Depression—There are at least two sides to every story. Depression. It’s not only a state of mind. The symptoms of depression Emotional Symptoms Include: Physical Symptoms Include: Sadness Vague aches and pains Loss of interest or pleasure Headache Overwhelmed Sleep disturbances Anxiety Fatigue Diminished ability to think or concentrate, indecisiveness Back pain Excessive or inappropriate guilt Significant change in appetite resulting in weight loss or gain Reference: Adapted from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition,Text Revision. Washington, DC; American Psychiatric Association. 2000:345-356,489. Depression – the physical presentation In primary care, physical symptoms are often the chief complaint in depressed patients In a New England Journal of Medicine study, 69% of diagnosed depressed patients reported unexplained physical symptoms as their chief compliant1 N = 1146 Primary care patients with major depression Reference: 1. Simon GE, et al. N Engl J Med. 1999;341(18):1329-1335. Aches/pain – a physical symptom of significance Aches/Pain as common as anxiety among depressed patients % of Depressed Patients 70 60 National Comorbidity Survey 58% 55% NIMH Epidemiology Study 50 38% 40 30 35% 37% 28% 25% 17% 20 10 0 Aches/Pain (Women) Aches/Pain (Men) Adapted from 1.Silverstein B. Am J Psychiatry. 1999;156(3):480-482. 2.Silverstein B. Am J Psychiatry. 2002;159(6):1051-1052. Anxiety Disorder Anxiety Disorder (Women) (Men) The importance of emotional and physical symptoms • 76% of compliant depressed patients with lingering symptoms of depression relapsed within 10 months1* 94% of depressed patients who experienced lingering symptoms had mild to moderate physical symptoms1 *Psychiatric inpatients and outpatients. Reference: 1. Adapted from: Paykel ES, et al. Psychol Med. 1995;25:1171-1180. Serotonin5HT and NorepinephrineNE in the brain Limbic System Prefrontal Cortex Raphe Nuclei (5-HT source) Cooper JR, Bloom FE. The Biochemical Basis of Neuropharmacology. 1996. Locus Ceruleus (NE Source) There are at least two sides to the neurotransmitter story Functional domains of Serotonin and Norepinephrine1-4 Serotonin (5-HT) Sex Depressed Mood Anxiety Norepinephrine (NE) Concentration Appetite Vague Aches and pain Interest Aggression Irritability Motivation Thought process • Both serotonin and norepinephrine mediate a broad spectrum of depressive symptoms References: 1. Adapted from: Stahl SM. In: Essential Psychopharmacology: Neuroscientific Basis and Practical Applications: 2nd ed. Cambridge University Press 2000. 2. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43. 3. Doraiswamy PM. J Clin Psychiatry. 2001;62(suppl 12):30-35. 4. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114. The neurotransmitter pathway story It’s not all in your head • Dysregulation of Serotonin (5HT) and Norepinephrine (NE) in the brain are strongly associated with depression • Dysregulation of 5HT and NE in the spinal cord may explain an increased pain perception among depressed patients1-3 • Imbalances of 5HT and NE may explain the presence of both emotional and physical symptoms of depression. Adapted from References: 1. Stahl SM. J. Clin Psych. 2002;63:203-220. 2. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114. 3. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43. Descending Pathway Descending Pathway Ascending Pathway Ascending Pathway Depression: Current treatment outcomes1 • Up to 70% of depressed patients respond ( 50% decrease in HAM-D score) to treatment but fail to achieve remission from their emotional and physical symptoms1* • Approximately 30% of depressed patients achieve remission ( 7 score on the HAM-D) with treatment1* * Antidepressant clinical drug trials. References: 1. O’Reardon JR, et al. Psychiatr Ann. 1998;28:633-640. Response and Remission defined Hamilton Depression Rating Scale (HAM-D): 17 Items, Total Score 0 - 52 HAM-D17 Scores 15 Depression (Major Depressive Disorder) Response 50% reduction from baseline HAM-D score 7 Remission: HAM-D Score 7 References: 1. Frank E. Conceptualization and rationale for consensus definition terms in MDD, Arch Gen Psych. 1991; 48:851-855. Treatment outcome:Effect on work & social functioning Social Adjustment Scale-SR (Mean ± SD) Higher Score indicates greater impairment 5 Remitted patients virtually equaled healthy controls on functioning levels at endpoint of 12-week treatment trial (Responders & non-responders did not) 3 * ** 2 * 1 Normal (n=482) Study in chronic depressed patients *p.05 vs nonresponse. **p.05 vs response. Miller IW, et al. J Clin Psychiatry. 1998;59(11):608-619. Remission (n=202) Response (n=122) Nonresponse (n=299) Many depressed patients are still depressed. Depressed patients continue to have needs that are not being fully addressed1 • Depressed patients present with emotional and physical symptoms. • Approximately 30% of depressed patients achieve remission in clinical trials2* • Up to 70% of patients who respond fail to remit2* • Incomplete relief from symptoms may increase the risk of relapse2,3 • Lingering emotional and physical symptoms may jeopardize achieving remission. References: 1. Nierenberg AA, et al. J Clin Psychiatry. 1999:60(suppl 22):7-11. 2. O’Reardon JR, et al. Psychiatr Ann. 1998;28:633-640. 3. Lynch ME. J Psychiatry Neurosci. 2001;26(1):30-36. *In antidepressant clinical drug trials.