[Monoamine oxidase inhibitors].

Monoamine Oxidase Inhibitors DEAR SIR, Dr Pare's article on †̃¿ The Present Status of Monoamine Oxidase Inhibitors' is one of a genre that marks the renaissance of these drugs (Murphy et al, 1984; White & Simpson, 1985). This is understandable given that the †̃¿ second generation' compounds are less exciting than hoped, that early use of phenelzine was often with inadequate dosage and that improved diagnostic criteria give some (still scanty) hope that the elusive †̃¿ MAO' responder might be found. There appears also to be a naive and wishful assumption that because their therapeutic potential may have been underestimated the side effects of MAO! were exaggerated. It would be more logical to conclude that adequate dosage and effective treatment might also increase the incidence of side effects above placebo level. This point may be illustrated by referring back to the original work that Professor Marley and I con ducted during a three year period, more than 20 years ago (Blackwell et a!, 1967). A careful epidemiologic assessment of the risk for hyper tensive crises in the contained population of a single hospital revealed that 8% of patients on tranylcy promine experienced the problem compared to l5% ofthose on phenelzine. Analysis of prescribing data showed that episodes on phenelzine occurred at higher dosage after longer duration of treatment, suggesting what has now been confirmed about the significance of adequate treatment. This observation was used as the basis for a carefully conducted clini cal pharmacology experiment in which the hyper tensive effects were shown to be related to the duration of treatment, proximity and dosage of phenelzine antecedent to a food challenge. A recent prospective controlled comparison (Rabkin et al, 1984) was made of the incidence of serious side effects in patients taking phenelzine, imipramine or placebo. Like the earlier study (Blackwell et al, 1967) it was conducted in a university research clinic by experts in psychopharmacology. The incidence of hypertensive crisis on phenelzine was exactly the same (8%) as previously reported with tranylcypromine. Eleven patients suffered a hypertensive crisis of whom six ate tyramine con taming foods †̃¿ despite meticulous dietary review and cautioning' and three took ephednne-containing medication. Four of the eleven patients obtained emergency medical treatment and a fifth was hospitalised in coma with intracranial bleeding due to an unsuspected aneurysm. What may happen in less carefully supervised environments is suggested by a report from a British counseling service (Wright, 1978). Despite warnings about foodstuffs and cold remedies thirty-five out of one hundred and nineteen patients suffered hypertensive crises ofwhich four were fatal. Wide discrepancies in the reported incidence of side effects are contributed to by pendulum swings from early over-reporting to later under-reporting. The way to truth is not to average good and bad data (gleaned from meaningless prescribing statistics and manufacturers myopic files) but to sift the wheat from the chaff. Based on the (to my knowledge) only 2 carefully conducted studies my own conclusions differ markedly from Dr Pare's view that the risk of hypertensive crisis has been exaggerated. These conclusions are: 1. In carefully observed university settings patients treated with adequate therapeutic dosages of an MAO! and warned to avoid foodstuffs and ephedrine medications the risk of hypertensive crisis is 1 in 12(8%). 2. It is impossible to predict which individual patients will be compliant (Blackwell, 1976) but about half will have unavoidable memory lapses. Fear-provoking messages are not likely to reduce the problem since they often facilitate forgetting. 3. Any patient with adequate MAO inhibition will experience hypertension if he ingests enough tyramine or any of the indirectly acting amines. A majority of these will remain unaware of raised blood pressure but a small minority will suffer serious consequences. The risks of MAO inhibitors are not confined to this one side-effect. In the study cited above (Rabkin et a!, 1984) the incidence of severe side effects was 14% on placebo, 27% on imipramine and 64% on