Ziprasidone Less Effective for Bipolar Patients With Elevated BMI

HONOLULU – The antipsychotic ziprasidone does not appear to work as well in patients with bipolar disorder who are either obese or hyperglycemic, according to a study funded by the drug’s maker, Pfizer.

Among 267 acutely manic patients on ziprasidone (Geodon) monotherapy for 2-3 weeks, those with body mass indexes below 28.8 kg/m² were about twice as likely to respond to ziprasidone or go into remission during treatment than were those with BMIs above 28.8 kg/m², which roughly defines the border between being overweight and obese.

Among other findings, 52% of patients below that cut-off responded to treatment; for those above it, the response rate was 37%.

Meanwhile, patients with randomly tested blood glucose levels below 140 mg/dL were more than three times more likely to go into remission and more than five times more likely to respond to treatment than were those with blood glucose levels at or above 140 mg/dL, a level rarely reached in people with normal glucose metabolism.

More than half of patients with randomly tested glucose levels below 140 mg/dL – but only 16% of patients who tested at or above that level – responded to treatment.

Obese and hyperglycemic patients also showed less improvement on Global Assessment of Functioning scores. The findings all were statistically significant.

"Patients with bipolar disorder who have elevated blood glucose and/or elevated BMI do not respond as well to ziprasidone treatment of acute mania" and "may have a lower probability of responding" to antipsychotics in general, said lead author Dr. Roger S. McIntyre, associate professor of psychiatry and pharmacology at the University of Toronto.

Obese patients might need higher-than-typical doses to overcome greater body mass, but that’s "not clear at this point. You can increase the drug dose all you want; it may not make any difference," said Dr. McIntyre, who also is head of the mood disorders psychopharmacology unit at University Health Network in Toronto.

In any case, he said the findings offer another good reason to encourage patients to lose weight, and also argue for using antipsychotics such as ziprasidone that are less likely than others to cause weight gain, since excess weight now appears to diminish the effects of antipsychotics.

The problem with hyperglycemia might be related to insulin dysregulation; there’s emerging consensus "that insulin dysregulation manifesting as hyperglycemia might be neurotoxic," Dr. McIntyre noted.

He and his colleagues pooled data from previous Pfizer studies to gauge the effects of BMI on response. "It’s intuitive if you have an [elevated] BMI, that the psychopharmacotherapies you are taking would have different distributions and different concentrations, [but] it’s almost never been studied," Dr. McIntyre said.

Based on the results, the research community needs to rethink the effect of BMI on response, he said. "It’s an important way to stratify data."

The patients in the study were at least moderately manic, with baseline Mania Rating Scale scores of 14 or greater. Remission was defined by a score dropped below 10 by the study’s end; response was defined by a greater than 50% score reduction.

HONOLULU – The antipsychotic ziprasidone does not appear to work as well in patients with bipolar disorder who are either obese or hyperglycemic, according to a study funded by the drug’s maker, Pfizer.

Among 267 acutely manic patients on ziprasidone (Geodon) monotherapy for 2-3 weeks, those with body mass indexes below 28.8 kg/m² were about twice as likely to respond to ziprasidone or go into remission during treatment than were those with BMIs above 28.8 kg/m², which roughly defines the border between being overweight and obese.

Among other findings, 52% of patients below that cut-off responded to treatment; for those above it, the response rate was 37%.

Meanwhile, patients with randomly tested blood glucose levels below 140 mg/dL were more than three times more likely to go into remission and more than five times more likely to respond to treatment than were those with blood glucose levels at or above 140 mg/dL, a level rarely reached in people with normal glucose metabolism.

More than half of patients with randomly tested glucose levels below 140 mg/dL – but only 16% of patients who tested at or above that level – responded to treatment.

Obese and hyperglycemic patients also showed less improvement on Global Assessment of Functioning scores. The findings all were statistically significant.

"Patients with bipolar disorder who have elevated blood glucose and/or elevated BMI do not respond as well to ziprasidone treatment of acute mania" and "may have a lower probability of responding" to antipsychotics in general, said lead author Dr. Roger S. McIntyre, associate professor of psychiatry and pharmacology at the University of Toronto.

Obese patients might need higher-than-typical doses to overcome greater body mass, but that’s "not clear at this point. You can increase the drug dose all you want; it may not make any difference," said Dr. McIntyre, who also is head of the mood disorders psychopharmacology unit at University Health Network in Toronto.

In any case, he said the findings offer another good reason to encourage patients to lose weight, and also argue for using antipsychotics such as ziprasidone that are less likely than others to cause weight gain, since excess weight now appears to diminish the effects of antipsychotics.

The problem with hyperglycemia might be related to insulin dysregulation; there’s emerging consensus "that insulin dysregulation manifesting as hyperglycemia might be neurotoxic," Dr. McIntyre noted.

He and his colleagues pooled data from previous Pfizer studies to gauge the effects of BMI on response. "It’s intuitive if you have an [elevated] BMI, that the psychopharmacotherapies you are taking would have different distributions and different concentrations, [but] it’s almost never been studied," Dr. McIntyre said.

Based on the results, the research community needs to rethink the effect of BMI on response, he said. "It’s an important way to stratify data."

The patients in the study were at least moderately manic, with baseline Mania Rating Scale scores of 14 or greater. Remission was defined by a score dropped below 10 by the study’s end; response was defined by a greater than 50% score reduction.

HONOLULU – The antipsychotic ziprasidone does not appear to work as well in patients with bipolar disorder who are either obese or hyperglycemic, according to a study funded by the drug’s maker, Pfizer.

Among 267 acutely manic patients on ziprasidone (Geodon) monotherapy for 2-3 weeks, those with body mass indexes below 28.8 kg/m² were about twice as likely to respond to ziprasidone or go into remission during treatment than were those with BMIs above 28.8 kg/m², which roughly defines the border between being overweight and obese.

Among other findings, 52% of patients below that cut-off responded to treatment; for those above it, the response rate was 37%.

Meanwhile, patients with randomly tested blood glucose levels below 140 mg/dL were more than three times more likely to go into remission and more than five times more likely to respond to treatment than were those with blood glucose levels at or above 140 mg/dL, a level rarely reached in people with normal glucose metabolism.

More than half of patients with randomly tested glucose levels below 140 mg/dL – but only 16% of patients who tested at or above that level – responded to treatment.

Obese and hyperglycemic patients also showed less improvement on Global Assessment of Functioning scores. The findings all were statistically significant.

"Patients with bipolar disorder who have elevated blood glucose and/or elevated BMI do not respond as well to ziprasidone treatment of acute mania" and "may have a lower probability of responding" to antipsychotics in general, said lead author Dr. Roger S. McIntyre, associate professor of psychiatry and pharmacology at the University of Toronto.

Obese patients might need higher-than-typical doses to overcome greater body mass, but that’s "not clear at this point. You can increase the drug dose all you want; it may not make any difference," said Dr. McIntyre, who also is head of the mood disorders psychopharmacology unit at University Health Network in Toronto.

In any case, he said the findings offer another good reason to encourage patients to lose weight, and also argue for using antipsychotics such as ziprasidone that are less likely than others to cause weight gain, since excess weight now appears to diminish the effects of antipsychotics.

The problem with hyperglycemia might be related to insulin dysregulation; there’s emerging consensus "that insulin dysregulation manifesting as hyperglycemia might be neurotoxic," Dr. McIntyre noted.

He and his colleagues pooled data from previous Pfizer studies to gauge the effects of BMI on response. "It’s intuitive if you have an [elevated] BMI, that the psychopharmacotherapies you are taking would have different distributions and different concentrations, [but] it’s almost never been studied," Dr. McIntyre said.

Based on the results, the research community needs to rethink the effect of BMI on response, he said. "It’s an important way to stratify data."

The patients in the study were at least moderately manic, with baseline Mania Rating Scale scores of 14 or greater. Remission was defined by a score dropped below 10 by the study’s end; response was defined by a greater than 50% score reduction.