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Recognizing the Physical Symptoms of Depression

Recognizing the Physical Symptoms of Depression. Volume 2 • Number 2 • August 2004. Introduction Alan F. Schatzberg, M.D. Physical Symptoms Common In Psychiatric Patients. Psychiatric Healthy Symptom Patients (%) Subjects (%) Tiredness, lack of energy 85 40 Headache, head pains 64 48

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Recognizing the Physical Symptoms of Depression

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  1. Recognizing the Physical Symptoms of Depression Volume 2 • Number 2 • August 2004

  2. IntroductionAlan F. Schatzberg, M.D.

  3. Physical Symptoms Common In Psychiatric Patients Psychiatric Healthy Symptom Patients (%) Subjects (%) Tiredness, lack of energy 85 40 Headache, head pains 64 48 Dizziness or faintness 60 14 Feeling of weakness in parts of body 57 23 Muscle pains, aches, rheumatism 53 27 Stomach pains 51 20 Chest pains 46 14 Data from Kellner R, Sheffield BF. The one-week prevalence of symptoms in neurotic patients and normals. Am J Psychiatry 1973;130:102–105

  4. Why Focus on Physical Symptoms? • A growing literature explores the mind-body connection in mental illness • Depression may have physical causes and consequences (like appetite and sleep disturbance, fatigue, and chronic pain) • The presence of physical symptoms in depression may affect response to treatment

  5. How Chronic Pain Affects the Symptoms of DepressionMaurice M. Ohayon, M.D., D.Sc., Ph.D.

  6. Patients With Major Depressive Disorder • Report only physical symptoms in up to 69% of primary care cases1 • E.g.,insomnia or hypersomnia, psychomotor agitation or retardation, changes in appetite, fatigue • Are at 4x greater risk than nondepressed patients for having a chronic painful physical condition (CPPC)2 • Are more likely than nondepressed patients to have long-term medical conditions3 1Simon GE, VonKorff M, Piccinelli M, et al. An international study of the relation between somatic symptoms and depression. N Engl J Med 1999;341:1329–1335 2Ohayon MM, Schatzberg AF. Using chronic pain to predict depressive morbidity in the general population. Arch Gen Psychiatry 2003;60:39–47 3Patten SB. Long-term medical conditions and major depression in a Canadian population study at waves 1 and 2. J Affect Disord 2001;63:35–41

  7. Influence of CPPCs on Depressive Symptoms • Method • General population respondents ≥ 15 years of age • Total N = 18,980 in 5 European countries • Interviewed by telephone using several instruments • Sleep-EVAL, DSM-IV, and International Classification of Sleep Disorders criteria, questions about painful physical conditions, and questions about psychological and physical symptoms of depression Ohayon MM. Specific characteristics of the pain/depression association in the general population. J Clin Psychiatry 2004;65(suppl 12):5–9

  8. Influence of CPPCs on Depressive Symptoms • Results • 17.1% of respondents with at least 1 CPPC • 4.0% of respondents with major depressive disorder (MDD) • Likelihood of either condition was higher among patients 25 and older and was higher among women Ohayon MM. Specific characteristics of the pain/depression association in the general population. J Clin Psychiatry 2004;65(suppl 12):5–9

  9. Prevalence of MDD by Presence of CPPC and Age Groupa aThe total of the 2 CPPC categories equals the total prevalence of MDD for each age group. Abbreviations: CPPC = Chronic Painful Physical Condition, MDD = Major Depressive Disorder. Reprinted with permission from Ohayon MM. Specific characteristics of the pain/depression association in the general population. J Clin Psychiatry 2004;65(suppl 12):5–9

  10. Subjects With MDD Plus At Least 1 CPPC • Represented 43.4% of subjects with MDD • Had a longer duration of current depressive episode than depressed subjects without a CPPC • 31.4 months vs. 24.3 months • Were more likely to have had a past depressive episode than depressed subjects without a CPPC • 24.4% vs. 17.4% Ohayon MM. Specific characteristics of the pain/depression association in the general population. J Clin Psychiatry 2004;65(suppl 12):5–9

  11. Frequency and Severity of Depressive Symptoms in Subjects With MDD and With or Without CPPC With Without CPPC CPPC (N = 330), (N = 429), OR Symptom % % (95% CI) Feeling sad, depressed nearly every day     Moderately 41.2*** 30.7 1.6 (1.2 to 2.1)     A lot/extremely 28.0*** 17.9 1.8 (1.3 to 2.5) Loss of interest in activities nearly every day     Moderately 28.3 24.8 1.2 (0.9 to 1.7)     A lot/extremely 26.5 21.5 1.3 (0.9 to 1.8) Psychomotor agitation nearly every day 13.8* 9.2 1.6 (1.0 to 2.5)     Moderately 7.9 5.4 1.5 (0.8 to 2.7)     A lot/extremely 5.9 3.8 1.6 (0.8 to 3.1) Psychomotor retardation nearly every day     Moderately 14.1 10.2 1.5 (0.9 to 2.2)     A lot/extremely 7.7*** 2.5 3.3 (1.6 to 6.7) Weight loss 28.9 23.6 1.3 (0.9 to 1.8) Weight gain 21.3** 10.4 2.3 (1.1 to 5.2) (cont.) *p < .05, **p < .01, ***p < .001 vs. patients without CPPC. Abbreviations: CPPC = Chronic Painful Physical Condition, MDD = Major Depressive Disorder. Ohayon MM. Specific characteristics of the pain/depression association in the general population. J Clin Psychiatry 2004;65(suppl 12):5–9

  12. Frequency and Severity of Depressive Symptoms in Subjects With MDD and With or Without CPPC (cont.) With Without CPPC CPPC (N = 330), (N = 429), OR Symptom % % (95% CI) Insomnia    3–4 nights/week 43.1 44.4 1.0 (0.7 to 1.3)   5–7 nights/week 31.1*** 12.2 3.3 (2.2 to 4.7) Hypersomnia    3–4 nights/week 8.2 10.5 0.8 (0.5 to 1.3)    5–7 nights/week 12.8 8.3 1.6 (1.0 to 2.6) Fatigue nearly every day    Moderately 17.2 15.5 1.1 (0.8 to 1.7)    A lot/extremely 13.0*** 2.7 5.4 (2.8 to 10.5) Feeling of worthlessness or guilt nearly every day     Moderately 12.3 7.9 1.6 (1.0 to 2.6)     A lot/extremely 7.4 6.7 1.1 (0.6 to 1.9) Impaired concentration    Moderately 16.5 11.9 1.5 (1.0 to 2.2)    A lot/extremely 13.4** 8.4 1.7 (1.1 to 2.7) Suicidal ideation 44.1 37.3 1.3 (1.0 to 1.8) *p < .05, **p < .01, ***p < .001 vs. patients without CPPC. Abbreviations: CPPC = Chronic Painful Physical Condition, MDD = Major Depressive Disorder. Ohayon MM. Specific characteristics of the pain/depression association in the general population. J Clin Psychiatry 2004;65(suppl 12):5–9

  13. Conclusions • CPPCs were extremely common in subjects with MDD • The presence of a CPPC statistically significantly increased the frequency and severity of 7 depressive symptoms • Feeling sad or depressed, psychomotor agitation, psychomotor retardation, weight gain, insomnia, fatigue, and impaired concentration • Some physical symptoms of depression may be attributable to chronic pain rather than depressive illness, but, conversely, physical symptoms may be due to MDD rather than chronic pain • Clinician vigilance and discernment is necessary to determine whether physical symptoms indicate depression

  14. Childhood Maltreatment and Adult Health and Psychiatric OutcomesBruce A. Arnow, Ph.D.

  15. Prevalence Estimates of Childhood Maltreatment Vary According to Study Methodology • Definition of terms • E.g., childhood and abuse • Survey tactics employed • E.g., mailed questionnaire, face-to-face interview • Respondent population • E.g., general public, primary care patients, psychiatric patients

  16. Estimated Prevalence in the General Population • Childhood sexual abuse1 • 8% to 32% in women • 1% to 16% in men • Childhood physical abuse2 • Approximately 20% in women and men 1Finkelhor D. Current information on the scope and nature of child sexual abuse. Future Child 1994;4:31–53 2Briere J, Elliot DM. Prevalence and psychological sequelae of self-reported childhood physical and sexual abuse in a general population sample of men and women. Child Abuse Negl 2003;27:1205–1222

  17. Higher Prevalence of Childhood Abuse in Specialized Settings • 44% of primary care patients reported sexual, physical, or emotional abuse as children1 • 53% of women in emergency psychiatric care reported childhood sexual abuse; 42% reported childhood physical abuse2 • 55% of female psychiatric inpatients reported multiple types of childhood abuse3 1Gould DA, Stevens NG, Ward A, et al. Self-reported childhood abuse in an adult population in a primary care setting: prevalence, correlates, and associated suicide attempts. Arch Fam Med 1994;3:252–256 2Briere J, Woo R, McRae B, et al. Lifetime victimization history, demographics, and clinical status in female psychiatric emergency room patients. J Nerv Ment Dis 1997;185:95–101 3Swett C, Alpert M. Reported history of physical and sexual abuse in relation to dissociation and other symptomatology in women psychiatric inpatients. J Interpersonal Violence 1993;8:545–555

  18. Adult Psychiatric Outcomes • Childhood maltreatment is associated with adult psychiatric sequelae • MDD, anxiety, substance abuse/dependence are especially common • Greater severity, frequency, and number of types of maltreatment exacerbate risk • In a community sample, childhood sexual abuse raised the rate of having at least 1 lifetime psychiatric disorder from 49% in women and 51% in men to 78% in women and 82% in men1 1Molnar BE, Buka SL, Kessler RC. Child sexual abuse and subsequent psychopathology: results from the National Comorbidity Survey. Am J Pub Health 2001;91:753–760

  19. Association Between Childhood Sexual and/or Physical Abuse and Adult Mental Health Symptoms in Primary Care *p < .001 vs. patients with no abuse. aHigh = upper 1/3 of score range on Symptom Checklist-22 Data from McCauley J, Kern DE, Kolodner K, et al. Clinical characteristics of women with a history of childhood abuse: unhealed wounds. JAMA 1997:277:1362–1368

  20. Relative Risk of MDD Among Adults Who Report Childhood Abuse Compared With Adults Who Do Not • Physical abuse: 2.4x greater • Sexual abuse: 1.8x greater • Both physical and sexual abuse: 3.3x greater Wise L, Zierler S, Krieger N, et al. Adult onset of major depressive disorder in relation to childhood and adolescent violence victimization: a case-control study. Lancet 2001;358:881–887

  21. Significant Associations of the Relationship Between Childhood Maltreatment and Adult MDD • Earlier onset of MDD1 • High comorbidity and chronicity of MDD1,2 • Suicide attempts in adulthood3 1Bernet CZ, Stein MB. Relationship of childhood maltreatment to the onset and course of major depression in adulthood. Depress Anxiety 1999;9:169–174 2Brown GW, Moran P. Clinical and psychosocial origins of chronic depressive episodes, pt.1: a community survey. Br J Psychiatry 1994;165:447–452 3Bifulco A, Moran P, Baines R, et al. Exploring psychological abuse in childhood, pt. 2: association with other abuse and adult clinical depression. Bull Menninger Clin 2002;66:241–258

  22. Physical Symptoms Linked to Childhood Victimization • Chronic pelvic pain1 • Fibromyalgia2 • Irritable bowel syndrome3 • Headache4 1Walker E, Katon W, Harrop-Griffiths J, et al. Relationships of chronic pelvic pain to psychiatric diagnoses and childhood sexual abuse. Am J Psychiatry 1988;145:75–80 2Walker EA, Keegan D, Gardner G, et al. Psychosocial factors in fibromyalgia compared with rheumatoid arthritis, pt. 2: sexual, physical, and emotional abuse and neglect. Psychosom Med 1997;59:572–577 3Talley NJ, Fett SL, Zinsmeister AR, et al. Gastrointestinal tract symptoms and self-reported abuse: a population-based study. Gastroenterology 1994;107:1040–1049 4Golding JM. Sexual assault history and headache: 5 general population studies. J Nerv Ment Dis 1999;187:624–629

  23. Other Adult Health Outcomes Associated With Childhood Maltreatment or Household Dysfunctiona • Correlated disease states1 • Heart disease, cancer, chronic lung disease, and liver disease • Increased health-risk behaviors • Alcoholism/drug abuse,2 driving while intoxicated,2 irregular seatbelt use,2 risky sexual behaviors,1,2 sedentary lifestyle,1,2 obesity,1,2 and cigarette smoking2 aE.g.,mental illness, imprisonment/criminality, substance abuse, and/or violence. 1Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. Am J Prev Med 1998;14:245–258 2Walker EA, Gelfand A, Katon WJ, et al. Adult health status of women with histories of childhood abuse and neglect. Am J Med 1999;107:332–339

  24. Medical Utilization • Elevated among adults with depression1 • Elevated among adults with a history of childhood abuse2 • Higher among adults with psychological distress + childhood sexual abuse than among adults with either condition alone3 • Higher still among adults with psychological distress + sexual abuse + physical abuse3 1Simon GE, VonKorff M, Barlow W. Health care costs of primary care patients with recognized depression. Arch Gen Psychiatry 1995;52:850–856 2Walker EA, Unutzer J, Rutter C, et al. Costs of health care use by women HMO members with a history of childhood abuse and neglect. Arch Gen Psychiatry 1999;56:609–613 3Arnow BA, Hart S, Hayward C, et al. Severity of child maltreatment, pain complaints, and medical utilization among women. J Psychiatr Res 2000;34:413–421

  25. Conclusions • Reported rates of childhood abuse are highest in psychiatric settings • Childhood maltreatment is associated with • Adult psychiatric sequelae, especially depression • Both medically explained and unexplained physical symptoms, especially chronic pain • Health-risk behaviors in adulthood • A graded relationship between severity of maltreatment and adult outcomes including poor psychological outcomes, pain complaints, and medical utilization

  26. The Nature of Depression and Its Treatment With Dual-Acting AntidepressantsPedro L. Delgado, M.D.

  27. Recurrence of MDD • 75% to 90% of people with depression will have multiple episodes1,2 • Each episode is more easily provoked than the last3 • Residual symptoms following recovery increase risk of recurrence4 1Angst J. How recurrent and predictable is depressive illness? In: Montgomery SA, Rouillon F, eds. Long-Term Treatment of Depressive Perspectives in Psychiatry, vol 3. Chichester, England: Wiley;1992:1–13 2Kupfer DJ. Long-term treatment of depression. J Clin Psychiatry 1991;52(suppl 5):28–34 3Kendler KS, Thornton LM, Gardner CO. Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the “kindling” hypothesis. Am J Psychiatry 2000;157:1243–1251 4Judd LL, Akiskal HS, Maser JD, et al. Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse. J Affect Disord 1998;50:97–108

  28. Why Aim to Prevent Recurrence of Depressive Episodes? • Much of the burden of MDD is linked to its chronic nature1,2 • Episodes tend to become more frequent, severe, and treatment resistant over time3 • Number (and duration) of previous episodes may predict relapse3 • Prolonged depression and multiple episodes may cause brain damage (loss of hippocampal volume)4,5 1Angst J. How recurrent and predictable is depressive illness? In: Montgomery SA, Rouillon F, eds. Long-Term Treatment of Depressive Perspectives in Psychiatry, vol 3. Chichester, England: Wiley;1992:1–13 2Kupfer DJ. Long-term treatment of depression. J Clin Psychiatry 1991;52(suppl 5):28–34 3Keller MB, Boland RJ. Implications of failing to achieve successful long-term maintenance treatment of recurrent unipolar major depression. Biol Psychiatry 1998;44:348–360 4Sheline YI, Sanghavi M, Mintun MA, et al. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 1999;19:5034–5043 5Bremner JD, Narayan M, Anderson ER, et al. Hippocampal volume reduction in major depression. Am J Psychiatry 2003;160:1516–1518

  29. Neurobiology of Depression: Serotonin and Norepinephrine • Are part of the body’s endogenous analgesic system • Play overlapping but divergent roles in depression • Are involved in the etiology of some physical and emotional symptoms of depression • Affect how medications work to treat depression • Some beneficial effects of antidepressant treatment may be due to neurogenesis (cell growth) in affected areas of the depressed brain

  30. Dual-Acting Antidepressants • Overall, dual-acting agents appear to be more effective than single-acting agents in improving mood, reducing pain, and increasing the chance of remission • Tricyclic antidepressant (TCA) imipramine induces neurogenesis even in mice genetically modified to have no 5-HT1A receptors1 • Serotonin-norepinephrine reuptake inhibitors (SNRIs) venlafaxine2 and duloxetine3 have reduced pain sensitivity in a dose-dependent manner in patients with diabetic neuropathy 1Santarelli L, Saxe MD, Gross C, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003;301:805–809 2Kunz NR, Goli V, Entsuah R, et al. Diabetic neuropathic pain management with venlafaxine extended release. Eur Neuropsychopharmacol 2000;10(suppl 3):S389 3Goldstein DJ, Lu Y, Iyengar S, et al. Duloxetine in the treatment of the pain associated with diabetic neuropathy. Presented at the 156th Annual Meeting of the American Psychiatric Association; May 17–22, 2003; San Francisco, Calif. Abstract NR185:68–69

  31. Conclusions • Early, aggressive, effective intervention in depression is recommended • Dual-acting antidepressants that inhibit reuptake of both serotonin and norepinephrine treat a wider array of depressive symptoms (psychological and physical) than antidepressants that target either neurotransmitter alone

  32. The Search for Better Outcomes in the Treatment of DepressionVivien K. Burt, M.D., Ph.D.

  33. Response and Remission • Response to antidepressant treatment frequently falls short of remission • Full remission is achieved more readily when the entire spectrum of depressive symptoms is targeted • With medication (single-acting vs. dual-acting agents) • With psychotherapy • Some special populations (such as women) may respond preferentially to certain antidepressant classes

  34. Dual- Versus Single-Acting Agents • Combination of fluoxetine (serotonergic action) and desipramine (noradrenergic action) was more effective in treating depression than either agent alone1 • Dual-acting TCAs were more effective in treating depression than single-acting TCAs or selective serotonin reuptake inhibitors (SSRIs)2–4 • TCAs have a considerable side effect profile, can be lethal in overdose 1Nelson J, Mazure C, Jatlow P, et al. Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study. Biol Psychiatry 2004;55:296–300 2Anderson IM. SSRIs versus tricyclic antidepressants in depressed inpatients: a meta-analysis of efficacy and tolerability. Depress Anxiety 1998;7(suppl 1):11–17 3Danish University Antidepressant Group. Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. J Affect Disord 1990;18:289–299 4Danish University Antidepressant Group. Citalopram: clinical effect profile in comparison with clomipramine: a controlled multicenter study. Psychopharmacology (Berl) 1986;90:131–138

  35. Dual- Versus Single-Acting Agents • Venlafaxine (SNRI) > SSRIs1 • 9% of venlafaxine-treated patients discontinued treatment vs. 7% of SSRI-treated patients • 45% of venlafaxine-treated patients achieved remission vs. 35% of SSRI-treated patients • Mirtazapine (noradrenergic and specific serotonergic antidepressant) > SSRIs2 • 13.4% of fluoxetine-treated patients discontinued treatment vs. 10.6% of mirtazapine-treated patients • Reduction in Hamilton Rating Scale for Depression (HAM-D) scores from baseline was greater with mirtazapine than fluoxetine 1Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001;178:234–241 2Wheatley D, van Moffaert M, Timmerman L, et al. Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. J Clin Psychiatry 1998;59:306–312

  36. Pain, Anxiety, and SNRIs • Venlafaxine (at higher doses) and duloxetine may be especially efficacious in alleviating physical, anxious, and negative mood symptoms of depression • Duloxetine showed a higher affinity than venlafaxine for serotonin and norepinephrine receptors1 • Compared with placebo, duloxetine significantly reduced overall HAM-D scores (p < .001),2 somatic symptoms (p = .013),2 pain (p < .001),2 and anxiety (p < .005)3 1Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology 2001;25:871–880 2Detke MJ, Lu Y, Goldstein DJ, et al. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry 2002;63:308–315 3Dunner D, Goldstein D, Mallinckrodt C, et al. Duloxetine in the treatment of anxiety symptoms associated with depression. Depress Anxiety 2003;18:53–61

  37. Duloxetine Versus Placebo in MDD *p < .001 vs. placebo. Abbreviations: HAM-D-17 = 17-item Hamilton Rating Scale for Depression, LS = least squares, MDD = Major Depressive Disorder, SNRI = serotonin-norepinephrine reuptake inhibitor. Reprinted with permission from Detke MJ, Lu Y, Goldstein DJ, et al. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry 2002;63:308–315

  38. Symptoms of Somatic and Pure Depression by Sex *p < .05 vs. patients with pure depression. Data from Silverstein B. Gender differences in the prevalence of clinical depression: the role played by depression associated with somatic symptoms. Am J Psychiatry 1999;156:480–482

  39. Duloxetine Efficacy for Overall Pain in Women by Age *p = .043, **p < .001 vs. placebo. Reprinted with permission from Burt VK. Plotting the course to remission: the search for better outcomes in the treatment of depression. J Clin Psychiatry 2004;65(suppl 12):20–25

  40. Conclusions • Dual-acting agents that modulate serotonin and norepinephrine are more effective than single-acting agents in treating the emotional and physical symptoms of depression • Including pain • Especially in women of perimenopausal age

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