Ronald A. Remick, MD, FRCP(C) Medical Director, Mood Disorder Association of British Columbia Sophia I. Zisman, Bsc Hons. St. George’s University of London An Overview and Update on Mood Disorders – 2013

① Depression affects one out of five Canadians ② Lifetime prevalence of major depression-8% ① - minor depression/dysthymia – 7% ② - bipolar I/II - ~2% ③ million Canadians afflicted at any one time Overview of depression

① $83 billion in direct medical costs/$25 billion in associated medical costs ② 1,000,000 person-years lost from work ③ Second leading medical cause of long term disability ④ Forth leading cause of global burden of disease Depressive disorders have a significant morbidity

Presenteeism (lost productivity while at work) – likely a more significant problem with mood disorders than previously recognized in Canada Presenteeism (lost productivity while at work) – likely a more significant problem with mood disorders than previously recognized in Canada Productivity loss from presenteeism due to depression is 4 hours/week while loss from absenteeism is but 1 hour/week (between $6 billion loss per annum )! Productivity loss from presenteeism due to depression is 4 hours/week while loss from absenteeism is but 1 hour/week (between $6 billion loss per annum )! Absenteeism vs. Presenteeism

What Causes Depression?

Genetic Brain Chemical Changes Psychological Adversity/Environment Personality/ Temperament Causes of Depression

About “one third’ of the ‘variance’ in major depression is related to hereditary factors (in bipolar illness it is likely “two thirds”) About “one third’ of the ‘variance’ in major depression is related to hereditary factors (in bipolar illness it is likely “two thirds”) What is inherited (e.g. brain biological changes, personality traits, etc) is yet to be determined. What is inherited (e.g. brain biological changes, personality traits, etc) is yet to be determined. Early-onset (before age 30), severe, recurrent depression more likely to have a ‘genetic’ basis. Early-onset (before age 30), severe, recurrent depression more likely to have a ‘genetic’ basis. No single gene but likely a complex multi-gene inheritance. No single gene but likely a complex multi-gene inheritance. Genetics

Individuals with the normal personality traits – avoidance of harm, anxiousness, and pessimism - are slightly more at risk to develop a depressive illness. Individuals with the normal personality traits – avoidance of harm, anxiousness, and pessimism - are slightly more at risk to develop a depressive illness. To a large degree, many personality traits are inherited. To a large degree, many personality traits are inherited. How significant this ‘cause’ of depression is, and the relationship between genetics (nature) and/or the environment (nurture) remains unclear. How significant this ‘cause’ of depression is, and the relationship between genetics (nature) and/or the environment (nurture) remains unclear. Personality/ Temperament

The effects of stress/adversity dependent: The effects of stress/adversity dependent: a. The timing of the stressor (prenatal, postnatal, late life) b. Severity of the stressor c. Repetition of the stressor Stress may be more important in: Stress may be more important in: a. The genetically vulnerable b. Lack of social support Resiliency: genetic versus learning Resiliency: genetic versus learning Environment/Psychological Adversity

The Monoamine Hypothesis: Depression is caused by the underactivity in the brain of monoamines such as dopamine, serotonin and norepinephrine (in reality a lot more chemicals may be involved). Mania is caused by the overactivity of these monoamines in the brain. The monoamine hypothesis forms the basis of the pharmaceutical treatment of depression Brain Chemical Changes

① 4% of all depressives die by their own hands ② 66% of all suicides are preceded by depression ③ Depression & cardiovascular disease: I. Risk of MI 4-5x higher in MDD II. Depression is biggest risk factor post MI Depression - Mortality

Depression is a factor in more than 65% of successful suicides…always be aware, always ask about suicide.

① ask, ask, ask! : ?thoughts of death/suicide; ?plan;?method;?means; ?said goodbyes/written note; ?what would precipitate or prevent ② Assess risk factors: Assessing suicide risk First nationsFirst nations MaleMale Advanced ageAdvanced age Single/living aloneSingle/living alone Previous attemptPrevious attempt Family hx of suicideFamily hx of suicide PsychoticPsychotic HopelessHopeless Concomitant medical illnessConcomitant medical illness Substance abuseSubstance abuse

1. Individuals at High Risk: chronic insomnia or fatigue, chronic pain, multiple somatic complaints (“thick charts”), chronic medical illness (RA, DM), acute cardiac events, recent trauma, family history of depression, previous episodes 2. Special Population: children/adolescents -irritable mood; geriatric –grief; certain cultures- physical symptoms Detecting depression

① A distinct mood change (depressed, irritable, anxious, etc) for at least two weeks ② Four or more SIGECAPS Diagnosis of depression Sleep Interest Guilt Energy Concentration Appetite Psychomotor Activity Suicide

“in the last month, have you been bothered by little interest or pleasure in doing things?” Screening Questions “…what about feeling down, depressed or hopeless?”

Patient Health Questionnaire PHQ- 9 Patient Health Questionnaire PHQ- 9 ( ( Health Screening Questionnaire

Major Depression: 1. “depressed” mood and >4+ SIGECAPS 1. “depressed” mood and >4+ SIGECAPS 2. two week duration 2. two week duration Dysthymic Disorder : 1. “depressed” mood and 2 or 3 SIGECAPS 1. “depressed” mood and 2 or 3 SIGECAPS 2. TWO YEAR duration 2. TWO YEAR duration Depression vs. Dysthymic Disorder The treatment for MDD and dysthymia are identical

Collateral information and collaboration with family is paramount in the successful treatment of mood disorders.

There is a plethora of self help, patient directed resources for understanding and treating depressive disorders – use them.

CANMAT Guidelines ources/CANMAT Patients : depression toolkit: ns ns Informative web- site: ntalhealthwww.library.nhs.uk/me ntalhealth Physician and patient resources

Expect full recovery (with treatment) in 65% Expect marked improvement in 25%. Less than 10% have a protracted chronic course of illness Depression – The Good News

The most common cause of a failed treatment intervention in depression is non compliance.

Effective treatments for mood disorders can be either psychological or biological…and combination of both is ideal

Cognitive Behavioral Therapy (CBT) is an effective intervention for mild/moderate major depression.

Not covered by medical insurance Private Psychologist The majority of outpatient psychiatry departments in hospitals offer group based CBT which is covered by MSP funding. Enquire at your local hospital or with your doctor! Public Resources - ‘anti- depressant skills workbook (free download)-an outstanding self directed CBT workbookwww.carmha.ca/publications Online Accessibility

The use of antidepressants should be accompanied by clinical management, including patient education, attention to adherence issues, and self- management techniques. Choose a specific antidepressant based on : Choose a specific antidepressant based on : -your comfort/familiarity level -your comfort/familiarity level -patient’s previous good/poor response -patient’s previous good/poor response -side effects -side effects -cost -cost -drug-drug interactions -drug-drug interactions -co morbid conditions -co morbid conditions -depressive subtype -depressive subtype Acute Treatment – Antidepressants

Antidepressants First LineUsual DoseCost ($) SSRI Citalopram (Celexa)20-40mg Fluvoxetine (Prozac)20-40mg Fluvoxamine (Luvox) mg Paroxetine (Paxil)20-40mg Sertraline (Zoloft)50-200mg RIMA Moclobemide (Manerix) mg

Antidepressants First LineUsual DoseCost ($) SNRI Venlafaxine (Effexor)75-225mg Duloxetine (Cymbalta)60-120mg Desvenlafaxine (Pristique) mg Novel Action Bupropion (Wellbutrin) mg Mirtazapine (Remeron)30-60mg

Antidepressants Second lineUsual DoseCost ($) TCA Amitriptyline (Elavil) mg Clomipramine (Anafranil) mg Desipramine (Norpramin) mg Imipramine (Tofranil) mg Nortriptyline (Aventyl)75-150mg Trimipramine (Surmontil)75-150mg Maprotiline (Ludiomil)75-150mg Antipsychotics Quetiapine

To promote adherence, ALL patients should be told : Antidepressants are not addictive Antidepressants are not addictive Take the medicine every day Take the medicine every day It may take 2-4 weeks before you notice improvement It may take 2-4 weeks before you notice improvement Mild side effects are common, but usually temporary Mild side effects are common, but usually temporary Do not stop meds even if feeling better Do not stop meds even if feeling better Call doctor if any questions Call doctor if any questions Acute Treatment -Antidepressants

Antidepressants - Response Initial mild Improvement (2-4 weeks) Good Clinical Response (4-8 weeks ) Remission of symptoms (8-12weeks ) Return to baseline function

① If no response (<20%) after 3-4 weeks, then raise the dose incrementally every week to maximum tolerated if still no response : ② Re-evaluate diagnostic issues (bipolar, medical/psych comorbidity, substance abuse, personality disorder) ③ Reassess treatment issues (compliance, side effects) ④ Consider SWITCH (if 30% response). Managing Poor/Incomplete Antidepressant Response

Augmentation strategies are effective and easy to use…and are currently underutilized in the medical treatment of major mood disorders.

rationale – 30% response in 2 weeks a. lithium 150mg bid x 5d and increase by 300mg 5d to 450 bid for 10d trial b. cytomel 25ugm x 5d, 50ugm for 10d trial c. dextroamphetamine 2.5-5mg qam; increase by 2.5-5mg q 3d to max 10mgqam + for 7d trial d. atypical antipsychotics (olanzapine 5-10mg, aripiprazole 1-4mg) Antidepressant Augmentation

Two adequate trials of serotonin reuptake inhibitors (SRIs) are enough…consider venlafaxine/duloxetine as an SRI in your treatment schema.

① Continue the same dose of the antidepressant after successful treatment for at least 6-9 months. ② Consider long term/indefinite treatment : I. Two or more serious episodes in less than five years. II. Episodes that have been present for >two years before successful treatment. III. Patients who have their first episode after the age of 50. IV. Severe (suicidality/ psychosis) Maintenance therapy with antidepressants

Electroconvulsive therapy (ECT) Electroconvulsive therapy (ECT) Phototherapy (light box) Phototherapy (light box) Transcranial magnetic stimulation(TMS) Transcranial magnetic stimulation(TMS) Vagal nerve stimulation (VNS) Vagal nerve stimulation (VNS) Deep brain stimulation (DBS) Deep brain stimulation (DBS) Other Treatments for Major Depressive Disorders

Borderline personality disorder (BPD) (affective instability with reactivity of mood with intense dysphoria, irritability, anxiety; chronic feelings of loneliness; excessive inappropriate anger; impulsive suicide attempts) – the key to the differential diagnosis is BPD mood swings lasts hours, rarely days. Depressive Temperament vs. Medical Syndrome