Trimipramine's mechanism of action differs from other tricyclic antidepressants. It is only a moderate reuptake inhibitor of norepinephrine, and a weak reuptake inhibitor of serotonin and dopamin. The main effects are due to considerable postynaptic blockage as follows:

strong : 5-HT2, Muscarinic, H1, H2, Alpha1
moderate : D2
weak : 5-HT1, Alpha2

The spectrum of effects (strong antidepressant activity, sedation and anxiolysis) and side-effects (strong anticholinergic and antiadrenergic side-effcts) is the same as with Doxepin. It is also a more effective sedative than Amitriptyline. Trimipramine is the only effective drug against insomnia known so far that does not alter the normal sleep architecture. In particular, it does not suppress REM-sleep. Moreover, dreams are said to brighten during treatment. Its relatively strong antagonistic activity at postsynaptic D2-receptors led to a clinical study trying Trimipramine as atypical neuroleptic. There it exerted good antipsychotic activity with a low incidence of extrapyramidal and other side-effects. But this study encompassed only 28 patients, so the use of Trimipramine as a neuroleptic needs further confirmation and can currently not be recommended. Trimipramine shows also useful activity against chronic pain.

Indications

Endogenous and neurotic depression with prominent agitation and anxiety
Depressive and non-depressive insomnia (suitable for long-term treatment)
Adjunctive therapy of alcohol and opioid withdrawal
Chronic pain of malignant and non-malignant origin

Trimipramine is an efficient antidepressant, sedative, and anxiolytic comparable to Doxepin.

Contraindications

absolute :

concomittant treatment with MAO-Inhibitors
known hypersensitivity to Trimipramine or other Tricyclics
acute intoxication with alcohol, sedatives, analgesics and other psychoactive drugs
acute Delirum tremens
untreated closed angle glaucoma
hypertrophy of the prostate with urine retention
paralytic ileus

relative :

hypertrophy of the prostate without urine retention
reduced function of the bone marrow
organic brain disorders
increased risk of seizures, preexisting epilepsy
preexisting cardial damage, particular some arrhythmias (impulse conductive disorders)

Side Effects

See the article on Doxepin. All side-effects of Doxepin are noted also during Trimipramine use with approximately the same frequency and intensity in equivalent doses.

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