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To investigate the role of psychiatric history and psychologic adjustment on aberrant drug-related behavior among patients prescribed opioids for noncancer pain.Two hundred twenty-eight patients prescribed opioids for chronic pain were classified as either high or low on psychiatric morbidity on the basis of their responses on the psychiatric subscale of the Prescription Drug Use Questionnaire (PDUQ). They also completed the Brief Pain Inventory (BPI), Screener and Opioid Assessment for Pain Patients (SOAPP), and the Current Medication Misuse Measure (COMM). Patients were followed for 5 months and submitted a urine toxicology screen, and their treating physician completed the Prescription Opioid Therapy Questionnaire (POTQ). On the basis of the results from the SOAPP, COMM, POTQ, and urine screens, patients were classified as positive or negative on the Drug Misuse Index (DMI).One hundred and three (N=103) of the patients (45%) were classified in the low psychiatric group (Low Psych) whereas 55% (N=125) were classified in the high psychiatric morbidity group (High Psych). High Psych patients were significantly younger than Low Psych patients and had been taking opioids longer (P<0.05). The High Psych group showed significantly higher SOAPP and COMM scores than the Low Psych patients (P<0.001), had a greater frequency of abnormal urine toxicology screens (P<0.01), and significantly higher scores on the DMI (P<0.001). A consistent association was found between psychiatric morbidity and prescription opioid misuse in chronic pain patients.Psychiatric factors, such as a history of mood disorder, psychologic problems, and psychosocial stressors, may place patients at risk for misuse of prescription opioids. Future studies to elucidate the risk of medication misuse and aberrant drug behavior among this patient population are needed.