Lecture 69 - Pharmacotherapy of Depression Flashcards
Risk of Recurrence for Depression
Risk of Recurrence:
1 episode: 50-60%
2 episodes: 70%
3 episodes: 90%
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
DSM-5 Diagnostic Criteria
At least one of the symptoms must be depressed mood or loss of interest or pleasure in doing things
DSM-5 Diagnostic Criteria Mnemonic
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
Self-administered rating scales
patient health questionnaire (PHQ-9): developed for primary care setting, used repeatedly to determine efficacy and treatment
mood disorder questionnaire (MDQ): can be used to rule out bipolar disorder
Goals of Treatment
- reduce or eliminate s/s of depression
- restore occupational and psychosocial functioning to baseline
- reduce the risk of relapse and recurrence
- reduce the risk of harmful consequences (suicidal ideation)
Phases of treatment
Acute: 6-12 weeks or remission of sx; goal is to induce remission
Continuation: 4-9 additional months, recommended for all pts; goal is to prevent relapse
Maintenance: patient-specific duration; often indefinite treatment if >/= 3 major depressive episodes; goal is to prevent recurrence
Risk of Suicidality
Boxed warning for suicidality in ALL antidepressant medications (for patients aged < 24 years of age)
*Decreased risk in ≥ 65 years old
SSRIs
citalopram
fluoxetine
fluvoxamine
paroxetine
sertraline
Citalopram
- Dose-dependent QTc prolongation
- Substrate of 2C19 and 3A4
Fluoxetine
- Long half-life (96-144 hours)
- Activating potential
- 2D6 inhibitor, 3A4 inhibitor (norfluoxetine)
Fluvoxamine
- Inhibitor 1A2, 2C19
Paroxetine/Paroxetine CR
- MUST taper due to anticholinergic effects
- Weight gain, sedation
- Septal wall defect risk to the fetus
- Inhibitor 2D6, 2B6
Sertraline
- More GI upset than other antidepressants
SSRIs – Adverse Effects/Key Points
Weight gain (paroxetine)
Weight loss (fluoxetine)
Increased bleeding risk (platelet inhibition)
Hyponatremia (especially in elderly)
Sexual dysfunction
SNRIs
desvenlafaxine
duloxetine
levomilnacipran
venlafaxine
Desvenlafaxine
- Active metabolite of venlafaxine
- Dose-limiting side effect: nausea
- No major CYP interactions
Duloxetine
- Slow titration or divided dosing help with nausea
- FDA warning for hepatotoxicity
- Inhibitor 2D6
Levomilnacipran
- MUST adjust in renal impairment or strong 3A4
- Substrate 3A4
Venlafaxine
- Must be >150 mg/day to have NE effects
- 2D6 inhibitor at higher doses
SNRIs – Adverse Effects/Key Points
Useful in pain syndrome, musculoskeletal pain, fibromyalgia, and neuropathic pain
Duloxetine: Obtain LFTs at baseline and when symptomatic or every 6 months
Blood pressure elevation
Nausea
TCAs
Amitriptyline (Elavil): Tertiary amine
* Used to lower doses for neuropathic pain
TCAs – Adverse Effects/Key Points
Side effects often limit higher doses:
* CNS: sedation, reduced seizure threshold, confusion
* Anticholinergic: blurred vision, urinary retention, constipation
* Cardiovascular: orthostatic hypotension, tachycardia
* Other: weight gain, sexual dysfunction
Narrow therapeutic index:
* Fatal in overdose as low as 1000 mg (~4-10 tablets) due to cardiac arrhythmias or seizures
MAO Inhibitors drugs
isocarboxazid
phenelzine
selegiline
tranylcypromaine
MAO Inhibitors Clinical Pearls
- Must have 2 week washout period before switching antidepressants (5 week washout period if switching from fluoxetine)
- All require tyramine diet except selegiline 6 mg/24 hour patch
- Caution due to hypertensive crisis and serotonin syndrome
Selegiline patch
Tyramine diet NOT required with the 6 mg patch
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)
Mechanism:
* Dopamine and norepinephrine reuptake inhibitor
* Stimulating – insomnia and appetite suppression
Pearls:
* 2D6 Inhibitor
* Contraindicated in active seizure disorder and eating disorders
* Can be used in combination with SSRI/SNRIs
Dosing:
SR/XL dosing
Mirtazapine (Remeron)
Dosing: Sedation and increased appetite occur with doses ≤ 15 mg/day
Pearls: Warnings: agranulocytosis, increased cholesterol; Can be used in combination with SSRI/SNRIs
Trazodone (Desyrel)
Mechanism: Selectively inhibits neuronal reuptake of serotonin and acts as an antagonist at 5HT1, 5HT2, H1 and α1
Dosing: Higher doses needed for depression
Side effects: Orthostatic hypotension; Risk of priapism – medical emergency
Vilazodone (Viibryd)
Mechanism:
* Primarily SSRI, may have some 5HT1a agonism which may provide anxiolytic effects
* Do not use in combination with SSRI/SNRIs
Pearls:
* Take with food - Significant nausea; Bioavailability increases with food
* Substrate 3A4
Vortioxetine (Trintellix)
Mechanism:
* SSRI + 5HT1A agonist + 5HT3 antagonist
* Do not use in combination with SSRI/SNRIs
Pearls:
* Possibly less sexual dysfunction
* Substrate 2D6
* Nausea
Serotonin Syndrome
Medical emergency due to excessive amounts of serotonin in the CNS
Serotonin Syndrome - Treatment
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
FDA-approved augmentation agents:
* Aripiprazole (Abilify)
* Brexpiprazole (Rexulti)
* Cariprazine (Vraylar)
* Quetiapine
Antidepressants for Specific Purposes
post-partum depression
treatment-resistant depression
Post-partum depression
allosteric modulator of alloprenanolone
* Brexanolone
* Zuranolone
Treatment-resistant depression
Esketamine Nasal Spray – NMDA receptor antagonist
Overall Key Counseling Points
Abrupt discontinuation can lead to antidepressant withdrawal syndrome
Possible increase in suicidal thinking during the first few weeks of therapy
