Management of Depression in Adults Jon van Niekerk

 WHO ranked depression the fourth global burden of disease  The largest non-fatal burden of disease, with nearly 12% of total years lived with disability [Ustün, 2004] Burden

 50 – 70 % of depression missed in primary care  Somatisation the most important factor [Tylee, 2007] Detection

 About two thirds of depressed patients present mainly with somatic symptoms [Tylee, 2005]  Detecting depression in connection with somatisation should be a core professional skill of ALL doctors Somatisation

 Asking patients open questions on what they think is the cause of their physical symptoms.  It is also worth inquiring about possible life events preceding the symptoms. Consultation

 Detection of depression can be improved by training in mental health and screening. [Tylee, 2007]  Patients at high risk in both primary care and general hospital settings can be screened for depression by asking two questions on mood and interest (Box 1). [Aroll, 2005] Training/Screening

 chronic medical illness,  chronic pain syndromes,  recent life events,  poor self rated health, and  unexplained physical symptoms Higher risk

1.During the past month have you often been bothered by feeling down, depressed, or hopeless? 2.During the past month have you often been bothered by having little interest or pleasure in doing things?  If patients answer yes to either question then the specificity of screening can be further increased by asking them whether they want help with their problems Two screening questions for depression

 Criteria met for depression?  Still clinical diagnosis – ask about impact on life Clinical diagnosis

Fig 1 Classification criteria for depression. Timonen M, and Liukkonen T BMJ 2008;336: ©2008 by British Medical Journal Publishing Group

 Hypothyroidism,  Hyperthyroidism,  Huntington’s disease,  Cushing’s disease, and  Addison’s disease Physical illness and depression

 Management must then be directed at the underlying condition rather than the depressive symptoms  More commonly several physical illnesses occur with depression; if so, treatment must be directed at the depression as well as the illness Physical illness and depression

 Depression also occurs commonly with anxiety disorders.  Depression requires treatment first when it is considered the primary diagnosis Anxiety

 Patients’ preferences,  concomitant psychiatric and physical disorders, drugs  patients’ experiences with previous treatments,  the severity of depressive symptoms,  risk of suicide,  and availability of treatment options Negotiating Management plan

 > 80% depression are managed in primary care.  Secondary care see those with more severe disease?  Indicated for patients displaying psychotic features or active suicidality.  Resistant to treatment or have recurrent depression.  A stepped care model Which treatment setting? (OR when to refer)

Fig 2 Stepped care model for treatment and management of depression in primary care. Timonen M, and Liukkonen T BMJ 2008;336: ©2008 by British Medical Journal Publishing Group

 In mild depression NICE recommends a further assessment within two weeks (watchful waiting) for those not agreeing to intervention and for those who healthcare professionals believe may recover spontaneously without intervention.  Otherwise the recommended first line treatments for mild depression on the basis of substantial research based evidence are guided self help as well as brief psychological interventions (6-8 sessions) including:  problem solving therapy,  brief cognitive behaviour therapy, and  counselling Psychological treatments

 Not first-line treatment in mild/recent onset: Moderate-to-severe  Generic SSRI – Sertraline/Fluoxetine  Withdrawal symptoms – all antidepressants  Treatment resistance – augmentation with Li or an antipsychotic/ second antidepressant  TWO or more episodes 0f depression – treat for at least 2 years  ECT in severe and treatment resistant depression Pharmacological treatment of depression (NICE)

 Use the lowest possible dose  Monitor closely in early stages – agitation/ restlessness/suicidality (< 30)  Taper doses gradually on stopping  Treat for 6 – 9 months after recovery Antidepressants

 Risk of recurrence is high – increases with every episode  Those with multiple episodes – Rx for many years  Chances of staying well is greatly improved by taking antidepressants  Continue at treatment dose (if s/e intolerable – change the medication)  Do not stop taking tablets abruptly/miss medications What patients should know

Antidepressants are:  Effective  Not addictive  Not known to lose efficacy over time  No long term side effects What patients should know

Recurrence is higher in :  Family history of depression  Concurrent psychiatric diagnosis  Females  Long episode of duration  Treatment resistance  Chronic medical illness  Social factors – lack of support  Severity of initial episode  Sub-optimal pharmacological treatment Recurrent depression

 Pragmatic effectiveness study  Remission of symptoms was main outcome  Consisted of patients with long history depression STAR-D (next steps)

Importance of STAR*D  The largest clinical trial of depression ever  Conducted in primary care as well as psychiatric settings  Few exclusion criteria, making it “real world”  Included large numbers of minority patients  Included cognitive therapy  Combined randomization and patient choice  The outcome was “remission” rather than “response”

Definitions of Response and Remission

Remission vs. Non-Remission: Significant Baseline Differences  Female gender  Being employed  Caucasian (vs. African- American)  Being married or co- habitating  Being more educated  Having private insurance  Having less medical problems  Having less psychiatric co- morbidities  Lower baseline severity  Better baseline physical and mental function  Greater life satisfaction  Shorter current episode

 Either switching to the same class of antidepressant (SSRI to SSRI) or to a different class (SSRI to non- SSRI) did not matter  Substantial differences in pharmacology did not translate into substantial clinical differences in efficacy Conclusions

 1. SSRI  2. SSRI/SNRI (Venlafaxine)  3. Switch to Mirtazapine OR augment with:  Mirtazapine OR atypical antipsychotic (Aripiprazole /Quetiapine [L] 150 ) OR Lithium OR T3 or Buspirone  4. Consider alternative augmentation strategy Treatment resistant Depression

 Use SSRIs as first line – most data for Fluoxetine  THEN SNRI  Avoid TCA and MAOIs – effects on weight and glucose homeostasis  Monitor blood glucose and HBA1C carefully when starting treatment Depression and diabetes

 30 – 40% survivors of stroke ? prophylaxis  Slows functional rehab  Fluoxetine, Sertraline appears to prevent depression  Mirtazepine may be both protective and treat Post Stroke depression

 Fluoxetine - small decrease in HR, minimal effect on BP and no effect on QTc. Evidence of safety post MI  Sertraline – minimal effect on HR, minimal effect on BP, no effect on QTc. Safe post MI and in heart failure  Mirtazapine – minimal change HR, minimal effect on BP, no effect on QTc. Evidence of safety post MI. Cardiac effects

 Also in poor compliance  Venlafaxine and Paroxetine (short half lives)  Flu-like symptoms, “shock-like” sensations, dizziness, insomnia, vivid dreaming, irritability, crying spells Discontinuation symptoms

 May be effective in mild-to-moderate depression  We do not know how much/side-effects  Less evidence of benefit in severe depression  Most preparations are unlicensed  Can interact with other medications – increased viral load in HIV, failure of OCP, reduced anticoagulant with warfarin etc. St. John’s Wort

Any Questions? Thank you!