Pharmacotherapy of depression Dr. Ott Flashcards by Mollie Modany

Risk of recurrence in depression

Risk of Recurrence
1 episode: 50-60%
2 episodes: 70%
3 episodes: 90%

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Recurrence

Risk becomes lower over time as duration of remission increases

Persistent mild symptoms during remission is a predictor of recurrence

Function deteriorates during the episode and goes back to baseline upon remission

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DSM-5 diagnostic criteria

At least one of the symptoms must be depressed mood or loss of interest or pleasure in doing things

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Diagnostic SIGE CAPS

Sleep
Interest decreased
Guilt/worthlessness
Energy loss/fatigue
Concentration difficulties
Concentration difficulties
Appetite change
Psychomotor agitation/ retardation
Suicidal ideation

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Self- administered rating scales

PHQ-9 and MOOD disorder questionnaire

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Goals of treatment

Reduce or eliminate signs and symptoms of depression

restore occupational and psychosocial functioning to baseline

reduce risk of relapse and recurrence

reduce the risk of harmful consequences

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Phases of treatment

ACUTE
- 6-12 weeks of remission of symptoms
goal: induce remission
CONTINUATION
- 4-9 additional months, recommended for all patients
goal: prevent relapse
MAINTENANCE
Patient specific duration
Often indefinite treatment if greater than or equaol to 3 major depressive episodes
goal: prevent recurrence

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Risk of Suicidality

Boxed warning for suicidality in all antidepressant medications for patients aged 24 and younger

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Citalopram

Celexa
10-40 mg/day
>60 years : do not excess 20 mg
Dose dependent QTc prolongation
substrate of 2C19 and 3A4

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Escitalopram

Lexapro
5-10mg/day

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Fluoxetine

Prozac
10-80mg/day
long half life
activating potential
2D6 and 3A4 inhibitor

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Fluvoxamine

Luvox
50-300mg/day
inhibitor 1A2 and 2C19

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Paroxetine/Paroxetine CR

Paxil
10-60mg/day
MUST taper due to anticholinergic effects
Weight gain and sedation
septal wall defect risk to the fetus -dont use in prego
Inhibitor 2D6, 2B6

not commonly used

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Sertraline

Zoloft
25-200mg/day
Most GI upset than other antidepressants - nausea
Inhibitor 2C19, 2D6, 3A4
very commonly used

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SSRIs Adverse effects

Weight gain - parozetine
Weight loss - fluoxetine
Increased bleeding risk - platelet inhibition
hyponatremia (especially in elderly)
sexual dysfunction

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Desvenlafaxine

Pristiq
active metabolite of venlafazine
dose limiting side effect: nausea
No major cyp interactions

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Duloxetine

Cymbalta
slow titration to avoid nausea
FDA warning for hepatotoxicity
Inhibitor 2D6 - liver function testing needed

go to SNRIs

Levomilnacipran

Fetzima
Must adjust in renal impairment or strong 3A4 Inhibitors
Substrate of 3A4

Venlafaxine

Effexor
must be >150mg/day to have NE effects
2D6 inhibitor at higher doses

SNRIs adverse effects

Useful in pain symdrome, musculoskeletal pain, fibromyalgia, and neuropathic pain

Duloxetine - obtain LFTs at baseline when symptomatic or every 6 months

Blood pressure elevation and nausea

Amitriptyline

Elavil
used to lower doses for neuropathic pain

TCAs adverse effects

sedation, reduces seizure threshold, confusion, blurred vision, urinary retention, constipation, orthostatic hypotension, tachycardia, weight gain, sexual dysfunction
fatal in overdose as low as 1000mg due to cardiac arrhythmias or seizures

MAO inhibitors clinical pearls

Must have 2 week washout period before switching antidepressant (5 week washout if switching from fluoxetine)
all require tyramine diet except selegiline 6mg/24hr patch
caution due to hypertensive crisis and serotonin syndrome

MAO inhibitors

Selegiline
Phenelzine
Isocarboxazid
tranylcypromaine

Bupropion

Wellbutrin dopamine and norepinephrine reuptake inhibitor stimulating - insomnia and appetite suppression 2D6 inhibitor Contraindicated in active seizure disorder and eating disorders can be used in combination with SSRI/SNRIS

Mirtazapine

remeron sedation and increased appetite occurs with doses less than 15mg/day warning: agranulocytosis, increased cholesterol Can be used in combination with SSRI/SNRIs

Trazodone

Desyrel Higher doses needed for depression SE: orthostatic hypotention, risk of priapism - medical emergency

Vilazodone

Viibryd primarily SSRI, MAY HAVE SOME 5HT1A agonism which may provide anxiolytic effects do not use in combination with SSRI/SNRIs take with food to avoid nausea, and increase bioavailability with food substrate 3A4

Vortioxetine

Trintellix SSRI + 5HT1a agonist + 5HT1a antagonist do not use in combo with SSRI/SNRI possibly less sexual dysfunction, substrate 2D6, nausea is common side effect

Serotonin syndrome

Medical emergency due to excessive amount of serotonin in the CNS

Serotonin syndrome treatment

Stop the offending agent and get supportive care could use cyproheptadine as seretonin blocker 70% of patients recover within 24hrs

Antidepressant withdrawal syndrome

Antidepressants with anticholinergic activity should be tapered no matter what common with all antidepressants except fluoxetine Not life threatening

Agumentation - Atypical antipsychotics

Aripiprazole (Abilify) Brexpiprazole (rexulti) Cariprazine (vraylar) Quetiapine (seroquel)

Key counseling points

Abrupt discontinuation can lead to antidepressant withdrawal syndrome Possible increase in suicidal thinking during the first few weeks of therapy

Steps to manage depression

1. Dose optimization 2. Switch antidepressants 3. Combine antidepressants 4. Augmentation 5. Esketamine (ECT,VNS,TMS)

2D6 INHIBITORS

Fluoxetine Paroxatine Sertreline Duloxetine Venlafaxine bupropion vortioxetine

3A4 Inhibitor

Fluoxetine Sertreline

3A4 substrate

Citalopram Levomilnacipran Vilazadone

2C19 inhibitor

Fluvoxamine Sertraline

2C19 substrate

Citalopram

1A2 inhibitor

Fluvoxamine