Venlafaxine risperidone

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

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

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... 

During the course of a study of the salts formed by saccharin with quinine, haloperidol, mirtazapine, pseudoephedrine, lamivudine, risperidone, sertraline, venlafaxine, zolpidem, and amlodipine, a 1 1 cocrystal of saccharin and piroxicam was detected [68]. In the crystal structure, the asymmetric unit was found to consist of one saccharin molecule and one zwitterionic piroxicam molecule that were linked by two sets of N—H O hydrogen bonds. The piroxicam-saccharin synthons were in turn linked through bridging C—H O hydrogen bonds. Interestingly, the drug substance solubility out of the cocrystal was found to be comparable to that of the marketed piroxicam product. 

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. 

Klockowski PM. Effect of venlafaxine on the pharmacokinetics of risperidone. J Clin Pharmacol 1999 39(3) 297-309. 

In eight patients with major depressive disorder without psychotic features, who did not respond to serotonin reuptake inhibitors therapy when risperidone was added, all improved within 1 week. Furthermore, risperidone also seemed to have beneficial effects on sleep disturbance and sexual dysfunction (272). In an open study in 30 healthy subjects who took risperidone 1 mg orally before and after venlafaxine dosing to steady state, the oral clearance of risperidone fell by 38% and the volume of distribution by 17%, resulting in a 32% increase in AUC renal clearance of 9-hydroxyrisperidone also fell by 20% (273). The authors concluded that these small effects were consistent with the fact that venlafaxine is unlikely to alter the clearance of risperidone, which is mainly by CYP2D6. 

Worsening of psychosis could have been an adverse event of topiramate in a 50-year-old woman with a long history of a schizoaffective disorder treated with risperidone 4 mg/day, venlafaxine 300 mg/day, and topiramate 200 mg/day (652). Her behavior worsened after topiramate was introduced. After it was withdrawn her mood, spontaneous speech, and psychomotor activity improved. 

IMATINIB 1. ANTIARRHYTHMICS -flecainide, mexiletine, propafenone 2. ANTIDEPRESSANTS - fluoxetine, paroxetine, TCAs, trazodone, venlafaxine 3. ANTIPSYCHOTICS -clozapine, haloperidol, perphenazine, risperidone, thioridazine 4. BETA-BLOCKERS - metoprolol, propanolol, timolol 5. DONEPEZIL 6. METHAMPHETAMINE Imatinib may cause t plasma concentrations of these drugs, with a risk of toxic effects Inhibition of CYP2D6-mediated metabolism of these drugs Watch for early features of toxicity of these drugs... 

CYP2D6 Antidepressants amitriptyline, clomipramine, imipramine, desipramine, nortriptyline, trimipramine, N-desmethyl-clomipramine, fluoxetine, norfluoxetine, paroxetine, venlafaxine, sertraline Neuroleptics chlorpromazine, thioridazine, perphenazine, haloperidol, reduced haloperidol, risperidone, clozapine, sertindole Others codeine, opiate, propranolol, dextromethorphan 4 no activity 25% in Caucasians 0%-10% in others 5 no activity 2%-10% in all groups 10 reduced activity 47%-70% in Asians <5% in others 17 reduced activity 25%-40% in blacks 0% in others 2XN increased activity 19%-29% in Arabs and Ethiopians <5% in others... 

At steady state, venlafaxine weakly inhibits the metabolism of risperidone however, this interaction is unlikely to be of clinical significance. Co-administration of milnacipran and levomepromazine increases the milnacipran plasma concentration because of a modification of the apparent total clearance of the drug. 

Augmentation is called for when there is partial or non-response to the above approaches. Combinations of SSRIs with buspirone, clonazepam, clonidine, inositol, lithium, pindolol, olanzapine, risperidone, trazodone, tryptophan, and venlafaxine have been reported, with limited benefit. To date, only two augmenting agents have been found to be effective in double-blind studies risperidone and pindolol. Augmentation of SSRIs with clomipramine (or vice versa) is a common practice in non-responders however, this combination may lead to a substantial increase in the level of tricyclics in the blood and/or increase the risk of serotonin syndrome. Phenelzine may be helpful in symmetry-related or other atypical obsessions. Electroconvulsive therapy (ECT) should be reserved for severely depressed and suicidal OCD patients. Neurosurgery is the last resort current operations include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leucotomy. The outcome of such operations is questionable. 

No clinically relevant pharmacokinetic interaction appears to occur between risperidone and venlafaxine. 

Steady-state venlafaxine 75 mg every 12 hours was found to increase the AUC of a single 1-mg oral dose of risperidone by about 32%, but the pharmacokinetic profile of the risperidone plus its active metabolite (9-hy-droxyrisperidone) was not significantly changed, nor were any adverse events seen. There would seem to be no reason for avoiding concurrent use. 

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