Risperidone fluoxetine

Bozikas V, Petrikis P, Karavatos A. Urinary retention caused after fluoxetine-risperidone combination. J Psychopharmacol 2001 15(2) 142-3. 

Conventional antipsychotic drugs such as chlorpromazine and haloperidol have long been used in the treatment of acute mania. More recently, atypical antipsychotic drugs including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasi-done have been approved for the treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood-stabilizing drugs.25 Aripiprazole and olanzapine are also approved for maintenance therapy. The combination of olanzapine and fluoxetine is approved for treatment of bipolar depression. Quetiapine is approved for treatment of... 

Risperidone Aripiprazole 2D6 > 3A4 2D6, 3A4 Carbamazepine and phenytoin topiramate hypericum (St. John s Wort). Paroxetine, fluoxetine, sertraline (high dose) grapefruit juice 2D6 or 3A4 substrates acting as competitive inhibitors. 

CYP3A4 TCAs, risperidone, carbamazepine, benzodiazepines, haloperidol, fluoxetine,... 

Alternatively, the current antidepressant may be augmented (potentiated) by the addition of another agent (e.g., lithium, T3), or an atypical antipsychotic (e.g., risperidone). Risperidone has been shown to be effective in combination with fluvoxamine, paroxetine, or citalopram in treatment-resistant depression. Olanzapine and fluoxetine have been found to be safe and effective in treatment-resistant depression. 

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

Inhibitors codeine, encainide, flecainide, fluoxetine, haloperidol, hydrocodone, 4-methoxy-amphetamine, metoprolol, mexiletine, oxycodone, paroxetine, propafenone, propoxyphene, risperidone, selegiline (deprenyl), thioridazine, most tricyclic antidepressants, timolol Fluoxetine, haloperidol, paroxetine, quinidine... 

Andrade, C. (1998) Risperidone may worsen fluoxetine-treated OCD. J Clin Psychiatry 59 255—256. 

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... 

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). 

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

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... 

Improvement in galactorrhea has also been observed in a case of trichotillomania refractory to a selective serotonin reuptake inhibitor (857). The patient only had a positive response with risperidone in combination with fluoxetine, but developed hyperprolactinemia and an intolerable galactorrhea. Olanzapine in combination with fluoxetine was started, with significant clinical improvement and without symptoms of galactorrhea however, the patient had undesired weight gain of 3.6 kg after 22 weeks. 

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. 

In a systematic open study in 11 hospitalized patients taking a steady dose of risperidone (4-6 mg/day), fluoxetine (20 mg/day) increased plasma concentrations of active antipsychotic medication (combined concentrations of risperidone and 9-hydroxyrisperidone) by 50% after treatment for 25 days (42). Despite this, the treatment was well tolerated and there were improvements in rating scales of psychosis and depressed mood. Whether this was due to the introduction of fluoxetine or the higher plasma concentrations of risperidone is not clear. Fluoxetine and norfluoxetine would require at least a further 2 weeks to reach steady state, so additional increases in risperidone concentrations might be anticipated over this time. 

A pharmacokinetic interaction of risperidone with fluoxetine has been reported (SEDA-22, 71). When 10 schizophrenic patients stabilized on risperidone 4-6 mg/ day took fluoxetine 20 mg/day for concomitant depression the mean plasma risperidone concentration increased from 12 to 56 ng/ml at week 4 the concentration of 9-hydroxyrisperidone was not significantly affected (51). One patient dropped out after 1 week because of akathi-sia associated with a markedly increased plasma risperidone concentration. 

In an open, 30-day trial, the pharmacokinetics, safety, and tolerability of a combination of risperidone 4 or 6 mg/ day with fluoxetine 20 mg/day were evaluated in 11 psychotic inpatients (52). CYP2D6 genotyping showed that three were poor metabolizers and eight were extensive metabolizers. The mean AUC of risperidone increased from 83 and 398 h.ng/ml to 341 and 514 h.ng/ml when risperidone was co-administered with fluoxetine in extensive and poor metabolizers respectively. However, despite this pharmacokinetic interaction, the severity and incidence of extrapyramidal symptoms and adverse events did not increase significantly when fluoxetine was added 10 of the 11 patients improved clinically. 

Catastrophic deterioration, with the severity of obsessive-compulsive symptoms returning to pretreatment levels, was observed in a 21-year-old man when risperidone was added to fluoxetine in a dosage that was stepped up to 3 mg/day (53). 

Bondolfi G, Eap CB, Bertschy G, Zullino D, Vermeulen A, Baumann P. The effect of fluoxetine on the pharmacokinetics and safety of risperidone in psychiatric patients. Pharmacopsychiatry 2002 35(2) 50-6. 

Spina E, Avenoso A, Scordo MG, Ancione M, Madia A, Gatti G, Perucca E. Inhibition of risperidone metabolism by fluoxetine in patients with schizophrenia a clinically relevant pharmacokinetic drug interaction. J Clin Psychopharmacol 2002 22(4) 419-23. 

It has been speculated that the antiserotonergic properties of risperidone could lead to obsessive and depressive symptoms, since a patient taking risperidone 4 mg/day developed major depression and obsessions, which resolved with fluoxetine 29 mg/day, relapsing when fluoxetine was withdrawn (130). 

An 11-year-old boy developed acute dysuria and increased frequency accompanied by gross hematuria. He was taking fluoxetine, valproic acid, benzatropine, haloperidol, clonidine, trazodone, and nasal desmopressin. One week before presentation, risperidone had been introduced instead of haloperidol to improve behavioral control. The risperidone was discontinued and haloperidol resumed, and his symptoms resolved during the following week. 

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