Steven D. Passik

A new tool to assess and document pain outcomes in chronic pain patients receiving opioid therapy.

BACKGROUND Opioid analgesics are the cornerstone of management for malignant pain. Their use in managing chronic, nonmalignant pain, albeit controversial, has increased in recent years. The decisions about whether to initiate opioid therapy or continue it over time should be guided by a comprehensive patient assessment. During long-term treatment, this assessment should focus on a broad range of outcomes, each of which should be documented in the medical record. OBJECTIVE The goal of this study was to develop an instrument, the Pain Assessment and Documentation Tool (PADT), to focus on key outcomes and provide a consistent way to document progress in pain management therapy over time. METHODS Items that assess 4 domains (pain relief, patient functioning, adverse events, and drug-related behaviors) were generated with input from a MEDLINE literature search and experts in pain and addiction management. The original tool was field tested by clinicians who applied it to the assessment of patients receiving long-term opioid therapy for the management of chronic, nonmalignant pain. Data analysis and debriefing telephone interviews with a formalized set of questions were then used to rephrase, delete, and refine items to create the final tool. RESULTS A 6-member expert panel contributed to the initial development of the PADT. Twenty-seven clinicians completed the preliminary version of PADT for 388 patients. The original 59-item tool was modified to create a 41-item tool. The revised PADT was formatted for use as a chart note designed to assist clinicians in assessing and documenting 4 main outcome domains during long-term opioid use. CONCLUSIONS In this study, the PADT appeared to be a useful tool for clinicians to guide the evaluation of several important outcomes during opioid therapy and provide a simple means of documenting patient care.

Fluoxetine Versus Placebo in Advanced Cancer Outpatients: A Double-Blinded Trial of the Hoosier Oncology Group

PURPOSE To determine whether fluoxetine improves overall quality of life (QOL) in advanced cancer patients with symptoms of depression revealed by a simple survey. PATIENTS AND METHODS One hundred sixty-three patients with an advanced solid tumor and expected survival between 3 and 24 months were randomly assigned in a double-blinded fashion to receive either fluoxetine (20 mg daily) or placebo for 12 weeks. Patients were screened for at least minimal depressive symptoms and assessed every 3 to 6 weeks for QOL and depression. Patients with recent exposure to antidepressants were excluded. RESULTS The groups were comparable at baseline in terms of age, sex, disease distribution, performance status, and level of depressive symptoms. One hundred twenty-nine patients (79%) completed at least one follow-up assessment. Analysis using generalized estimating equation modeling revealed that patients treated with fluoxetine exhibited a significant improvement in QOL as shown by the Functional Assessment of Cancer Therapy-General, compared with patients given placebo (P =.01). Specifically, the level of depressive symptoms expressed was lower in patients treated with fluoxetine (P =.0005), and the subgroup of patients showing higher levels of depressive symptoms on the two-question screening survey were the most likely to benefit from treatment. CONCLUSION In this mix of patients with advanced cancer who had symptoms of depression as determined by a two-question bedside survey, use of fluoxetine was well tolerated, overall QOL was improved, and depressive symptoms were reduced.

A Phase I Trial of Olanzapine (Zyprexa) for the Prevention of Delayed Emesis in Cancer Patients: A Hoosier Oncology Group Study

Chemotherapy-induced delayed emesis (DE) can affect up to 50% to 70% of patients receiving moderately and highly emetogenic chemotherapy, although rates are improving. DE most commonly occurs within the first 24 to 48 hours of chemotherapy administration and can persist for 2 to 5 days. Olanzapine, due to its activity at multiple dopaminergic, serotonergic, muscarinic, and histaminic receptor sites, has potential as antiemetic therapy. A phase I study was designed with olanzapine, using a four-cohort dose escalation of 3 to 6 patients per cohort, for the prevention of DE in cancer patients receiving their first cycle of chemotherapy consisting of cyclophosphamide, doxorubicin, platinum, and/or irinotecan. All patients received standard premedication. Olanzapine was administered on days − 2 and − 1 prior to chemotherapy and continued for 8 days (days 0–7). Episodes of vomiting as well as daily measurements of nausea, sedation, and toxicity were monitored at each dose level. Fifteen patients completed the protocol. No grade 4 toxicities were seen, and three patients experienced a dose-limiting toxicity (grade 3) of a depressed level of consciousness during the study. The maximum tolerated dose appeared to be 5 mg (for days − 2 and − 1) and 10 mg (for days 0–7). Four of six patients receiving highly emetogenic chemotherapy (cisplatin, ≥ 70 mg/m2) and nine of nine patients receiving moderately emetogenic chemotherapy (doxorubicin, ≥ 50 mg/m2) had complete control (no vomiting episodes) of DE. Therefore, olanzapine may be an effective agent for the prevention of chemotherapy-induced DE. A phase II trial is underway.

Opioid therapy in patients with a history of substance abuse.

A range of aberrant drug-taking behaviours can occur in patients who are undergoing treatment for chronic pain, especially if opioid therapy is involved. Assessing and understanding these behaviours, and their relationship to addiction (or substance use disorder), can be difficult but it is necessary for assuring quality pain management. Aberrant drug-taking behaviour may be evident, for example, when a patient with pain is unilaterally escalating doses of opioids or using the medications to treat other symptoms or when prescriptions are being mishandled. In patients with a history of substance abuse, these are often serious developments to which a clinician must know how to react. These complex behaviours may be indicative of addiction or may be simply a reaction to under-medicated pain. The clinician therefore is challenged to understand such behaviours and plan interventions accordingly.Although it is becoming increasingly common to avoid opioid therapy in patients demonstrating such challenging behaviours for fear of regulatory scrutiny, clinical management can be tailored to address the many possibilities that might be giving rise to such behaviours. In addition, control over prescriptions can be accomplished without necessarily terminating the prescribing of controlled substances entirely. Optimal medical management of chronic pain in those patients with addiction problems or engaging in problematic behaviours involves careful, ongoing assessment by the clinician as well as a tailored management approach. This approach should use multiple structures including strict contracts, prudent drug selection and frequent follow-ups to pain and addiction treatments, including the use of urine toxicology screening, to maximise the likelihood of a good outcome.

A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients.

Chemotherapy-induced delayed emesis (DE) affects approximately 50-70% of patients receiving moderately and highly emetogenic chemotherapy. DE most commonly occurs within the first 24-48 hours of chemotherapy administration and can persist for 2-5 days. Olanzapine, which has been used anecdotally for chronic nausea in advanced cancer patients, might be a useful treatment for the prevention of delayed emesis in chemotherapy patients. We conducted a chart review to explore this hypothesis and to plan potential studies. Using pharmacy records or an electronic medical record, we identified all patients who had received olanzapine in the oncology clinic (n = 98). We reviewed these records and selected all patients (n = 28) who had received olanzapine for the prevention of delayed emesis for structured review. There were 17 women (60.7%) and 11 men (39.3%). Eleven patients (39.3%) had at least one instance of nausea recorded while undergoing olanzapine treatment and seven (25%) had an episode of vomiting recorded. During 95 total cycles of chemotherapy with olanzapine (mean = 3.4 cycles per patient), there were 21 incidents of nausea (22.1%) and 10 instances of vomiting (10.5%). Side effects were rarely noted. These data suggest that olanzapine was well tolerated and may reduce the incidence of delayed emesis in patients receiving moderate to highly emetogenic chemotherapy. A series of prospective trials are underway.

Use of a Depression Screening Tool and a Fluoxetine-Based Algorithm to Improve the Recognition and Treatment of Depression in Cancer Patients: A Demonstration Project

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.

Initial validation of a scale to measure purposelessness, understimulation, and boredom in cancer patients: Toward a redefinition of depression in advanced disease

OBJECTIVE The problem of boredom in people with cancer has received little research attention, and yet clinical experience suggests that it has the potential to profoundly affect quality of life in those patients. We were interested in developing a Purposelessness, Understimulation, and Boredom (PUB) Scale to identify this problem and to begin to differentiate it from depression. METHODS Cancer patients and professionals were interviewed using a semi-structured format to elicit their perceptions of the incidence, causes, scope, and consequences of boredom. From their responses, 45 questions were developed, edited for clarity, and piloted. A total of 100 cancer patients were recruited to participate in the study. Preliminary validation of the PUB using a cross-sectional survey of the measure was conducted. Other instruments used for purposes of convergent and divergent validity included the Functional Assessment of Cancer Therapy Scale-Anemia, Zung Self-Rating Depression Scale, Boredom Proneness Scale, Leisure Boredom Scale, Cancer Behavior Inventory, Systems of Belief Inventory, and the Eastern Cooperative Oncology Group Performance Status Scale. RESULTS The average age of the sample was 62.37 years (SD = 13.43) and was comprised of 60 women (60.00%) and 40 men (40.00%). The results of a factor analysis on the 45 initial items (selected on the basis of professional and patient interviews) created a two-factor scale. The eight items from the strongest factor (items 1, 2, 3, 4, 5, 6, 9, 10) seemed to best tap the construct that could be deemed as overt boredom whereas the six items of the second factor (items 36, 38, 39, 42, 44, 45) seemed to tap the construct of boredom related to meaning and spirituality. Total scale internal consistency, when all 14 items were included in the analysis, yielded a coefficient alpha of 0.84 and good test-retest reliability at 2 weeks (r = .80, p < .001). The novel 14-item PUB Scale was significantly correlated to other measures of boredom; the Boredom Proneness Scale (r = -.588, p < .001) and the Leisure Boredom Scale (r = .576, p < .001). SIGNIFICANCE OF RESULTS The PUB Scale was found to be a statistically viable tool with the ability to detect boredom and differentiate it from depression. In many respects this work is in concert with much of the current research and clinical effort going on in psycho-oncology that defines components of distress that in sum, redefines depression in advanced cancer.

Difficulties in screening for adjustment disorder, Part I: Use of existing screening instruments in cancer patients undergoing bone marrow transplantation

OBJECTIVE Although success rates for bone marrow transplantation (BMT) continue to improve, there is still a high level of morbidity and physical and emotional distress associated with BMT. To date, limited research has focused on the assessment of and screening for specific psychiatric disorders of patients facing BMT. This is especially true with regard to identifying adjustment disorder (AD), despite the fact that AD is the most prevalent psychiatric diagnosis in cancer patients. METHODS A sample of 95 BMT patients were interviewed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (SCID) and completed several commonly used self-report instruments to determine if these tools could be used to identify patients with adjustment disorder in need of further assessment and intervention. RESULTS Of these patients, 34.7% were diagnosed with adjustment disorder, 11.6% with major depression, and 5.3% with generalized anxiety disorder. The instruments were not found to be predictive of AD. However, the results of a regression analysis showed that the Social Subscale of the Functional Assessment of Cancer Therapy-General (R2 delta = 0.04, F = 4.30, p < 0.05) was a significant predictor of adjustment disorder. SIGNIFICANCE OF RESULTS We conclude that there is little efficacy in using existing scales for detecting adjustment disorders in cancer patients undergoing bone marrow transplantation, and that other tools for identifying patients with adjustment disorder who might benefit from counseling are needed.

A feasibility study of dignity psychotherapy delivered via telemedicine.

OBJECTIVE Dignity Psychotherapy has shown great promise as a value-affirming intervention for patients with advanced disease. We delivered the Dignity Psychotherapy intervention in a feasibility study of a series of eight cancer patients via videophone technology to deliver the therapy into their homes. METHODS Once eligible patients were consented on this IRB-approved study, they completed baseline assessments and were scheduled to have the videophone placed in their homes. The Dignity Therapy sessions then encompassed a first session, which was transcribed and edited, followed by a second session to go over the edited transcript and allow the patient to make changes. Patients then filled out follow-up questionnaires and had the telemedicine equipment removed from their homes, and their legacy document delivered. RESULTS Participants had a mean age of 56.32 years (range = 41-66, SD = 7.65) and were diagnosed with lung (n = 5, 62.5%), breast (n = 2, 25%), or colon cancer (n = 1, 12.5%). They reported overall benefit from the intervention along with a high level of satisfaction. We were able to deliver the intervention in a timely fashion, with minimal length between sessions and transcript delivery and few technical difficulties. SIGNIFICANCE OF RESULTS Telemedicine can greatly extend the benefits of Dignity Psychotherapy by bringing it to patients who are dying at home. Our very preliminary work suggests that delivering the intervention to patients who are too ill to leave their homes or who are in rural locations may be a feasible way to help them.

An open label pilot study of citalopram for depression and boredom in ambulatory cancer patients.

OBJECTIVE Significant levels of depressive symptoms are an impediment to adjustment and affect greater than one-third of people with cancer. The clinical diagnosis of major depression is estimated to occur in 25%. Depression is dramatically underrecognized by oncologists and oncology nurses, and as a result, often undertreated. Clinical experience suggests that antidepressants of virtually all types are well tolerated and potentially efficacious. There is, however, a lack of an evidence base for the use of antidepressants in cancer patients. METHODS We undertook an open-label pilot study using citalopram in 30 cancer patients who reported a high level of depressive symptoms on the Zung Self-Rating Depression Scale (ZSDS). In addition to the ZSDS, eligible patients completed a series of visual analog scales for pain, depression, and sleep disturbance; the Functional Assessment of Cancer Therapy-General Module; and the Purposelessness, Understimulation, and Boredom Scale developed by the research team. Patients began a 2-month course of therapy with citalopram 20 mg, increasing to 40 mg at the end of the fourth week if the patient was in the same range of depressive symptoms as measured by the ZSDS. RESULTS Twenty-one of 30 patients completed the protocol. The average age of the sample was 57.32 years (SD = 12.6) and was comprised of 11 women (52.4%) and 10 men (47.6%). Depressive symptoms decreased and quality of life improved during the 8-week treatment period. Of special interest was the rate of improvement in boredom, and using the total boredom score of the PUB, significant improvement compared to baseline was seen in weeks 6 (F = 5.266, p < .05) and 8 (F = 9.248, p < .01). SIGNIFICANCE OF RESULTS Overall, the positive findings suggest the need for a randomized, double-blind, placebo-controlled trial of citalopram in cancer patients. Regarding the interplay of boredom and depression, the relationship between improvements in depressive symptoms and boredom is complex. This is illustrated by the way in which the different elements respond to antidepressant treatment. Depression began to improve almost immediately upon initiation of treatment whereas improvement in boredom does not become evident until week 6.