Medically Unexplained Symptoms

1. Medically Unexplained Symptoms LWCC New Orleans, LA October 13, 2011 David Randolph, MD, MPH Trang Nguyen MD, PhD

2. What is meant by “Medically Unexplained Symptoms”??? • This term is applied to a clinical presentation which cannot be explained through contemporary medical, anatomic, physiologic and/or scientific methods. • We will be discussing clinical scenarios and issues which address potential explanations for medically unexplained symptoms. • It is our goal to have you consider these in your clinical practices as you approach patients with pain complaints. • A panel discussion will follow, so please write down your questions.

3. Case presentation: MUS • John is a 47 year old truck driver. In May, 2006 he slipped (no fall)exiting his truck and felt pain in his low back. He has had multiple diagnostic studies with no clear etiology of his complaints(MRI shows multilevel “degenerative changes” with no neurologic impingement). • Multiple interventions have produced no change in his symptoms. Repeated exams have shown no evidence of radiculopathy, he repeatedly references “aching” in his low back. He has remained off work. He has unsuccessfully applied for SSDI. • He complains of generalized discomfort in his low back, with normal reflexes, sensation, motor strength and no atrophy.

4. A few terms: • OBJECTIVE • SUBJECTIVE • PAIN • VALIDITY • RELIABILITY • “INTER-RATER” vs. “INTRA-RATER” RELIABILITY • “COIN TOSS” • “SPASMS”/TRIGGER POINTS, TENDERNESS • RADICULOPATHY • “SYNDROME” (HUMPTY DUMPTY)

5. IPSE DIXIT • “It’s true because I say so” is not science • Eminence vs. Evidence based practices • Nothing wrong with using experience to guide treatments, but experience should consider peer reviewed literature • George Washington (bled to death) • James Garfield (Sepsis from GSW)

6. CAUSATION ANALYSIS • A science • Used to establish cause of pathology/disease processes • Utilizes history, exam findings, objective medical findings to systematically address clinical processes leading to a disease state • “Hill’s Criteria” named for Sir Austin Bradford-Hill, British Epidemiologist (smoking and lung cancer)

7. Hill’s Criteria • 1-Temporal Relationship • 2-Strength of Association • 3-Dose Response • 4-Replication of Findings • 5-Biologic Plausibility • 6-Consideration of Alternate Explanations • 7-Cessation of Exposure • 8-Consistency • 9-Specificity

8. To Establish Causation • Use 1, 2, 3, 4, and 7 to ESTABLISH • 1-Temporal Relationship • 2-Strength of Association • 3-Dose Response • 4-Replication of Findings • 7-Cessation of Exposure • C. Ralph Buncher Sc.D.

9. To Establish Causation • Temporal Relationship • Cause before effect is essential. (It is not possible for an effect to precede it’s cause) • The other four are helpful but not one is essential. One can conclude causation even if one or two are not available as information. • C. Ralph Buncher Sc.D.

10. To EXPLAIN Causation • Use 5, 6, 8, 9 to EXPLAIN • 5-Biologic Plausibility • 6-Consideration of Alternate Explanations • 8-Consistency • 9-Specificity • C. Ralph Buncher Sc.D.

11. So What? • Human aspects of ineffective medical care • What have we done for this person? • What have we done to this person? • What are the consequences of “disability”? • See “Black Box Warning” for disability • “If the patient becomes disabled then this should be deemed as a failure on our part as physicians”. • Gordon Waddell

12. Hypothetical new prescription medication:Black Box Warning This drug: (DIASBILITY) Can be detrimental to a person’s mental health Can be associated with elevated rates of substance abuse Can be associated with higher incidence of depression, anxiety and suicide. Can be associated with abuse, domestic violence and family breakdown References available on request

13. SWITCHING GEARS: A FEW WORDS ABOUT ANXIETY • Generalized anxiety disorder is characterized by excessive anxiety and worry about a variety of topics (such as work, school, family, health) occurring more days than not for at least six months. People with GAD find it difficult to control their worry, and often experience other related symptoms including restlessness, irritability, and muscle tension.

14. TYPES OF ANXIETY • anxiety disorders include generalized anxiety disorder (GAD), social anxiety disorder (also known as social phobia), specific phobia, panic disorder with and without agoraphobia, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), anxiety secondary to medical condition, acute stress disorder (ASD), and substance-induced anxiety disorder.

15. PREVALENCE OF ANXIETY • Anxiety is one of the most prevalent of all psychiatric disorders in the general population. Simple phobia is the most common anxiety disorder, with up to 49% of people reporting an unreasonably strong fear and 25% of those people meeting criteria for simple phobia. Social anxiety disorder is the next most common disorder of anxiety, with roughly 13% of people reporting symptoms that meet the DSM criteria. PTSD, which is often unrecognized, afflicts approximately 7.8% of the overall population and 12% of women, in whom it is significantly more common. In victims of war trauma, PTSD prevalence reaches 20%.

16. ANXIETY RISK FACTORS • Genetic risk factors are being studied, and researchers have found genetic predisposition for two broad groups of anxiety disorders: a panic-generalized anxiety-agoraphobia group and a specific phobias group.4More clinically important risk factors include co morbid substance abuse and family history. One 20-year study of the offspring of depressed parents found a threefold increase in anxiety disorders, including greater substance abuse, younger onset, and more significant physical health concerns

17. SOMATOFORM DISORDERS • According to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), somatoform disorders are characterized by "the occurrence of one or more physical complaints for which appropriate medical evaluation reveals no explanatory physical pathology or pathophysiologic mechanism, or, when pathology is present, the physical complaints or resulting impairment are grossly in excess of what would be expected from the physical findings."Pain disorder is one of the somatoform disorders.

18. ANXIETY: Physical Manifestations • Stress affects immune responses through the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system. • Emotional distress can cause muscular pains and headaches through increased muscular tension. • Psychologically induced changes in behavior, such as compulsive activity or prolonged bed rest, lead to secondary physiologic changes and attendant symptoms.

19. ANXIETY REFERENCES • Kessler R, Demier O, Frank R, et al: Prevalence and treatment of mental disorders 1990-2003. N Engl J Med. 2005, 352: 2515-2523. • Hettema J, Prescott C, Meyers J, et al: The structure of genetic and environmental risk factors for anxiety disorders in men and women. Arch Gen Psychiatry. 2005, 62: 182-189. • Weissman M, Wickramaratne P, Nomura Y, et al: Offspring of depressed parents: 20 years later. Am J Psychiatry. 2006, 163: 1001-1008. • Hoehn-Sark R, McLeod D, Funderburk F, et al: Somatic symptoms and physiologic responses in generalized anxiety disorder and panic disorder. Arch Gen Psychiatry. 2004, 61: 913-921. • Rapaport M, Clary C, Fayyad R, Endicott J. Quality of life impairment in depressive and anxiety disorders. Am J Psychiatry. 2005, 162: 1171-1178.

20. DEPRESSION • NO DIAGNOSIS OF “DEPRESSION” IN DSM-IV-TR • MDD • MAJOR DEPRESSIVE EPISODE • BIPOLAR • “DEPRESSION” is a normal human response to unfortunate circumstances.

21. MAJOR DEPRESSIVE DISORDER • Major Depressive Disorder is a condition characterized by one or more Major Depressive Episodes without a history of Manic, Mixed, or Hypomanic Episodes. These Major Depressive Episodes are not due to a medical condition, medication, abused substance, or Psychosis. If Manic, Mixed, or Hypomanic Episodes develop, the diagnosis is changed to Bipolar Disorder.

22. CAUSE/COMORBIDITIES • Alcoholism and illicit drug abuse dramatically worsen the course of this illness, and are frequently associated with it. Dysthymic Disorder often precedes the onset of this disorder for 10%-25% of individuals. This disorder also increases risk of also having Panic Disorder, Obsessive-Compulsive Disorder, Anorexia Nervosa, Bulimia Nervosa, and Emotionally Unstable (Borderline) Personality Disorder.

23. BEESDO (J soc psych epi 2010, 45:89-104 • Among those with any lifetime unexplained pain • symptoms (UPS): • 1055 (65.0%) have lifetime UPS only • 575 (35.0%) have any lifetime PD • 445 (24.2%) have any 12-month anxiety disorder • 307 (17.8%) have any 12-month depressive disorder

24. BEESDO • Among those with any 12-month anxiety disorder : • 671 (92.6%) have any significant lifetime pain • 445 (60.9%) have any lifetime UPS • 199 (27.9%) have any lifetime PD • 243 (33.5%) have any 12-month depressive disorder

25. BEESDO • Among those with any 12-month depressive disorder: • 468 (91.3%) have any significant lifetime pain • 307 (59.8%) have any lifetime UPS • 149 (28.8%) have any lifetime PD • 243 (44.6%) have any 12-month anxiety disorder

26. BEESDO • “Pain is strongly associated with specific anxiety and depressive disorders. In light of the individual and societal burden due to pain, and the demonstrated role of co morbid anxiety or/and depression, our results call for further investigation of the underlying mechanisms for this association as well as targeted treatments for these co morbidities.” • When patients have subjective complaints and a lack of objective findings, and fail to respond to normal and standard interventions, a non physical source of symptoms should be considered.

28. MEDICALLY UNEXPLAINED SYMPTOMS • Sooooo…when someone has a normal physical exam, does not respond to standard interventions, continuously demonstrates behaviors not consistent with physical pathology….maybe we should consider other interventions before “medicalization” • Keep in mind, just as digitalis will not help appendicitis, opiates, muscle relaxers, injections and more PT will not help anxiety and/or depression • Such interventions would be considered ineffective and unnecessary.

29. Case #1 (LBP) • Mrs. B (a 52 yo F schoolteacher)was injured in a MVA on 12/21/04. She was the restrained driver of a Chevy suburban traveling on an interstate at about 15 mph in heavy but slowed traffic near a large shopping mall. She was rear ended by a Toyota Celica traveling at 20 mph. No air bag deployment occurred. Due to traffic, both drivers exchanged information and a police report not immediately filed.

30. Case #1 • 10 days after the accident, Mrs. B noted LBP. She was seen by her FP. Xrays showed “arthritis”. She was given opiates and a muscle relaxer and sent for PT. He refilled her Fosamax, Cymbalta and Geodon and placed her off work. After 4 weeks of PT, she was seen by a Chiropractic Doctor who ordered an MRI. This was interpreted as showing DDD at L3-4, L4-5, L5-S1 with spondylosis at these levels, and “minimal” spondylolisthesis of L5 on S1. No herniations were described, and no neurologic impingement noted.

31. Case #1 • She then underwent a six week course of “spinal decompression”. This was accompanied by HP, US, EGS, and manipulation. Worsening symptoms were described. Mrs. B was referred to a surgeon and a pain specialist. • A PE showed “painful” ROM and no neurologic abnormalities. A discogram showed concurrent pain at all 3 levels and a fusion from L3 to S1 recommended if a trial of facet blocks and ESI series proved unsuccessful.

32. TIME OUT!! • YOU are the Treating Physician (TP), Reviewing Physician (RP), or consulting physician (CP) • Most physicians here will assume more than one role • Be prepared to “change hats” • Sooooooo….what do you think about treatment to date?

33. TIME OUT!!! • What about the mechanics of the accident? • How would you differ from these treatments (TP,RP, CP) • What about the meds? (Opiates, muscle relaxers, Geodon, Cymbalta?) • Discuss the intervention (PT, chiropractic treatment, PT/Chiropractic modalities, MRI) • Discogram? • Surgery?

34. Red Flags: • Fosamax: The drug can cause bone pain, arthralgia, joint swelling and myalgia. This can be severe and incapacitating. Bisphosphonates should be considered a cause for any patient who presents with severe severe musculoskeletal or joint pain.

35. Red Flags: Why is she taking Fosamax? • First-line therapy for postmenopausal osteoporosis • Approved for prevention in postmenopausal women

36. Red Flags: Osteopenia and Osteoporosis Osteoporosis: Disease of decreased bone mass and change in microarchitecture of the skeleton Diagnosed: • Acute fracture • Generalized osteopenia Etiologies: Bone marrow disorders; Endocrinopathy; Liver disease; GI disease; Drugs

37. Red Flags: (?MUS) • Geodon (ziprasidone) • Atypical antipsychotic • FDA approved: - Acute psychosis - Agitation - Bipolar disorder - Mania - Schizophrenia

38. Case#1 • Her pain physician increased her medications to include Oxycontin, 80mg 3x/d, Methadone for “breakthrough” pain, Lyrica for “neuropathic pain”. No exam was documented. Facet blocks and ESI at L3-4, 4-5 and 5-1 bilaterally were provided with no benefit. A fusion procedure was performed. She remains off work and had successfully applied for retirement benefits.

39. Discussion on Case #1 She presents to your office with dilated pupils and diffuse psychomotor slowing. She complains of increasing pain complaints and wants you to increase her Oxycontin. An exam shows no focal neurologic abnormalities, but extremely limited function in terms of range of motion, ADL’s . Your review of records shows no physical exam for the past 6 months, no UDS, her current meds include Oxycontin (80 mg tid), Methadose (10 mg tid for “breakthrough” pain, Amitryptyline, Risperdal, Norvasc, Zocor, Soma (tid)

40. Discussion case #1 • What is her daily Morphine equivalent dose? • www.globalrph.com/narcoticonv.htm • 360+112.5=472.5 MEQ/day • What is the recommended maximum for benign pain? • Discuss the medication combination and potential interactions • What drug-drug interactions are possible here? • CYP450 inhibitions may become irreversible, QT interval (methadone)

41. Discussion Case#1 • A UDS shows the following positives opiates, opioids, benzoylecognine. • What does this mean? • What do you want to do now?

42. Red Flag: !!! • Was methadone positive?

43. Discussion Case#1 • How do you determine the need for detox? • How do you accomplish this? • Where is the evidence this treatment is helping?

44. MEDICALLY UNEXPLAINED SX • BE CAUTIOUS when confronted with multiple subjective complaints without objective correlation • Death rate from prescribed narcotics is climbing • Always consider alternate non physical explanation • THANK YOU VERY MUCH !!