These data suggest that AIDS patients with histories of substance abuse receiving opioid therapy are more symptomatic, have more distress, experience more interference from residual pain, and engage in more problematic drug-related behaviors than patients with no history of drug abuse receiving opioids for cancer pain. Treatment of substance abusers with pain requires skills that complement best practices in opioid prescribing. Better approaches to the long-term treatment of these populations are needed.

This open-label pilot study explored the antiemetic activity of olanzapine, an atypical antipsychotic, in patients with advanced cancer requiring opioid analgesics for pain. Fifteen patients received 2 days of a washout and placebo "run-in" followed by two day periods on each of three doses of olanzapine (2.5 mgs, 5 mgs, and 10 mgs). Patients completed a daily food journal as well as the Mini Mental State Exam, Simpson Angus Scale, Barnes Akathisia Scale, and the Functional Assessment of Cancer Therapy-General across four time periods, with special attention being placed on the nausea item. Eleven women and 4 men with varied primary cancer sites participated. The average age of the sample was 58 years (SD = 16.8). All three dose levels were associated with significant reductions in nausea compared to baseline. Diary entries recorded by the subjects suggested substantial benefits to overall well being and the 5mg condition was associated with statistically significant improvement in overall quality of life over baseline (F = 12.0, p < 0.005). No extrapyramidal symptoms were noted and mental status exams were not changed over the course of the eight days. These results suggest an antiemetic effect for olanzapine and indicate the need for a controlled trial.

We performed a pilot open-label, crossover trial of mirtazapine (15 and 30 mg at night) in advanced cancer patients with pain and other distressing symptoms. Twenty patients completed the trial and sixteen dropped out. Following a baseline assessment, patients completed a one-week observation period and were then randomized to a starting dose of either 15 mg or 30 mg of mirtazapine given at bedtime. After three weeks, subjects were switched to the alternate dose and followed by an additional three-week period, completing the treatment. The average age of the completers was 60.2 years and consisted of 7 women and 13 men. The majority were Caucasian (n = 18, 90%) and married (n = 18, 90%). The drop-out group did not significantly differ from the completers based on age, gender, race, marital status, or tumor type. We examined the impact of mirtazapine therapy on patients' levels of depression, pain intensity, appetite, insomnia, weight, and overall quality of life. A series of repeated measures ANOVAs were conducted to compare the completers' status at Weeks 1, 4, and 7 compared to baseline and to examine the interaction with starting dose and baseline observations. Scores on the Zung self-rating Depression Scale (F = 8.20, P < 0.05) and the Functional Assessment of Cancer Therapy - General Measure (F = 5.73, P < 0.05) were significantly improved at study end (Week 7) and were not dependent on mirtazapine dosage. Patients' weights were significantly higher at both Week 4 and Week 7, independent of dosage. Trend level differences were found on Memorial Pain Assessment Card items for pain, pain relief, and mood and on numeric rating scales measuring nausea, anxiety, insomnia, and appetite. This open-label pilot study suggests that mirtazapine may be effective for improving multiple symptoms, depression and quality of life in patients with advanced cancer. A controlled trial of this drug would be valuable.

The assessment of addiction-related outcomes is crucial to the management of chronic pain with opioid drugs in all patients. Pain management for patients who have concomitant drug abuse or addiction issues is a particularly complex task involving a need for a common nomenclature as well as empirically derived data to support management strategies during treatment regimens. Complicating the issue is the notion of pseudoaddiction, which is an abuse of medications driven by unrelieved pain that appears on the surface to be very similar to the behavior patterns of addicts. For proper adherence to medical therapy and safety during treatment, it is necessary to address and manage substance abuse-related behaviors. Aberrant drug-taking behavior presents many threats to the integrity of pain treatment. Unfortunately, the current state of the art still has a long way to go before clear guidelines for treatment and management can emerge. What is ultimately needed is a broad-based spectrum of research that highlights the epidemiology of drug-taking behaviors for different medical illnesses ranging from cancer to back pain. This article focuses on some of these issues as well as recounting attempts by our research group to address these issues systematically in hopes of shedding light on the nature of abuse issues in the medically ill. Although advances have been made, there is a definite need for large-scale studies that address the issues of identification and treatment of aberrant behavior in medically ill patients in the effort to provide the best possible outcomes for patients with chronic pain.

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