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Journey of the depressed patient

Journey of the depressed patient. Dr Acha Okoko MBBS, MSc, DPM, MRCPsych, MSc, LLM, FMCPsych Consultant Psychiatrist. Burden of Disease in High Income Countries (2004).

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Journey of the depressed patient

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  1. Journey of the depressed patient Dr Acha Okoko MBBS, MSc, DPM, MRCPsych, MSc, LLM, FMCPsych Consultant Psychiatrist

  2. Burden of Disease in High Income Countries (2004) DALY – disability adjusted life year for a disease or injury cause are calculated as the sum of the years of life lost due to premature mortality (YLL) in the population and the years lost due to disability (YLD) for incident cases of the disease or injury.. UKCYM00844 The global burden of disease: 2004 update. World health Organisation

  3. Depression increases morbidity and mortality from common physical disease COPD – depressive symptoms almost double the risk of mortality.2 39% increase in mortality in cancer patients diagnosed with depression.1 Depression associated with 60% increased risk of developing diabetes3, increased mortality4 and significantly higher risk of adverse microvascular and macrovascular outcomes5 Depression associated with 60% increased risk for CHD6 and 2X risk of death in CHD patients with depression.7 COPD = chronic obstructive pulmonary disease CHD = coronary heart disease 1. Satin JR Cancer 2009;115: 5349-5361 2. de Voogd JN et al. Chest 2009;135:619-625 3. Mezuk B et al. Diabetes care 2008; 31:2383-2390 4. Katon W et al. J Gen Inern Med 2008;23:1571-1575 5. Lin EHB et al. Diabetes Care 2010;33: 264-269 6. Wulsin LR and Singal BM. Psychosomatic Medicine 2003;65:201-10 7. Barth J et al. Psychosomatic Medicine 2004;:66:802-13 UKCYM00844

  4. Summary • Depression is a common, severe, disabling and life shortening illness. • Depression is not just a mental illness but has significant physical consequences. • Treatment to full clinical remission is the goal of treatment as this improves functional outcomes and reduces the risk of relapse. • Primary care physicians are well placed to recognise and effectively treat the majority of cases of major depression. UKCYM00844

  5. Clinical Symptoms

  6. Effect of Chief Complaint on Psychiatric Diagnosis in Primary Care • Of patients with only a psychological complaint, 94% of psychiatric illnesses were recognised by the family doctor • When physical complaints predominated, only 50% of psychiatric disorders were detected by the doctors UKCYM00843 Bridges KW, Goldberg DP. J Psychosom Res. 1985;29:563–569.

  7. Emotional symptoms Feelings of guilt Suicidal Lack of interest Sadness Depression – more than just mood Associated symptoms • Brooding • Obsessive rumination • Irritability • Excessive worry over physical health • Pain • Tearfulness • Anxiety or phobias Physical symptoms • Lack of energy • Decreased concentration • Change in appetite • Change in sleep • Change in psychomotor skills At least one of the symptoms is either 1) depressed mood or 2) loss of interest or pleasure (do not include symptoms that are clearly due to general medical condition or mood-incongruent delusions or hallucinations). UKCYM00844 American Psychiatric Association (APA). DSM-IV-TR; 2000:352,356.

  8. Symptoms of depressed patients attending primary care physicians Headache Exhaustion Back pain Neck tension/hardening Palpitation Muscle pain Stomach troubles Abdominal disorders Weakness Neuralgia Dizziness Tightness in the chest Drowsiness A clinicalstudywith 1146 depressedpatientsshowedthat 69% visitedtheirprimarycarephysicianonlybecauseofphysical symptoms.1 31% Other 69% Physical symptoms A review of 14 studies found a mean of 65% of depressed patients experienced clinically significant painful symptoms. 2 UKCYM00844 Simon GE et al. N Engl J Med. 1999;341:1329-1335. Bair MJ et al. Arch Intern Med 2003;163:2433-2445

  9. Aetiology of mood disorders • Genetic causes • Personality • Early environment • Precipitating factors • Psychological • Neurobiological

  10. Cognitive model of depression Enduring vulnerability: Genetic and personality factors Early negative life events Formation of negative schemas (Cognitive vulnerability) Remain dormant until activated by later life events Information processing bias (memory, attention, interpretation Daily life stressors Cognitive reactivity (negative self attitudes) DEPRESSION UKCYM00844 Adapted from Beck AT. Am J Psychiatry 2008;165:969-977

  11. Negative Bias in Depression “No-one really likes me” “Everything I do ends in failure” “I will never be a success” “My life is worthless” “There's no point in going on” “I’m hopeless at everything” UKCYM00844

  12. Limbic System Prefrontal cortex Raphe nuclei (5-HT source) Amygdala Locus coeruleus (NA source) Hippocampus Descending5-HT pathways Descending NA pathways Ascendingpain pathways Serotonin and noradrenaline pathways are widespread across the CNS 5-HT=serotonin; NA=noradrenaline. Adapted from: 1. Bymaster FP, et al. Curr Pharm Des. 2005;11:1475–1493. 2. Fields H. Nat Rev Neurosci. 2004;5:565–575. 3. Fields HL, et al. Annu Rev Neurosci. 1991;14:219–245. UKCYM00844

  13. Examining the role of serotonin and noradrenaline in human emotion and cognition Manipulation of brain serotonin and noradrenaline levels via depletion and reuptake inhibition Tryptophan depletion Brain serotonin SSRI AMPT = α-methyl-para-tyrosine Brain noradrenaline NARI *Note AMPT α-methylparatyrosine depletes noradrenaline and dopamine UKCYM00844 SSRI = selective serotonin reuptake inhibitor. NARI = noradrenaline reuptake inhibitor

  14. Depression: Reduced activity from descending 5HT and NA pathways. • Virtually all drugs that are effective in treating MDD affect the function of serotonin (5-HT) and/or noradrenaline (NA)1 • The CNS processes pain information and modulates pain responses through descending pain pathways2 • 5-HT and noradrenaline (NA) are key modulatory neurotransmitters in the descending inhibitory pathway and are part of the body’s endogenous analgesic system3 Ascending pain pathway Descending inhibiting pain pathway (5-HT+NA) 1. Blier P, Abbott FV. J Psychiatry Neurosci. 2001;26:37–43. 2. Verma S, Gallagher RM. Int Rev Psychiatry. 2000;12:103–114. 3. Stahl SM. J Clin Psychiatry. 2002;63:382–383. UKCYM00844

  15. Monoamines in mood and cognition - summary • Brain serotonin and noradrenaline networks are numerous and important in control of mood and cognitions. • A reduction of monoamines appears to impair positive attentional bias and induce negative attentional bias. • Depression however is not caused by a simple reduction in monoamines. • The availability of serotonin seems essential to maintain an antidepressant response to an SSRI and the availability of NA seems essential to maintain response to a NARI. • Antidepressants reduce negative bias and increase positive bias and may therefore work in a similar way to cognitive therapies. UKCYM00844

  16. Early life stress and HPA function • Early life stress can prime and alter the function of the stress (HPA) axis. • This may leave an individual vulnerable to the development of depression and other psychiatric disorders. • Serotonin transporter genes may explain some of the association between environmental stress and depression. • they may mediate stress reactivity • they may modify response to serotonergic antidepressants. • Stress may also impact on brain neurotrophic factors important in the normal development and health of the brain. UKCYM00844

  17. Depression and Pain

  18. Depressive Episode – conventional descriptions • Although ICD-10 and DSM-IV definitions of depression both mention pain it is described as a secondary or uncommon symptom. • Most other symptoms are either secondary to, or easily understood in the context of, such changes Disturbance in mood is the predominant feature. • This emphasis on affective symptoms may contribute to under-recognition of pain in patients presenting with depression. Katona C et al. Clinical Med 2005;5:390-395 UKCYM00843

  19. Pain • An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. (International Association for the Study of Pain).1 • Emotion has a moderating effect on pain.2 • positive mood reduces pain perception • negative mood increases pain perception UKCYM00843UKCYM00772 Merskey H et al. Adhoc subcommittee on the IASP task force on taxonomy Pain 1994 Villemure C and Bushnell MC. Pain 2002;95:195-199 UKCYM00843

  20. Pain and depression • Painful symptoms are common in people with major depression. • Pain is modulated via both serotonergic and noradrenergic pathways on the central nervous system. UKCYM00844

  21. Overall Summary • Depression is a serious mental illness that also modifies outcome in physical disease. • Remission is the overall treatment goal. • The monoamines serotonin and noradrenaline are both implicated in the neurobiology of depression. • they may moderate cognitive bias and neurotrophic factors in the brain. • they are the targets of antidepressants • Stress is undoubtedly involved in the aetiology of depression • maternal, childhood and adult stress can increase vulnerability to depression • Genes also influence a persons vulnerability to depression. • genes interact with environmental factors • Pain is a common symptom of major depression and reduces the chance of good outcome • serotonin andnoradrenaline are involved in the moderation of pain. UKCYM00844

  22. Overall Summary • Depression is a serious mental illness that also modifies outcome in physical disease. • Remission is the overall treatment goal. • The monoamines serotonin and noradrenaline are both implicated in the neurobiology of depression. • they may moderate cognitive bias and neurotrophic factors in the brain. • they are the targets of antidepressants • Stress is undoubtedly involved in the aetiology of depression • maternal, childhood and adult stress can increase vulnerability to depression • Genes also influence a persons vulnerability to depression. • genes interact with environmental factors • Pain is a common symptom of major depression and reduces the chance of good outcome • serotonin andnoradrenaline are involved in the moderation of pain. UKCYM00844

  23. The neurobiology of depression and pain - summary • Pain is a sensory and emotional experience • similar areas of the brain are involved in both pain processing and depression. • Neural networks involved in pain processing may be dysfunctional in depressed patients. • Cognitive and attentional bias present in depression may alter pain perception. • Serotonin and noradrenaline pathways in the spinal cord are essential to normal pain modulation and these pathways are disrupted in depression. UKCYM00843UKCYM00772 UKCYM00843

  24. Pain and DepressionJust coincidence or more? • Physical symptoms should be taken seriously as integral part of depression. • The patient’s “outcome” matters! • Rapid decrease of emotional and physical symptoms during treatment of depression • Remission as major therapeutic goal • Selective, dual-effective antidepressants, e.g. duloxetine, offer therapeutic options • Mechanism of action, dosage, safety, tolerability UKCYM00843UKCYM00772 UKCYM00843

  25. Consensus Group on Depression and Pain: Recommendations on Clinical Assessment • Pay attention to pain in the presence of depression • Avoid unnecessary tests • Avoid “normalisation” • Effective communication skills Katona C et al. Clinical Med 2005;5:390-395 UKCYM00843

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