Major Depressive Disorder Therapy

what are the 3 main symptoms of MDD

• emotional: sadness, anhedonia, pessimism, etc.

• physical: sleep disturbance, pain, wt gain/loss, etc.

• cognitive: memory difficulties, decreased concentration, slowed thinking

diagnosing criteria for MDD based on DSM-5 TR

• >5 of the listed symptoms (and at least 1 bolded symptom)

• must be present nearly everyday for at least 2 weeks

• symptoms affect level of functioning

SIG E CAPS acronym

S = sleep (increase/decrease)

I = interest (decrease)

G = guilt

E = energy (decrease)

C = concentration

A = appetite (increase/decrease)

P = psychomotor agitation (increase/decrease)

S = suicidal ideation

what’s included in the differential diagnosis for MDD

• substance use (i.e. alcohol)

• Medications: CV (BB or clonidine), CNS (BZDs or opioids), hormonal (corticosteroids or contraception)

• conditions: stroke, Parkinson’s, hypothyroid, chronic pain

• other psych conditions: BPD, adjustment disorder

risks for MDD

• women

• primary relative with MDD

• adverse childhood

• stressful life events

• neurotic personality

• decrease socioeconomic status

• widow/separated/divorce

• comorbid psych disorders

• serious med conditions

typical onset of MDD

avg age = 20 years

may take days - wks or sudden

typical duration of MDD if left untreated

6-12 months

what are some risks for suicide in patients with MDD

• mental illness

• substance use

• prev. attempts

• FH of suicide

protective mechanisms against suicide for pts with MDD

• effective coping/problem-solving

• reasons for living

• cultural/religious/moral objections against suicide

psychotherapy for mild-mod MDD

may be used with or without antidepressant

psychotherapy for severe MDD

cannot be used as monotherapy; add on antidepressant

ECT and uses

high response and rapid onset

severe, psychotic and treatment resistant cases

rTMS

magnetic stimulation that is non-evasive

approved after vat least 1 failed trial in the current episode

vagus nerve stimulation (VNS)

surgically implanted; must fail at least 4 treatments

what are some lifestyle/CAMs to recommend to MDD patients

• exercise = well-established benefits

• St. John’s wort = 1st line for mild cases; 2nd line for mod. cases **3A4 inducer

• others = light therapy, acupuncture, L-methyl folate, SAMe, etc.

antidepressants uses in MDD and expected response rate

treat by increasing concentration of neurotransmitters in CNS to increase mood and other treatments

60-70% response rate

common ADRs seen with serotoninergic agents

• CNS

• GI (N/D)

• sexual dysfunction

common ADRs seen with noradrenergic agents

• tremor

• tachycardia

• increased BP

common ADRs seen with dopaminergic agents

• psychomotor effects

ADRs associated with SSRIs

• serotonergic

• hyponatremia / SIADH (elderly)

• increased bleeding risk

ADRs associated with SNRIs

• serotonergic

• NE-related (increased BP, HR - venlafax)

• hepatotoxic (dulox)

ADRs associated with bupropion

• CNS activation

• N/V

• seizures

ADRs associated with mirtazepine

• sedation

• wt gain

ADRs associated with vortioxetine

• GI (N/V)

ADRs associated with vilazodone

GI (N/V)

ADRs associated with SARIs

• nausea

• sedation (traz > nefaz)

• orthostasis (traz > nefaz)

• priapism (traz)

ADRs associated with TCAs

• sexual dysfunction

• seizures

• cardiac conduction slowing *dirty drugs*

ADRs associated with MAOIs

• wt gain

• orthostatic hypotension

• edema

• sexual dysfunction

top medications associated with sedation

• abilify

• mirtazapine

• trazodone

top medications associated with wt gain

• abilify

• remeron

• paroxetine

top medications associated with activating effects

• fluoxetine

• bupropion

• sertraline

• venlafaxine

top medications associated with GI upset

• vilazodone

• vortioxetine

• venlafaxine

• sertraline

top medications associated with sexual dysfunction

SSRIs and SNRIs

best management strategies for sexual dysfunction for patients

• adjunctive therapy (prn or routine)

• bupropion

• amantadine

• remeron

• buspar

• sildenafil

• or switch with lower risk

which antidepressants have high risk additive effects

• TCAs

• mirtazepine

• trazodone

which antidepressants have high risk for increased risk of bleeding

serotonergic agents

which antidepressants are 3A4 inhibitors

nefazodone and fluxoamine

which antidepressants are 2D6 inhibitors

• paroxetine

• fluoxetine

• duloxetine

• wellbutrin

which antidepressants are 2C inhibitors

• fluoxetine

• fluvoxamine

• sertraline

which antidepressants inhibit 1A2

fluvoxamine

which agents are 3A4 SUBSTRATES

• TCA (tertiary amines)

• citalopram

• SGAs

• CCBs

• statins

• sildenafil

which agents are 2D6 SUBSTRATES

• TCAs (secondary amines)

• SNRIs

• SSRIs

• mirtazapine

• FGAs

• BB

• class 1 antiarrhythmics

which agents are 2C9 SUBSTRATES

• fluoxetine

• phenytoin

• warfarin

• NSAIDs

• tolbutamine

which agents are 2C19 SUBSTRATES

• TCAs (tert amine)

• sertraline

• citalopram

• escitalopram

• diazepam

what agents are 1A2 SUBSTRATES

• TCAs (tert)

• duloxetine

• mirtazepine

• clozapine

• olanzapine

• theophylline

what are the preferred antidepressants

• SNRIs

• SSRIs

• bupropion

• Mirtazapine

• vilazodone

• vortioxetine

options if pt is at max dose or target dose and they still are suboptimal

switch antidepressant (in class or between classes)

options if pt has minimal response and want to decrease ADRs

• combine with another antidepressant

• augment with SGA or other meds

• augment with psychotherapy

treatment options for severe or refractory depression

• esketamine

• TCA or MAOI

• brain stimulation

antidepressant option for comorbid chronic pain

duloxetine

antidepressant option for comorbid neuropathic pain

duloxetine and TCA

antidepressant option for comorbid migraines

venlafaxine and TCA

when to expect physical improvement of symptoms

1-2 weeks

when to expect emotional improvement of symptoms

2-4 weeks

when to expect remission of symptoms

6-12 weeks

when should agents be switched

little/no response or poor tolerability

when should adjunctive therapy be considered

partial response and minimal/no tolerability issues