Phenelzine and tranylcypromine are the two most frequently used monoamine oxidase inhibitors (Table 1). These drugs inhibit both monoamine oxidase isozymes
(monoamine oxidase A and monoamine oxidase B), which raises the level of norepinephrine (noradrenaline), serotonin, and dopamine in the synaptic cleft as well as the level of exogenous monoamines taken up by the gastrointestinal tract. The therapeutic effect of monoamine oxidase inhibitors is believed to be due to the inhibition of the monoamine oxidase isozymes, leading to increased aminergic activity. Potential effects on intracellular second-messenger systems are also considered. The sympathomimetic pressor amine tyramine, delivered by food to the gastrointestinal tract, can rise to high levels during monoamine oxidase inhibitor therapy and lead to potentially lethal hypertensive crises. A tyramine-low diet is recommended in patients taking monoamine oxidase inhibitors and a washout period is necessary before starting other antidepressants, since monoamine oxidase levels return to baseline only after approximately 10 days.
Monoamine oxidase inhibitors have a very low affinity for postsynaptic receptors and therefore many of the side-effects seen with cyclic antidepressants are absent. However, insomnia is seen frequently and often requires treatment (e.g. with trazodone).
The dietary restrictions and the risk of potentially lethal hypertensive crises preclude the use of monoamine oxidase inhibitors as a first-line drug. However, depressed patients with atypical features (hypersomnia, hyperphagia, and severe psychomotor retardation to the degree of 'leaden paralysis'), anxiety, and hostility may respond better to monoamine oxidase inhibitors than to cyclic antidepressants.
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