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Medication Access Alert: Should the Risk of Diabetes Limit Atypical Antipsychotic Medication Access?

Recently in Texas, efforts were mounted to require prior authorization for olanzapine (and not other atypical antipsychotic medications) based on the assumption that this medication produces a greater risk of diabetes. While the outcome in Texas is not final, we believed it would be useful for NAMI leaders to understand the risks posed by antipsychotic medications and the policy implications. Our review leads us to the following conclusions:

  • NAMI policy opposes prior authorization approaches to limit access to medications.
  • Research has not yet made clear the differential risk of diabetes and other metabolic side-effects of antipsychotic medications.
  • All medications pose both benefits and risks, including the risk of diabetes; consumers and clinicians must work together to identify the optimal pharmacotherapy.
  • Clinicians and consumers can be guided in their decision-making by such mechanisms as medication algorithms, which provide research-based information and may lead to cost savings.
  • All consumers taking antipsychotic medications must be provided information about the early signs of diabetes and how they can minimize this risk.
  • Further research is needed to discern the differential impact of antipsychotic medications and to lead to the development of new and more effective agents.

NAMI will be releasing further information on managing the risks of psychotropic medications in the months ahead.

Medication Access Issues

First, we must remind ourselves of the environment in which decisions about medication access are being made: severe fiscal situations in most states’ budgets and double digit growth in costs of the state Medicaid programs—including rapidly rising pharmaceutical costs (although medicines still make up but a small part of the overall Medicaid budget). As you know, limiting medication access generally, and psychotropic medication access specifically, has become one of the levers by which state policy-makers have sought to cut Medicaid costs. Many of you are engaged in medication access wars and may see this argument emerge as policy-makers continue to seek to control medication costs.

Another reminder is NAMI’s position on the issue: persons with severe mental illness should be prescribed medications based on sound clinical judgment for the individual patient and not on the basis of macro-economic factors. NAMI opposes the use of Medicaid prior authorization programs to control prescription drug costs, as they are blunt and high risk cost containment strategies that evidence shows will not work in the long-term, either in terms of reducing overall health spending or promoting optimal treatment outcomes. A full discussion of NAMI’s position on medication access can be found in the NAMI Policy Research Institute’s January 2003 Task Force Report "Access to Medication."

Before summarizing the research on diabetes risks posed by atypical antipsychotic medications, another point must be emphasized. No medication, including no atypical antipsychotic medications, is risk free. Unfortunately, research to date does not clarify how any one particular antipsychotic medication will affect an individual patient—positively or negatively. Therefore, prescription drug decision-making necessarily must occur one consumer at a time, with the consumer and the clinician considering the potential benefits and risks of a medication for the individual.

That does not mean that health policy and clinical guidance cannot improve medication use. Studies have shown that most clinicians fail to put into practice what the best research evidence reveals about medication choices. Therefore, policy-makers can help improve prescription practices by implementing strategies such as medication algorithm programs --that help guide clinicians and consumers in a science-based and systematic way, but mindful of individual preferences and experiences, in the selection of pharmacologic agents. Recent data suggest that such an approach can even save systems money. The bottom line is that states have options for improving health care in a fiscally responsible way, without resorting to mindless restriction of access to essential medications.

Diabetes Risk in Schizophrenia

The risk of diabetes associated with atypical antipsychotic medications must be understood in the context of diabetes risks in general. Research has indicated that diabetes is more common among people with schizophrenia and that the prevalence of diabetes is increasing in the general population.

Many studies suggest that antipsychotic medications, both old and newer ones, impact, to varying extents, weight, glucose metabolism, lipid metabolism, and the new occurrence or exacerbation of diabetes mellitus. Case reports have also been published on the development of diabetic ketoacidosis, which is rare but associated with severe risks and even death.

The mechanism by which antipsychotic medications may lead to or exacerbate diabetes is not known. And while most of the previous reports link clozapine or olanzapine to changes in blood glucose and lipid metabolism and diabetes, reports have also been published showing the linkage with risperidone, quetiapine, and older antipsychotic medications.

Below is a summary of articles reporting data from various kinds of studies on the issue of diabetes and schizophrenia treatment, excluding case reports, published since January 2001 and listed on PubMed. Seven studies are summarized.

Sernyak and colleagues reported on the linkage between neuroleptic treatment and diabetes found through a large database in the VA. Specifically, the presence of diabetes was analyzed among 38,632 patients, 15,984 of whom received older neuroleptics and 22,648 who received clozapine, olanzapine, risperidone, or quetiapine. Individuals who received an atypical neuroleptic were 9 percent more likely to have diabetes than those receiving an older neuroleptic, even when controlling for age. The prevalence of diabetes was significantly increased for patients who received clozapine, olanzapine, and quetiapine, but not risperidone. However, for patients less than 40 years old, all of the atypical neuroleptics were associated with an increased prevalence of diabetes.

In another study by Sernyak and colleagues, fasting blood glucose problems , previously unidentified, was found to be common among veterans taking clozapine, especially among older patients and those diagnosed with bipolar disorder.

Another study published by Reginold and colleagues also showed a link between increased levels of blood glucose problems and diabetes among patients with bipolar disorder and schizoaffective disorder, regardless of medication.

Lund and colleagues examined an Iowa Medicaid database to discern incident rates for diabetes and hyperlipidemia among patients receiving older antipsychotic medications and clozapine. No difference was found overall, however among young patients a significantly increased risk of diabetes and hyperlipidemia was found with clozapine use.

Koro and colleagues examined data from the United Kingdom based General Practice Research Database, which contains data from approximately 400 general practices with 3.5 million patients in England and Wales. New cases of diabetes for 19,637 patients with schizophrenia between the years 1987 and 2000 were examined. 451 patients developed diabetes over a mean follow-up time of 5.2 years. The incidence rate was calculated as 4.4 per 1000 person years among this population, with 10.0/100 per years for olanzapine, 5.4/1000 person years for risperidone, and 5.1/1000 person years for conventional antipsychotics. All persons taking antipsychotic medications were found to have an increased risk of diabetes. Olanzapine use was more highly linked to diabetes when compared with the other antipsychotic medications.

Lindenmayer and colleagues, in the only prospective study identified in the literature search, examined blood glucose and cholesteral changes among 157 patients taking clozapine, olanzapine, or haloperidol. Clozapine, olanzapine, and haloperidol resulted in significant increases in blood glucose. Clozapine and olanzapine were associated with an increase in cholesterol levels. Weight gain was noted in all treatment groups but not associated with the blood glucose and cholesterol changes.

Meyer examined the charts of 94 patients under 60 years of age at Oregon State Hospital who entered during July and August of 1999 to discern any association between disruptions in lipid and glucose metabolism and the atypical antipsychotic medications olanzapine and risperidone. While both groups showed similar changes in weight, greater metabolic changes were seen in individuals taking olanzapine. Weight gain was enhanced by lithium for both groups, but weight gain did not correlate with the glucose and lipid metabolic changes.

In conclusion, while some of the published research literature links clozapine and olanzapine more closely than other antipsychotic medications to blood glucose and lipid problems as well as diabetes, all antipsychotic medications significantly impact metabolism and weight. Further research is needed to clarify the variable risks associated with specific medications and metabolic disorders as well as the mechanism by which the disruptions are caused. It is critical, however, that blood glucose and lipid levels and diabetes be routinely monitored for in all individuals with schizophrenia and especially among those taking any antipsychotic medications or with a personal or family history of diabetes. Further research is needed to develop more effective antipsychotic medications with fewer side-effects.


Dixon, L., et al., "Prevalence and Correlates of Diabetes in National Schizophrenia Samples," Schizophrenia Bulletin 26:903-912, 2000.

Koro, C.E., et alk, "Assessment of Independent Effect of Olanzapine and Risperidone on Risk of Diabetes Among Patients with Schizophrenia: Population Based Nested Case-Control Study," British Medical Journal 325: 1-5, 2002.

Lindenmayer et al., "Changes in Glucose and Cholesterol Levels in Patients with Schizophrenia Treated with Typical or Atypical Antipsychotics," American Journal of Psychiatry 160: 290-296, 2003.

Meyer, J.M., "A Retrospective Comparison of Weight, Lipid, and Glucose Changes Between Risperidone- and Olanzapine-Treated Inpatients: Metabolic Outcomes After 1 Year," J Clin Psychiatry 63(5): 425-33, 2002

Regenold, W.T., et al., "Increased Prevalence of Type 2 Diabetes Mellitus Among Psychiatric Inpatients with Bipolar I Affective and Schizoaffective Disorders Independent of Psychotropic Drug Use," J Affect Disord 73(3): 301-2, 2003.

Ryan, M.C., et al., "Impaired Fasting Glucose Tolerance in First-Episode, Drug-Naïve Patients with Schizophrenia," American J Psychiatry 160(2): 284-9, 2003.

Sernyak, M.J., et al., "Association of Diabetes Mellitus with Use of Atypical Neuroleptics in the Treatment of Schizophrenia," The American Journal of Psychiatry, 159: 561-566, 2002.

Sernyak, M.J., et al., "Undiagnosed hyperglycemia in Clozapine-treated Patients with Schizophrenia," J Clin Psychiatry 64(5): 605-8, 2003.