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Effects of the withdrawal of opioids and benzodiazepines on cognitive functioning in the context of an interdisciplinary c...
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Effects of the withdrawal of opioids and benzodiazepines on cognitive functioning in the context of an interdisciplinary chronic pain rehabilitation program

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Numerous studies have demonstrated the efficacy of an interdisciplinary approach in the treatment of patients with intractable chronic pain and functional impairment. This approach addresses multiple pathologies in this population, and thus incorporates medical, psychological, physical and occupational rehabilitation.1-6 Opioids and benzodiazepines are widely used in patients with chronic pain and may cause significant undesired effects. It has been suggested that they may not only impair overall functioning but also lead to impaired concentration. These impairments can be further exacerbated by the individual\'s emotional state.7-13 Individuals with chronic pain often experience depression that isolates and further debilitates them.1, 14 Given the extensive affective modulation produced by opioids and benzodiazepines, it is important to determine their contributions to the patient’s function and dysfunction, and to distinguish this from the effects of mood disorder. It was hypothesized that CPRP treatment would lead to improved cognition, and that this benefit would be primarily in those in whom benzodiazepines and opioids were eliminated.
Numerous studies have demonstrated the efficacy of an interdisciplinary approach in the treatment of patients with intractable chronic pain and functional impairment. This approach addresses multiple pathologies in this population, and thus incorporates medical, psychological, physical and occupational rehabilitation.1-6 Opioids and benzodiazepines are widely used in patients with chronic pain and may cause significant undesired effects. It has been suggested that they may not only impair overall functioning but also lead to impaired concentration. These impairments can be further exacerbated by the individual\'s emotional state.7-13 Individuals with chronic pain often experience depression that isolates and further debilitates them.1, 14 Given the extensive affective modulation produced by opioids and benzodiazepines, it is important to determine their contributions to the patient’s function and dysfunction, and to distinguish this from the effects of mood disorder. It was hypothesized that CPRP treatment would lead to improved cognition, and that this benefit would be primarily in those in whom benzodiazepines and opioids were eliminated.

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Transcript of "Effects of the withdrawal of opioids and benzodiazepines on cognitive functioning in the context of an interdisciplinary chronic pain rehabilitation program"

  1. 1. Effects of the withdrawal of opioids and benzodiazepines on cognitive functioning in the context of an interdisciplinary chronic pain rehabilitation program Daniel Fishman MA Judith Scheman PhD Edward Covington MD Neurological Center for Pain, Cleveland Clinic Foundation Hierarchical Linear Regression continued ment. However, no significant difference was observed be- Measures: Study information was collected upon admission to and Mixed 2-way ANOVA Introduction discharge from CPRP. tween groups dummy coded for admission opioid and ben- Multiple Regression Analysis for ΔDSST by AMS, ΔPDI, ΔPI and ΔBDI 15-17 Treatment Effects on DS & DSST zodiazepine status. Recall that the patient’s admission medi- Numerous studies have demonstrated the efficacy of an in- Mood: Assessed with the Beck Depression Inventory – II (BDI-II). (within subjects Mixed 2-way ANOVA) Independent Variable B Std. Error Beta t p  cation status was dummy coded to represent neither opioidsterdisciplinary approach in the treatment of patients with in- 10.27 10.02 AMS -0.34 0.218 -0.122 -1.565 0.120 Cognitive Functioning: Assessed with Digit Span (DS) and Digit Sym- 9.77  or benzodiazepine, opioids alone, benzodiazepines alone, ortractable chronic pain and functional impairment. This ap- bol Substitution Test (DSST). 10, 18 8.75  ΔPDI -0.015 0.017 -0.082 -0.884 0.378proach addresses multiple pathologies in this population,  both classes of medication. Thus the lack of difference be- 0.12 0.109 0.098 1.103 0.272and thus incorporates medical, psychological, physical and Pain Intensity (PI): Assessed via self-report on a 10 point Likert scale, ΔPI tween these groups in cognitive improvement strongly sug- 1-6 -0.077* 0.025 -0.257* -3.014 0.003occupational rehabilitation. Opioids and benzodiazepines with 0 representing no pain and 10 representing the worst pain im- ΔBDI gests that these medications were not a significant cause ofare widely used in patients with chronic pain and may cause aginable. pre-treatment cognitive impairment.significant undesired effects. It has been suggested that they Digit Span Scaled Score Admission Digit Symbol Substitution Scaled Score Discharge *Error bars represent standard error of the mean (SEM) R2 = 0.078; F(1,159) = 9.014 p=0.003may not only impair overall functioning but also lead to im- Pain Related Functioning: Assessed with the Pain Disability Index (PDI) which measures functional impairment secondary to painpaired concentration. These impairments can be further ex-  Digit symbol substitution scaled score improvement was remarkably more pronounced Correlation Matrix and Descriptive Statistics for AMS, ΔPDI, ΔPI, ΔBDI and ΔDSST Hierarchical Linear Regression Modeling (HLRM): The HLRM 7-13 within 7 domains of daily living. Total scores range from 0 (no func- -58 than was digit symbol (F = 496.22, p = 4.31x10 vs F = 6.48, p = 0.012).acerbated by the individuals emotional state. Individuals tional impairment) to 70 (total impairment). 19, 20 ΔDSST AMS ΔPDI ΔPI ΔBDI analyses demonstrate that mood change (ΔBDI) does predictwith chronic pain often experience depression that isolates  The use/discontinuation of opioids and benzodiazepines was not significantly associated ΔDSST AMS 1.000 -0.065 1.000 cognitive improvement (ΔDSST) 1, 14and further debilitates them. Given the extensive affec- with cognitive improvement. ΔPDI -0.127 -0.005 1.000tive modulation produced by opioids and benzodiazepines, it Analyses ΔPI ΔBDI -0.006 -0.235 -0.027 -0.233 0.513 0.373 1.000 0.251 1.000is important to determine their contributions to the patient’s Admission medication status (AMS) was dummy coded to reflect  Within-subjects contrast analysis demonstrated little crossover between treatment and Mean 1.17 2.09 -27.70 -2.70 -13.78 We, therefore, conclude that cognitive inefficiencies AMS (DS*AMS: F = 0.77, p = 0.51; DSST*AMS: F = 0.44, p = 0.72).function and dysfunction, and to distinguish this from the Standard Deviation 3.00 1.08 16.19 2.44 9.95 seen in chronic pain patients may be less a conse- presence of opioids, benzodiazepines, neither, or both.effects of mood disorder. It was hypothesized that CPRP Hierarchical Linear Regression Note: N = 166. ΔDSST is the dependent variable. The correlation between ΔBDI and ΔDSST is quence of sedating drugs than of comorbid moodtreatment would lead to improved cognition, and that this significant at p =0.001. No other correlations were found to be statistically significant Paired samples t-tests were used to compare admission and dis-benefit would be primarily in those in whom benzodiaze- Correlation Matrix and Descriptive Statistics for AMS, ΔPDI, ΔPI, ΔBDI and ΔDS  disorder. charge scores of pain (PI), mood (BDI), and functioning (PDI).pines and opioids were eliminated. ΔDS AMS ΔPDI ΔPI ΔBDI  The overall model generated with AMS, ΔBDI, ΔPDI, & ΔPI as IVs predicting ΔDSST was ΔDS 1.000 found to account for 7.8% of the variance in ΔDSST (R2 = 0.078; F(1,159) = 9.014 Mixed 2-way ANOVA analysis was employed to AMS -0.117 1.000 p=0.003). References Objective 1. compare pre- and post-treatment scores for DS and DSST ΔPDI ΔPI 0.067 -0.039 -0.004 -0.026 1.000 0.509 1.000  Mood (ΔBDI) was found to have a statistically significant, indirect relationship with ΔBDI -0.076 -0.235 0.388 0.270 1.000 cognitive function (ΔDSST; beta = -0.257, t(159) = -3.002, p = 0.003). 1. Adams N, Poole H, Richardson C. Psychological approaches to chronic pain management: part 1. J Clin Nurs. 2006;15(3):290– 2. Compare cognitive changes in those taking and not taking opi- 300. To examine the relationships of: oids/BZs on admission Mean 0.41 2.09 -27.80 -2.71 -13.68  AMS was NOT found to significantly predict ΔDSST. 2. Andrasik F, Flor H, Turk DC. An expanded view of psychological aspects in head pain: the biopsychosocial model. Neurol Sci. 2005;26 Suppl 2:s87–91. Standard Deviation 2.75 1.08 16.10 2.43 9.90 3. Andrasik F, Rime C. Can behavioural therapy influence neuromodulation? Neurol Sci. 2007;28 Suppl 2:S124–9. 1) opioids/benzodiazepines 4. Currie SR, Hodgins DC, Crabtree A, Jacobi J, Armstrong S. Outcome from integrated pain management treatment for recovering Note: N = 165. ΔDS is the dependent variable. None of the correlations were found to be substance abusers. J Pain. 2003;4(2):91–100. 2) mood A Hierarchical linear regression model was then used to determine statistically significant. 5. Karjalainen K, Malmivaara A, van Tulder M, et al. Multidisciplinary biopsychosocial rehabilitation for subacute low back pain among working age adults. Cochrane Database Syst Rev. 2003;(2):CD002193. to cognitive function the extent to which admission medication use vs change in mood Discussion 6. Lemstra M, Olszynski WP. The effectiveness of multidisciplinary rehabilitation in the treatment of fibromyalgia: a randomized controlled trial. Clin J Pain. 2005;21(2):166–74. predicted cognitive gains while controlling for pain and function 7. Deshpande A, Furlan A, Mailis-Gagnon A, Atlas S, Turk D. Opioids for chronic low-back pain. Cochrane Database Syst Rev. 2007; (3):CD004959. Multiple Regression Analysis for ΔDS by AMS, ΔPDI, ΔPI and ΔBDI 8. Dunbar SA, Katz NP. Chronic opioid therapy for nonmalignant pain in patients with a history of substance abuse: report of 20 cas- Methods (ΔPDI & ΔPI). Paired Sample t-tests: The paired t-test analyses demon- es. J Pain Symptom Manage. 1996;11(3):163–171. 9. Gilson AM, Joranson DE. Controlled substances and pain management: changes in knowledge and attitudes of state medical reg- Independent Variable B Std. Error Beta b p strated significant change in BDI, PDI and PI with treatment. ulators. J Pain Symptom Manage. 2001;21(3):227–237. 10. Jamison RN, Schein JR, Vallow S, et al. Neuropsychological effects of long-term opioid use in chronic pain patients. J Pain Symp-Participants: A convenience sample of 225 patients who completedtreatment as well as follow-up in the Cleveland Clinic Chronic Pain Results Mood, function, and pain intensity are arguably the most tom Manage. 2003;26(4):913–21. 11. Martell BA, O’Connor PG, Kerns RD, et al. Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and AMS -0.395 0.203 -0.155 -1.945 0.054 association with addiction. Ann. Intern. Med. 2007;146(2):116–127.Rehabilitation Program (CCCPRP) during the 1999 calendar year. salient outcome measures in the treatment of chronic pain. 12. Mintzer MZ, Stitzer ML. Cognitive impairment in methadone maintenance patients. Drug Alcohol Depend. 2002;67(1):41–51. Paired Sample t-test ΔPDI 0.029 0.016 0.171 1.811 0.072 13. Nedeljkovic SS, Wasan A, Jamison RN. Assessment of efficacy of long-term opioid therapy in pain patients with substance abuse These analyses demonstrate significant benefit of the CPRP potential. Clin J Pain. 2002;18(4 Suppl):S39–51. 68% Female with a mean age of 47 years  ΔPI -0.1 0.102 -0.089 -0.982 0.328 14. Rome JD, Townsend CO, Bruce BK, et al. Chronic noncancer pain rehabilitation with opioid withdrawal: comparison of treat-  Range of duration of pain of 1 – 49 years (Mean = 9.5y) treatment model. ment outcomes based on opioid use status at admission. Mayo Clin. Proc. 2004;79(6):759–768. 15. Cohen A. The underlying structure of the Beck Depression Inventory II: A multidimensional scaling approach. Journal of Re- BDI: t (214) = 20.23, p < 0.001 search in Personality. 2008;42(3):779–786. ΔBDI -0.043 0.024 -0.155 -1.783 0.077 16. Lee EJ, Kim JB, Shin IH, et al. Current Use of Depression Rating Scales in Mental Health Setting. Psychiatry Investig. 2010;7 PDI: t (172) = 21.92, p < 0.001Treatment: 3-4 week intensive (all-day) outpatient, interdisciplinary PI: t (201) = 16.02, p < 0.001 (3):170–176. 17. Segal DL, Coolidge FL, Cahill BS, O’Riley AA. Psychometric properties of the Beck Depression Inventory-II (BDI-II) among com-treatment program including: occupational therapy, physical therapy, R2 = 0.045; F(1,160) = 3.178 p=0.077 Mixed-2-Way ANOVA: The ANOVA analyses demonstrated munity-dwelling older adults. Behavior Modification. 2008;32(1):3–20. 18. Kurita GP, de Mattos Pimenta CA. Cognitive impairment in cancer pain patients receiving opioids: a pilot study. Cancer Nurs. 31relaxation training, psychophysiological pain and stress management, that treatment in the CPRP resulted in significant improve- (1):49–57. 19. Chibnall JT, Tait RC. The Pain Disability Index: factor structure and normative data. Archives of Physical Medicine and Rehabilita-group and individual psychotherapy as well as medication manage- Digit span improvement was not significantly predicted by admission medication use, tion. 1994;75(10):1082–6.ment including weaning from all addictive substances.  ment in cognitive functioning. Furthermore, DSST was 20. Tait RC, Pollard CA, Margolis RB, Duckro PN, Krause SJ. The Pain Disability Index: psychometric and validity data. Archives of depression, function, or pain intensity. (AMS, ΔBDI, ΔPDI, & ΔPI) Physical Medicine and Rehabilitation. 1987;68(7):438–41 *Error bars represent standard error of the mean (SEM) shown to be more sensitive to change resulting from treat-

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