Supported in part by Arkansas Blue Cross and Blue Shield and the Office of the Arkansas Drug Director and in partnership with the Arkansas Academy of Family Physicians (AAFP), the Arkansas Medical Society (AMS), the Arkansas State Medical Board (ASMB), the Arkansas Department of Health (ADH) and its Division of Substance Misuse and Injury Prevention (Prescription Drug Monitoring Program—PDMP) Continuing Education Credit: TEXT: 501-406-0076 Event ID:29925-24581

Part 1: Depression in the Patient with Chronic Pain Shona Ray-Griffith, MD Assistant Professor University of Arkansas for Medical Sciences

Disclosures I receive clinical trial support from Neuronetics. I have received clinical trial support from Sage Therapeutics. Neither will be discussed today.

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Objectives Define ‘depression’ Review literature exploring the association between depression and chronic pain

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What is depression? Depression is a symptom and not a diagnosis Depression commonly refers to: Major Depressive Disorder (MDD, unipolar depression) Bipolar Disorder, current episode MDD (bipolar depression) MDD is further defined as Single or recurrent episode Severity Mild Moderate Severe With or without psychosis

DSM-5 Diagnosis: MDD 5 or more of the following symptoms during the same 2 week period and represent a change from previous functioning: Depressed mood Anhedonia Change in appetite or weight (5% in a month) Insomnia or hypersomnia Psychomotor agitation or retardation Fatigue Feelings of worthlessness or guilt Poor concentration or indecisiveness Suicidal ideation

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PHQ-9 Over the last 2 weeks, how often have you been bothered by any of the following problems? Little interest or pleasure in doing things Feeling down, depressed, or hopeless Trouble falling or staying asleep, or sleeping too much Feeling tired or having little energy Poor appetite or overeating Feeling bad about yourself or that you are a failure or have let yourself or your family down Trouble concentrating on things, such as reading the newspaper or watching television Moving or speaking so slowly that other people could have noticed or the opposite being so fidgety or restless that you have been moving around a lot more than usual Thoughts that you would be better off dead, or of hurting yourself

PHQ-9 0-3 Likert Scale Validated in chronic pain High sensitivity If you checked off any problems, how difficult at all have these problems made it for you to do your work, take care of things at home, or get along with other people? 0-3 Likert Scale Validated in chronic pain High sensitivity High specificity Total Score Depression Severity 1-4 Minimal depression 5-9 Mild depression 10-14 Moderate depression 15-19 Moderately severe depression 20-27 Severe depression

Other Screening Tools Beck Depression Inventory – II (BDI) 20 items Hospital Anxiety and Depression Scale (HADS) 7 items Both depression and anxiety measured

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Depression and Chronic Pain MDD

Depression First Pinheiro MB et al. “Symptoms of Depression and Risk of New Episodes of Low Back Pain: A Systematic Review and Meta-analysis” 2015 19 articles (reporting data from 16 studies) N=28,326 Depressive symptoms increased the odds of developing a new case of LBP (OR 1.59, 95% CI 1.26-2.01, I2 = 59%) Pooled OR for the most severe level of depression (OR 2.51, 95% CI 1.58-3.99, I2 = 36%) was higher than that for the lowest level (OR 1.51, 95% CI 0.89-2.56, I2 = 48%)

Depression First 65% of depressed patients report pain Specifically, depressed patients complain of headache, abdominal pain, joint pain, and chest pain Somatic symptoms are the primary presenting complaints of MDD in primary care Increased rates of suicidal ideation, suicide attempts, and suicide completion Unclear how treatment of MDD is impacted by comorbid pain

Chronic Pain First Rayner L et al. “Depression in patients with chronic pain attending specialised pain treatment centre: prevalence and impact on health care costs” 2016 PHQ-9, N=1204 60.8% (CI 58.0-63.6) met criteria for probable MDD 5.7% mild MDD; 21.3% moderate MDD; 33.8% severe MDD 15.2% reported suicidal thoughts Patients with depression reported Unable to work because of ill health Of those in employment, they were more likely to have taken >21 days of sick leave/past year Greater number of pain regions Greater healthcare use and costs Duration of pain and extent of relief from treatment did not differ

Chronic Pain First Chronic pain patients with MDD 52% in pain clinics or inpatient pain programs 38% in psychiatric clinics or psychiatric consultation 27% in primary care clinics Multiple pain complaints increase the probability of MDD Studies of more defined pain disorders (e.g., peripheral neuropathy) report lower MDD rates than studies of medically unexplained pain Back pain and migraine headaches are specifically associated with MDD Co-occurring MDD is better predictor of disability than pain severity

Chronic Pain First Greater pain intensity, more pain persistence, and greater interference from pain Pain often improves with improvement in depressive symptoms (another case of the chicken and the egg) MDD is the most consistent and strongest predictor of suicidal ideation and behaviors in patients with chronic pain

Chronic Pain and MDD Comorbidity is associated with Poorer treatment outcomes of both Decreased recognition of MDD Increased functional limitations The association between depression and pain becomes stronger as the severity of either condition increases

Neurobiology Share common neural circuity Depression and Pain follow the same descending pathway of the CNS Serotonergic and noradrenergic pathways involve mood regulation and modulation of pain stimuli If depleted (as in MDD), lost of modulation of pain occurs

MDD, Chronic Pain, and Opioids Patient with MDD are more likely to be prescribed opioids and receive higher doses of opioids Comorbidity is associated with more severe symptomatology MDD is associated with vulnerability to opioid use disorder Comorbidity may influence both patient's and provider’s perception of overall distress Opioids may treat both physical and mental pain

MDD, Chronic Pain, and Opioids Goesling J, et al. “Symptoms of depression are associated with opioid use regardless of pain severity and physical functioning among treatment-seeking patients with chronic pain” 2015 Outpatient tertiary pain clinic N=2104 Opioid use was associated with higher depressive and anxiety symptoms (HADS), greater pain severity, worse physical functioning Pts with depressive symptoms and opioid use reported higher median daily opioid dosage For depressed patients, the predicted probabilities of opioid use remain constant across pain severity (opposite seen with nondepressed pts) At a similar level of functioning, depressed patients had a higher probability of being on opioids

MDD, Chronic Pain, and Opioids Mazereeuw G, Sullivan MD, Juurlink DN. “Depression in chronic pain: might opioids be responsible?” PAIN 2018 Activation of kappa receptor by opioids = dysphoria Most currently used opioids are selective for mu receptor; however, chronic opioid use increases activity at kappa receptor Opioids exhibit a dose-dependent association with depression Prolonged opioid therapy is associated with depression Opioids predispose to antidepressant failure Opioid dose reduction may improve depressive symptoms

Part 2: Treatment of Depression in Patients with Chronic Pain Coming March 20, 2019

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