Depression

What can cause depression symptoms?

What is meant by uncomplicated and complicated depression?

Uncomplicated: no comorbidities

Complicated: comorbidities such as: 

• Catatonia

• Psychotic depression

• Severe suicidality

• History of previous ECT success

• Need for rapid response

• Risks for other treatments

• History of poor response to antidepressants

How to treat someone who just has depression by itself

How to treat someone who has depression with complications?

Treatment: Psychotherapy PLUS pharmacotherapy ECT with or without psychotherapy

What is the BBW for all antidepressants?

Increased risk of thoughts and behavior ages 24 and younger

• Increased monitoring first 3 months (but can be anytime)

• Risk decreases with advancing age

What is shared is between all antidepressants

Use of antidepressant monotherapy in patients with underlying bipolar disorder can precipitate a switch to mania

Formulations: do not crush or chew sustained/extended release, liquids may contain alcohol

Drug interactions: majority 2D6

How to navigate antidepressant side effects?

• If experience anxiety: lower doses and titrate slowly

• If insomnia or sedation: switch administration time

• If headache: can treat with OTC PRN for few days trial to resolve

• Gastrointestinal: give with food

• Weight gain: explore diet/exercise or switch agents if needed

• Sexual side effects: usually switch needed. Alternatives:

• Bupropion, vortioxetine other off-label options 

What drugs are SSRIs?

Citalopram

Escitalopram

Fluoxetine

Fluvoxamine

Paroxetine

Sertraline

Citalopram

SSRI

indicated only for MDD

ADRs: QT prolongation

Maximum dose for elderly over 60 years: 20mg/day

Escitalopram

SSRI 

indicated for MDD (12-17 yrs), generalized anxiety disorder (GAD)

Risk of use in patients with concomitant illness

Maximum dose for elderly over 60 years: 10mg/day

Fluoxetine

SSRI 

Indicated for: MDD (8-17 yrs), OCD (7-17 yrs), Panic, Premenstrual dysphoric disorder (PMDD), bulimia nervosa 

• Reduced appetite and weight

• Anxiety and insomnia

• Long half-life (only SSRI with a once weekly dose option)

Fluvoxamine

SSRI

Indication: OCD (8-17 yo)

Many significant drug interactions

Not approved for MDD

Paroxetine

SSRI

Indication: MDD, GAD, OCD, Panic, PTSD, PMDD, and SAD 

Risk for use in pregnancy

Risk of bone fractures

Akathisia

Short half-life and anticholinergic side effects

Sertraline

SSRI

Indication: MDD, OCD (6-12 yrs), Panic disorders, PTSD, PMDD, and SAD

What are universal things shared across SSRIs?

ADRs: Increased bleeding, hyponatremia, serotonin syndrome, sexual side effects, seizures, activation of mania, angle closure glaucoma, discontinuation syndrome.

First dose monitoring considerations: cognitive/motor impairment-use caution with first dose

Monitor for any potential allergic reaction with first dose

First few days/weeks: increased anxiety, GI symptoms, headache

What are the SNRIs?

Desvenlafaxine

Duloxetine

Venlafaxine

Levomilnacipran

Desvenlafaxine

SNRI

Indication: MDD

Duloxetine

SNRI

Indication: MDD, GAD (7-17 yo), Fibromyalgia, Neuropathic pain

Venlafaxine

SNRI

Indication: MDD, GAD, Panic disorder, social phobia (social

anxiety disorder)

Levomilnacipran

SNRI

Indication: MDD

What is shared amongst the SNRIs?

Same as SSRIS + increased risk of BP elevation (noradrenergic action)

What are the TCAs?

What are the indications for TCAs?

ADRs for TCAs: 

Avoid tyramine containing foods, sympathomimetic agents; NO overlap switch other AD

nefazodone is contraindicated and general monitoring of liver function tests (every 3 to 6 months with discontinuation if LFT are 3x or greater upper limit

Esketamine causes increase in BP and sedation 

Brexanolone induced sedation and LOC

Monoamine oxidase inhibitor (MAO-I) names: 

Isocarboxazid

Selegiline PATCH

Phenelzine

Tranylcypromine

Note: Phenelzine and tranylcypromine are nonselective MAO inhibitors

Isocarboxazid

Nonselective irreversible MAO inhibitor

Increase 5-HT, NE and DA in synapse

CI: CVD, HTN or treatment with BP meds, hepatic impairment,

severe renal impairment, history of headache, excessive caffeine intake

Selegiline

Irreversible selective MAO-B inhibitor (selectivity dose dependent)

MAO-B at clinical doses, MAO-A at higher doses

Phenelzine

Nonselective irreversible MAO inhibitor

CI: heart failure, hypertension or treatment with BP meds, hepatic impairment, severe renal impairment

Avoid in pregnancy

Peripheral neuropathy reported

Tranylcypromine

Nonselective irreversible MAO inhibitor

• Has additional effects like amphetamines (increase DA release into the synapse and inhibits NE at higher doses)

CI: CVD, HTN or treatment with BP meds, hepatic impairment, history of headache

What is there to know about MAOIs?

when switching: 

• 2 weeks wash out before starting another MAO!

• 5 weeks when switch from fluoxetine

Bupropion

MOA: Inhibits NE and DA transporters, increasing their concentrations in the synapse.

Contraindications in addition to “universal”

• Seizure disorder or any other condition predisposing risk (such as abrupt discontinuation of alcohol, BZD, AED -will lower threshold)

• Current or prior diagnosis of bulimia or anorexia nervosa

ADRs: 

• May increase blood pressure

• Wakefulness/Activation and insomnia

• Associated with less sexual side effects compared to other AD

Bupropion with Dextromethorphan

Dextromethorphan: NMDA (N-methyl-D-aspartate) receptor antagonist

Contraindications in addition to “universal”

• Seizure disorder or any other condition predisposing risk (such as abrupt discontinuation of alcohol, BZD, AED -will lower threshold)

• Current or prior diagnosis of bulimia or anorexia nervosa

ADRs: 

• risk of serotonin syndrome is greater, embryo-fetal toxicity,

  may cause hyperhidrosis

Brexanolone, Zuranolone

MOA: Positive allosteric modulation of GABAA receptors

Indication: approved for post-partum depression (after birth!

Esketamine

Mechanism of action: NMDA (N-methyl-D-aspartate) receptor antagonist

Indicated for Adults only: Treatment Resistant Depression (TRD) monotherapy or in combination with an oral AD

• TRD=Failure of at least two other drugs

Contraindications: in addition to “universal”

• History of intracerebral hemorrhage

• Aneurysmal vascular disease or arteriovenous malformation (AVM

Mirtazapine

• Increased appetite and weight gain

• Drowsiness that generally continues

• Elevated cholesterol and triglycerides

Gepirone

Contraindications

• Prolonged QTc interval at baseline (greater than 450msec)

• Congenital long QTc syndrome

• Severe hepatic impairment 

Serotonin modulators names

Vortioxetine

Vilazodone

Trazodone

Nefazodone

Vortioxetine

serotonin modulator

Adverse effects unique difference:

• Sexual side effects (drug holiday to mitigate not effective due to long T1/2)

• Discontinuation syndrome (not as significant due to T1/2

Vilazodone

serotonin modulator

Take with food to increase effectiveness (absorption) and reduce GI ADR

Trazodone 

serotonin modulator 

MOA: Weak inhibition of 5-HT, alpha-1 receptor antagonism, 5-HT2 receptor antagonism

Considerations/warnings/cautions

• Hyponatremia

• Arrhythmogenic potential in those with underlying CVD

• Abnormal bleeding

• Priapism

Nefazodone

serotonin modulator

MOA:

• Weak inhibition of 5-HT, alpha-1 receptor antagonism, 5-HT2 receptor antagonism

• also inhibits NE

Contraindications in addition to universal: Previous (or current) liver injury

How to treat depression in children?

FDA approved pediatric AD: escitalopram and fluoxetine are

the only approved for pediatric depression

How to treat depression in elderly?

• Monotherapy preferred, least complicated regimens

• SSRI preferred (avoid paroxetine)

• TCA and MAO-I not recommended unless no other option