trimipramine trimipramine 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. trimipramineclinical datatrade namessurmontil, othersother namestrimeproprimine; if-6120; il-6001; rp-7162; 2'-methylimipramine; β-methylimipramineahfs/drugs.commedlineplusa602010license data us fda: trimipramine pregnancycategory au: c routes ofadministrationoral, intramuscular injection, intravenousatc coden06aa10 (who) legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) us: ℞-only pharmacokinetic databioavailability41%protein binding94.9%metabolismhepaticelimination half-life23–24 hoursexcretionrenalidentifiers iupac name (±)-3-(10,11-dihydro-5h-dibenzoazepin-5-yl)-n,n,2-trimethylpropan-1-amine cas number739-71-9 y 521-78-8 (maleate)pubchem cid5584iuphar/bps7317drugbankdb00726 ychemspider5382 yunii6s082c9ndtkeggd00394 ychebichebi:9738 ychemblchembl644 ycomptox dashboard (epa)dtxsid8023715 echa infocard100.010.917 chemical and physical dataformulac20h26n2molar mass294.442 g·mol−13d model (jsmol)interactive image smiles c1cc3c(cc1)ccc2c(cccc2)n3cc(c)cn(c)c inchi inchi=1s/c20h26n2/c1-16(14-21(2)3)15-22-19-10-6-4-8-17(19)12-13-18-9-5-7-11-20(18)22/h4-11,16h,12-15h2,1-3h3 ykey:zscdbowyzjwbiy-uhfffaoysa-n y (verify) 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 4 weeks of 0.55 (95% ci –0.11 to 1.21). the certainty of evidence was rated as very low, and no data were available for longer-term treatment (3 months). for comparison, the other sedating antihistamines assessed, doxepin and doxylamine, had effect sizes (smd) at 4 weeks 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 300 mg/day. doses of trimipramine used for insomnia range from 25 to 200 mg/day. however, it has been advised that doses be kept as low as possible, and a low dose of 25 mg/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 sedative effects. however, trimipramine has also been said to be associated with a different side effect profile compared to other tcas and in general with fewer side effects, chiefly due to its lack of norepinephrine reuptake inhibition and relatively lower anticholinergic effects (although it is still a potent anticholinergic). somnolence is the most common side effect of the drug. dry mouth is the most common anticholinergic side effect, but others like constipation, urinary retention, and blurred vision are also present. it is described as being associated with minimal or no orthostatic hypotension, at least in comparison to clomipramine, in spite of its potent and comparable activity as an alpha-1 blocker. however, it has also been said to have a rate of orthostatic hypotension similar to that of other tcas. trimipramine is said to be less epileptogenic than other tcas, although seizures have still been reported in association with it. it is also less cardiotoxic than other tcas and cardiotoxicity is said to be minimal, with a "very favorable profile". heavy exposure to any tricyclic antidepressants was associated with an elevated rate ratio for breast cancer 11–15 years later. however, on tests done on drosophila melanogaster, nongenotoxic tcas (amitriptyline, maprotiline, nortriptyline, and protriptyline), and genotoxic tcas (amoxapine, clomipramine, desipramine, doxepin, imipramine, and trimipramine) were identified. list of side effects common adverse effects include: sedation — especially common with trimipramine compared to the other tcas anticholinergic effects including: - dry mouth - blurred vision - mydriasis - decreased lacrimation - constipation - urinary hesitancy or retention - reduced gi motility - tachycardia (high heart rate) - anticholinergic delirium (particularly in the elderly and in parkinson's disease) weight gain orthostatic hypotension sexual dysfunction including impotence, loss of libido and other sexual adverse effects tremor dizziness sweating anxiety insomnia agitation rash adverse effects with an unknown incidence includes: confusion nausea vomiting extrapyramidal side effects (e.g. parkinsonism, dystonia, etc.) tinnitus paraesthesia ecg changes increased liver function tests rare adverse effects include: seizures syndrome of inappropriate secretion of antidiuretic hormone blood dyscrasias including: agranulocytosis thrombocytopenia eosinophilia leukopenia myocardial infarction heart block qtc interval prolongation sudden cardiac death depression worsening suicidal ideation overdose main article: tricyclic antidepressant overdose compared to other tcas, trimipramine is relatively safe in overdose, although it is more dangerous than the selective serotonin reuptake inhibitors (ssris) and serotonin–norepinephrine reuptake inhibitors (snris) but less dangerous than bupropion in cases of overdose. interactions trimipramine should not be given with sympathomimetic agents such as epinephrine (adrenaline), ephedrine, isoprenaline, norepinephrine (noradrenaline), phenylephrine and phenylpropanolamine. barbiturates may increase the rate of metabolism. trimipramine should be administered with care in patients receiving therapy for hyperthyrodism. pharmacology pharmacodynamics