(845) Psychiatric comorbidity diminishes opioid analgesia inpatients with discogenic low back pain

A. Wasan, G. Davar, R. Jamison; Brigham and Women‘s Hospital/Harvard Med-ical School, Boston, MAPsychiatric comorbidity (primarily depression, anxiety, or neuroticism)afflicts approximately 50% of all patients with chronic pain and dimin-ishes the effectiveness of many treatments. In cancer and postoperativepain, psychiatric comorbidity increases opioid requirements. This studytests the hypothesis that psychiatric comorbidity diminishes opioid an-algesia in patients with low back pain. In an ongoing trial, 75 patientswith chronic discogenic low back pain (confirmed by history, exam, andMRI) are enrolled in a double blind, placebo controlled, crossover de-signed trial of intravenous morphine (4-6 mg dosed by ideal bodyweight) vs. placebo. Patients are stratified into three groups of psychi-atric symptom severity (LOW, MOD, and HIGH), based on compositescores on depression, anxiety for pain, and neuroticism scales, using theBeck Depression Inventory, Pain Anxiety Symptom Scale, and NEO per-sonality inventory. They then receive IV morphine or placebo in randomorder on separate visits and complete a VAS score, pain relief rating,SF-MPQ, and lumbar flexion/extension measurements every 20 minutesfor 3 hours. To date, 47 subjects have completed the study (14 HIGHpsych group, 13 MOD psych, and 20 LOW psych). Between groups therewere nonsignificant differences in age, sex distribution, baseline pain(avg. 5.8/10), and morphine dose (5.1mg). On TOTPAR and SPID analyses,subtracting placebo responses, ANOVA reveals that the LOW group had48.3% pain relief vs. only 20% in the HIGH group, p�.028. The LOWgroup had SPID�23.3 vs. 7.9 in the HIGH group, p�.034. High levels ofpsychiatric comorbidity diminish opioid analgesia in patients with disco-genic low back pain. This has implications for the treatment of postop-erative pain with opioids and more importantly, for the prescription oforal opioids in patients with chronic pain and psychiatric comorbidity.These results give impetus for the investigation of mechanisms by whichaffective illness diminishes opioid analgesia.

(846) Transdermal fentanyl is associated with fewer adverseevents than sustained release morphine in patientswith chronic pain

L. Allan, A. Clark, G. Horbay, F. Camacho, R. Vermeulen; Northwick Park & St.Mark‘s NHS Trust, HarrowIndividual clinical trials do not always provide the most accurate inci-dence of adverse events (AEs). Hence a meta-analysis of AE rates wasconducted using comparative data from 8 studies involving over 2500patients receiving transdermal fentanyl (TDF) or sustained release mor-phine (SRM) for chronic pain. Data from studies of 752 patients withcancer pain (CP, 4 studies) and 1773 patients with non-cancer pain (NCP,4 studies) were included in the analysis. Studies had a duration of �28days. All AEs were recoded for consistency and AEs within the first 28days of treatment were tabulated and summarized. Between treatmentincidences of AEs were compared using Fisher’s exact test. Data wereavailable from 1884 patients receiving TDF and 641 receiving SRM. Ofthese, 1349 (72%) in the TDF group and 558 (87%) in the SRM groupreported �1 AE (p�0.001). Incidence rates for 4 of the 5 most commonAEs were significantly lower in the TDF group vs. SRM (constipation 17%vs. 48%, nausea 31% vs. 38%, somnolence 13% vs. 25%, dizziness 8% vs.13%; all p�0.001): vomiting was similar (20% vs. 21%; ND). Age (�70 vs.�70) and weight (�50kg vs. �50kg) subgroups showed similar patterns.Patients with NCP reported a similar incidence of AEs as those with CP(71% vs. 72% for TDF, 87% vs. 86% for SRM) but a lower incidence ofserious AEs (SAE) (TDF: 4% NCP vs. 15% CP, SRM: 4% NCP vs. 33% CP).This was significantly different between treatment groups in the CPpatients (p�0.001). In conclusion, patients receiving TDF for chronic painreported significantly fewer AEs than those receiving SRM. This differ-ence was apparent in all age groups, body weights and pain types. Weconclude that transdermal fentanyl is better tolerated than sustainedrelease morphine. Supported by Janssen-Cilag and Janssen Ortho Inc.

(847) CR-oxycodone for long-term, non-malignant pain treat-ment: Relationship of pain to continuation of treatment

J. Farrar, R. Portenoy, C. Cleeland, M. Backonja, P. Richards, K. Yang, S. Colucci,M. Friedman; Purdue Pharma LP, Stamford, CTThe aim was to evaluate characteristics of subjects who remained onlong-term treatment with controlled-release (CR)-oxycodone HCl (Oxy-Contin®) for moderate-to-severe non-malignant pain. Baseline demo-graphics, dose, and Brief Pain Inventory of subjects who participated inan open-label trial of CR-oxycodone for up to 36 months for osteoar-thritic pain (OA), low back pain (LBP), and diabetic neuropathic pain(DNP) were analyzed. Of 233 subjects enrolled, dosing and safety dataexist for 219 and 227 subjects, respectively. Seventeen percent, 8%, 12%,and 21% discontinued due to adverse events [AE], ineffective treat-ment, lost to follow-up, and other reason, respectively. One hundredforty-one, 86, and 39 subjects have 12, 24, and 36-months data, respec-tively and 61 were still on treatment when study terminated. Racialdistribution and gender did not affect duration in study. Sixty percent ofDNP, 40% of LBP, and 39% of OA subjects had completed 36 months orwere on treatment when study terminated. After initial titration, sub-jects who remained in study had lower average pain score (4.2�0.15) atMonth 3 than subjects who discontinued (5.5�0.33) with differenceseen through Month 15. Subjects who continued had higher mean dailydose (58.2�4.2mg) than those who discontinued (47.7�3.3mg). Baselineaverage pain scores (6.6�0.35) were higher in the subset of subjects whodiscontinued due to ineffective treatment than those who continued(5.8�1.9). Most frequent (�1%) causes of discontinuation due to AE inthe safety population were constipation (4.0%) and nausea (2.6%). Re-lationship of pain to continuation of treatment is complex. Subjects whodiscontinued had more pain and were on lower doses of CR-oxycodonethan those who continued, suggesting inadequate titration of their painmedication. Thus, baseline pain level and pain control on therapy seemto be factors in determining whether subjects remain on treatment.Support for this study provided by Purdue Pharma L.P., Stamford, CT.

(848) Depression and pain: The relationship between chroniclow back pain, depression, and opioid therapy

N. Katz, M. Kosinski, J. Schein, S. Ascher, S. Vallow, C. Harte, G. Vorsanger,M. Clark; QualityMetric Incorporated, Lincoln, RI

Depression and chronic pain are highly prevalent and co-morbid condi-tions. Treatment of co-morbid depression has been shown to improvethe outcomes of several medical conditions; if the same were true forchronic pain this could imply that treatment of depression may improvethe outcomes of opioid or other analgesic treatments. The objective wasto compare pain outcomes – specifically health-related quality of life(HRQoL) scores - in chronic pain patients, stratified by the presence orabsence of depression. Six month, open-label, randomized, multicenter,two-way cross-over study of 229 subjects with chronic non-cancer lowback pain. Patients received transdermal fentanyl for three months fol-lowed by treatment with oxycodone/acetaminophen for three months,or vice versa. Depression was defined with two criteria: a score of �42 onthe SF-36 mental health scale; and a score of �18 on the Beck DepressionInventory (moderate depression). HRQoL outcome scores (based onmodified TOPS and SF-36) were compared based on depression status.Significance testing consisted of Student t-tests for continuous changescores and chi-square tests for categorical changes. Both depressed andnon-depressed patients treated with either transdermal fentanyl or oxy-codone/acetaminophen showed significant improvement in severalHRQoL outcomes, whether using the SF-36 or BDI definition. Relative todepressed patients, non-depressed patients showed significantlygreater improvement in physical functioning (p�0.049), vitality(p�0.035), social functioning (p�0.029), mental health (p�0.022), andthe physical summary scale (p�0.039). Improvements on the TOPS per-ceived disability and total pain summary scales reached statistical signif-icance (p�0.004, and p�0.005, respectively). Patients on concomitantantidepressants experienced greater improvements in SF-36 physicaland mental summary scales and the TOPS total pain summary. Treat-ment of chronic low back pain may be compromised by the presence ofco-morbid depressed mood. Further research is warranted to comparethe outcomes of various pain populations while stratifying by depres-sion status and treatment.

70 Abstracts