Tranylcypromine indications

Examples of monoamine oxidase inhibitors are phenelzine, tranylcypromine, isocarboxazid and mo-clobemide. They are indicated for atypical depression. Changes in the neurotransmitter levels are seen in several days but the clinical effect may lag by several weeks. Phenelzine is a non-selective hydrazine-type monoamine oxidase inhibitor while the also non-selective inhibitor tranylcypromine is of the non-hydrazine-type. Phenelzine, tranylcypromine and isocarboxazid are irreversible inhibitors. Phenelzine is partly metabolized by acetylation and slow acetylators are more prone to toxicity. It has anxiolytic properties and superior efficiacy in treating severe anxiety. 

In the United States, the three MAOIS available for the treatment of psychiatric conditions are phenelzine (Nardil), tranylcypromine (Parnate), and isocarboxazid (Marplan). All three agents have indications for adult major depression (>16 years old) and, more specifically, atypical depression (anergia, hypersomnia, hy-perphagia, somatization, and anxiety symptoms). Although not indicated for anxiety, the MAOIs can also be particularly helpful in treatment of these disorders. Selegiline or L-deprenyl (Eldepryl) is also available in the United States and indicated for symptoms of Parkinson s disease and depression. 

Results of crossover studies indicate that lithium is efficacious in treating acute depression in bipolar subjects unequivocally (36%, 29/80) and partially (43%. 34/80). respectively (Xomberg and Pope, 1993 Keck and McElroy, 2002). Various antidepressants have shown variable rates of efficacy in the treatment of acute bipolar depression, i.e. desipramine (50%), maprotiline (67%), imipra-mine (40 60%), tranylcypromine (87%), moclobemide (53%) and fluoxetine (60%) (Keck and McElroy, 2002). Among the anticonvulsants, valproic add and lamotrigine appear to have some potential efficacy in the treatment of acute bipolar depression (Calabrese et al., 1992, 1999 Fatemi et al., 1997). 

The efficacy of phenelzine and tranylcypromine has now been well established by several large, double-blind studies, which found them equal to tertiary amine TCAs and clearly superior to placebo (Table 7-11 and Table 7-12) (185). Other studies indicate that atypical depressions may respond better to MAOIs and typical depressions to TCAs however, most find that their similarities are more obvious than their differences ( 186). One research group has suggested that anergic, bipolar patients respond particularly well to tranylcypromine and other MAOIs ( 187). Extensive clinical experience indicates the MAOIs are often effective when TCAs have failed. 

Although clinical experience indicates tranylcypromine may be an effective antipanic agent, there are no controlled trials confirming this observation. Phenelzine, however, has been found to be very effective in both open and controlled designs ( 21, 116, 117). Onset of action is similar to that of other antidepressants, and although adverse effects tend to be less troublesome than with tricyclics, dietary restrictions may limit the usefulness of MAOIs in some patients. Unfortunately, the relapse rate may be comparable to that seen with BZDs and TCAs. For example, Kelly et al., in a follow-up of 246 patients, found that 50% who had discontinued MAOIs relapsed within 1 year (118). 

It was initially believed that the antidepressant effectiveness of MAOIs was the direct result of MAO inhibition. This acute effect decreases degradation of monoamines (e.g., norepinephrine, serotonin, or dopamine) stored in presynaptic neurons, thereby resulting in an increased amount of these neurotransmitters available at the synapse. More recent research indicates that this model does not fully explain the mechanism of MAOIs efficacy. For example, the positive (h-) stereoisomer of tranylcypromine is a poor antidepressant despite inhibiting MAO. The main pharmacologic difference between the negative (-) and + isomers of tranylcypromine is that the former has much weaker effects as a norepinephrine reuptake inhibitor in relation to its potency as an MAOI. The other MAOIs may also block the reuptake of selected neurotransmitters. However, like the non-MAOI uptake inhibitors, these acute effects often precede clinical antidepressant effects by weeks. More consistent with the 2- to 4-week lag in therapeutic effect, chronic treatment with a diverse number of MAOIs has been shown to reduce the number of a2- and P-adrenergic and serotonin (5-HT2) postsynaptic binding sites in the brain. 

Tranylcypromine, a monoamine oxidase alpha inhibitor (30 mg/day in divided doses), is indicated for the treatment of depression (see Figure 37). 

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