to the WHO International Center for Drug Monitoring (personal communication), and such a relationship is now under study ("Depression associated with diltiazem"; manuscript). There is not enough biochemical knowledge about the mechanism of depression possibly caused by calciumchannel blockers or the antimanic effect of verapamil, neither about why these effects are present in some patients and not in others. The documentation of an interaction between phenelzine and calciumchannel blockers is limited to this very case report.

It has been known for a long time that MAO-inhibitors can moderately potentiate the effect of thiazides (7). The use of such diuretics could also be a choice in the treatment of this patient under careful control. 1 Goodman and Gilman, The pharmacological basis of therapeutics. 1980; 6th ed: 427-430 2 Sjöqvist F: Toxic interactions between monoamine oxidase inhibitors (MAOI) and other drugs. Proceedings of the 3rd International Pharmacological Meeting July 24-30, 1966; 10: 61-74 3 Drugline nr 04058 4 Hansten PD, Horn JR: Nifedipine-H2 antagonist interactions. Drug Interact Newslett 1987; 7: 49-52 5 Hansten PD, Horn JR: Calcium channel blocker-induced drug interactions: evidence for metabolic inhibition. Drug Interact Newslett 1986; 6: 35-40 6 Dubovsky SL, Franks RD, Schrier D: Phenelzine-induced hypomania: effect of verapamil. Biol Psychiatry 1985; 20: 1009-1014 (bifogas) 7 Goldberg LI: Monoamine oxidase inhibitors. JAMA 1964; 190: 456-462