Depression – CANMAT Guideline 2009

1. In a patient with a diagnosis of depression: 

a) Assess the patient for the risk of suicide.
b) Decide on appropriate management (i.e., hospitalization or close follow-up, which will depend, for example, on severity of symptoms, psychotic features, and suicide risk).

Assessment

1. Suicidality
2. Bipolarity
3. Comorbidity & concomitant medications
4. Special features (psychosis, atypical features, seasonality)
5. B/W if clinically indicated: LFT, metabolic workup

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2 Screen for depression and diagnose it in high-risk groups (e.g., certain socio-economic groups, those who suffer from substance abuse, postpartum women, people with chronic pain).

7 In patients presenting with depression, inquire about abuse: – sexual, physical, and emotional abuse (past and current, witnessed or inflicted). – substance abuse.

Risk Factors

• Female, age 25-45
• Family Hx of depression / mood disorder
• Negative childhood experience
• Physical or mental Abuse
• Substance abuse
• Stressors
• Poor social support
• Dementia, post stroke/MI, postpartum <6mo
• HIV
• Chronic pain or chronic dz / chronic insomnia / fatigue
• Multiple unexplained somatic complaints

Screen with patient health questionnaire (2 Qs)

• During the past month, have you often been bothered by
  1. Feeling down, depressed or helpless?
  2. Little interest or pleasure doing things?

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3 In a patient presenting with multiple somatic complaints for which no organic cause is found after appropriate investigations, consider the diagnosis of depression and explore this possibility with the patient.

Dx (Hx): > 2 wk of depressed mood or anhedonia most of the day, nearly every day + >= 5 of SIGECAPS

• Sleep
• Interest
• Guilt / hopelessness
• Energy
• Concentration
• Appetite
• Psychomotor retardation
• Suicidal ideation

R/o mania episodes, psychosis, anxiety symptoms or substance abuse

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8 In a patient with depression, differentiate major depression from adjustment disorder, dysthymia, and a grief reaction.

Dysthymia:

• Chronically depressed mood for 2 yrs with 2 SIGECAPS
• no MDE is present in this period

Adjustment Disoer

• Stressor < 3mo and resolves in < 6mo

Grief reaction

• Loss, resolves <3mo

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10 In the very young and elderly presenting with changes in behaviour, consider the diagnosis of depression (as they may not present with classic features).

Atypical:

• Reactive mood, over sleeping, over eating, leaden paralysis, interpersonal rejection, sensitivity

Children:

• More cognitive and fewer vegetative symptoms
• Irritable vs depressed mood
• S/Sx: insomnia, boredom, low self-esteem, deteriorating school performance, social withdrawal
• SNRI is the third line Tx – increase SI

Elderly

• Somatic c/o: wt change, sleep and energy issues, anxiety symptoms
• increased suicide risk
• screen with GDS

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4 After a diagnosis of depression is made, look for and diagnose other co-morbid psychiatric conditions (e.g., anxiety, bipolar disorder, personality disorder).

9 Following failure of an appropriate treatment in a patient with depression, consider other diagnoses (e.g., bipolar disorder, schizoaffective disorder, organic disease).

• See Anxiety and personality disorder posts

Bipolar: DIGFAST

• Distractibility
• Imulsivity
• Grandiosity
• Flight of ideas
• Activities
• Sleep, decrease need
• Talkative

Bipolar I – >=1 manic episode – Tx with Lithium or valproic acid

• screen for pregnancy, order TSH, lipids, BUN, Cr, ECG before Lithium Rx (causes Diabetes insipidus and hypothyroidism)

Bipolar 2 >= 1 hypomanic episode + 1 MDE – Tx with antipsychotics

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6 In a patient presenting with symptoms consistent with depression, consider and rule out serious organic pathology, using a targeted history, physical examination, and investigations (especially in elderly or difficult patients).

Organic causes

• Substance abuse
• DM, Thyroid, Pituitary, Vit B12, anemia, Calcium
• Dementia, Parkin’s, MS
• CVA, hepatitis
• OCPs, BZDs, betablockers, EtOH

Ix:

• CBC (r/o anemia), Lytes, Creatinine, TSH, folate, B12, LFTs
• ECG (prolonged QT is a contraindication for meds)
• Urine drug screen

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5 In a patient diagnosed with depression, treat appropriately: – drugs, psychotherapy. – monitor response to therapy. – active modification (e.g., augmentation, dose changes, drug changes). – referral as necessary.

Best outcome resulted from antidepressants + CBT

• Monitor adherence & educate self-management techniques
• Carefully monitored Q1-2 wk at the onset of pharmacotherapy, f/u Q2-4 wk or longer
• Monitor with validated outcome scales – PHQ-9

Antidepressant

• individualized based on symptom profile, comorbidity, tolerability, previous response, potential interactions, pt preference, cost

1st line: CBT & IPT

1. SSRI
   • Fluoxetine (Prozac 20-80mg) & SSRIs – 1st line in pregnancy
     • (except paroxetine – cardiac malformations)
   • Citalopram (Celexa 20-60mg), nortriptyline, sertraline, paroxetine – 1st line in nursing mother
   • Fluoxetine & Citalopram – 1st line in children
     • (2nd line: Paroxetine ↑ S/E & 3rd line: Venlafaxine – ↑suicidality)
2. SNRI (Venlafaxine – effexor 75-275mg & Duloxetine – cymbalta 60-120mg)
3. NDRI (Bupropion – wellbutrin 150-300mg)
4. α2 adrenergic agonist & 5-HT2 antagonist (Mirtazapine – remeron 30-60mg)

2nd line:

1. TCAs (Amitriptyline), MAOi (Selegiline – emsam),
2. SRI/5-HT2 antagonist (trazodone),
3. Atypical antipsychotic (quetiapine XR)
   • MDD + psychotic features, Tx w/ antidepressants + antipsychotic

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Pt factors:

1. Age & sex & comorbid disorders
2. Severity, Dx subtype, potential of biomarkers
3. Past response, sensitive to s/e

Tx factors

1. Efficacy – effectiveness
2. tolerability, simplicity of use, discontinuation syndrome
3. safety, potential drug-drug interactions
4. Cost, branded vs generic

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Management Algorithm

Tx 1st line antidepressant

1. No improvement (<20% ↑) or intolerant
   • Evaluate s/e and switch to a second agent with evidence for superiority
   • (Duloxetine, escitalopram, mirtazapine, sertraline -Zoloft 50-200mg, venlafaxine)
     • if less than full remission – augment/combine with another agent
     • (Apripiprazole, Lithium, olanzapine, Risperidone)
2. Some improvement (>20%) but not in remission
   • augment/combine with another agent
3. Remission  – maintenance therapy – same dose as acute dosage for >6mo after clinical remission (2yr if older, psychotic features, chronic episodes (>2yr of MDE), frequent episodes >2 / 5yr)

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Common S/E:

1. GI: nausea, diarrhea
2. CNS: Headache, insomnia, sedation, nervousness, tremor
3. Metabolic: ↑appetite, Wt gain, abn lipid profile, glucose homeostatis
   • Monitor in treated pt
4. Adverse events: Alter HR & BP; ↑ liver enzymes
5. Withdrawal symptoms from abrupt d/c, dose reduction / tapering
6. Sexual dysfunction
   • Tx w/ dose reduction or switch to another antidepressant
     • bupropion, mirtazapine, selegiline

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Serious adverse effects

1. Emergent suicidality in children and adolescents
   1. shouldn’t discourage initiation of Tx but balance benefits & risk
2. Serotonin syndrome or neuroleptic malignant syndrome-like events
   • ↑ in SSRIs/SNRIs + MAOi or other serotonergic agents
3. ↑upper GI bleeding with SSRIs, especially w/ NSAIDs
4. ↑osteoporosis and fractures in the elderly with SSRIs
5. Hyponatremia and agranulocytosis
6. ↑ seizures with TCAs at therapeutic doses

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