Mianserin Carbamazepine

Bertschy G., C. Bryois, G. Bondolfi, A. Velardi, P. Budry, D. Dascal, C. Martinet, D. Baettig, and P. Baumann (1997). The association of carbamazepine-mianserin In opiate withdrawal A double blind pilot study versus clonidine. Pharmacological Research 35 451-456. 

In a systematic review of 32 randomized trials in which 1389 patients took lithium and 2069 took another agent (carbamazepine, divalproex, lamotrigine, or the antidepressants amitriptyline, fluvoxamine, mianserin, and maprotiline), among the seven studies that reported suicides, lithium-treated patients had significantly fewer completed events (242). These included two suicides on lithium (out of 503, 0.4%) and 11 suicides on other agents (two placebo, two amitriptyline, six carbamazepine, and one lamotrigine, out of a total of 601,1.8%) (OR = 0.26 95% Cl = 0.09, 0.77). 

TCAs CARBAMAZEPINE 1. t risk of bone marrow depression in patients on chemotherapy when used with TCAs 2.1 plasma concentrations of mianserin 1. Additive effects 2. t metabolism of mianserin 1. Avoid concurrent use during chemotherapy 2. Be aware and watch for signs of 1 antidepressant effect of mianserin... 

In 12 patients, carbamazepine (400 mg/day for 4 weeks) markedly reduced the plasma concentrations of concomitantly administered mianserin, probably through enzyme induction (100). The concentration of 5-mianserin, the more potent of the enantiomers of mianserin, fell by 45%, while the plasma concentrations of desmethyhnian-serin changed only slightly. These data suggest that patients co-medicated with carbamazepine may require higher dosages of mianserin. 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

Simultaneous metabolites, amitriptyline, carbamazepine, chlorprothixene, clomipramine, levomepromazine, nortriptyline Interfering mianserine, perphenazine, zuclopenthixol... 

Simultaneous amitriptyline, caffeine, carbamazepine, chlordiazepoxide, chlorpromazine, clonazepam, desipramine, flunitrazepam, flimazepam, haloperidol, imipramine, levome-promazine, maprotiline, mianserin, nitrazepam, nortriptyhne, perphenazine, phenobar-bital, phen5d oin, sulpride, thioridazine, triazolam... 

Simultaneous amoxapine, clovoxamine, desipramine, fenfluramine, fluvoxamine, nor-fluoxetine, nortriptyline, propranolol, protriptyline, sertraline Noninterfering amitriptyline, atenolol, bupropion, carbamazepine, chlordiazepoxide, ci-talopram, clomipramine, clozapine, cyclobenzaprine, doxepin, imipramine, loxapine, me-toprolol, mianserin, moclobemide, nomifensine, pindolol, thioridazine, tranyl[Pg.626]

Carbamazepine induces hepatic catabolic enzymes, with a consequent reduction in serum levels of antidepressants (mainly described with amitriptyline, desipramine, doxepin, imipramine, mianserin, and nortriptyline). A decrease in bupropion serum levels was also reported with carbamazepine. These effects were not observed with clomipramine. Fluoxetine and fluvoxamine inhibit the metabolism of carbamazepine and valproate (up to 30% and 50% increases in serum levels, respectively). No significant interaction has yet been found between paroxetine and carbamazepine or valproate. 

Ampicillin, cefotaxime, ceftazidine, ciprofloxacin, methicillin, sulfathiazole, sulfamethoxazole Carbamazepine, felbamate, mesantoin, phenytoin, valproic acid Cimetidine, ranitidine Amodiaquin, chloroquine, quinine Chlorpromazine, clozapine, mianserin... 

Mianserin is a chiral tetracyclic antidepressant for which the S enantiomer is the eutomer. The influence of carbamazepine, an enzyme inducer of CYP3A4, on mianserin enantiomer concentrations was examined in 12 inpatients treated for depression [141]. The patients received at least 7 days of therapy with mianserin (60 mg per day) prior to study. In the control situation (before carbamazepine), the S R ratios of 12h postdose mianserin plasma concentrations were approximately twofold. At that point, the patients were coadministered carbamazepine 400mg/day for 4 weeks along with their daily dose of mianserin. By week 4 of carbamazepine treatment, concentrations of the S and R enantiomers had declined by 49% and 38%, respectively. This corresponded with 2.0- and 1.6-fold increases, respectively, in the S- and R- desmethylmianserin mianserin ratios. The findings confirmed the involvement of CYP3A4 in the metabolism of mianserin enantiomers to desmethylmianserine. Because of the possibility of a therapeutic window for S-mianserin, it was suggested that the dose of mianserin would need to be increased by a factor of two in the presence of carbamazepine [141]. 

Plasma levels of mianserin can be markedly reduced by the concurrent use of carbamazepine, phenobarbital or phenytoin. 

A comparative study in 6 epileptics and 6 healthy subjects showed that phenytoin with either phenobarbital or carbamazepine markedly reduced the plasma levels of a single dose of mianserin. The mean half-life of mianserin was reduced by 75% (from 16.9 to 4.8 hours) and the AUC was reduced by 86%. Another study in 4 patients found that carbamazepine reduced serum mianserin levels by 70%. In another study 12 patients taking mianserin 60 mg daily were also given carbamazepine 400 mg daily for 4 weeks. Average plasma levels of total S-mianserin (the more potent enantiomer) and total R-mianserin were reduced by about 45% in the presence of carbamazepine. ... 

It seems probable that these antiepileptics increase the metabolism of mianserin by the liver, thereby increasing its loss from the body. Carbamazepine may increase the metabolism of mianserin by cytochrome P450 isoenzyme CYP3A4. ... 

Information seems to be limited to these studies, but the interaction appears to be established and of clinical importance. Monitor concurrent use and increase the dosage of mianserin as necessary. One study suggests that the dose of mianserin may need to be approximately doubled if carbamazepine 400 mg daily is added. ... 

Eap CB, YasuiN, Kaneko S, Baumann P, Powell K, Otani K. Effects of carbamazepine coad-ministration on plasma concentrations of the enantiomers of mianserin and of its metabolites. Ther Drug Monit (1999) 21,166-70. 

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