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.

We examined issues of criterion validity and detection of depression employing the Zung Self-Rating Depression Scale (ZSDS) as a "lab test" to trigger follow-up interviews of ambulatory oncology patients by oncology staff and the possibility of subsequent algorithm-based antidepressant treatment. Sixty oncology patients were screened with the ZSDS and then interviewed using the Mini-International Neuropsychiatric Interview (MINI). We examined the sensitivity and specificity of various cutoffs on the ZSDS and a briefer version, the Brief Zung Self-Rating Depression Scale (BZSDS) as they predicted results of the MINI, which was used as the criterion. Mean age of patients was 58.3 years (SD = 11.9). Thirty-two were female (53.3%) and 28 were male (46.7%). The correlation of the ZSDS (r = -0.66, P <.0001) and BZSDS (r = -0.57, P <.0001) with the MINI overall suggested acceptable levels of criterion validity. Additionally, we examined various cutoff scores on the ZSDS and BZSDS to explore the false negative and false positive rates that are associated with each. For example, using the mild cutoff on the Zung (score > 48) to determine depression or adjustment disorder, 14 false negatives and 2 false positives were found. When the more stringent moderate cutoff (score > 56) was used, 25 false negatives and 0 false positives were found. Oncology staff can utilize such data to make decisions about where to set cut-offs that trigger follow-up based on the amount of error that is allowable in their attempts to identify depressive symptoms in their patients. We discuss that such decisions might be based on many factors including the resources available in a particular site for follow-up or the comfort of particular oncologists and nurses managing and prescribing psychotropic medications, or in providing supportive counseling.

We examined oncologists' and nurses' ability to recognize depressive symptoms in two cancer patients who were interviewed on videotape. The study was conducted in a rural community, hospital-based outreach network. Staff were given a one-hour in-service on the use of the Mini International Neuropsychiatric Interview (MINI)-a brief diagnostic interview-to provide a differential diagnosis (no psychiatric diagnosis, major depressive disorder, or adjustment disorder with depressed mood). Next, the staff viewed a videotape of an investigator (S.P.) utilizing the MINI to interview two depressed breast cancer patients. Staff subsequently rated depressive symptoms on the MINI and made a diagnosis. Findings indicated a high concordance among staff regarding symptom ratings on a straightforward example of major depressive disorder. Concordance on diagnosis, severity level, and specific symptoms declined slightly on a more difficult case involving primarily cognitive symptoms and a diagnosis of adjustment disorder. Following brief didactic training on depressive disorders, oncologists and nurses were able to identify depressive symptoms in cancer patients on videotape. Learning to use a semistructured interview can increase oncologists' awareness of depressive symptoms and may be a good training model.

Helping oncologists to identify and treat depression is an important step in improving the overall care of people with cancer. In previous work performed in our community-based, ambulatory oncology outreach network, we validated a depression screening tool, put into place depression screening programs, and taught oncologists how to follow up on screening with brief, reliable clinical interviews. Subsequently, we provided these oncologists with a fluoxetine-based antidepressant algorithm to follow for the treatment of their depressed patients. In this article, we report on the initial experience identifying and treating 35 ambulatory oncology patients who were screened with the Zung Self-rating Depression Scale (ZSDS). Structured follow-up interviews by their oncologist determined whether the patients qualified for a diagnosis of a major depressive episode. These patients then received 1 of 4 treatments based on the algorithm (no treatment, fluoxetine alone, fluoxetine plus bedtime doxepin, or fluoxetine plus methylphenidate). Patients were matched by their oncologist to a prototype patient for each treatment arm based on their symptomatic presentation (i.e., patients requiring a side effect minimization approach were to be placed on fluoxetine alone; patients who had significant insomnia, weight loss, or neuropathic pain were placed on the fluoxetine plus doxepin regimen; those with prominent fatigue were to receive fluoxetine plus methylphenidate). Patients were followed weekly for one month, and then every two weeks for two more months, with telephone assessments of their depression, associated symptoms and overall quality of life. Results suggested that oncologists most often chose the simplest regimen (fluoxetine alone) but that patients uniformly benefited in terms of improved mood and overall quality of life throughout the 12 weeks of follow-up. Our initial experience suggests that oncologists can be empowered to recognize and treat depression in their patients with a screen-and-intervene approach. Such an approach may benefit patients, and, if kept simple, can be incorporated into day-to-day care of people with cancer.