Trimipramine dosing

A 25-year-old woman taking venlafaxine 150 mg daily and trimipramine 50 mg daily for depression developed seizures within 11 days of the trimipramine dose being increased to 100 mg daily. Both drugs were stopped and the patient had no further seizures. ... 

Imipramine, amitriptyline, doxepin, desipramine, clomipramine, and trimipramine therapy can be initiated at 25-50 mg/day. Divided dosing may be used at first to minimize side effects, but eventually the entire dose can be given at bedtime. The dose can be increased to 150 mg/day the second week, 225 mg/day the third week, and 300 mg/ day the fourth week. The dose of clomipramine should not exceed 250 mg/day because of an increased risk of seizures at higher doses. 

A single oral dose of 50 mg administered to 9 subjects, resulted in peak plasma concentrations of 0.015 to 0.051 pg/ml (mean 0.028) in 1 to 6 hours (D. R. Abernethye a/., Clin. Pharmac. Ther., 1984, 35, 348-353). Following daily oral doses of 75 or 150 mg to 29 subjects, the following steady-state plasma concentrations were reported trimipramine 0.01 to... 

Trimipramine, a tricyclic antidepressant (75 mg/day in divided doses), is indicated in the management of depres-... 

The pharmacokinetics for trimipramine are shown in Table 21.9. Trimipramine is rapidly absorbed. Trimipramine demonstrates stereoselectivity in its metabolism to its three major metabolites. (-)-Trimipramine is primarily metabolized via CY2D6 hydroxylation to 2-hydroxytrimipramine, whereas (+)-trimipramine is preferentially metabolized by CYP2C19 N-demethylation to desmethyltrimipramine. Desmethyltrimipramine is further hydroxylated to 2-hydroxydesmethyltrimipramine. (-)-Trimipramine is metabolized by CYP3A4/5 to an unknown metabolite (63,64). Most of the oral dose is excreted in urine in 72 hours, primarily as N-demethylated or hydroxylated and conjugated metabolites. The pharmacokinetics of trimipramine in geriatric individuals (S65 years of age) do not differ substantially from those in younger adults. 

A single-dose study in healthy subjects found that quinidine 200 mg daily reduced the clearance of imipramine 100 mg by 30% and desipramine 100 mg by 85%. A further study in 2 healthy subjects similarly found that quinidine 50 mg almost doubled the half-life of a single 75-mg dose of trimipramine, which was reflected in some waking EEG changes. ... 

Schlienger RG, Klink MH, Eggenberger C, Drewe J. Seizures associated with therapeutic doses of venlafaxine and trimipramine. Arm Pharmacother (2000) 34,1402-5. 

Trimipramine maleate. Adult dose 50 to 75 mg initially and increased as necessary to 150 to 300 mg. 

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