Use of augmenting agents in schizophrenia is a common practice in response to resistant symptoms or comorbid illness. Increasingly, clinicians are combining more than one antipsychotic agent, despite a lack of evidence from controlled studies to support this approach. A rationale can be made for adding higher-potency agents to clozapine in an attempt to optimize D2 dopamine receptor blockade, but this strategy requires further study before it should be adopted in clinical practice. Older reports have explored the use of antidepressants, mood stabilizers, and anxiolytics as augmenting agents. These agents appear to improve comorbid affective or anxiety symptoms, but earlier evidence of improvement in psychotic or negative symptoms has not been replicated consistently. Glutamatergic agents acting at the glycine coagonist site of the N-methyl-D-aspartate receptor, including glycine, D-cycloserine, and D-serine, have demonstrated impressive therapeutic effects for negative symptoms when added to conventional neuroleptic agents, but do not appear to enhance clozapine efficacy. Given the high rates of symptom persistence and disability associated with schizophrenia, the need for augmentation strategies is great, but no approach has clearly emerged as effective for a substantial portion of patients. Although certain approaches may prove helpful for individual patients, augmentation should not be used unless monotherapy has been optimized, and should not be continued long-term unless benefits are clear.

Thomas was a 40-year-old, white male, with a 16-year history of schizoaffective disorder (Slide 1). He first became ill at 24 years of age and had an unstable course for ∼10 years, characterized by frequent hospitalizations and partial adherence. Unfortunately, during episodes of psychosis, he was also extremely violent. During his first hospitalization, risperidone was initiated, which he used intermittently for ∼10 years. There are no records documenting his weight and metabolic parameters at 24 years of age prior to receiving psychiatric medications. During his last psychiatric hospitalization at 34 years of age, olanzapine was prescribed and he stabilized. He entered a period of stable outpatient treatment and had not had a psychiatric hospitalization for 6 years.

When Thomas began taking olanzapine, his weight was 200 lbs, which, given his height, corresponds to a body mass index (BMI) of 28, putting him in the overweight category. However, he had no metabolic monitoring for 3 years. After 3 years of treatment with olanzapine, he had gained substantial weight, increasing to 258 lbs, which corresponds to a BMI of 36 and class 2 obesity.