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Treatment of MDD in children and Youth

1st: CBT or IPT (1), internet based psychotherapy (1)
2nd: fluoxetine (1), escitalopram, sertraline, citalopram (2)
3rd: venlafaxine (2), TCA (2)


MDD in children youth-- minimal/no response

1st: add SSRI to psychotherapy (1)
2nd: switch to another SSRI (if not responsive to fluoxetine) (2)
3rd Venlafaxine, TCA (2)


MDD in children/youth-- treatment resistant

1st: SSRI + psychotherapy (2)
2nd: switch to another SSRI if non responsive to fluoxetine (2)
3rd venlafaxine (2), TCA (3) or neurostimulation (ECT or rTMS)(3)


Mild to moderate MDD in pregnancy

1st: CBT or IPT (individual or group) (1)
2nd: citalopram, escitalopram, sertraline (3)
3rd: structured exercise, acupuncture, bright light tx (2)
3rd meds: fluoxetine, fluvoxamine, venlafaxine, desvenlafaxine, duloxetine, mirtazapine, bupropion, TCA (caution with clomipramine) (3 or 4)
ECT -- severe, psychotic or tx resistant (3)
Therapist assisted internet CBT, mindfulness based CBT, supportive psychotherapy, couple therapy, rTMS (4)
Combination SSRI and CBT/IPT (4)


Mild to Moderate postpartum depression breast feeding

1st: CBT or IPT (individual or group) (1)
2nd: citalopram, escitalopram, sertraline (2) or combination SSRI and IPT/CBT (2)
3rd: structured exercise, acupuncture, therapist assisted internet CBT or behavioural activation (2)
meds: fluoxetine, fluvoxamine, paroxetine, TCA (except doxepin) (2), venlafaxine, desvenlafaxine, duloxetine, bupropion, mirtazapine (3)
rTMA, bright light tx (3)
ECT for severe, psychotic or treatment resistant (3)
mindfulness based CBT, supportive psychotx, couples, psychodynamic psychotx (4)


Perimenopausal depression tx

1st desvenlafaxine (1), CBT (2)
2nd: transdermal estradiol (2), citalopram, escitalopram, duloxetine, venlafaxine XR, mirtazapine, quetiapine XR, (3)
fluoxetine, paroxetine, sertraline, nortriptaline (4)
Omega 3 FA (4)
3rd: mindfulness based CBT, supportive psychotx


Late Life Depression algorithmic approach

1st: duloxetine, mirtazapine, nortriptyline (1)
citalopram/escitalopram, sertraline, vortioxetine, venlafaxine, desvenlafaxine, duloxetine, bupropion (2)
2nd: Switch to: notriptyline (1), moclobemide, phenelzine, quetiapine or trazodone (2), bupropion (3)
Combine with: aripiprazole, lithium (1), methylphenidate (2)
3rd: switch to: amitriptyline, imipramine (2)
combine SSRI or SNRI with bupropion or SSRI


CANMAT depression 2016 suicide risk factors

Non-Modifiable: prior suicide attempt, hx of self harm, older men, identify as sexual minority, family hx of suicide, hx of legal problems
Modifiable sx/life events: active SI, hopelessness, psychotic sx, anxiety, impulsivity, stressful life events ie financial stress, victimization
modifiable comorbidities: SUD (esp EtOH), PTSD, Pas (esp B), chronic painful medical conditions (migraines, arthritis), cancer


Depression scales- CANMAT 2016

symptoms: Hamilton depression rating scale (clinician), PHQ-9 (pt)
function: WHO-DAS (clinician and self)
side effects: UKU side effect rating scales (clinician), frequency, intensity and burden of side effect rating (FIBSER- pt)
QoL: QoL interview (QOLI- clinician), quality of life, enjoyment and satisfaction questionnaire


CANMAT 2016- depression tx phases

acute- 8-12 week
-goal is symptom remission-- full remission (residual sx high relapse), restore premorbid function, establish therapeutic alliance, educate, tx and monitor
Maintenance- 6-24 months
-prevent recurrence- healthy life strategies, address vulnerabilities, return to full function, educate/support, rehabilitate, tx comrobidities, monitor for recurrence


Risk factors for recurrence (depression- CANMAT 2016)

-early age onset
-greater number of prior episodes
-severity of initial episode (number of sx, SI, psychomotor agitation)
-disrupted sleep wake cycle
-comorbidites (esp with PDD)
-family hx of psychiatric illness
-negative cognitions
-high neuroticism
-poor social supports
-stressful life events


CANMAT 2016 Depression- recommendations for specifiers/comorbidities

GAD- antidepressant indicated for GAD
Catatonic features- benzos
psychotic features- antidepressant with antipsychotic
mixed features- lurasidone, ziprasidone
cognitive dysfunction- vortioxetine (1), bupropion, duloxetine, SSRI (2), moclobemide (3)
sleep disturbance- agomelatine (1), mirtazapine, quetiapine, trazodone (2)
somatic sx: duloxetine (1-pain), bupropion (1- fatigue), other SNRI (2-pain), SSRI (2-fatigue), duloxetine (2- energy)


antidepressants with superior efficacy (depression- CANMAT 2016)

level 1: escitalopram, sertraline, venlafaxine, mirtazapine
level 2: citalopram, agomelatine
-about 5% superior efficacy


antidepressants with lower sexual side effects (CANMAT 2016)

agomelatine, bupropion, mirtazapine, vilazadone, vortioxetine


duration of treatment (CANMAT 2016)

-early improvement of 20-40% sx reduction at 2-4 weeks
-duration- 6-9 months after symptomatic remission
-2 yrs with risk factors for recurrence incl: frequent, recurrent MDEs, severe MDEs, chronic episodes, comorbid psychiatric or medical conditions, presence of residual sx, difficult to treat episodes


Adjuncts for depression (CANMAT 2016)

1st: aripiprazole, quetiapine, risperidone (1)
2nd: brexipiprazole (1), bupropion, lithium, mirtazapine, modafinil (2), olanzapine (1), triiodothyronine (2)
3rd: other antidepressants (3), other stimulants (methylphenidate etc) (3), TCA (2), ziprasidone (3)
Experimental: ketamine
Not recommended: pindolol


Neurostimulation Tx Depression (CANMAT 2016)

1st: rTMS (failed 1 antidepressant), ECT (some clinical situations)
2nd: ECT
3rd: transcranial direct current stimulation, vagus nerve stimulation
investigational: deep brain stimulation, magnetic seizure therapy


Repetitive Transcranial Magnetic Stimulation

1st line for pt failed at least 1 antidepressant
-high frequency to left DLPFC or low frequency to right DLPFC
2nd line- switch protocols
-daily, 5x/week until sx resolve, up to 20-30 sessions
-maintenance prn-- high rates of relapse
-adverse: scalp pain, no cognitive sx
contraindicated with seizure hx, metallic hardware, cardiac pacemakers, implantable defibrillators, brain lesions


ECT 1st line indications (CANMAT 2016)

-acute SI
-MDD with psychotic features
-Treatment resistant depression
-repeated medication intolerance
-catatonic features
-prior favourable response to ECT
-rapidly deteriorating physical status
-pregnancy + any of the above
-patient preference


ECT relative contraindications (CANMAT 2016)

space occupying lesion in brain, increased ICP, recent MI, recent cerebral hemorrhage, unstable vascular aneurysm/malformation, pheochromocytoma, class 4/5 anesthesia risk


Depression- Complementary and Alternative Med (CANMAT 2016)

Exercise- mild/mod MDD, 1st line (1) monotx; mod/severe MDD, 2nd line (1) adj
Light tx- seasonal MDD 1st line (1) monotx; mild/mod MDD 2nd (2) monotx
Yoga- mild/mod MDD 2nd line (2) adj
Acupuncture mild/mod MDD 3rd line (2) adj
Sleep deprivation mod/severe MDD 3rd (2) Adj


Light therapy (Depression CANMAT 2016)

seasonal MDD: 1st line (1) monotx
mild/mod MDD: 2nd line (2) monotx
-daily exposure
-10 000 lux for 30 min in morning for up to 6 weeks
-response in 1-3 weeks


Exercise - Depression (CANMAT 2016)

Level 1 evidence
1st line monotx for mild-mod MDD
2nd line adj for mod/severe MDD
structured physical activity
cardiovascular or resistance training
-30min 3x/week for >9 weeks of supervised moderate intensity


St John's Wort (CANMAT Depression 2016)

• St John's Wort
• Perennial plant sued for centuries in total extracts-- effects serotonin receptos, monoamine oxidase inhibition and neurocrine/ion channels
○ Formulations vary widely-- dose range 500-1800mg/day for 4-12 weeks
○ Comparable efficacy to antidepressants
○ Side effects-- GI upset, skin irritation, headahces, photosensitivity, dry mouth
○ Risks of serotonin syndrome and hypomania when used with antidepressants
○ Higher potency extracts can cause drug interactions (P450)
• First line monotherapy in mild to moderate MDD (level 1) and 2nd line adjunctive for moderate-severe (level 2)