Marie Fallon St Columba s Hospice Chair of Palliative Medicine University of Edinburgh Depression in Cancer EAPC Glasgow 2010
Are cancer pain and depression interdependent? Laird BJA, Boyd AC, Colvin LA, Fallon MT. Psycho-oncology 2008
Background 90% of cancer patients experience pain Depression most common psychiatric condition in cancer patients ~ 25% Combined prevalence of 22-49% As pain and depression often present together is there a possible interdependent relationship? Caraceni, Portenoy. Pain 1999;82(3):263-74 Lloyd-Williams et al. Palliat Med 2004;18(6):568-63 Laird et al. Psycho-Oncol 2008 DOI: 10.1002/pon.1431
Cancer Pain Affected by many variables. 1 Present in 90% of patients. 80% cancer pain controllable by WHO ladder. 2 20% cancer pain difficult to control 1. Andersen G, Sjogren P. [Epidemiology of cancer pain]. Ugeskr Laeger 1998;160(18):2681-4. 2. Ventafridda V, Tamburini M, Caraceni A, De Conno F, Naldi F. A validation study of the WHO method for cancer pain relief. Cancer 1987;59(4):850-6.
Depression Most common psychiatric condition in cancer 1 Approx 1 in 4 patients 4 x as common ~ general population 2 Under diagnosed 3 1. Lloyd-Williams M, Dennis M, Taylor F. A prospective study to determine the association between physical symptoms and depression in patients with advanced cancer. Palliat Med 2004;18(6):558-63. 2. Derogatis LR, Morrow GR, Fetting J, Penman D, Piasetsky S, Schmale AM, et al. The prevalence of psychiatric disorders among cancer patients. JAMA 1983;249(6):751-7. 3. Block SD. Assessing and managing depression in the terminally ill patient. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians - American Society of Internal Medicine. Ann Intern Med 2000;132(3):209-18.
Why is depression so common? Common in general population Multiple losses, future uncertain and feared Pain, constipation, metabolic upsets, drug SE Cancer effect Clinicians increasingly aware Other conditions misdiagnosed as depression
Pain & depression non cancer ARTIST study 1 2000 patients Pain is a strong predictor of depression Patients with severe pain ~ 4x less likely to respond to depression txt. As pain decreased, depression treatment response increased 1. Bair MJ, Robinson RL, Eckert GJ, Stang PE, Croghan TW, Kroenke K. Impact of pain on depression treatment response in primary care. Psychosom Med 2004;66(1):17-22.
Methods Medline (1950-2007), Embase (1988-2007), CINAHL (1982-2007) and the Cochrane Database of Systematic Reviews (Issue 2 2007). search terms cancer AND pain AND depression, using MeSH terms; all subheadings were included. Results were limited to English language journals and studies involving humans. Hand-searched: Palliative Medicine, Journal of Pain and Symptom Management, Progress in Palliative Care and the European Journal of Palliative Care. The date of the last literature search was 19 th June 2007.
Inclusion Criteria Cancer patients of any tumour type, at any stage of the disease. Define depression using a recognised tool. Eligible studies also had to assess pain. Studies were required to explore the relationship between the two variables, pain and depression. Systematic reviews were deemed eligible.
Exclusion Criteria Not a cancer population Depression and pain not defined Studies which did not present original material were excluded, as were critical and narrative reviews. Non-malignant disease were also excluded
Results 892 articles identified. The titles reviewed by one author and if appropriate, selected for further analysis. 167 abstracts reviewed in greater detail and possibly relevant selected for further analysis. 41 articles reviewed independently by two authors. Fourteen articles appropriate for inclusion
Excluded articles pain and/or depression were not defined, relationship between these two entities was not examined. 3 reviews, 2 qualitative studies, one crossover trial, one intervention study, one consensus statement one paper examining views of caregivers. failed to define depression and instead looked at general areas such suffering - clear boundaries and definition are lacking.
Reference Sample size Depression Assessment Cross sectional Studies Pain Assessment Lin CC et al 484 POMS BPI Heim and Oei 47 BDI MPQ Sze FK et al 70 HADS VAS Ciaramella and Poli 100 SCID+ VAS Endicott Mystakidou et al 120 HADS BPI Chen et al 203 HADS VAS Glover et al 369 POMS Numerical Aukst-Margetic et al 115 CES-D VAS Kelsen et al 130 BDI MPAC Sist et al 190 BDI MPQ Mystakidou et al 82 BDI BPI Spiegel et al 96 POMS /CES-D Cohort Studies VAS Zimmerman et al 60 BSI MPQ Williamson and Schulz 268 CES-D Numerical
Reference Depression Assessment tool Depression Prevalence (%) Sist et al BDI 22.1 Sze et al HADS 29.0 Ciaramella and Poli SCID + Endicott 49.0 Spiegel et al SCID 46.0 POMS Profile of Mood States, BDI Beck Depression Inventory, HADS Hospital Anxiety and Depression Score, SCID Structured Clinical Interview for Depression, CES-D Centre for Epidemiological Studies Depression Scale, Endicott Endicott diagnostic criteria for depression BPI Brief Pain Inventory, MPQ McGill Pain Questionnaire, VAS Visual Analogue Score MPAC Memorial Pain Assessment Card
Epidemiology of cancer pain & depression Different tools makes assessment difficult Prevalence varies depending on tools used Mean prevalence 36.5% Depression least prevalent using BDI highest using SCID Depression more prevalent when pain severity is increased Pain less severe depression less prevalent Depression more common in females and older patients
Pain Intensity Correlated positively with depression (p<0.05) 1,2,3 Depressed patients higher pain intensity than non depressed patients. 2 Increased pain increased depression 4 1. Kelsen DP, Portenoy RK, Thaler HT, Niedzwiecki D, Passik SD, Tao Y, et al. Pain and depression in patients with newly diagnosed pancreas cancer. J Clin Oncol 1995;13(3):748-55. 2. Sist TC, Florio GA, Miner MF, Lema MJ, Zevon MA. The relationship between depression and pain language in cancer and chronic non-cancer pain patients. Journal of Pain & Symptom Management 1998;15(6):350-8. 3. Ciaramella A, Poli P. Assessment of depression among cancer patients: the role of pain, cancer type and treatment. Psycho- Oncology 2001;10(2):156-65 4. Spiegel D, Sands S, Koopman C. Pain and depression in patients with cancer. Cancer 1994;74(9):2570-8.
Pain descriptors MPQ descriptors Depressed patients higher affective pain intensity scores + affective pain descriptors Punishment and tension sections chosen by patients with pain and depression Worst pain & enjoyment of life (BPI) correlated significantly with depression. 1 1. Mystakidou K, Tsilika E, Parpa E, Pathiaki M, Patiraki E, Galanos A, et al. Exploring the relationships between depression, hopelessness, cognitive status, pain, and spirituality in patients with advanced cancer. Arch Psychiatr Nurs 2007;21(3):150-61
Pain duration Longer the duration of pain greater the risk of depression 1,2 As pain increases over time so does depressed affect 3 1. Kelsen DP, Portenoy RK, Thaler HT, Niedzwiecki D, Passik SD, Tao Y, et al. Pain and depression in patients with newly diagnosed pancreas cancer. J Clin Oncol 1995;13(3):748-55. 2. Glover J, Dibble SL, Dodd MJ, Miaskowski C. Mood states of oncology outpatients: does pain make a difference? Journal of Pain & Symptom Management 1995;10(2):120-8. 3. Williamson GM, Schulz R. Activity restriction mediates the association between pain and depressed affect: A study of younger and older adult cancer patients. Psychology & Aging 1995;10(3):369-378.
Are pain and depression interdependent? Highly prevalent Specific pain features are related to depression Pain depression closely linked common central pathways Associated but not enough evidence to assign causality
Are cancer pain and depression interdependent? Laird BJA, Boyd AC, Colvin LA, Fallon MT. Psycho-oncology 2008. DOI: 10.1002/pon.1431 SR of literature examining pain and depression in cancer 14 papers met eligibility criteria Pain intensity, duration and certain descriptors (MPQ) associated with depression. Pain and depression both highly prevalent Certain pain features correlated with depression Not possible to assess causality No appropriately designed longitudinal studies to assess the relationship between pain and depression
What happens when pain is treated?
Overview A secondary analysis of two existing clinical trial datasets Patients attending one of two regional oncology centres in the UK All patients had CIBP Pain > 4 (0-10) All patients received palliative radiotherapy for CIBP Life expectancy > 2 months Patients permitted analgesia and anti-depressant medication during the course of the study Pain treated No intervention given for depression
Baseline BPI HADS Pain intervention 4 8 weeks Endpoint BPI HADS BPI Brief Pain Inventory Multidimensional pain assessment tool Extensively validated Pain intensity & interference Daut, Cleeland. Pain 1983;17(2):197-210 Portenoy, Payne. Pain 1999;81(1-2):129-34 HADS Hospital Anxiety & Depression Scale Assesses pain and depression Validated in cancer population Combined score >15 Major depressive disorder Zigmond, Snaith. Acta Psych Scand 1983;67(6):361-70 Walker et al. J Psych Res 2007;63(1):83-91
Pain Responder: total BPI score decreased > 30% Non-Responder: total BPI score decreased < 30% Depression Combined HADS score > 15 Distress Combined HADS score >10 Statistics Analysis was undertaken of all patients. Divided into responders and non-responders. Baseline BPI and HADS summarised using medians and IQR Fishers exact test was performed.
RESULTS
Demographics 69 patients - 50 Pain improved (responders) Mean age: 67.1 years (SD 10.4, range 38-88) Characteristic n % Sex Male 40 58 Female 29 42 Type of cancer Prostate 26 38 Breast 24 35 Lung 14 20 Melanoma 1 1 Renal 1 1 Colorectal 1 1 Larnyx 1 1 Bladder 1 1
Medication Baseline 62 (90%) taking strong opioids Mean MEDD 76mg 2 patients taking antidepressants Endpoint 59 (86%) taking strong opioids Mean MEDD 90mg Same2 patients taking antidepressants
Baseline & Endpoint: HADS BPI HADS Baseline Total Endpoint Total Non-Responders Median (IQR) 11(8-16) 14(8-17) Responders Median (IQR) 10(8-14) 6 (4-11) BPI Baseline Total Endpoint Total Non-Responders Median (IQR) 52(38-61) 55(39-65) Responders Median (IQR) 49(34-62) 11 (2-20)
Pain and depression not adjusted for baseline p=0.0203 Not Depressed (at endpoint) Depressed (at endpoint) Non-Responders 11 (57.9%) 8 (42.1%) Responders 43 (86.0%) 7 (14.0%) Pain and depression adjusted for baseline p=0.06 NOT Depressed at BASELINE (n=51) Not Depressed (at endpoint) Depressed (at endpoint) Depressed at BASELINE (n=18) Not Depressed (at endpoint) Depressed (at endpoint) Non- 9 (69.2%) 4 (30.1%) 2 (33.3%) 4 (66.7%) Responders Responders 35 (92.1%) 3 (7.9%) 8 (66.7%) 4 (33.3%)
Pain and distress not adjusted for baseline p=0.0048 NOT Distressed Distressed (at endpoint) (at endpoint) Non-Responders 6 (31.6%) 13 (16.4%) Responders 36 (72.0%) 14 (28.0%) Pain and distress adjusted for baseline p=0.07 NOT Distressed at BASELINE (n=31) Not Distressed (at endpoint) Distressed (at endpoint) Distressed at BASELINE (n=38) Not Distressed (at endpoint) Distressed (at endpoint) Non- 4 (57.1%) 3 (42.9%) 2 (16.7%) 10 (83.3%) Responders Responders 23 (95.8%) 1 (4.2%) 13 (50.0%) 13 (50.0%)
Effect of Pain on HADS score Mean change (S.D.) minimum, maximum Non-Responders 0.73 (5.36) -10, 8 (n=19) Responders (n=50) -2.52 (5.47) -16, 18 F-test p=0.006. Difference in LS means=4.6 In those whose pain improved, HADS score reduced
Results - Summary Treating pain reduces the HADS score If pain does not improve, the HADS score increases A trend towards an improvement in depression and distress when pain is treated Findings suggests a possible unidirectional relationship between pain and depression/distress Supports the theory that depression and distress may be influenced by pain, but not vice-versa.
Limitations Defining depression and distress Small sample size Heterogeneous population Other variables difficult to minimize effect of these e.g. clinical trial Medications
A Relationship between Pain and Could be at two levels: Depression One symptom may impact directly on the other pain may cause distress, depression may magnify pain Common underlying pathways Same areas of cerebral cortex Shared Neurotransmitters Norepinephrine and 5-HT (involved in depression and descending pain pathways)..likely to be a combination of these