Trimipramine, sold under the brand name Surmontil among others, is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of insomnia, anxiety disorders, and psychosis, respectively. The drug is described as an atypical or "second-generation" TCA because, unlike other TCAs, it seems to be a fairly weak monoamine reuptake inhibitor. Similarly to other TCAs however, trimipramine does have antihistamine, antiserotonergic, antiadrenergic, antidopaminergic, and anticholinergic activities. Medical uses Trimipramine's primary use in medicine is in the treatment of major depressive disorder, especially where sedation is helpful due to its prominent sedative effects. The drug is also an effective anxiolytic, and can be used in the treatment of anxiety. In addition to depression and anxiety, trimipramine is effective in the treatment of insomnia, and unlike most other hypnotics, does not alter the normal sleep architecture. In particular, it does not suppress REM sleep, and dreams are said to "brighten" during treatment. Trimipramine also has some weak antipsychotic effects with a profile of activity described as similar to that of clozapine, and may be useful in the treatment of psychotic symptoms such as in delusional depression or schizophrenia. A major systematic review and network meta-analysis of medications for the treatment of insomnia published in 2022 found that trimipramine had an effect size (standardized mean difference (SMD)) against placebo for treatment of insomnia at 4weeks of 0.55 (95% –0.11 to 1.21). The certainty of evidence was rated as very low, and no data were available for longer-term treatment (3months). For comparison, the other sedating antihistamines assessed, doxepin and doxylamine, had effect sizes (SMD) at 4weeks of 0.30 (95% CI –0.05 to 0.64) (very low certainty evidence) and 0.47 (95% CI 0.06 to 0.89) (moderate certainty evidence), respectively. The effective dosage of trimipramine in depression is 150 to 300mg/day. Doses of trimipramine used for insomnia range from 25 to 200mg/day. However, it has been advised that doses be kept as low as possible, and a low dose of 25mg/day has been recommended. Contraindications Contraindications include: Recent myocardial infarction Any degree of heart block or other cardiac arrhythmias Mania Severe liver disease During breastfeeding Hypersensitivity to trimipramine or to any of the excipients Side effects The side effects of trimipramine have been said to be similar to those of other tertiary amine TCAs, with a preponderance of anticholinergic and