Disclosures. Major depressive disorder (MDD) Depression and Chronic Pain: Mechanisms and Treatment

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1 Depression and Chronic Pain: Mechanisms and Treatment Disclosures Grant Support: NIMH, Takeda, Brain Resources, Brainsway, Assurex, Charles DeBattista, MD Professor of Psychiatry and Behavioral Sciences Director: Depression Clinic and Research Program Stanford University School of Medicine Advisory Boards: Genentech, Pfizer Facts about depression Major depressive disorder (MDD) Affects about 10% of the U.S. (Gemignani, 2001) Prevalence among school age children and adolescents is 4.6% (Wagner, 2003) Millions do not seek treatment due to inadequate benefits and the stigma associated with depression (U.S. Surgeon General, 2000) Effective pharmacotherapy combined with psychotherapy has been shown to reduce healthcare costs and the rate of suicide attempts (Ballenger, 1999) Average disability length as well as disability relapse are greater for depression than most comparison medical groups (Conti and Burton, 1994)

2 Depressed Patients Usually Present with Physical Symptoms 69% Presented ONLY With Physical Symptoms Other N = 1146 patients with major depress 1. Simon GE, et al. N. Engl J Med. 1999;341(18): Global Burden of Disease Year Ischemic heart disease 2. Major Depression 3. Traffic accidents 4. Cerebrovascular disease 5. COPD Murray and Lopez, 199 PAIN CRISES Pain accounts for 20% of all clinic visits Analgesics = 12% of all prescriptions (# 2) $100 billion dollars/yr in health care costs Excessive surgery (e.g., back pain) Leading cause of work loss & disability Leading reason for alternative medicine Consequences of Undertreatment of Chronic Pain Physiologic (CV, GI, immune) Psychological (depression, anxiety) Diminished quality of Life Impairment of activities Large impact on working age adults Absenteeism, unemployment, and underemployment

3 Pain: 5 th Vital Sign in Primary Care and Association with Depression 301 primary care Veteran patients Mean age = 60; 91% men; 85% white Depression in 28% (PHQ 9 10) Pain in 76% Mild 21% (score of 1 3) Moderate 31% (score of 4 6) Severe 22% (score of 7 10) Pain: 5 th Vital Sign in Primary Care and Association with Depression 301 primary care Veteran patients Mean age = 60; 91% men; 85% white Depression in 28% (PHQ 9 10) Pain in 76% Mild 21% (score of 1 3) Moderate 31% (score of 4 6) Severe 22% (score of 7 10) Bair MJ, Williams LS, Kroenke K. J Gen Intern Med 2004;19 (Supplement 1):123. Bair MJ, Williams LS, Kroenke K. J Gen Intern Med 2004;19 (Supplement 1):123. RECIPROCAL RELATIONSHIP Pain Depression Pain and Negative Depression Outcomes PAIN ASSOCIATED WITH: depressive symptoms functional limitations unemployment rate frequent use of opioid analgesics frequent pain related doctor visits worse self rated health Von Korff M. Grading the severity of chronic pain. Pain 1992; 50:

4 Severity of Pain is Associated with Poor Depression Outcome What Symptoms are the Most Resistant? Odds Ratio for Poor Depression Response** Relative to Patients Without Pain *P<.05 vs patients with no baseline pain N= Bair MJ, et al. Psychosom Med. 2004;66(1): Baseline Pain Severity * 2.0 * 4.1 (n=144) (n=170) (n=81) Mild Moderate Severe No effect relative to patients without pain at baseline ARTIST=A Randomized Trial Investigating SSRI Treatment. **Poor depression treatment response defined as Symptom Checklist-20 >1.3. Pain severity was measured by the SF-36 pain severity item Improvement Treatment Effect Size 1.4 N= Emotional Physical Baseline 1 Month 3 Months 6 Months 9 Months ARTIST=A Randomized Trial Investigating SSRI Treatment. Adapted from: Greco T, et al. J Gen Intern Med. 2004;19(8): Nonsomatic depressive Sx Positive well-being Non-pain somatic Sx Pain somatic Sx Residual Symptoms Predict Relapse Integrated Model % Relapse % 94% had Physical Symptoms Patients With Residual Depressive Symptoms 25% Patients With No Residual Depressive Symptoms Physical Symptoms Psychological Symptoms *Based on Item 13 (general somatic symptoms) of the HAM-D 17. Paykel ES, et al. Psychol Med. 1995;25(6): NogginStorm Labs PAIN is the most common physical symptom DEPRESSION most common psychological symptom

5 Serotonin and norepinephrine: Modulation of mood and pain perception Interactions between serotonin and norepinephrine neurons The role of antidepressants and neurotrophic factors in the network hypothesis of depression: Rerouting aberrant patterns BDNF, depression, and antidepressants

6 Successful antidepressant treatment can be associated with BDNF increase Rates of recovery diminish with duration of major depressive episode Pain symptom improvement increases chances of remission Pain predicts time to remission

7 Progression of depression kindling phenomenon: Adverse effects of each successive episode Symptoms of depression: DSM- 5 Criteria Occurring over a two week period Depressed mood and or Anhedonia Helplessness/hopelessness Fatigue\ Guilt Poor concentration/executive function Sleep disturbance (initiating and/or maintaining sleep) Suicidal ideation or thoughts of death Appetite disturbance (typically weight loss, but can be weight gain). Symptoms of depression Depressed mood Tearfulness Irritability Low energy level Guilt Pain perception Is it all in my head? Emotional aspects of pain Biology of pain perception Cultural factors

8 Models of pain Peripheral vs. Central Disease vs. illness-behavior Reductionistic vs. systems Biomedical vs. Biopsychosocial Medical vs. Self-Management Assessment of chronic pain and depression Patient Health Questionnaire (PHQ) Zung Depression Inventory (ZDI) Beck Depression Inventory (BDI) Assessment of chronic pain and depression Standardized Instruments Pain Patient Profile (P-3) P-3 is a test that helps screen for the presence of depression, anxiety, and somatization the factors most frequently associated with chronic pain. Assessment of chronic pain and depression Clinical interview (Biopsychosocial factors) Substance abuse evaluation (prescription and/or illicit) Suicide assessment Case management

9 Psychological management of chronic pain: Psychological management of chronic pain: Locus of control (internal vs. external) Stress Management Assertiveness Training Exercise The role of attention focus and complaint Treatment personnel The faith factor Accessing support systems Lifestyle changes Psychological management of chronic pain: Medication use (indications/contraindications) Cognitive-behavioral approaches Family systems approaches Case Management Barriers to treatment: Inadequate assessment/missed diagnoses Co-morbid conditions (such as diabetes, stroke, cancer etc) Substance abuse Lack of available resources Poor continuity of care Inappropriate medication dosing/titrating Lack of behavioral health treatment providers in rural areas

10 TCAs Pharmacotherapy of Comorbid Depression and Pain Imipramine Amitriptyline SNRIs Duloxetine: Neuropathy, Fibromylgia, Chronic Pain Milnacipran: Fibromyalgia Desvenlafaxine Venlafaxine Levomilnacipran Other Pharmacotherapies Anticonvulsants Gabapentin Pregabalin Antipsychotics Quetiapine Lurasidone Other Somatic Interventions Transcranial Magnetic Stimulation Trigemeninal Stimulation Deep Brain Stimulation Conclusions Depression and Pain are highly comorbid They share a common pathophysiology Treating co morbid pain improves depression outcome and visa versa Psychosocial treatments play an important role in treatment Somatic interventions including TCAs, SNRIs, and devices play a growing role