Maprotiline Hydrochloride

• Major depressive disorder

Maprotiline hydrochloride tablets are indicated for the treatment of depressive illness in patients with depressive neurosis (dysthymic disorder) and manic depressive illness, depressed type (major depressive disorder). Maprotiline is also effective for the relief of anxiety associated with depression

N/A

Maprotiline hydrochloride tab lets are contraindicated in patients hypersensitive to maprotiline and in patients with known or suspected seizure disorders. It should not be given concomitantly with monoamine oxidase (MAO) inhibitors. A minimum of 14 days should be allowed to elapse after discontinuation of MAO inhibitors before treatment with maprotiline is initiated. Effects should be monitored with gradual increase in dosage until optimum response is achieved. The drug is not recommended for use during the acute phase of myocardial infarction.

The mechanism of action of maprotiline is not precisely known. It does not act primarily by stimulation of the central nervous system and is not a monoamine oxidase inhibitor. The postulated mechanism of maprotiline is that it acts primarily by potentiation of central adrenergic synapses by blocking reuptake of norepinephrine at nerve endings. This pharmacologic action is thought to be responsible for the drug's antidepressant and anxiolytic effects.

Close supervision and careful adjustment of dosage are required when administering maprotiline concomitantly with anticholinergic or sympathomimetic drugs because of the possibility of additive atropine-like effects. Concurrent administration of maprotiline with electroshock therapy should be avoided because of the lack of experience in this area.Caution should be exercised when administering maprotiline to hyperthyroid patients or those on thyroid medication because of the possibility of enhanced potential for cardiovascular toxicity of maprotiline.Maprotiline should be used with caution in patients receiving guanethidine or similar agents since it may block the pharmacologic effects of these drugs.The risk of seizures may be increased when maprotiline is taken concomitantly with phenothiazines or when the dosage of benzodiazepines is rapidly tapered in patients receiving maprotiline.Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), as has occurred red with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases

Cardiovascular: Rare occurrences of hypotension, hypertension, tachycardia, palpitation, arrhythmia, heart block, and syncope have been reported with maprotiline.Psychiatric: Nervousness (6%), anxiety (3%), insomnia (2%), and agitation (2%); rarely, confusional states (especially in the elderly), hallucinations, disorientation, delusions, restlessness, nightmares, hypomania, mania, exacerbation of psychosis, decrease in memory, and feelings of unreality Neurological: Drowsiness (16%), dizziness (8%), tremor (3%), and, rarely, numbness, tingling, motor hyperactivity, akathisia, seizures, EEG alterations, tinnitus, extrapyramidal symptoms, ataxia, and dysarthria.Anticholinergic: Dry mouth (22%), constipation (6%), and blurred vision (4%); rarely, accommodation disturbances, mydriasis, urinary retention, and delayed micturition.Allergic: Rare instances of skin rash, petechiae, itching, photosensitization, edema, and drug fever.Gastrointestinal: Nausea (2%) and, rarely, vomiting, epigastric distress, diarrhea, bitter taste, abdominal cramps and dysphagia.Endocrine: Rare instances of increased or decreased libido, impotence, and elevation or depression of blood sugar levels.

Pregnancy Category B. Reproduction studies have been performed in female laboratory rabbits, mice, and rats at doses up to 1.3, 7, and 9 times the maximum daily human dose respectively and have revealed no evidence of impaired fertility or harm to the fetus due to maprotiline. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.Labor and Delivery: Although the effect of maprotiline on labor and delivery is unknown, caution should be exercised as with any drug with CNS depressant action.Nursing Mothers: Maprotiline is excreted in breast milk. At steady-state, the concentrations in milk correspond closely to the concentrations in whole blood. Caution should be exercised when maprotiline hydrochloride is administered to a nursing woman.

The possibility of suicide in seriously depressed patients is inherent in their illness and may persist until significant remission occurs. Therefore, patients must be carefully supervised during all phases of treatment with maprotiline, and prescriptions should be written for the smallest number of tablets consistent with good patient management. Hypomanic or manic episodes have been known to occur in some patients taking tricyclic antidepressant drugs, particularly in patients with cyclic disorders. Such occurrences have also been noted, rarely, with maprotiline. Prior to elective surgery, ma protiline should be discontinued for as long as clinically feasible, since little is known about the interaction between maprotiline and general anesthetics. Maprotiline should be administered with caution in patients with a history of urinary retention, or a history of narrow-angle glaucoma because of the drug’s anticholinergic properties.