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Commentary: When medical illness complicates schizophrenia and bipolar disorder

Vol. 3, No. 12 / December 2004

Patients with schizophrenia or bipolar disorder face a higher risk of premature death, compared with the general population. Their overall mortality rate is elevated not only by higher suicide rates but also by higher rates of medical comorbidities, including obesity, diabetes mellitus, cardiovascular and pulmonary diseases, HIV infection, and cancer.1,2

Schizophrenia and bipolar disorder are also frequently complicated by psychiatric comorbidities including alcohol and substance use disorders (such as nicotine dependence), anxiety disorders, and eating disorders (such as binge eating).3,4 Even so, the impact of psychiatric comorbidity on medical morbidity and mortality has not been adequately investigated and has—until rather recently—received little attention from clinical researchers.

Within the past 5 years or so, epidemiologic and population studies have shown increased morbidity and mortality from medical illnesses in patients with serious and persistent mental illness.5,6 These findings have sparked renewed interest in behavioral, biological, and psychosocial factors associated with schizophrenia and bipolar disorder that may contribute to comorbid medical illnesses. These factors include:

  • negative and depressive symptoms
  • physical inactivity and poor diet
  • hypothalamic-pituitary-adrenal axis dysregulation associated with acute psychotic and affective episodes
  • amotivation
  • social isolation
  • limited access to primary and preventive health care. 7

The degree to which these factors may elevate medical comorbidity rates in patients with Commentary these serious psychiatric illnesses has not been well-studied or described.


These observations raise concerns about safe and effective use of medications by patients with schizophrenia or bipolar disorder as well as medical illness. Issues for clinicians to consider include:

  • possible pharmacokinetic and pharmacodynamic interactions in patients taking concomitant medications for psychiatric and medical illnesses
  • potential beneficial and adverse effects of psychotropics on medical illnesses
  • and—conversely—potential beneficial and adverse effects on mood and psychotic disorders of medications used to treat medical illnesses.

Being aware of metabolic effects when prescribing psychotropics is not a new idea. Lithium, for example, has long been known to cause weight gain, suppress thyroid hormone, and interact with thiazide diuretics when used to treat bipolar disorder. Thus, therapeutic blood monitoring is recommended for patients receiving acute and maintenance lithium therapy.

More recently, atypical antipsychotics such as olanzapine and clozapine (and risperidone and quetiapine to a lesser extent) have been shown to produce substantial weight gain and other metabolic effects that increase the risk of diabetes and cardiovascular disease.7 As a result, the American Diabetes Association—along with the American Psychiatric Association and other groups—now recommends that psychiatrists and other physicians monitor patients’ body weight and body mass index, vital signs, serum glucose, and lipids when prescribing these agents.7-11 Careful monitoring should improve the medical care of patients with schizophrenia and bipolar disorder and help protect them from the medical risks associated with overweight and obesity.

Similar precautions are needed when schizophrenia and bipolar disorder co-occur with other medical illnesses treated by complex pharmacologic regimens, such as pulmonary disease, cancer, and HIV. Three points to keep in mind are:

  • careful selection of treatments for co-occurring medical illnesses, considering potential effects on the primary psychiatric disorder
  • the impact of psychotropics on patients’ medical illnesses
  • and the potential for drug interactions.


1. Kilbourne AM, Cornelius JR, Han X, et al. Burden of general medical conditions among individuals with bipolar disorder. Bipolar Disord 2004;6:368-73.

2. Meyer JM, Nasrallah HA. Medical illness and schizophrenia Washington, DC: American Psychiatric Press, Inc, 2003.

3. McElroy SL, Altshuler LL, Suppes T, et al. Axis I psychiatric comorbidity and its relationship with historical illness variables in 288 patients with bipolar disorder. Am J Psychiatry 2001;158:420-6.

4. Green AI, Canuso CM, Brenner MJ, et al. Detection and management of comorbidity in patients with schizophrenia. Psychiatr Clin North Am 2003;26:115-39.

5. Buda M, Tsuang MT, Fleming JA. Causes of death in DSM-III schizophrenics and other psychotics (atypical group). Comparison with the general population. Arch Gen Psychiatry 1988;45:283-5.

6. Osby U, Brandt L, Correia N, et al. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry 2001;58:844-50.

7. Keck PE, Jr, Buse JB, Dagago-Jack S, et al. Managing metabolic concerns in patients with severe mental illness: a special report (Postgrad Med). Minneapolis, MN: McGraw-Hill, 2003.

8. American Diabetes Association. Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care 2004;27:596-601.

9. Marder SR, Essock SM, Miller AL, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry 2004;161:1334-9.

10. Chue P, Kovacs CS. Safety and tolerability of atypical antipsychotics in patients with bipolar disorder: prevalence, monitoring and management. Bipolar Disord 2003;5(suppl 2):62-79.

11. Nasrallah HA, Newcomer JW. Atypical antipsychotics and metabolic dysregulation. Evaluating the risk/benefit equation and improving standard of care. J Clin Psychopharmacol 2004;24(suppl 2):S7-S14.

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