Är tranylcypromin mindre neurotoxiskt än isocarboxazid?

Fråga: Är tranylcypromin mindre neurotoxiskt än isocarboxazid?

Sammanfattning: It has not been documented in the literature that tranylcypromine may cause symptoms of paraesthesia of the extremities. In spite of its different structure it is usually considered to produce qualitatively similar toxic effects as the hydrazine-group MAOI which has documented neurotoxic effects. In our view this suspicion is not well founded. The possibility of this side-effect in patients on tranylcypromine should nevertheless be kept in mind by close monitoring of symptoms.

Svar: The most frequent side-effects of tranylcypromine ranging from 5 to 12 per cent of the patients treated are those of the central stimulating and cardiovascular effects, as insomnia, dizziness, headache, agitation, hypotension and palpitation. Then, the other less common side-effects include dry mouth, weakness, anxiety, fatigue and gastrointestinal reactions. Rare effects are edema, blurred vision, chills, impotence,skin rash and hepatitis (1). In addition, the incidence of paradoxical hypertensive crisis due to monoamine oxidase inhibition by tranylcypromine may be higher than for other MAO-inhibitors (2). Deaths have been reported with the administration of this drug due to hyperthermia and circulatory collapse (3) and to cerebral haemorrage secondary to antihypertensive crisis.

Peripheral neuropathic symptoms including sensory defects as numbness, tingling, or burning of the extremities or face have been reported to be caused by a variety of commonly used drugs. Most antidepressants of the tricyclic group as imipramine and amitriptyline, the hydrazine-group monoamine oxidase inhibitors (MAOI) as phenelzine and the hydrazidegroup MAOI as iproniazide, and non MAOI hydrazides as isoniazide were claimed to be among this group of neurotoxic drugs (4). We cannot find any reports in the literature that an antidepressant with a chemical structure related to amphetamine such as tranylcypromine caused paresthesia symptoms of the extremities. However, Maling et al (5) in an exclusive animal study found that centrally mediated neurologic effects as tremor, nystagmus and ataxia were produced by hydrazinegroup MAOI phenelzine and hydrazidegroup MAOI isocarboxazide, nialamide, iproniazide as well and that tremor and ataxia but not nystagmus were produced by non MAOI amphetamine and isoniazid. These symptoms were unrelated to the elevated serotonin or other monoamine levels in the brain and were not prevented by prior administration of pyridoxine. In another study by Levy it was demonstrated that drug-induced peripheral neuropathy in human by isoniazid administration was related to the formation of hydrazone in the body which inhibited the enzyme pyridoxal kinase resulting in vitamin B6 deficiency.

Since tranylcypromine is usually considered to produce qualitatively similar toxic effects as phenelzine (2), the possibility of its producing neuropathic symptoms either via central or via peripheral mechanism awaits further investigation.