pharmacotherapy of depression Flashcards by Brianna Lent

what are pathologies related to depression

Stroke
Chronic pain syndrome: Fibromyalgia, Low back pain / Chronic pelvic pain, Bone or disease related pain
Multiple sclerosis
Hypo / hyperthyroidism
Traumatic Brain Injury (TBI)

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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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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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What is SIGE CAPS

Sleep (insomnia/hypersomnia
Interest decreased (anhedonia)
Guilt/worthlessness
Energy loss/fatigue
Concentration difficulties
Appetite change (increase or decrease)
Psychomotor agitation/retardation
Suicidal ideation

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Self administered rating scales

Patient Health Questionnaire:(PHQ-9) Developed for the primary care setting
Mood Disorder Questionnaire (MDQ):Can be used to rule out bipolar disorder

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What is the boxed warning risk for all antidepressant medications

Boxed warning for suicidality in ALL antidepressant medications (2004)
(for patients aged < 24 years of age)

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what is the acute phase of depression treatment.

6-12 weeks or remission of symptoms
*Goal: induce remission

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What is the continuation phase of depression treatment

4-9 additional months, recommended for all patients
Goal: prevent relapse

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What is the maintenance phase of depression treatment

Patient-specific duration Often indefinite
treatment if ≥ 3 major depressive episodes
Goal: prevent recurrence Maintenance

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What are SSRIs

Citalopram (Celexa)
Escitalopram (Lexapro)
Fluoxetine (Prozac)
Fluvoxamine (Luvox)
Paroxetine/Paroxetine CR (Paxil)
Sertraline (Zoloft)

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What are Citalopram (Celexa) clinical pearls

Dose-dependent QTc prolongation
Substrate of 2C19 and 3A4

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What are Fluoxetine (Prozac) clinical pearls

Long half-life (96-144 hours)
Activating potential
2D6 inhibitor, 3A4 inhibitor (norfluoxetine

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Fluvoxamine (Luvox) clinical pearls

inhibitor 1A2, 2C19

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Paroxetine/Paroxetine CR (Paxil) clinical pearls

MUST taper due to anticholinergic effects
Weight gain, sedation
Septal wall defect risk to the fetus
Inhibitor 2D6, 2B6

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Sertraline (Zoloft) clinical pearls

More GI upset than other antidepressant

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What drugs are SNRIs

Desvenlafaxine (Pristiq)
Duloxetine (Cymbalta)
Levomilnacipran (Fetzima)
Milnacipran (Savella)
Venlafaxine (Effexor)

What are the adverse effects of SSRIs

Weight gain (paroxetine)
Weight loss (fluoxetine)
Increased bleeding risk (platelet inhibition)
Hyponatremia (especially in elderly)
Sexual dysfunction

Desvenlafaxine (Pristiq) clinical pearls

Active metabolite of venlafaxine
Dose-limiting side effect: nausea
No major CYP interactions

Duloxetine (Cymbalta) clinical pearls

nausea
FDA warning for hepatotoxicity
Inhibitor 2D6

Levomilnacipran (Fetzima) clinical pearls

MUST adjust in renal impairment or strong 3A4 inhibitors
Substrate 3A4

Venlafaxine (Effexor) clinical pearls

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

SNRI adverse effects

blood pressure elevation and nausea useful in pain syndrome musculoskeletal pain fibromyalgia and neuropathic pain
duloxetine obtain LFTs at baseline and when symptomatic or every 6 months

what are TCAs

Blockade of reuptake transporter (DAT, SERT, NET) -> inhibits the reuptake of serotonin, norepinephrine, and dopamine
Amitriptyline (Elavil) Tertiary amine

TCAs – Adverse Effects/Key Points

CNS: sedation, reduced seizure threshold, confusion
Anticholinergic: blurred vision, urinary retention, constipation
Cardiovascular: orthostatic hypotension, tachycardia
Other: weight gain, sexual dysfunction
Side effects often limit higher doses:
Narrow therapeutic index: Fatal in overdose as low as 1000 mg (~4-10 tablets) due to cardiac arrhythmias or
seizures

MAOis hypertensive Crisis

Tyramine diet is required with MAOis, Tyramine is degraded by monoamine oxidase → MAOis inhibit monoamine oxidase → Increase in tyramine increases blood pressure What is included in a tyramine diet?: Smoked, aged, pickled meats or fish; sauerkraut; aged cheeses; yeast extracts; flava beans; beer; wine What about in small amounts? Beer, wine, avocados, meat extracts, caffeine, chocolate

Bupropion(wellbutrin)

MOA: Dopamine and norepinephrine reuptake inhibitor Stimulating – insomnia and appetite suppression XL 2D6 Inhibitor Contraindicated in active seizure disorder and eating disorders Can be used in combination with SSRI/SNRIs

Mirtazapine (Remeron)

Sedation and increased appetite occur with doses ≤ 15 mg/day Warnings: agranulocytosis, increased cholesterol Can be used in combination with SSRI/SNRIs

Trazodone (Desyrel)

Higher doses needed for depression Side Effects Orthostatic hypotension 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 Significant nausea Bioavailability increases with food Substrate 3A4

Vortioxetine (Trintellix)

SSRI + 5HT1A agonist + 5HT3 antagonist Do not use in combination with SSRI/SNRIs Possibly less sexual dysfunction Substrate 2D6 Nausea

Serotonin Syndrome

Medical emergency due to excessive amounts of serotonin in the CNS May be caused by: Overdose Combined use of serotonergic drugs Drug interactions Stop the offending agent + supportive care Potentially could use serotonin blockers Cyproheptadine → variable efficacy 70% of patients recover within 24 hours

Antidepressant Withdrawal syndrome

Common with ALL antidepressants EXCEPT fluoxetine Antidepressants with anticholinergic activity should be tapered no matter what

Augmentation – Atypical Antipsychotics

Aripiprazole (Abilify) * Brexpiprazole (Rexulti) * Cariprazine (Vraylar) * Quetiapine

Antidepressants for PPD

Post-partum depression – allosteric modulator of alloprenanolone Brexanolone – IV only, 60 hour infusion, excessive sedation boxed warning, REMS program Zuranolone – oral dose, 14-day dosing, boxed warning for impaired driving – CNS depression

Antidepressants for treatment resistant depression

Treatment-resistant depression Esketamine Nasal Spray – NMDA receptor antagonist Also used for MDD with suicidal ideation induction and maintenance phases, REMS program to give in clinic, stay in clinic for 2 hours post- dose

Overall Key Counseling Points

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

what is Electroconvulsive Therapy (ECT)

Unilateral or bilateral placement of electrodes 10–15-minute procedure Administration: 2-3 times weekly as induction, Usual course is 6-12 treatments Continue until maximal response Can use maintenance ECT Advantages: Efficacy in treatment resistance, Can continue drug therapy, Age is not a factor Safe in pregnancy Disadvantages: Temporary memory loss Stigma Contraindicated in recent MI or hemorrhagic stroke or if loose teeth