Patients with bipolar affective disorder should not receive antidepressants whilst in a manic phase, as antidepressants can worsen mania. Absolute
Hypersensitivity to maprotiline or to other TCAs and TeCAs
Hypertrophy of the prostate gland with urine hesitancy
Closed angle glaucoma

Special caution needed
Concomitant treatment with a MAO inhibitor
Serious impairment of liver and kidney function
Epilepsy and other conditions that lower the seizure threshold (active brain tumors, alcohol withdrawal, other medications)
Serious cardiovascular conditions (arrhythmias, heart insufficience, state after myocardial infarction etc.) Treatment of patients under age 18

Suicidal patients
Same as other antidepressants, maprotiline increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of maprotiline or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Maprotiline is not approved for use in pediatric patients.
The concomitant application with fluoxetine or fluvoxamine may lead to significantly increased plasma-levels of maprotiline with a high incidence of maprotiline side effects. Due to the long half-lives of fluoxetine and fluvoxamine this effect may persist. Pharmacology
Pharmacodynamics
Maprotiline exhibits strong effects as a norepinephrine reuptake inhibitor with only weak actions 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.The pharmacological profile of maprotiline explains its antidepressant, sedative, anxiolytic, and sympathomimetic activities. In accordance to the pharmacological characteristics it is used in the treatment of depression, such as depression associated with agitation or anxiety. Additionally, it shows strong antagonism against reserpine-induced effects in animal studies, as do the other classical antidepressants. Although maprotiline behaves in most regards as a first-generation antidepressant it is commonly referred to as second-generation antidepressant. 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 pharmacological action is thought to be primarily responsible for the drugs antidepressant and anxiolytic effects. It is a strong norepinephrine reuptake inhibitor with only weak effects on serotonin and dopamine reuptake.