Olanzapine Valproate

Olanzapine Valproate Clomipramine Citalopram Isoflurane Clomipramine... 

OLANZAPINE VALPROATE Risk of bone marrow toxicity Additive effect Monitor FBC closely warn patients to report sore throat, fevers, etc. 

Olanzapine Valproate induces olanzapine metabolism slightly, but in extreme situations (high valproate concentrations and/ or low olanzapine doses) the effect could be clinically important [350 j. 

Olanzapine Zyprexa 20, 30 mg Tablets 2.5, 5, 7.5, 10, 5-20 mg/day in 1 or 2 doses combination with lithium or valproate for the acute treatment of mania or mixed states for bipolar I disorder. Olanzapine and aripiprazole are approved for relapse prevention as well as for acute therapy... 

Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. 

First, optimize current mood stabilizer or initiate mood-stabilizing medication lithium,0 valproate,0 or carba-mazepine0 Consider adding a benzodiazepine (lorazepam or clonazepam) for short-term adjunctive treatment of agitation or insomnia if needed Alternative medication treatment options carbam-azepine0 if patient does not respond or tolerate, consider atypical antipsychotic (e.g., olanzapine, quetiapine, risperidone) or oxcarbazepine. 

Ari pi prazole, olanzapine, quetiapine, risperidone, and ziprasidone are effective as monotherapy or as add-on therapy to lithium or valproate for acute mania. Prophylactic use of antipsychotics can be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed in view of long-term side effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). 

Valproate is as effective as lithium and olanzapine for pure mania, and it can be more effective than lithium for rapid cycling, mixed states, and bipolar disorder with substance abuse. It reduces the frequency of recurrent manic, depressive, and mixed episodes. 

Another serious side effect of clozapine is a risk of seizures. This mainly occurs at higher doses of the drug, and having a seizure is not necessarily a sufficient reason to stop clozapine permanently. If the clozapine has been especially helpful, an anticonvulsant can be added to protect against further seizures. Valproate (Depakote) may be best in this regard because it not only provides protection from seizures but also may help to relieve some of the symptoms of schizophrenia. Recently, it has become clear that two atypical antipsychotic drugs, clozapine and olanzapine, are associated with an increased risk for the development of type II diabetes. 

Combination therapy When coadministered with lithium or valproate, generally begin olanzapine dosing with 10 mg once daily without regard to meals. The safety of doses above 20 mg/day has not been evaluated in... 

Tohen M, Roy Chengappa KN, Suppes TR, et al. Efficacy of olanzapine added to valproate or lithium in the treatment of bipolar I disorder. Presented at the American Psychiatric Association Annual Meeting, Chicago, May 13-18, 2000. 

Until recently, lithium carbonate was the universally preferred treatment for bipolar disorder, especially in the manic phase. With the approval of valproate, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone for this indication, a smaller percentage of bipolar patients now receive lithium. This trend is reinforced by the slow onset of action of lithium, which has often been supplemented with concurrent use of antipsychotic drugs or potent benzodiazepines in severely manic patients. The overall success rate for achieving remission from the manic phase of bipolar disorder can be as high as 80% but lower among patients who require hospitalization. A similar situation applies to maintenance treatment, which is about 60% effective overall but less in severely ill patients. These considerations have led to increased use of combined treatment in severe cases. After mania is controlled, the antipsychotic drug may be stopped and benzodiazepines and lithium continued as maintenance therapy. 

Valproate (+olanzapine or risperidone) II Schizophrenia Abbott Laboratories... 

Lithium is an alkaline earth element that is used medicinally in the form of salts such as lithium chloride and lithium carbonate. Its main use is in the prevention or attenuation of recurrent episodes of mania and depression in individuals with bipolar mood disorder (manic depression). Lithium also has clearly established antima-nic activity, although its relatively slow onset of action often necessitates the use of ancillary drugs, such as antipsychotic drugs and/or benzodiazepines, at the start of therapy. If lithium alone is ineffective for recurrent bipolar mood disorder, combining it or replacing it with car-bamazepine or valproate may be of value reports with lamotrigine and olanzapine are also encouraging. 

While there are no absolute contraindications to lithium, patients with advanced kidney disease or unstable fluid/ electrolyte balance may be more safely treated with an alternative mood stabilizer, such as carbamazepine, valproate, lamotrigine, or olanzapine. 

In a double-blind study of 344 patients inadequately responsive to lithium or valproate who were randomized to olanzapine or lithium for 6 weeks, 21% gained weight on lithium plus olanzapine compared with 4.9% taking lithium and placebo (632). Whether lithium contributed to weight gain in the olanzapine group is unclear. 

Tohen M, Chengappa KN, Suppes T, Zarate CA Jr, Calabrese JR, Bowden CL, Sachs GS, Kupfer DJ, Baker RW, Risser RC, Keeter EL, Feldman PD, Tollefson GD, Breier A. Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy. Arch Gen Psychiatry 2002 59(l) 62-9. 

The efficacy of adding olanzapine to either valproate or lithium alone in acute manic or mixed bipolar episodes has been studied in a 6-week, double-blind, randomized, placebo-controlled trial (110). Compared with valproate or lithium alone, the addition of olanzapine provided better efficacy. Olanzapine was associated with somnolence, dry mouth, weight gain, increased appetite, tremor, and slurred speech. 

Although mania has been associated with olanzapine (SEDA-24, 68 SEDA-25, 68 SEDA-26, 62), it has also been used in the treatment of acute mania. In a 12-week, double-blind, double-dummy, randomized trial, 120 patients with bipolar disorder type I hospitalized for an acute manic episode were randomly assigned to either sodium valproate (n = 63) or olanzapine (n = 57) and were followed in hospital for up to 21 days (60). Valproate and olanzapine had similar short-term effects on clinical or health-related quality of life outcomes in bipolar disorder adverse effects that occurred in a higher percentage of olanzapine-treated than valproate-treated patients included somnolence (47% versus 29%), weight gain (25% versus 10%), rhinitis (14% versus 3%), edema (14% versus 0%), and slurred speech (7% versus 0%) no adverse events occurred significantly more often with valproate. 

In a recent pooled analysis, three previously published trials have been reviewed to compare the efficacy, safety, and tolerability of oral-loaded valproate with standard-titration valproate, lithium, olanzapine, or placebo in patients with acute mania associated with bipolar I disorder (61). Valproate loading was as well tolerated as the other active treatment or better tolerated, as measured by adverse events and changes in laboratory parameters, and was of better efficacy than placebo however, there were... 

In a placebo-controlled study of the addition of olanzapine for 6 weeks to lithium or valproate in 344 manic... 

A 17-year-old woman who was taking valproate 1000 mg/day and olanzapine 20 mg/day was changed to olanzapine monotherapy 25 mg/day after 12 days her white blood cell count fell to 3.9 x 109/1 and the absolute neutrophil count to 1.2 x 109/1 the counts returned to baseline when olanzapine was withdrawn (207). 

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