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Maprotiline: A Review of its Pharmacological Properties and Therapeutic Efficacy in Mental Depressive States

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Summary

Maprotiline1, 1-(3-methylaminopropyl) dibenzo(b,e) bicyclo (2.2.2) octadiene, is a tetracyclic drug, distinguished from conventional tricyclic antidepressants only by the rigid flexure of itsmolecular skeleton. In contrast to amitriptyline or imipramine, maprotiline has sedative and tranquillising properties in animals, appears to have negligible effects on the cardiovascular system in man, and does not influence the central metabolism of 5-hydroxytryptamine. It is indicated for use in the treatment of all types of mental depression or depressive mood disorders, but seems to offer no compelling advantages over the tricyclic antidepressants.

Maprotiline is slowly and completely absorbed following oral administration in man. Its blood half-life is about two days, and dose-dependent steady-state blood levels are attained after one week of repeated administration. Maprotiline is slowly eliminated, principally as metabolites and mostly as glucuronides, with about two-thirds of the dose appearing in the urine and one-third in the faeces. In limited placebo-controlled trials in mixed groups of patients with various types of depression maprotiline has not been shown to be superior to placebo.

Controlled trials under standardised conditions in hospital inpatients, outpatients attending hospital clinics, and in depressed patients in general practice, have generally failed to find a significant difference between the antidepressant effects of maprotiline and those of amitriptyline or imipramine, though some trials have suggested that maprotiline is more rapid in its action. Maprotiline appears to have a broad spectrum of activity in the various types of depression, producing significant improvement in about two-thirds of both agitated and retarded patients, though it may be more effective in cases of neurotic depression than in those of the endogenous type. In a comparative trial as prophylactic treatment for affective disorders, maprotiline was significantly inferior to lithium carbonate over one year.

Maprotiline causes side-effects similar to those of the tricyclic antidepressants, principally drowsiness and dry mouth. Skin rashes have been markedly more prominent with maprotiline, but in controlled trials there has generally been little to distinguish the drug from amitriptyline or imipramine in terms of the overall incidence and severity of side-effects. Its potential for accidental or suicidal overdosage seems to be similar to that of the tricyclic antidepressants.

Maprotiline is usually given orally, though treatment may be initiated by the intravenous or intramuscular routes in cases of severe depression or when a particularly rapid effect is desired. The initial dose in depression in 25mg 3 times daily, or more usually 75mg at night, with twice that amount in more severe or resistant cases. Patients with depressive mood disorders, as well as the young or elderly, may receive 10mg 3 times daily increasing to 25 or 50mg as necessary. The usual range of daily dosage in depression is 75 to 150mg, and it may be advantageous to give this as a single dose taken at night. Depressive inpatients may need at least 150mg daily, and this dose should probably be given from the first day of treatment.

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  1. Australasian Drug Information Services, P.O. Box 34-030, Birkenhead, Auckland 10, New Zealand

    R. M. Pinder, R. N. Brogden, T. M. Speight & G. S. Avery

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  1. R. M. Pinder
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  2. R. N. Brogden
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  3. T. M. Speight
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  4. G. S. Avery
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Manuscript reviewed by: G.D. Burrows, Department of Psychiatry, University of Melbourne, Royal Melbourne Hospital, Victoria, Australia. J.G. Claghorn, Texas Research Institute of Mental Sciences, Houston, Texas, USA. L.E. Hollister, Veterans Administration Hospital, Palo Alto, California, USA. P. Kielholz, Psychiatrische Universitatsklinik, Basel, Switzerland. H. E. Lehmann, Department of Psychiatry, McGill University, Montreal, Canada.

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Pinder, R.M., Brogden, R.N., Speight, T.M. et al. Maprotiline: A Review of its Pharmacological Properties and Therapeutic Efficacy in Mental Depressive States. Drugs 13, 321–352 (1977). https://doi.org/10.2165/00003495-197713050-00001

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  • DOI: https://doi.org/10.2165/00003495-197713050-00001

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