Ziprasidone lithium

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. 

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). 

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 Blockade of 5HT2A receptors > blockade of D2 receptors Some a blockade (clozapine, risperidone, ziprasidone) and M-receptor blockade (clozapine, olanzapine) variable receptor blockade (all) Schizophrenia—improve both positive and negative symptoms bipolar disorder (olanzapine or risperidone adjunctive with lithium) agitation in Alzheimer s and Parkinson s (low doses) major depression (aripiprazole) Toxicity Agranulocytosis (clozapine), diabetes (clozapine, olanzapine), hypercholesterolemia (clozapine, olanzapine), hyperprolactinemia (risperidone), QT prolongation (ziprasidone), weight gain (clozapine, olanzapine)... 

Two patients with schizoaffective illness developed new signs of mild lithium toxicity after intramuscular injections of ziprasidone (610). 

In 34 healthy men, ziprasidone did not alter serum lithium concentrations or renal lithium clearance (640). 

In a placebo-controlled, open-label study in 25 healthy subjects there were no changes in serum lithium concentration or renal lithium clearance when ziprasidone (40-80 mg/day) was added for 7 days (640). 

Apseloff G, Mullet D, Wilner KD, Anziano RJ, Tensfeldt TG, Pelletier SM, Gerber N. The effects of ziprasidone on steady-state lithium levels and renal clearance of lithium. Br J Chn Pharmacol 2000 49(Suppl 1) 61S-4S. 

Pfizer, the marketing authorization holder of ziprasidone, has promoted several pharmacokinetic studies. Oral contraceptives (ethinylestradiol 30 pg/day plus levonorgestrel 150 pg/day) (34), lithium 900 mg/day (35), ketoconazole 400 mg/day (36), and carbamazepine (100-400 mg/day)... 

Ziprasidone does not appear to aiter the pharmacokinetics of lithium. 

A randomised, placebo-controlled study in 25 healthy subjects taking lithium carbonate 450 mg twice daily for 15 days, found that ziprasidone 20 mg twice daily on days 9 to 11, followed by 40 mg twice daily on days 12 to 15 caused only a small increase in the steady-state serum-lithium levels (14% compared with 11% in the placebo group). A 5% reduction in renal clearance was seen in the ziprasidone group and a 9% reduction was seen in the placebo group. These differences were neither statistically nor clinically significant. No special precautions would therefore seem to be necessary if ziprasidone is given to patients taking lithium. 

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