Clozapine citalopram

Waschgler R, Hubmann MR, Conca A, MoU W, Konig P. 2002. Simultaneous quantification of citalopram, clozapine, fluoxetine, norfluoxetine, maprotiline, desmethylmaprotiline and trazodone in human serum by HPLC analysis. Int J Clin Pharmacol Ther 40(12) 554-559. 

Hubmann, M.R. Waschgler, R. Moll, W. Conca, A. Konig, R Simultaneous drug monitoring of citalo-pram, clozapine, fluoxetine, maprotiline, and trazodone by HPLC analysis (Abstract 41). Ther.Drug Monit., 1995, 17, 393 [simultaneous citalopram, clozapine, fluoxetine, maprotiline, trazodone LOQ 50 ng/mL]... 

Citalopram 25 Citracal 20 Citrate 82 Clafbran 22 Clarithromydn 25 Claritin 46 Claritin-D 73 Clavulanate 72 Clavulanic acid 82 Clemastine 25, 82 Cleocin 25 Cleocin-T 25 Climara 33 Clindarnydn HCL 25 Clinoril S2 Clo imine 25 Clomipramine 25 Clonazepam 25 Clonidne 25 Clopidogrel 25 Clorazepate 26 Clotrimazole 26, 77 Clozapine 26... 

CypP450 3A3 /4 Antidepressants tricyclics, nefazodone, fluoxetine, fluvoxamine, citalopram, mirtazepine, venlafaxine Antipsychotics chlorpromazine, clozapine, pimozide, quetiapine, risperidone... 

In most cases, SSRIs are the first choice for drugs to combat OCD. Clomipramine, fluvoxamine, fluoxetine, paroxetine, sertraline, and citalopram are all SSRIs that have been proven effective in reducing OCD symptoms. However, in about 40 to 60% of patients, these drugs do not completely alleviate all the symptoms. When this is the case, a second type of drug called a neuroleptic is often added. Neuroleptic drugs, such as haloperidol, clozapine, risperidone, and chlorpromazine... 

The effect of citalopram on plasma concentrations of clozapine have been prospectively studied in 15 patients with schizophrenia taking clozapine 200-400 mg/day (32). The addition of citalopram 40 mg/day did not alter plasma clozapine concentrations. 

However, in a 39-year-old man with a schizoaffective disorder, citalopram 40 mg/day appeared to increase plasma clozapine concentrations and increased adverse effects (33). The adverse effects settled within 2 weeks of a reduction in citalopram dosage to 20 mg/day, with a corresponding 25% fall in clozapine concentrations. It is possible that at higher doses, citalopram can increase clozapine concentrations, perhaps through inhibition of CYP1A2 or CYP3A4. 

Avenoso A, Facciola G, Scordo MG, Gitto C, Ferrante GD. No effect of citalopram on plasma levels of clozapine, risperidone and their active metabolites in patients with chronic schizophrenia. Clin Drug Invest 1998 16 393-8. 

Borba CP, Henderson DC. Citalopram and clozapine potential drug interaction. J Clin Psychiatry 2000 61(4) 301-2. 

The addition of citalopram 40 mg/day did not alter plasma clozapine concentrations. 

Citalopram had no effect on plasma concentrations of clozapine (n = 8), risperidone (n = 7), or their active metabolites over 8 weeks (263). However, a possible interaction of clozapine with citalopram has been reported, with increased serum clozapine concentrations, perhaps dose-related (264). 

Clozapine Fluoxetine, paroxetine, sertraline, and possibly citalopram can raise serum clozapine levels. Particularly large increases can occur with fluvoxamine. Toxicity has been seen in some patients. 

Oxidative metabolism of clozapine was found to correlate with caffeine metabolism (462)and is thus largely carried out by cytochrome P4501A2 (CYP1A2). No correlation with CYP2D6 polymorphism was found (461, 462). Several interaction studies of clozapine with SSRI antidepressants have been reported (465-469). Fluvoxamine increased plasma concentrations of clozapine in schizophrenic patients (463,464), presumably through inhibition of CYP1A2 catalyzed N-demethylation (465). Fluoxetine was found to increase the plasma concentrations of clozapine and its major metabolites, suggesting that this SSRI must interfere with pathways other than N-demethylation and N-dealkylation (466). Two other SSRIs, paroxetine (463) and citalopram (467), had no apparent effects on clozapine levels. 

Amitriptyline, barbiturates, chlorproguanil, citalopram, clomipramine, clozapine, cyclophosphamide, diazepam, hexobarbital, imipramine, pentamidine, phenobarbital, phenytoin, propranolol, quinine, (S)- and (Jf)-warfarin, zidovudine... 

Ajmaline, alprenolol, amiflamine, amphetamine, aprindine, captopril, chlorpheniramine, cinnarizine, citalopram, clomipramine, clozapine, codeine, desipramine, dolasteron, encainide, flecainide, fluoxetine, fluphenazine, haloperidol, hydrocordone, imipramine, loratidine, methoxyphenamine, 3,4-methylenedioxymethamphetamine, metoprolol, mexiletine, (S)- and (i )-mianserin, nifedipine, olanzapine, omeprazole, oxycodone, perhexiline, phenformin, propaphenone, propranolol, remoxipride, ritonavir, saquinavir, selegiline, tamsulosin, timolol, tomoxetine, tramadol, trifluperidol, zolpidem... 

Citalopram does not interfere with the metabolism of APDs. At a dose of 40 mg/day, citalopram caused no significant changes in plasma concentrations of chlorpromazine, clozapine, haloperidol, perphenazine, thioridazine, or zuclopenthixol. Anecdotal data suggest that citalopram may increase the serum levels of levomepromazine. 

Antidepressants Fluvoxamlne, a potent inhibitor of the cytochrome P450 enzymes CYP1A2 and CYP2C19 and a moderate inhibitor of CYP3A4, has been reported to cause a 5-10-fold elevation of plasma clozapine concentration. Fluoxetine and paroxetine may also increase plasma clozapine concentrations, while citalopram and sertraline have been reported to cause minimal or no elevation of plasma levels of clozapine. To date, in vivo studies with a combined olanzapine-imipramine regimen have not revealed any pharmacokinetic interactions. 

Preliminary studies in 5 patients found that their mean plasma clozapine levels were unchanged by citalopram. Another study in 8 patients found similar results. However, a patient who was stable taking clozapine developed sedation, hypersalivation and confusion shortly after he started to take citalopram 40 mg daily. When total clozapine serum levels were measured they were found to be 1097 nanograms/mL. The citalopram dose was reduced to 20 mg daily, the symptoms resolved over the following 2 weeks, and the total clozapine level dropped to 792 nanograms/mL. ... 

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