Trimipramine (Dosage)

Trimipramine is a tricyclic antidepressant used primarily for the treatment of major depressive disorder. The drug is also used for the treatment of insomnia, anxiety and psychosis due to its sedative, anxiolytic and antipsychotic properties, respectively. Its effectiveness and tolerability are associated with the presence of certain genetic variants in the CYP2C19 and CYP2D6 cytochromes may also favor the occurrence of adverse effects, which underlines the importance of adjusting the dosage appropriately.

Trimipramine is used for the treatment of various psychiatric disorders. It is widely used for the treatment of major depression, especially when the sedative effect is useful. It is also an effective anxiolytic, sedative and antipsychotic which make it useful in the treatment of other psychiatric conditions such as obsessive-compulsive disorder, anxiety, post-traumatic stress disorder or neuropathic pain, among others.

MECHANISM OF ACTION

Tricyclic antidepressants exert their action by inhibiting the reuptake of serotonin and norepinephrine, increasing the bioavailability of neurotransmitters in the central nervous system, which produces the antidepressant effect. However, this inhibitory capacity is relatively weaker compared to other antidepressants of the same family. Although the effects on neurotransmitters occur immediately, the therapeutic effects are not evident until weeks later, probably because changes in receptors in the cerebral cortex and hippocampus must occur. Tricyclic antidepressants are also very useful in the treatment of neuropathic pain and, although their mechanism at this level is not well understood, they are thought to modulate anti-pain opioid systems in the CNS.

CONTRAINDICATIONS

Trimipramine is contraindicated in patients who have previously shown hypersensitivity to this drug or to other antidepressants of the same family. It should not be used in the recovery of patients who have suffered an acute myocardial infarction or patients with other cardiac problems such as arrhythmias. It is also not recommended for use in people with liver disease or during breastfeeding.

It is important to take into account that important adverse effects may appear when combined with other drugs such as other antidepressants, MAO inhibitors, opiates, epinephrine, barbiturates, alcohol or medicinal herbs, among others. In addition, it should be administered with caution in patients being treated for hyperthyroidism. Therefore, it is important that, if you are taking other medications or supplements, you consult your doctor.

Trimipramine should also be used with caution in patients at increased risk of glaucoma or urinary tract problems.

SIDE EFFECTS

In addition to inhibiting the reception of certain neurotransmitters, these drugs can also block other receptors (histamine, alpha-adrenergic, muscarinic), so their side effects are frequent.

The most common side effect is drowsiness, followed by dry mouth, constipation, urinary retention or blurred vision. Also, although somewhat less frequently, it can cause hypotension, weight loss, hot flushes, skin reactions, tachycardia, mood changes and increased risk of bone fractures in prolonged treatment.

BRAND NAMES

  • Surmontil®
  • Herphonal®
  • Rhotrimine®
  • Sapilent®
  • Stangyl®
  • Tydamine®

Genes analyzed

CYP2C19 CYP2D6

Bibliography

Hicks JK, Swen JJ, Thorn CF, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants. Clin Pharmacol Ther, 2013; 93(5):402–8.

Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017 Jul;102(1):37-44.

Kirchheiner J, Müller G, Meineke I, et al. Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics. J Clin Psychopharmacol. 2003 Oct;23(5):459-66.

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Trimipramine. 2020 Apr 5. PMID: 31643192.

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