Maprotiline

Uses

Maprotiline hydrochloride tablets are used 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.

Maprotiline is also used to associated treatment for these conditions: Anxiety, Depression, Dysthymic Disorder, Major Depressive Disorder (MDD), Manic depressive illness

How Maprotiline works

Maprotiline exerts its antidepressant action by inhibition of presynaptic uptake of catecholamines, thereby increasing their concentration at the synaptic clefts of the brain. In single doses, the effect of maprotiline on the EEG revealed a rise in the alpha-wave density, a reduction of the alpha-wave frequency and an increase in the alpha-wave amplitude. However, as with other tricyclic antidepressants, maprotiline lowers the convulsive threshold. Maprotiline acts as an antagonist at central presynaptic α₂-adrenergic inhibitory autoreceptors and hetero-receptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity. Maprotiline is also a moderate peripheral α₁ adrenergic antagonist, which may explain the occasional orthostatic hypotension reported in association with its use. Maprotiline also inhibits the amine transporter, delaying the reuptake of noradrenaline and norepinephrine. Lastly, maprotiline is a strong inhibitor of the histamine H₁ receptor, which explains its sedative actions.

Dosage

Maprotiline dosage

Adult: As hydrochloride: 25-75 mg daily in 3 divided doses, gradually increased in 25 mg increments at 1-2 wk intervals to 150 mg/day if necessary. Up to 225 mg/day in severely depressed patients.

Elderly: Initial: 25 mg daily. May increase slowly according to response to 50-75 mg daily if needed.

May be taken with or without food.

Side Effects

Dry mouth, constipation, blurred vision, drowsiness, dizziness, tremor, nervousness, anxiety, insomnia, agitation, confusion, nausea, weakness and fatigue, headache, CV disorders, altered liver function, changes in blood glucose concentrations, allergic skin manifestations.

Toxicity

LD₅₀=~900 mg/kg (Orally in rats); LD₅₀=90 mg/kg (Orally in women); Signs of overdose include motor unrest, muscular twitching and rigidity, tremor, ataxia, convulsions, hyperpyrexia, vertigo, mydriasis, vomiting, cyanosis, hypotension, shock, tachycardia, cardiac arrhythmias, impaired cardiac conduction, respiratory depression, and disturbances of consciousness up to deep coma.

Precaution

Urinary retention, prostatic hyperplasia, chronic constipation, untreated angle-closure glaucoma; hyperthyroidism; risk of suicide; may precipitate mania or psychotic symptoms; withdraw gradually; may impair ability to operate machinery. Pregnancy and lactation; elderly.

Interaction

Close super vision 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 a voided 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 dos age 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 occur red with tricyclic antidepressants. Adjustment of the dosage of maprotiline hydrochloride may therefore be necessary in such cases

Food Interaction

• Limit caffeine intake.
• Take with or without food.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Maprotiline Drug Interaction

Major: clozapine, duloxetineModerate: donepezil, lorazepam, diphenhydramine, albuterol / ipratropium, divalproex sodium, diltiazem, metronidazole, tamsulosin, triazolam, clonazepam, metoprolol, metoprolol, budesonide / formoterolUnknown: aspirin, ubiquinone, glucose, cyanocobalamin, cholecalciferol

Maprotiline Disease Interaction

Major: CVD, myocardial infarction, seizure disorders, anticholinergic effects, cardiovascular disease, pheochromocytoma, bipolar screening, depression, hypotension, neutropeniaModerate: urinary retention, diabetes, renal/liver disease, schizophrenia/bipolar disorder, tardive dyskinesia, glaucoma

Volume of Distribution

Maprotiline and its metabolites may be detected in the lungs, liver, brain, and kidneys; lower concentrations may be found in the adrenal glands, heart and muscle. Maprotiline is readily distributed into breast milk to similar concentrations as those in maternal blood.

Elimination Route

Slowly, but completely absorbed from the GI tract following oral administration.

Half Life

Average ~ 51 hours (range: 27-58 hours)

Elimination Route

Approximately 60% of a single orally administered dose is excreted in urine as conjugated metabolites within 21 days; 30% is eliminated in feces.

Pregnancy & Breastfeeding use

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 themaximum 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. Be cause 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.

Contraindication

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.

Acute Overdose

Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate overdose. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after overdose. There fore, hospital monitoring is required as soon as possible.

Storage Condition

Store at 20° to 25°C. Protect from light. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Innovators Monograph

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