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1 인제대학교서울백병원김원

2 * decreased appetite * decreased sleep * psychomotor agitaion * poor concentraion * psychomotor retardation * anhedonia depressed mood * low energy * guilt suicidal ideation * < 0.05 * total controls past MDD current MDD Psychiatry Res, 2002

3 Painless somatic symptoms in depression vague and exaggerated multiple somatic complaints (usually 3) fatigue, weakness, non-specific and painless musculoskeletal problems, sensations of heaviness or lightness in at least one part of the body, gastrointestinal dysfunction, shortness of breath, palpitations, dizziness, double vision, changes in sleep patterns and appetite, and polyuria Painful somatic symptoms joint pains, lumbar pain and headache Age, female gender, and unemployment associated with the presence of somatic symptoms. The severity of the depression is greater in patients with moderate to severe discomfort due to somatic symptoms.

4 DSM system emphasize psychological sx. as key fx. of MDD underestimate somatic depression Masked depression in primary care 1 st stage, 442 patients, 1.8% prevalent. 2 nd stage, 62 patients with high somatization score, 39 (63%) prevalent. Most were diagnosed with Musculoskeletal disease Underestimation is crucial in minority population. Posse and Hallstrom, 1998

5 Nakao and Yano (2006) 1066 Japanese workers (mean age 35 years), annual health examinations, in 2 successive years, Prediction of depression in the following year 3.4~3.7% MDD seen among the Japanese workers WHO reported that 77% of Japanese depressive subjects complained of somatic symptoms. Fatigue was the most common and powerful predictor of core depressive symptoms Insomnia was closely related to depressive mood and diminished interest or pleasure. Headache was the second most common symptom, less predictive than fatigue and insomnia.

6 Depressed mood Montgomery Asberg Depression Rating Scale (MADRS) Only 3 items : physical symptoms Hamilton depression rating scale (HAM-D) 8 items : physical symptoms 18/56 point (32%) PHQ-9 Somatic symptoms Patient Health Questionnaire- 15 (PHQ-15) Somatic Symptom Inventory (SSI) Visual Analog Scale (VAS) for pain (DeLoach et al., 1998) 20 (on a scale of 0 100) Symptom questionnaire

7 Patient Health Questionnaire-15 (PHQ-15) self-report, somatic symptom type and severity over, the prior 4 weeks Somatic Symptom Inventory (SSI) 26-item questionnaire, painless and painful patients' degree of discomfort for each symptom is rated from 1 to 5 (1 = absent; 3 = moderate; 5 = a great deal) MADRS relies less than HAM-D does on somatic symptoms.

8 MDD patients 0wk 8wk Change on somatic symptoms correlated with global improvement in MDD wk of HAMD-S HAMD-17 HAMD-S MADRS MADRS-S Nonremitter vs Remitter based on MADRS p= nonremitting responder remitter Improvement in somatic symptoms is highly correlated with a favorable outcome in depression. Nonremitting responders had a significant smaller baseline-to-end point decrease in somatic symptoms. J Psychosom Res. 2006

9 Improvement Treatment Effect Size N=573 Emotional Symptoms Nonsomatic depressive symptoms Positive well-being Physical Symptoms Nonpain somatic symptoms Pain somatic symptoms Baseline 1 Month 3 Months 6 Months 9 Months A Randomized Trial Investigating SSRI Treatment Adapted from: Greco T, et al. J Gen Intern Med. 2004;19(8):

10 Gender differences in prevalence of MDD may be due to the high prevalence of anxious depression, atypical depression and somatic depression in women. These three subtypes of depression are also very prevalent during pregnancy, the post partum period, perimenstrually and during the menopause transition (perimenopause) period vulnerability and hormone instability in their pathobiology.

11 Atypical depression Mood reactivity 1 Increased appetite 1 Increased weight 1 Hypersomnia 1 Leaden paralysis 1 Sensitivity to interpersonal rejection 1 Intensified mood reactivity 2 Mood Lability 2 Anxiety, Irritability 2 Anxious depression phenotype 3 Depressed mood Negative self-evaluation Discouragement Diurnal variation Depersonalization or derealization Somatic overconcern Difficulty concentrating Insomnia Lack of energy Psychomotor agitation Subjectively experienced anger Distrustfulness Nonreactivity of mood to changes in circumstances Somatic Depression 4 Depression Sleep disturbances Fatigue Anxiety Diversified pain and aches 1 APA, West and Dally, Clayton PJ et al, Silverstein, 1999, 2002.

12 Lifetime prevalence of somatic depression (F: 15.2%, M: 7.5%) but a prevalence of pure depression (F: 6.9%, M: 6%) Somatic depression have a tendency with coexisting anxiety disorder Silverstein, 1999

13 Depressed mood Serotonin (5-HT) and norepinephrine (NE) pathways mediate various functions in the brain 1-3 Descending spinal projections modulate nociception 2,3 Disturbance in these pathways are thought to be associated with the emotional and physical symptoms of depression 3 Suicidal ideation Dorsal raphe nuclei Changes in appetite/ Lack of pleasure Caudal raphe nuclei Locus ceruleus Sleep disturbances Lateral tegmental NA cell system Headaches GI complaints Vague pain in joints, limbs, back, abdomen, etc Adapted from: 1 Kaplan HI, Sadock BJ. In: Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. 8th ed. Lippincott Williams & Wilkins; 1998: Fields HL, et al. Annu Rev Neurosci. 1991;14: Stahl SM. J Clin Psychiatry. 2002;63: HT NE Modulatory effects on nociception

14 Atypical depression MAOI > TCA, still in debate SSRI + benzodiazepine Somatic depression Very few studies Secondary analysis Chronic pain TCA = SNRI? > SSRI TCA + anticonvulsant => gabapentin? Antonijevic, 2006; Matza et al., 2003

15 SNRI Venlafaxine, Milnacipran, Duloxetine Analgesic effect via descending pain pathway

16 Venlafaxine XR in the Reduction of Anxiety- Somatization Symptoms Associated with MDD * Pooled Data from 7 Randomized Placebo-Controlled Studies Mean HAM-D Score on 6 Anxiety- Somatization Factor Items* Venlafaxine XR (N=1136) Placebo (N=691) Week P<0.05 venlafaxine XR vs placebo; P<0.001 venlafaxine XR vs placebo *HAM-D Anxiety-Somatization Factors include Anxiety-Psychic, Anxiety-Somatic, Somatic-Gastrointestinal, Somatic-General, Hypochondriasis, and Insight. Data on File, Wyeth Pharmaceuticals

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18 In Depressed Patients Effective in reducing pain associated with depression Mean Reduction in VAS following treatment Placebo Duloxetine Detke et al, 2003 Overall Head Back Shoulder *p<0.05 vs. placebo

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20 Effectiveness of mirtazapine in the treatment of depression with associated somatic symptoms. García Campayo. Actas Esp Psiquiatr Jan-Feb;36(1): Somatic section on HAM-D, SPPI

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24 Quetiapine Antipsychotics for anxious depression? perphenazine

25 Omega-3 fatty acid (DHA & EPA) The deficit of omega-3 PUFAs is associated with depression. Societies that consume a small amount of omega-3 PUFAs appear to have a higher prevalence of MDD. depressive pt. showed a lower level of omega-3 PUFAs the antidepressant effect of PUFAs had been reported in a number of clinical trials. EPA and DHA are not synthesized in human body and can only be obtained directly from fish. the role of n-3 fatty acids in psychoneuroimmunology, somatic presentation, and medical illness comorbidity of depression. Su KP, Asia Pac J Clin Nutr.2008

26 Education Caffeine, alcohol Psychotherapy Supportive Cognitive-behavioral Mindfulness Biofeedback, relaxation Exercise Meditation, Yoga

27 New dimension of diagnosis Detailed and precise measurement of somatic symptoms New pharmacotherapy tailored to

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