Maprotiline

 ( Alpha-1 Blockers ) 

• Dizziness
• Drowsiness
• Somnolence
• Fatigue
• Xerostomia (and complications of long-term uncontrolled dry mouth such as dental caries)
• Constipation
• Vertigo
• Nausea (rare, incidence of ~2%) and vomiting
• Increased appetite and weight gain
• Orthostatic hypotension, hypertension, sinus tachycardia, heart-block, arrhythmias and other cardiac effects
• Sexual dysfunction in men: impotence, priapism, delayed ejaculation, anejaculation, decreased libido
• Sexual dysfunction in women: decreased libido, vaginal dryness, Dyspareunia, anorgasmia
• Allergic skin reactions such as rash or urticaria (more often than with other antidepressants). Rarely, severe skin reactions such as erythema multiforme can occur.
• Photosensitivity
• Agitation, confusion
• Induction of hypomania or mania in patients with underlying bipolar affective disorder
• Psychotic symptoms
• Tremor
• Extrapyramidal symptoms
• Headache
• (at high doses)
• Rare haematological complications: leukopenia and agranulocytosis (dangerous fall in white blood cells)
• Fever
• Urinary retention

Maprotiline causes a strong initial sedation (first 2 to 3 weeks of therapy) and is therefore indicated to treat agitated patients or those with suicidal risks. It causes anticholinergic side effects (dry mouth, constipation, urinary hesitancy, etc.) with much lower incidence than amitriptyline. Originally, the manufacturer claimed that maprotiline is better tolerated than other TCAs and TeCAs. However, seizures, leukopenia and skin reactions occur more often with maprotiline than with comparable drugs (e.g., amitriptyline, protriptyline, mirtazapine). Indeed, seizures are greater risk for concern with maprotiline than with all other tricyclic antidepressants (rising from 75 mg, becoming significant at daily doses ≥ 200 m.g.), including clomipramine. It should thus be prescribed with particular, if not extreme, caution to people with a history of epilepsy/seizures of any other kind. In any case, the total daily dose should be kept to ≤ 225 milligrams.

Maprotiline has no known potential for abuse and psychological dependence.

Increased drug actions:

• Other antidepressants, barbiturates, narcotics, sedating antihistamines, anticonvulsive drugs, alcohol resulting in increased central depression and necessitating some caution when using any of these drugs alongside maprotiline
• Drugs with potential anti-muscarinic/anti-cholinergic activity (antiparkinsonian agents, atropine, amantadine, clozapine and tricyclic antidepressants besides maprotiline) resulting in increased anti-muscarinic effects (dry mouth, constipation, etc.)
• Sympathomimetics (also those used in local anesthetics like noradrenaline) sympathomimetic effects increased (increased blood-pressure, pulse-rate, paleness of skin, etc.)
• Nitrates and antihypertensives (e.g., beta-blockers) increased antihypertensive action with pronounced fall in blood pressure

Although concurrent administration of tricyclic antidepressants (likewise with SSRIs) and MAOIs has been considered particularly dangerous, even fatal, across various medical and pharmaceutical lines across the decades, the premise for this line of thinking, although commonly accepted, may be erroneous. Specialist-research into this and practical clinical experience involving the co-administration of tricyclics and MAOIs have suggested that it is only tricyclics with strong specific serotonin-reuptake inhibitory action (clomipramine and, to a lesser extent, imipramine) that are dangerous to give in combination with MAOIs. Other antidepressants; which may or may not have a significant serotoninergic background otherwise but either way lack in particularly appreciable reuptake-inhibition therein specifically (e.g., mirtazapine, amitriptyline, trazodone, lofepramine, nortriptyline); may be safe to take alongside MAOIs, where the likes of venlafaxine, SSRIs and clomipramine are not. With maprotiline, this has been demonstrated to be the case with moclobemide, a drug it is often compared and considered somewhat analogous (along certain lines) to, and, tentatively, brofaromine (a research-agent MAOI which was never brought to full marketing development). Moclobemide specifically, however, may increase maprptiline plasma-levels and may necessitate dose-modification(s).

In any case, however, it is very-strongly advised that an MAOI is added to the (compatible) tricyclic and not the other way around, as adding a tricyclic to an existing treatment-regime involving an MAOI may significantly increase the risk of going into hypertensive crisis.

Decreased drug actions:

• Guanethidine, reserpine, guanfacine: anti-hypertensive effects decreased
• Clonidine: anti-hypertensive effects decreased and risk of (massive) rebound hypertension.

Other types of interaction:

• Drugs which induce certain enzymes in the liver, e.g., barbiturates, phenytoin, carbamazepine and oral anti-conceptive drugs, enhance the elimination of maprotiline and decrease its antidepressant effects. Additionally the blood-concentrations of phenytoin or carbamazepine may be increased, leading to a higher incidents of side effects.
• The concomitant use of maprotiline and antipsychotics can lead to increased maprotiline blood-levels and to seizures. Combining maprotiline and thioridazine could induce severe arrhythmias.
• Additionally, increased blood-levels of maprotiline are possible, if certain beta-blocking agents (e.g., propranolol) are given concomitantly.
• Maprotiline may amplify the actions of coumarin-type anticoagulants (e.g., warfarin, phenprocoumon). The plasma-prothrombin-activity must be assessed closely in order to avoid overt bleedings.
• Maprotiline can increase the actions of oral antidiabetic drugs (sulfonylureas) and insulin. Diabetic patients should have regular assessments of their blood-glucose-levels.
• The concomitant application with fluoxetine or fluvoxamine may lead to significantly increased plasma-levels of maprotiline, with a correspondingly (and substantially) incidence of maprotiline side effects. Owing to the long half-lives of fluoxetine and fluvoxamine, this effect may persist for quite-some time.

Maprotiline exhibits strong effects as a norepinephrine reuptake inhibitor with only weak actions for the reuptake of serotonin and dopamine. It is also a strong antagonist of the H₁ receptor, a moderate antagonist of the 5-HT₂ and α₁-adrenergic receptors, and a weak antagonist of the D₂ and muscarinic acetylcholine receptors. Maprotiline has also more recently been identified as a potent antagonist of the 5-HT₇ receptor, with this action potentially playing an important role in its antidepressant effectiveness. The drug is a strong antihistamine, but unlike most TCAs, has minimal anticholinergic effects.