What is the highest recommended dose of mianserin that has been documented?

Fråga: What is the highest recommended dose of mianserin that has been documented?

Sammanfattning: At least a 10-fold interindividual variation can be detected in the pharmacokinetics of mianserin. The usually recommended dosage of mianserin is 30-90 mg daily, but divided doses of up to 200 mg daily have been documented. It is possible that some individuals, ie ultrarapid metabolisers with respect to the CYP2D6 enzyme, may require and tolerate even higher mianserin doses. A plasma concentration is recommended in cases of poor response to treatment with ordinary doses.

Svar: According to pharmacological handbooks the effective mianserin dosage usually ranges from 30-90 mg daily, divided or given as a single dose at night. Divided doses of up to 150 mg (1) or 200 mg daily (2) may be necessary in some cases.

The pharmacokinetics of mianserin indicate that the interindividual variation in the dose-concentration ratio may be as large as for most tricyclic antidepressants (TCAs), for which an up to 40-fold variation has been documented (3). Mianserin is metabolised by the same polymorphic enzyme, CYP2D6, as the TCAs. Approximately 7 per cent of a caucasian population lacks this enzyme activity, whereas 1-2 per cent have an increased activity, leading to ultrarapid metabolism and very low concentrations of CYP2D6 substrates. Dahl et al describe the metabolism of a 30 mg oral mianserin dose in 15 healthy volunteers with different CYP2D6 genotypes. The maximum serum concentration varied from 35 to 315 nmol/l and the 12 hour AUC (area under the concentration-time curve) varied from 179 to 1528 nmol/lxh in this study (4).

According to a study in 66 Japanese depressed patients, treated with 30 mg mianserin, trough concentrations in steady state varied between approximately 45 to 300 nmol/l (5).

No information has been found in pharmacological handbooks concerning the concentration-effect relationship for mianserin. 1 Dollery, Therapeutic drugs, 1991 2 Martindale, The extra pharmacopoeia. 1996; 31th ed: 3 Hammer W, Sjöqvist F: Plasma levels of monomethylated tricyclic antidepressants during treatment with imipramine-like compounds. Life Science 1967; 6: 1895-1903 4 Dahl ML, Tybring G, Elwin CE, Alm C, Andreasson K, Gyllenpalm M, Bertilsson L: Stereoselective disposition of mianserin is related to debrisoquin hydroxylation polymorphism. Clin Pharmacol Ther 1994; 56: 176-83 5 Tybring G, Otani K, Kaneko S, Mihara K, Fukushima Y, Bertilsson L: Enantioselective determination of mianserin and its desmethyl metabolite in plasma during treatment of depressed Japanese patients. Ther Drug Monit 1995; 17: 516-21