Fluoxetine clozapine

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. 

Clozapine Fluoxetine Amitriptyline Antidepressants Enflurane Antidepressants... 

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. 

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]... 

Physical examination revealed tachycardia with irregular heart rate, shallow respiration, decreased bowel sounds, dilated pupils, and hypertheimia. An ECG revealed a widened QRS complex with diffuse T wave changes. If this patient had taken a drug overdose the most likely causative agent was (A) Clozapine Fluoxetine Lithium Thioridazine Zolpidem... 

Non-motor signs of the disorder are also treatable with symptomatic medications. The frequent mood disorder can be treated with standard antidepressants, including tricyclics (such as amitryptiline) or serotonin reuptake inhibitors (SSRIs, such as fluoxetine or sertraline). This treatment is not without risks in these patients, as it may trigger manic episodes or may even precipitate suicide. Anxiety responds to benzodiazepines, as well as to effective treatment of depression. Long-acting benzodiazepines are favored over short-acting ones because of the lesser abuse potential. Some of the behavioral abnormalities may respond to treatment with the neuroleptics as well. The use of atypical neuroleptics, such as clozapine is preferred over the typical neuroleptics as they may help to control dyskinesias with relatively few extrapyramidal side-effects (Ch. 54). 

Eerslew KE, Hagardom AN, Harlan GC, McCormick WE. 1998. A fatal drug interaction between clozapine and fluoxetine. J Forensic Sci 43 1082. 

Olanzapine (Zyprexa). The olanzapine molecule is structurally very similar to clozapine and therefore exerts very similar effects on brain receptors. The dose range of olanzapine for treating schizophrenia is from 5 to 30mg/day. Like clozapine, olanzapine appears to treat both positive and negative symptoms. It is also approved for the treatment of the manic phase of bipolar disorder. It has also been shown to augment the antidepressant effects of fluoxetine in refractory patients. 

Antidepressants tricyclics, mirtazepine, fluoxetine Antipsychotics clozapine, haloperidol, olanzapine, phenothiazines... 

Antidepressants tricyclics, fluoxetine, paroxetine, sertraline, mirtazepine, venlafaxine, mianserin Antipsychotics phenothiazines, haloperidol, clozapine, olanzapine, quetiapine... 

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

Another practical example of a pharmacokinetic drug interaction concerns the incidence of seizures in patients given a standard (300 mg/ day) dose of clozapine. Should the patient be given an SSRI antidepressant (such as fluoxetine, fluvoxamine, sertraline or paroxetine) concurrently then the clearance of clozapine could be reduced by up to 50%, an effect which would be comparable with a doubling of the dose. This could lead to a threefold increase in the risk of the patient suffering a seizure. 

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... 

P450 IID6 -fin women Inhibited by OCs Hydroxylation of nortriptyline and desipramine, haloperidol, clozapine, risperidone, venlafaxine Fluoxetine, fluvoxamine, paroxetine, sertraline... 

Cassady SL, Taker GK Addition of fluoxetine to clozapine (letter). Am J Psychiatry 149 1274, 1992... 

Recent case reports have suggested that atypical antipsychotics may also benefit patients with PTSD. For example, low doses of risperidone in combination with an antidepressant or mood stabilizer were reported effective for nightmares and flashbacks in patients with treatment-refractory PTSD ( 292). Both clozapine and olanzapine have also been reported to reduce PTSD symptoms in patients with a co-morbid psychotic disorder ( 293, 294). Finally, olanzapine added to fluoxetine resulted in significant improvement of hyperarousal symptoms in a patient with treatment-refractory PTSD caused by severe childhood physical and sexual abuse (295). 

D6 Bufuralol, bupranolol, clomipramine, clozapine, codeine, debrisoquin, dextromethorphan, encainide, flecainide, fluoxetine, guanoxan, haloperidol, hydrocodone, 4-methoxy-amphetamine, metoprolol, mexile-tine, oxycodone, paroxetine, phenformin, propafenone, propoxyphene, risperidone, selegiline (deprenyl), sparteine, thioridazine, timolol, tricyclic antidepressants Unknown Quinidine, paroxetine... 

A2 Tertiary amine TCAs, duloxetine, theophylline, phenacetin, TCAs (demethylation), clozapine, diazepam, caffeine Fluvoxamine, fluoxetine, moclobemide, ramelteon Tobacco, omeprazole... 

D6 Tricyclic antidepressants (TCAs), benztropine, perphenazine, clozapine, haloperidol, codeine/oxycodone, risperidone, class Ic antiarrhythmics, 3 blockers, trazodone, paroxetine, maprotiline, amoxapine, duloxetine, mirtazapine (partly), venlafaxine, bupropion Fluoxetine, paroxetine, duloxetine, hydroxybupropion, methadone, cimetidine, haloperidol, quinidine, ritonavir Phenobarbital, rifampin... 

Cyt 2D6 metabolizes haloperidol, risperidone, thioridazine, sertindole, olanzapine and clozapine common substrates - fluoxetine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, propranolol, metoprolol, timolol, codeine, encainide, flecanide. Common inhibitors - paroxetine, sertraline, fluoxetine. 

Cyt 3A3/4 metabolizes clozapine, sertindole, quetiapine common substrates -tricyclic antidepressants, nefazodone, sertraline, carbamazepine, ethosuximide, terfenadine, benzodiazepines, diltiazem, nifedipine, verapamil, erythromycin, cyclosporine, lidocaine, quinidine, cisapride, paracetamol. Common inhibitors -nefazodone, fluvoxamine, fluoxetine, ketoconazole. 

In 10 patients stabilized on clozapine (200-450 mg/day) who took fluoxetine (20 mg/day) for 8 weeks, mean plasma concentrations of clozapine, norclozapine, and clozapine N-oxide increased significantly by 58%, 36%, and 38% respectively (44). 

In two cases ingestion of clozapine and fluoxetine had a fatal outcome (45). The blood fluoxetine concentration was... 

Dual effects were observed in a 44-year-old schizophrenic patient taking clozapine with both fluoxetine and sertraline for mood stabilization (46). Clinical and motor status improved with both fluoxetine and sertraline cognitive function improved with clozapine and fluoxetine, but was not sustained with sertraline. 

Spina E, Avenoso A, Facciola G, Fabrazzo M, Monteleone P, Maj M, Perucca E, Caputi AP. Effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenia. Int Clin Psychopharmacol 1998 13(3) 141-5. 

Clozapine and SSRIs are often used together, because depressive syndromes are common in patients with schizophrenia. Clozapine carries a relatively high risk of agranulocytosis, but this adverse effect is very rarely seen with SSRIs, although a case of possible fluoxetine-induced neutropenia has been described (SEDA-22, 15). Two cases in which the addition of paroxetine to clozapine was associated with neutropenia have been reported (11). The patients had been taking stable doses of clozapine for 6-12 months and had previously tolerated other SSRIs without adverse hematological consequences. In both cases the white cell count recovered when clozapine was withdrawn, although paroxetine was continued. 

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