pharmacotherapy of depression Flashcards
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)
DSM-5 diagnostic criteria
At least one of the symptoms must be depressed mood or
loss of interest or pleasure in doing things
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
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
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
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)
what is the acute phase of depression treatment.
6-12 weeks or remission of symptoms
*Goal: induce remission
What is the continuation phase of depression treatment
4-9 additional months, recommended for all patients
Goal: prevent relapse
What is the maintenance phase of depression treatment
Patient-specific duration Often indefinite
treatment if ≥ 3 major depressive episodes
Goal: prevent recurrence Maintenance
What are SSRIs
Citalopram (Celexa)
Escitalopram (Lexapro)
Fluoxetine (Prozac)
Fluvoxamine (Luvox)
Paroxetine/Paroxetine CR (Paxil)
Sertraline (Zoloft)
What are Citalopram (Celexa) clinical pearls
10-40 mg/day
>60 years: do not excess 20 mg
Dose-dependent QTc prolongation
Substrate of 2C19 and 3A4
What are Fluoxetine (Prozac) clinical pearls
10-80 mg/day
Long half-life (96-144 hours)
Activating potential
2D6 inhibitor, 3A4 inhibitor (norfluoxetine
Fluvoxamine (Luvox) clinical pearls
50-300 mg/day inhibitor 1A2, 2C19
Paroxetine/Paroxetine CR (Paxil) clinical pearls
10-60 mg/day
12.5-75 mg/day
MUST taper due to anticholinergic effects
Weight gain, sedation
Septal wall defect risk to the fetus
Inhibitor 2D6, 2B6
Sertraline (Zoloft) clinical pearls
25-200 mg/day More GI upset than other antidepressant
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
Buporopion(wellbutrin)
MOA: Dopamine and norepinephrine reuptake inhibitor Stimulating – insomnia and appetite suppression
SR/XL dosing: 150-450mg/day
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)
Mechanism Selectively inhibits neuronal reuptake of serotonin and acts as an antagonist at 5HT1, 5HT2, H1 and α1
Dosing: 150-600 mg/day Higher doses needed for depression Insomnia (off-label): 50-150 mg at bedtime
Drug Interactions:
Trazodone → (3A4) →m-CPP → (2D6) →inactive metabolites
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
