Journey of the depressed patient

Dr Acha OkokoMBBS, MSc, DPM, MRCPsych, MSc, LLM, FMCPsych

Consultant Psychiatrist

Burden of Disease in High Income Countries (2004)

Rank Disease or Injury DALYs (millions) % of total DALYs

1 Unipolar depressive disorders 10 8.2

2 Ischemic heart disease 7.7 6.3

3 Cerebrovascular disease 4.8 3.9

4 Alzheimer and other dementias 4.4 3.6

5 Alcohol use disorders 4.2 3.4

6 Hearing loss, adult onset 4.2 3.4

7 COPD 3.7 3.0

8 Diabetes Mellitus 3.6 3.0

9 Trachea, bronchus, lung cancers 3.6 3.0

10 Road traffic accidents 3.1 2.6

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..

The global burden of disease: 2004 update. World health Organisation UKCYM00844

Depression increases morbidity and mortality from common physical disease

39% increase in mortality in cancer patients diagnosed with depression.1

1. Satin JR Cancer 2009;115: 5349-5361 2. de Voogd JN et al. Chest 2009;135:619-6253. Mezuk B et al. Diabetes care 2008; 31:2383-2390 4. Katon W et al. J Gen Inern Med 2008;23:1571-15755. 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

COPD – depressive symptoms almost double the risk of mortality.2

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 diseaseCHD = coronary heart disease

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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.

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Clinical Symptoms

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

Bridges KW, Goldberg DP. J Psychosom Res. 1985;29:563–569. UKCYM00843

Depression – more than just mood

Physical symptoms Lack of energy Decreased concentration Change in appetite Change in sleep Change in psychomotor

skills

Associated symptoms Brooding Obsessive rumination Irritability Excessive worry over physical

health Pain Tearfulness Anxiety or phobias

American Psychiatric Association (APA). DSM-IV-TR; 2000:352,356.

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).

Emotional symptoms• Feelings of guilt

• Suicidal

• Lack of interest

• Sadness

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69%Physical symptoms

31%Other

1. Simon GE et al. N Engl J Med. 1999;341:1329-1335.2. Bair MJ et al. Arch Intern Med 2003;163:2433-2445

Muscle pain

NeuralgiaTightness in the chest

Abdominal disorders

Exhaustion

Weakness

PalpitationBack pain

Headache

Neck tension/hardening

Stomach troubles

Drowsiness

Dizziness

Symptoms of depressed patients attending primary care physicians

A clinical study with 1146 depressed patients showed that 69% visited their primary care physician only because of physical symptoms.1

A review of 14 studies found a mean of 65% of depressed patients experienced clinically significant painful symptoms. 2

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Aetiology of mood disorders

• Genetic causes• Personality• Early environment• Precipitating factors• Psychological • Neurobiological

Cognitive model of depression

Formation of negative schemas

(Cognitive vulnerability)

Early negative life eventsEnduring vulnerability:Genetic and personality factors

Remain dormant until activated by later life events

DEPRESSION

Daily life stressorsInformation processing bias

(memory, attention, interpretationCognitive reactivity

(negative self attitudes)

Adapted from Beck AT. Am J Psychiatry 2008;165:969-977 UKCYM00844

Negative Bias in Depression

“No-one really likes me” “Everything I do ends in failure”

“I will never be a success”

“I’m hopeless at everything”

“My life is worthless”

“There's no point in going on”

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Serotonin and noradrenaline pathways are widespread across the CNS

Locuscoeruleus

(NA source)

Raphe nuclei(5-HT source)

Amygdala

Hippocampus

Descending NA pathways

Descending5-HT pathways

Ascendingpain pathways

Limbic SystemPrefrontal

cortex

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.

5-HT=serotonin; NA=noradrenaline.

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Examining the role of serotonin and noradrenaline in human emotion and cognition

Manipulation of brain serotonin and noradrenaline levels via depletion and reuptake inhibition

Brain serotonin Tryptophan depletion

SSRI

Brain noradrenaline

NARI

SSRI = selective serotonin reuptake inhibitor. NARI = noradrenaline reuptake inhibitor

AMPT = α-methyl-para-tyrosine

*Note AMPT α-methylparatyrosine depletes noradrenaline and dopamineUKCYM00844

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

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.

Ascending pain pathwayDescending inhibiting

pain pathway(5-HT + NA)

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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.

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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.

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Depression and Pain

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

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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

1. Merskey H et al. Adhoc subcommittee on the IASP task force on taxonomy Pain 19942. Villemure C and Bushnell MC. Pain 2002;95:195-199 UKCYM00843

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.

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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 and noradrenaline are involved in the moderation of pain.

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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 and noradrenaline are involved in the moderation of pain.

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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.

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Pain and Depression Just 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

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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