1. K.E..Badoe MBChB., FRCPC Medical Director, Trellis Mental Health and Developmental Services, Guelph MEDICAL FIESTA August 9 th 2012

2.  Review an approach to diagnosis of Depressive Disorders  Examine the clinical course of MDD  Consider the rationale behind the drive to achieve remission  Evidence-based selection of treatment options

3. “ Depression”

4. “Doctor, I am depressed” because...  My lotto numbers did not “drop” this week  My wife left me last week  My husband died three years ago  There is no reason for me to feel this way

5.  Diagnosis and treatment of “depression” depended on the clinician’s perspective

6.  Psychological - nurture  biological - nature

7.  Causation -life events, “stressors”  Diagnosis – Reactive depression, Neurotic depression  Treatment - psychotherapy “tell me about your mother.... Your finances, your husband, boss

8.  One man’s stress, is another man’s pleasure  “If I look hard enough, I will find stress”  e.g. travelling to Ghana, jet lag, preparing for a presentation, carrying back kobe

9.  Diagnosis – Endogenous depression  Treatment - Biological –medication, ECT

10.  No one would consider putting someone on an antidepressant because of a lotto ticket  What about the man who has lost 30 pounds, cannot sleep, has been thinking of suicide for the past two months, because of the lotto ticket?  And on what basis would one decide which treatment?

11.  Somewhere in between

12.  Symptoms clusters that responded biological interventions  Mood disturbance that seemed to be autonomous, impairment in in parametres such as sleep, energy, appetite, concentration  Precipitants/stressors – not relevant to the diagnosis of MDD (except bereavement)

13.  A. At least Five of the following symptoms  present during the same 2-week period  represent a change from previous functioning

14.  Of five at least one of the symptoms is EITHER (1) depressed mood most of the day, nearly every day, either subjective report (e.g., feels sad or empty) or observation by others (e.g., appears tearful). In children and adolescents, can be irritable mood. OR (2) markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day.

15. (3) significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains. (4) insomnia or hypersomnia nearly every day

16. (5) psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) (6) fatigue or loss of energy nearly every day

17.  (7) feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick) (8) diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others) (9) recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a specific plan for committing suicide or a suicide attempt

18.  B. The symptoms do not meet criteria for a Mixed Episode. C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).

19.  E. The symptoms are not better accounted for by Bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

20.  Major depressive disorder ◦ Major depressive disorder, single episode ◦ Major depressive disorder, recurrent - (two or more episodes)  Dysthymic disorder  Depressive Disorder NOS  (Adjustment Disorder – depressed mood)

21.  Major depressive disorder ◦ Major depressive disorder, single episode ◦ Major depressive disorder, recurrent - (two or more episodes)

22.  Mild  Moderate  Severe without psychotic features  Severe with psychotic features  In partial remission  In remission

23.  Melancholic depression - loss of pleasure in most or all activities,, a quality of depressed mood more pronounced than that of grief or loss, a worsening of symptoms in the morning hours, early- morning waking, psychomotor retardation, excessive weight loss, excessive guilt.  Atypical depression - mood reactivity (paradoxical anhedonia) and positivity, significant weight gain or increased appetite (comfort eating), hypersomnia,), a sensation of heaviness in limbs known as leaden paralysis, and significant social impairment as a consequence of rejection hypersensitivity

24.  Catatonic depression - rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Patient is mute and almost stuporous, immobile or engages in purposeless or even bizarre movements. Rule out schizophrenia /neuroleptic malignant syndrome.  Post partum depression -10–15% among new mothers onset occur within one month of delivery  Seasonal affective Disorder (SAD) – onset fall/autumn subsides following spring,at least two episodes have occurred in colder months with none at other times, over at least a two-year period

25.  Normal bereavement – 2 months  Bipolar depression - previous (hypomanic) episode  DYTHYMIC DISORDER Chronic “Low grade” 2 years  Adjustment Disorder- depressed mood  Other mental disorders e.g. schizoaffective  Substance induced  Medical – e.g. Hypothyroidism,

26.  $15 billion / yr (USA)  2030 - second leading cause of disability (WHO) after HIV  Morbidity – presenteeism, absenteeism, relationship, occupational, obesity, diabetes, cancers  Comorbidity ( worse prognosis)– anxiety disorders, substance use disorders, personality disorders,

27.  Mortality - lifetime risk of suicide in the US estimated at “3.4%”, Men -almost 7% Women- 1% The estimate is substantially lower than a previously accepted figure of 15%, which had been derived from older studies of hospitalized patients -15%

28.  Mortality – lifetime risk of suicide in untreated major depressive disorder 20%  Less than 25% of those with MDD adequately treated

29.  smoking and obesity -increased likelihood  cardiovascular disease -1.5- to 2-fold increased risk, independent of other known risk factors  colorectal cancer  - Up to 43% greater risk in depressed women  - "dose-response" relationship observed  - o verweight women had highest

30. Higher incidence in medical conditions  e.g. obesity, chronic pain, diabetes neurological conditions such as strokes, Parkinson's disease, MS

31. Lifetime prevalence (8% -12%) Gender differential  Adolescent and adult females : males - 2:1 Age of onset  rare before puberty  average age at onset is the late 20s.  may begin at any age, but peak 25-44

32. Clinical course  Initial episode may be triggered by stressor  develop over days to weeks  Prodromal symptoms -generalized anxiety, panic attacks, phobias, or depressive symptoms that do not meet the diagnostic threshold may occur over the preceding several months.

33. Clinical course  mean duration of a major depressive episode 16 weeks  Untreated -6 months or longer  median time to recovery from a major depressive episode is approximately 20 weeks

34. Recurrence risk  After one episode – 50-60% for 2nd  After 2nd episode – 70% for 3rd  After 3rd episode - 90% +

35. Episodes may become  more frequent  More prolonged  Less treatment responsive  More spontaneous/autonomous

36. Partial remission - higher risk for relapse Longer episode duration- poorer prognosis More episodes – poorer prognosis Maintenance of full therapeutic dose for 6-12 months reduces relapse risk by 50%

37. Implications  Treat Early  Aim for remission  Maintain treatment dose for 6-12 months in remission or indefinitely

38.  Response  Relapse  Remission  Recurrence  Return to premorbid functioning

39.  Symptom remission  Treat comorbid disorders  Restore premorbid functioning  Attempt to limit disease progression.

40.  Safety – where to treat (clinic, hospital)  How to treat  With whom to treat

41.  I General  II Psychotherapy –CBT, IPT  III Biological -Medication, ECT  IV Other – TMS, VNS, deep brain stimulation

42.  Promote treatment adherence  Pschoeducation – re: illness, treatment options, patient preference  Exercise – minimum 150 min/wk  Establishing a routine with modest goals

43.  Cognitive behavioural therapy  Interpersonal therapy  Solution focused therapy

44.  Antidepressants  Augmenting agents  Combinations

45. SSRI - Fluvoxamine, Citalopram, Paroxetine, Escitalopram, Sertraline, Fluoxetine SNRI - Duloxetine, Venlafaxine, Desvenlafaxine RIMA - Moclobemide Miscellaneous – Bupropion, Mirtazapine,

46. Quetiapine Tricyclic antidepressants – e.g. nortriptyline, imipramine, chlomopramine

47.  Monoamine oxidase inhibitors (MAOIs) e.g phenelzine, tranylcipramine

48.  Evidence for superior efficacy/safety/tolerability

49.  Escitalopram,  Sertraline,  Venlafaxine

50.  Duloxetine  Mirtazapine

51.  Early indication of response after 2-4 weeks  With response allow for a further 2 – 4 weeks  If clear but inadequate response then ADD  If poor response then CHANGE

52. Previously - change classes e.g. SSRI’S to SNRI BUT No evidence of benefit over change to same class

53. Use other agents in the “superior “ group.  duloxetine,  escitalopram,  mirtazapine,  sertraline,  venlafaxine

54.  lithium  triiodothyronine,  atypical antipsychotic

55.  venlafaxine/mirtazepine - “California Rocket fuel”  buproprion/SSRI - (Escitalopram/citalopram)  nortriptyline/SSRI’s

56.  Commonly done, but limited data to support this practice

57.  Create a controlled seizure  Right unilateral or bilateral  Increases mono amine neurotransmitters  ECT has the highest rates of response and remission of any form of antidepressant treatment, with 70%–90% of patients treated showing improvement  Potential cognitive side effects

58.  Transcranial Magnetic Stimulation  Light therapy ( even for non seasonal affective disorder)  Deep brain stimulation  Vagus Nerve stimulation

59. Recurrence - Risk factors ◦ Persistence of subthreshold depressive symptoms (relapse) ◦ Prior history of multiple episodes of major depressive disorder ◦ Severity of initial and any subsequent episodes ◦ Earlier age at onset ◦ Presence of an additional nonaffective psychiatric diagnosis ◦ Presence of a chronic general medical disorder ◦ Persistent sleep disturbances

60.  common, occurring in 20% of patients within 6 months following remission.

61. Remission rates (STAR*D)  First trial - 36.8%,  Second trial - 30.6%,  Third trial - 13.7%,  Fourth trial - 13.0%  Total - 67% with trials, augmentation and combination strategies

62.  Depressed mood or appears depressed for two years or more,  WITH two or more of: ◦ decreased or increased appetite ◦ decreased or increased sleep (insomnia or hypersomnia) ◦ fatigue or low energy ◦ Reduced self-esteem ◦ Decreased concentration or problems making decisions ◦ Feels hopeless or pessimistic

63.  Symptoms never absent longer than two consecutive months.  No major depressive episode during first two years  No manic hypomanic or mixed episodes  The patient has never fulfilled criteria for cyclothymic disorder.  The depression does not exist only as part of a chronic psychosis  The symptoms not directly caused by a medical illness or by substances, including drug abuse, or other medications.  The symptoms may cause significant problems or distress in social, work, academic, or other major areas of life functioning.

64.  major depression,  anxiety disorders (up to 50%)  personality disorders (20–40% or more among those with early-onset DD),  somatoform disorders (2.8%–45.2%),  substance abuse (up to 50%).

65.  As per MDD but response may take longer  More likely to maintain treatment indefinitely

66.  Criteria not met for MDD or DD  Exclude the exclusion criteria  Treatment options to consider as per MDD

67.  Common, more common in women than men  recurrent, progressive, chronic,  Associated with morbidity, comorbidity, mortality  Repercussions –personal, relationship, societal  Goal of treatment – symptom relief, limit disease progression, restore premorbid function.  Using pharmacotherapy, psychotherapy and other strategies, the majority can be helped