DEPRESSIVE DISORDERS

K.E. .Badoe MBChB., FRCPCMedical Director, Trellis Mental Health and Developmental

Services, Guelph

MEDICAL FIESTA August 9th 2012

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

Objectives

“ Depression”

“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

“Depression”

Diagnosis and treatment of “depression”

depended on the clinician’s perspective

 

Historically

Psychological - nurture

biological - nature

Historical perspectives

Causation -life events, “stressors”

Diagnosis – Reactive depression, Neurotic depression

Treatment - psychotherapy “tell me about your mother.... Your finances, your husband, boss

Psychodynamic-“nurture”

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

Depression

Diagnosis – Endogenous depression

Treatment - Biological –medication, ECT

Biological – “nature”

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?

Is everything biology?

Somewhere in between

The “truth?”

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)

Cluster analysis

A. At least Five of the following symptoms

present during the same 2-week period

represent a change from previous functioning

Major Depressive Episode DSM IV TR

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 .

Major Depressive Episode

(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

Major Depressive Episode

(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

Major Depressive Episode

(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

Major Depressive Episode

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).

Major Depressive Episode

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.

Major Depressive Episode

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)

Depressive disorders

Major depressive disorder

◦ Major depressive disorder, single episode◦ Major depressive disorder, recurrent - (two or

more episodes)

Depressive disorders

Mild Moderate Severe without psychotic features

Severe with psychotic features In partial remission In remission

Major Depressive Disorder –Severity

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

Major Depressive Disorder -subtypes

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

Major Depressive Disorder -subtypes

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,

Differential diagnosis -“depression”

$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,

Disease burden

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%

Disease burden

Mortality – lifetime risk of suicide in untreated major depressive disorder 20%

Less than 25% of those with MDD adequately treated

Disease burden

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 - overweight women had highest

Disease burden

Higher incidence in medical conditions e.g. obesity, chronic pain , diabetes

neurological conditions such as strokes, Parkinson's disease, MS

Disease burden

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

Epidemiology

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.

Epidemiology

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

Epidemiology

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

Clinical course of MDD

Episodes may become

more frequent More prolonged Less treatment responsive More spontaneous/autonomous

Clinical course of MDD

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%

Clinical course of MDD

Implications

Treat Early

Aim for remission

Maintain treatment dose for 6-12 months in remission or indefinitely

Clinical course of MDD

Response Relapse Remission Recurrence Return to premorbid functioning

Outcomes

Symptom remissionTreat comorbid disordersRestore premorbid functioning Attempt to limit disease progression.

Treatment - goals

Safety – where to treat (clinic, hospital)

How to treat

With whom to treat

Clinical environment

I General

II Psychotherapy –CBT, IPT

III Biological -Medication, ECT

IV Other – TMS, VNS, deep brain stimulation

Treatment options

Promote treatment adherence

Pschoeducation – re: illness, treatment options, patient preference

Exercise – minimum 150 min/wk

Establishing a routine with modest goals

I General

Cognitive behavioural therapy Interpersonal therapy Solution focused therapy

II Psychotherapy

AntidepressantsAugmenting agentsCombinations

III Biological

SSRI - Fluvoxamine, Citalopram, Paroxetine , Escitalopram, Sertraline, Fluoxetine

SNRI - Duloxetine, Venlafaxine, Desvenlafaxine

RIMA - Moclobemide

Miscellaneous – Bupropion, Mirtazapine ,

First-line antidepressants

Quetiapine Tricyclic antidepressants – e.g.

nortriptyline, imipramine, chlomopramine

Second-line antidepressants

Monoamine oxidase inhibitors (MAOIs)

e.g phenelzine, tranylcipramine

Third-line antidepressants

Evidence for superior efficacy/safety/tolerability

First-line antidepressants

Escitalopram, Sertraline, Venlafaxine

Antidepressant Comparator(s)Level of evidence 1

Duloxetine Mirtazapine

Antidepressant Comparator(s)Level of evidence 2

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

Clinical outcome

Previously - change classes e.g. SSRI’S to SNRI

BUT

No evidence of benefit over change to same class

What if the first choice is a failure?

Use other agents in the “superior “ group.

duloxetine, escitalopram, mirtazapine, sertraline, venlafaxine

What if the first choice is a failure?

lithiumtriiodothyronine, atypical antipsychotic

AUGMENTATIION -adding a second agent that is not an antidepressant

venlafaxine/mirtazepine -“California Rocket fuel”

buproprion/SSRI - (Escitalopram/citalopram)

nortriptyline/SSRI’s

COMBINATION -adding a second antidepressant

Commonly done, but limited data to support this practice

COMBINATION -adding a second antidepressant

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

ECT

Transcranial Magnetic Stimulation Light therapy ( even for non seasonal affective disorder)

Deep brain stimulation Vagus Nerve stimulation

IV Others

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

Treatment outcomes

common, occurring in 20% of patients

within 6 months following remission.

Treatment outcomes- recurrence

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

Treatment outcomes -remission

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

Dysthymic Disorder

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.

Dysthymic Disorder

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%).

Dysthymic Disorder- Comorbidity

As per MDD but response may take longer

More likely to maintain treatment indefinitely

treatment

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

Depressive Disorder - NOS

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

Conclusions – Depressive disorders