Ziprasidone and aripiprazole

Ziprasidone 40 to 160 mg/day appears to have efficacy similar to other SGAs, with response rates increasing at doses greater than 80 mg daily. Aripiprazole has established efficacy at 15 to 30 mg/day. ° Both aripiprazole and ziprasidone have significantly less potential to produce weight gain than other SGAs. 

Olanzapine, quetiapine, and risperidone are preferred alternative atypicals aripiprazole and ziprasidone are newer agents and may initially cause akathisia-like reactions clozapine is usually reserved for treatment-resistant mania or mixed states. 

Several modem, better-tolerated antipsychotic agents (olanzapine, quetiapine, and risperidone) have recently received FDA approval for use in acute mania. There is also evidence of antimanic efficacy for aripiprazole and ziprasidone. Olanzapine is FDA-approved for its long-term effectiveness in bipolar disorder 1. Other atypical antipsychotic drugs are under investigation for long-term prophylactic treatment of bipolar disorder. 

Moteshafi H, Stip E. Comparing tolerability profQe of quetiapine, risperidone, aripiprazole and ziprasidone in schizophrenia and affective disorders a meta-analysis. Expert Opin Drug Saf 2012 ll(5) 713-32. 

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. 

Aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone are FDA approved for the treatment of acute manic episodes in bipolar I disorder. 

Priapism Rare cases of priapism have been associated with risperidone, ziprasidone, quetiapine, aripiprazole, and olanzapine. 

Gl dysmotility Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Use quetiapine, ziprasidone, risperidone, olanzapine, aripiprazole, and others cautiously in patients at risk for aspiration pneumonia. Hypersensitivity reactions Patients who have demonstrated a hypersensitivity reaction (eg, blood dyscrasias, jaundice) with a phenothiazine should not be re-exposed to any phenothiazine unless the potential benefits of treatment outweigh the possible hazards. 

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. 

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. 

Aripiprazole, 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 he needed for some patients with recurrent mania or mixed states, hut 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). 

Adverse Neurological Effects Many neurological syndromes, particularly involving the extrapyramidal motor system, occur following the use of most antipsychotic drugs, especially with the high-potency D -receptor antagonists (tricyclic piperazines and butyrophenones). Acute adverse extrapyramidal effects are less likely with aripiprazole, clozapine, quetiapine, thioridazine, and ziprasidone, or low doses of olanzapine or risperidone. 

A challenging special population is Parkinson s disease patients with psychotic symptoms related to dopaminergic therapy (see Chapter 20). Standard neuroleptics, risperidone (even in small doses), and olanzapine often produce unacceptable worsening of bradykinesia-akinesia. Clozapine is relatively well tolerated and effective, though more complicated to use. Use of moderate doses of newer agents withvery low risk of parkinsonism (aripiprazole, quetiapine, ziprasidone) requires further study. 

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