Affective and anxiety disorders are 3-4 times more common among adult diabetics than they are in the general population. The course of these illnesses in diabetics is particularly chronic compared to similarly afflicted patients who are otherwise medically well. These psychiatric disorders are associated with poor glucose regulation, but the mechanism or importance of this association is not fully understood. It is well recognized that poor metabolic control in diabetics is associated with increased complications of this chronic disease, yet no information from systematic studies is available to determine if treatment of the psychiatric disorder will have a beneficial impact on glucose regulation. This information would have direct clinical relevance. In this proposal a novel, controlled, double-blinded study is planned to examine the effects of conventional psychotropic agents on glucose regulation in diabetic subjects with actively symptomatic affective or anxiety disorders. Fifty diabetics with major depression, 50 with generalized anxiety disorder, and 50 without psychiatric illness will participate. All subjects will have poorly controlled diabetes (HbAl>10%). Treatment with therapeutic dosages of nortriptyline or alprazolam will be utilized (for depression and anxiety respectively); psychiatrically well patients in each treatment arm will also receive similar dosages of these agents. Thus, the study design is capable of determining if any resultant effects of this pharmacotherapy on glucose regulation are independent of measurable effects on psychiatric illness. Compliance behavior will be comprehensively assessed via serial monitoring of nortriptyline plasma levels, memory glucometers, and electronic monitors which record the date and time medication is removed from a dispensing device. A followup of all patients is planned to study: the course of these psychiatric disorders in diabetes and; 2. the relationship of treatment outcome to subsequent utilization of health services and to patients' economic productivity.
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