Trimipramine

This medication is used to treat depression. It may help improve your mood and sense of well-being and allow you to enjoy everyday life more. Trimipramine is a tricyclic antidepressant. It works by restoring the balance of certain natural substances (neurotransmitters) in the brain.

Trimipramine is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic.

Adult: Initially 50-75 mg daily, increased gradually as necessary to 150-300 mg daily. May be given in divided doses during the day or as a single dose at night.

Elderly: Initial 50-75 mg daily, increased gradually if necessary. Max: 100 mg daily.

Administration

May be taken with or without food

Decreased antihypertensive effects of guanethidine, guanfacine, debrisoquine, betanidine and possibly clonidine. Increased CNS depression with CNS depressants such as alcohol, sedatives, hypnotics or barbiturates. Increased trimipramine levels with protease inhibitors, SSRIs, selegiline, tramadol, quinidine, diltiazem and verapamil. Decreased trimipramine levels with barbiturates. Increased risk of arrhythmias with drugs that prolong QT intervals. Increased risk of serotonin syndrome with linezolid. Increased antimuscarinic adverse effects with nefopam. Risk of neurotoxicity and serotonin syndrome with lithium.

Recent MI, cardiac arrhythmias, heart block; mania; porphyria, severe liver disease. Neonates and children. Lactation.

Dry mouth, accommodation disturbances, tachycardia, constipation, hesitancy of micturation, drowsiness, sweating, postural hypotension, skin rashes, cholestatic jaundice, hypomania, convulsions, cardiac arrhythmias and peripheral neuropathy. Agitation, confusion (elderly).

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Narrow-angle glaucoma; prostatic hypertrophy; history of epilepsy; hyperthyroidism; patients requiring anaesthesia. Pregnancy. Withdraw gradually to decrease risk of withdrawal symptoms. Monitor liver function in long term treatment. May impair ability to drive or operate machinery.

Symptoms: Hypotensive collapse, convulsions, cardiac arrhythmias, acidosis and coma.

Management: Gastric lavage should be carried out as soon as possible. Treatment is supportive and symptomatic with ECG monitoring. Intubate and ventilate the patient before convulsions develop. If convulsions occur, treat with IV diazepam. Treatment should be continued for at least 3 days even if the patient appears to have recovered, due to the long half life of trimipramine.

Tricyclic & related anti-depressant drugs.