Atypical Antipsychotics with the Lowest Risk of Weight Gain

September 30, 2011 · Posted in Current Treatments 

Possible Weight GainThere is a major problem of overweight and obesity in the US, with about 50% of the population affected. Patients with mood disorders, and particularly bipolar disorder, appear to be at increased risk for weight gain, which often accompanies depression. Thus, it is important that when treating these patients, doctors prescribe medications with low likelihood of weight gain.

Among the atypical antipsychotics that are widely used not only in schizophrenia but also in bipolar disorder and sometimes as adjunctive treatments in unipolar depression, there are wide differences in potential for weight gain and alterations in metabolic indices such as cholesterol, triglycerides, and blood glucose. Clozapine and olanzapine convey the greatest risk for abnormalities in these indices; risperidone and quetiapine convey moderate risk, and aripiprazole and ziprasidone are the least likely to affect metabolic indices. Newly approved lurasidone also has a mild side-effects profile.

The atypical ziprasidone (Geodon) appears to be truly weight-neutral and to have minimal impact on metabolic indices, but is not widely used due to two potential complications, neither of which must necessarily cause problems. One is the difficulty of dose titration with this drug. Surprisingly, low doses of the drug may be somewhat activating. (Atypicals are usually sedating.) Studies suggest that starting treatment with higher doses or increasing doses more quickly may be better tolerated. So rather than starting at 20mg twice a day, 40mg twice a day with rapid increases towards the range of 80mg twice a day may be associated with better tolerability.

Ziprasidone must be taken with food, because absorption on an empty stomach leads to much lower bioavailability and lower blood levels of the drug, which could further obscure the therapeutic efficacy of the drug.

The other reason for hesitation about prescribing ziprasidone is concern about its ability to increase the QTc interval, a measure of electrical activity in the heart. An increased QTc interval is theoretically associated with an increased risk of serious cardiac arrhythmias. However, there is ample recent data from post-marketing surveillance and formal clinical trials that suggest that the ability of ziprasidone to increase the QTc interval is not likely to be problematic. Among these studies was a randomization of 18,000 patients, half to olanzapine, which does not increase the QTc interval, and half to ziprasidone, which does. Incidence of cardiac events was similar in both groups. These and other data suggest that initial concerns about increases in the QTc interval precipitating cardiac arrhythmias should no longer preclude the use of this drug.

In addition to data from formal controlled clinical trials, new data on the naturalistic use of ziprasidone in a substantial number of patients in the STEP-BD Network is also available.

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