MDD Flashcards by Annika Larson

MDD typical onset age

Late 20s
sharp increase from 12-16, increase gradually in 40s

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MDD risk factors

chronic medical conditions, family history, lower socioeconomic status, marital status, adverse life events

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Brain structure abnormalities

Overactive amygdala and hippocampus, shrinks with each depressive episode

Enlarged lateral ventricles, smaller caudate and putamen, altered prefrontal cortex activity

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Monoamine hypothesis

Decreased levels of 5-HT, DA, NE

Increases in neurotransmitters happens rapidly with antidepressant initiation

However, clinical effect is delayed

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Dysregulation Hypothesis

Depression due to dysregulated NT altering pre- and post-synaptic receptors

Adaptive changes in receptor sensitization or downregulation

Normalization of receptors after antidepressant therapy explains delay

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Chronic stress model

Increase in substance P
HPA axis secretes glucocorticoids and cortisol
Decrease in BDNF

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Diagnostic Evaluation

PMH: anemia, stroke, Parkinsons, infection, HIV/AIDs, vit D deficiency, hypothyroidism, cancer, epilepsy, diabetes, HD

Meds: isotretinoin, anticonvulsants, BB, ACEi, CCB, clonidine, steroids, montelukast, substance-related

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Common rating scales

PHQ-9
HAM-D
MADRS
BDI

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MDD DSM-V definition

≥ 1 depressive episode with no history of mania
≥ 5 of the following present nearly every day for ≥ 2 wks
-depressed mood (important)
-reduced interest (important)
-weight loss/gain
-sleep disturbances
-psychomotor agitation
-fatigue
-feeling worthless
-difficulty concentrating
-suicidal thoughts

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MDD SIG E CAPS

S –> sleep disturbances
I –> Interest (loss of)
G –> Guilt
E –> Energy (reduced)
C –> Concentration (impaired)
A –> Appetite changes
P –> Psychomotor agitation/retardation
S –> Suicidal thoughts

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Treatment goals: Response

50% decrease in symptoms in 4-8 weeks

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Treatment goals: Remission

few to no symptoms over ≥ 3 weeks

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Duration of episode

20 weeks with treatment to recovery
≥ 6 months if untreated

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Acute phase

6-12 weeks
goal is remission
optimize dose/regimen

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Continuation phase

4-9 months
goal is to prevent relapse
continue agent/dose that led to remission

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Maintenance phase

13-36 months
goal to prevent recurrence
recommended if ≥ 3 depressive episodes or symptoms

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Treatment first line

Psychotherapy + first line therapy
SSRI, SNRI, bupropion, mirtazapine, vortioxetine
x 4-8 weeks

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Treatment after adequate response

continue at optimal dose and re-evaluate at 6, 8, 12 weeks

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Treatment with persistent symptoms

increase dose, switch, augment or consider 2nd generation + psychotherapy

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if < 50% improvement after 8 weeks,

consider switching medications

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Key takeaways from STAR*D trial

There are conflicting theories about increasing dose, switching, and augmenting as the best strategy

Maximizing dose is important

8-12 weeks necessary to determine effectiveness

Switch is possible

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Strategies for partial/non-response

Switching (cross taper 1-2 weeks)
Augmentation

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Treatment Resistance

failure to respond to 2 separate trials of diff. antidepressants of adequate dose and duration

Switch to another AD
Augment with lithium, triiodothyronine, SGA

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Psychotherapy

Talk therapy -CBT, IPT, group psychoeducation

Direct Current Therapy

vagus nerve stimulation ECT rTMS

non-pharm other options

Exercise Bright light therapy

Rank SSRI by 1/2 life: Citalopram, Sertraline, Fluoxetine, Fluvoxamine, Escitalopram, Paroxetine

Longest Fluoxetine Citalopram Escitalopram Sertraline Paroxetine Fluvoxamine Shortest

MDD medications

SSRI, SNRI, Bupropion, Mirtazapine, TCA, MAOi, Mood stabilizers, Antipsychotics

Increases serotonin, norepinephrine availability within synapses

SSRI, SNRI, TCA

Increase dopamine and serotonin

bupropion

inhibition of alpha-2 receptors

mirtazapine

inhibition of MAO which breaks down neurotransmitters

MAOi

modulation of serotonin receptions with partial agonism

trazodone, vortioxetine

St. Johns Wart

"efficacy" at 600-1200 mg PO daily divided in 3 doses Lots of DDI SE: dry mouth, nausea, itching, photosensitivity, fatigue, dizziness, insomnia, headache Serious ADE: infertility, worsening of underlying psychiatric conditions ONLY for young healthy adults taking no other meds

Lithium Augmention

In combo with TCA Response within 48-72 hours

Triiodothyronine Augmentation

May lead to hyperthyroidism

Antipsychotic Augmentation

Aripiprazole Brexpiprazole Quetiapine

Buspirone

mixed efficacy useful in concomitant anxiety

Stimulants (modafinil, methylphenidate

fatigue and apathy

Hormone supplementation

Testosterone no benefit seen unless concurrent hypogonadism Estrogen some effect on depression if perimenopausal vasomotor symptoms

NMDA receptor antagonists

Mechanism includes alterations to inhibitory tone of interneurons and/or direct modulation of glutamate neurotransmission action on postsynaptic NMDA receptor Ketamine, Dextromethorphan

Esketamine

NMDA antagonist CI: history of intracerebral hemorrhage, aneurysms, or arteriovenous malformations BBW: risk of sedation and dissociation, potential for misuse

Esketamine

NMDA antagonist CI: history of intracerebral hemorrhage, aneurysms, or arteriovenous malformations BBW: risk of sedation and dissociation, potential for misuse

Dextromethorphan/bupropion (Auvelity)

non-selective, uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist

Cardiac risk of QT prolongation

Preferred: Sertraline Avoid: citalopram, escitalopram, TCA

Tobacco Use

Preferred: Bupropion Avoid: No CI

Seizure disorder

Preferred: No Avoid: Bupropion, TCA

Peripheral neuropathy or pain

Preferred: Duloxetine, high-dose venlafaxine, TCAs Avoid: No CI

Pregnancy

Preferred: No meds, if severe citalopram, escitalopram, sertraline Avoid: paroxetine, MAOi, vortioxetine

Daytime Sedation

Preferred: fluoxetine, bupropion, vorioxetine, duloxetine Avoid: paroxetine, mirtazapine, trazodone

Cognitive dysfunction

Preferred: Vortioxetine, bupropion, duloxetine, SSRI Avoid: anticholinergic meds

Insomnia

Preferred: mirtazapine Avoid: activating medications later in the day

Sexual dysfunction

Preferred: bupropion, mirtazapine, vortioxetine Avoid: SSRI, SNRI, paroxetine, venlafaxine

Weight gain

preferred: SSRI (not paroxetine) or SNRI Avoid: paroxetine and venlafaxine

polypharmacy

Preferred: escitalopram, sertraline, mirtazapine Avoid: fluoxetine, paroxetine, MAOi

Suicide risk

Preferred: SSRI, mirtazapine AvoidL TCA, MAOi, citalopram used with caution

Special populations: Pregnancy

All SSRI are Category C, except paroxetine (D) All TCA are Category C, except maprotiline (B) All SNRI, mirtazapine, bupropion are Category C Avoid MAOI – teratogenic in animal studies

Special populations: Lactation

Monotherapy with sertraline or paroxetine at lowest effective dose preferred Imipramine or nortriptyline may also be recommended Doxepin, St. John’s Wort are contraindicated All SSRI and TCA (except doxepin) are low risk Bupropion and SNRI are not well studied, variable risk