PHRM 845-FINAL EXAM Flashcards
Pharmacotherapy of depression
Should we wait to start pt on antidepressant med until the criteria are met?
No; not if someone can really benefit from them
Risk factors for depression
-Female
-White
-Physical disability
-Prior episode/suicide attempt
-Middle age
-Low socioeconomic status
-Lack of social support
-Co-morbid medical disorder
-Single marital status
-Unemployed
-Stressful life events/adverse childhood experiences
-Co-morbid SUD
Risk of recurrence for depression
1 episode: 50-60% chance of having another episode
2 episodes: 70%
3 episodes: 90%
We want to treat patient to remission. Many patients will respond better if dose is ___. Many patients ___ (do/do not) get the dose they need.
Increased
Do not
Disease course
-Occurs at any age, but commonly seen in early adulthood 20s and 30s
-Symptoms may develop over days to weeks
-Usually see a response to treatment, but not aggressive enough to achieve remission
What is remission?
A period of 2 or more months with no symptoms or only 1-2 symptoms. –Remember that as humans, we all have sad/down days at some point in our lives.
**For depression diagnosis, 5-6 symptoms are needed.
**Remission is possible and is the tx goal
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–help a patient remember their baseline and try to get back there.
DSM-5 diagnosis criteria for depression
At least one of the symptoms must be depressed mood or loss of interest or pleasure in doing things.
**Must cause clinically significant impairment in functioning
**No hx of mania or hypomania (Bipolar disorder)
**Not attributed to physiological effects of a substance of another condition
DSM-5 Diagnostic criteria mnemonic: SIGE CAPS
S: Sleep (insomnia/hypersomnia)–difficulty sleeping even though they are in bed all the time
I: Interest decreased (anhedonia)
G: Guilt/worthlessness
E: Energy loss/fatigue
C: Concentration difficulties – if this is the biggest complaint, check for depression (if not the biggest complaint, remember this can be a sx of ADHD or other mental health disorders)
A: Appetite change (increase or decrease)
P: Psychomotor agitation (revved up/restless) or retardation (no energy to get up and get around)
S: Suicidal ideation (QPR)–Question, plan, resources
Self-administered rating skills for depression
-Patient Health Questionnaire (PHQ-9)
-Quick inventory of depressive symptomatology self-report (QIDS-SR-16)
-Mood disorder questionnaire (MDQ)–to determine depression and rule out bipolar disorder
Goals of depression tx
- Reduce or eliminate signs and symptoms of depression
- Restore occupational and psychological functioning to baseline
- Reduce the risk of relapse and recurrence
- Reduce the risk of harmful consequences (suicidal ideation)
Choosing pharmacotherapy
**Similar efficacy between and within antidepressant classes
-Pt preference
-Prior med response: how pt used it, SE experienced, concerns for trying again, etc.
-Safety, tolerability, SE
-Co-occurring psychiatric and medical conditions
-Pharmacological properties
-Cost
Phases of treatment
Acute:
-6-12 weeks
-Goal: induce remission
Continuation:
-4-9 additional months (recommended for all pts)
-Goal: prevent relapse
Maintenance:
-pt specific duration
-often indefinite tx if greater than or equal to 3 major depressive episodes
-Goal: prevent reoccurrence
Risk of suicidality
Boxed warning for suicidality in ALL antidepressant medications (for pts 24 y/o or younger)
**Closely monitor pt for increased suicidality and changes in behavior during first 1-2 months of therapy and after any dosage changes
Pharmacological classes of antidepressants
-SSRI (widely used)
-SNRI (widely used)
-TCA
-MAO-i
-Novel agents/others
-Augmentation agents
Citalopram
*Drug Class
*Important info
SSRI
-Dose-dependent QTc prolongation
-Substrate for 2C19 and 3A4
Fluoxetine
*Drug Class
*Important info
SSRI
-Long half-life (96-144 hours)
-Activating potential
-ONLY ONE THAT DOES NOT HAVE TO BE TAPERED
-2D6 and 3A4 inhibitor (norfluoxetine is the metabolite)
Fluvoxamine
*Drug class
*Important info
SSRI
-Only SSRI for OCD
-1A2 and 2C19 inhibitor
Paroxetine
*Drug class
*Important info
SSRI
-MUST taper dose due to anticholinergic effects *only 1 that is anticholinergic
-Weight gain, sedation
-Septal wall defect risk to fetus (NOT USED FOR PREGNANT PATIENTS OR PATIENTS <18 Y/O)
-2D6 and 2B6 inhibitor
Sertraline
*Drug class
*Important info
SSRI
-More GI upset than other antidepressants
SSRI adverse events and key points
-Onset of action: 1-2 weeks
-4-6 weeks for full dose response
-Variable sedation
-Weight gain (Paroxetine)
-Weight loss (Fluoxetine)
-Increased bleeding risk (platelet inhibition)
-Hyponatremia (especially in elderly)
-Sexual dysfunction (70-75%)
-Anxiety/agitation upon initiation
-Emotional blunting
-Decreased BMD
Desvenlafaxine
*Drug class
*Important info
SNRI
-Active metabolite of venlafaxine
-Dose-limiting side effect: N/V
-No major CYP interactions
Duloxetine
*Drug class
*Important info
SNRI
-Slow titration or divided dosing to help with nausea
-FDA warning for hepatotoxicity (MUST get liver function test)
-2D6 inhibitor
-Obtain LFTs at baseline and when symptomatic or q6mos
Levomilnacipran
*Drug class
*Important info
SNRI
-MUST adjust in renal impairment or strong 3A4
-3A4 substrate
Milnacipran
*Drug class
*Important info
SNRI
-Not FDA approved for depression in the US
Venlafaxine
*Drug class
*Important info
SNRI
-Must be <150 mg/day to have NE effects (SSRI until they get to ~ 150 mg/day)
-2D6 inhibitor at high doses
SNRI adverse events and key points
-Onset of action in 1-2 weeks (full effect in 4-6 weeks)
-Useful in pain syndrome, musculoskeletal pain, fibromyalgia, and neuropathic pain
-Blood pressure elevation (from adrenergic SE)
-Sweating
-Variable sedation
-Increased bleeding risk (platelet inhibition)
-Hyponatremia (especially in elderly)
-Sexual dysfunction
-Anxiety and agitation
-Nausea (from adrenergic SE)
-Decreased BMD
TCA (essentially SNRI)
-MOA
-Example
-Blockade of reuptake transporter (DAT, SERT, NET)–inhibits reuptake of serotonin, NE and DA
-Amitriptyline is a tertiary amine with a normal dose between 50-300 mg/day
~Used to lower doses for neuropathic pain
TCA adverse effects and key points
-More often used for neuropathic pain syndromes than depression (amitriptyline and nortriptyline)
-Side effects often limit higher doses (why we are concerned about them)
~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 OD as low as 1000 mg (4-10 tablets) due to cardiac arrhythmias or seizures.
MAO-i key points
-Not used very often
-Very effective
-Should always be used by themselves (not in combo)
-All increase monoamines
Examples of MAO-i
-Isocarboxazid
-Phenelzine
-Selegiline
-Tranylcypromaine
What is the only patch formulation of antidepressant?
Selegiline
Clinical pearls of MAO-i
-Must have 2 week washout period before switching antidepressants (5 week washout if switching from fluoxetine)
-All require tyramine-restricted diet except selegiline 6 mg/24 hr patch
-Caution due to HTN crisis and serotonin syndrome
Selegiline patch
-Selective MAO-B inhibitor at lower doses
-Rotate patch daily to prevent irritation
-Do not cut patch
-Do not expose patch to direct heat while wearing
-Tyramine-restricted diet is not required for 6 mg patch (is required for 9 and 12 mg)
-Adverse events: hypotension, dry mouth, insomnia, HA, GI upset
MAO-i contraindications
-Pheochromocytoma (fluctuating BP)
-Hepatic/renal dysfunction
-Cerebrovascular disease
-Excessive caffeine use
-Elective surgery
-Concomitant sympathomimetics
-CVD
-Use of other serotonergic meds
Bupropion
-MOA
-Dosing
-Clinical Pearls
-DA and NE reuptake inhibitor (only one that does not impact 5HT)
-Stimulates insomnia and appetite suppression
-Available in SR/XL dosing: XL is preferred because SR has lots of peaks and troughs that fluctuate too much and could lead to a seizure (if using SR, must give second dose no later than 4 pm)
-2D6 inhibitor
-C/I in active seizure disorder and eating disorder
-Can be used in combo with SSRI/SNRI
Mirtazapine
-Not an SSRI
-MOA
-Dosing
-Clinical pearls
MOA: presynaptic alpha-2 blockade, 5HT2, 5HT3, and H2 blockade
Dosing: Sedation and increased appetite occur with doses less then or equal to 15 mg/day
Pearls: Warning for agranulocytosis and increased cholesterol (not common to routinely get lipid profiles or CBC count)
~Can be used in combo with SSRI/SNRI
Trazodone
-MOA
-Dosing
-Side effects
-MOA: selectively inhibits neuronal reuptake of serotonin and acts as 5HT1, 5HT2, H1, and alpha 1 antagonist
-Dosing: higher doses are needed for depression
-Side effects: Orthostatic hypotension, risk of priapism generally from doses > 200 mg (medical emergency)
Vilazodone
-MOA
-Clinical pearls
-MOA: Primarily SSRI, may have some 5HT1a agonism which may provide anxiolytic effects
**DO NOT COMBINE WITH SSRI/SNRI
-Pearls: Take with food because of significant nausea and bioavailability is increased with food
-3A4 substrate
Vortioxetine
-MOA
-Clinical pearls
-MOA: SSRI + 5HT1A agonist + 5HT3 antagonist
**DO NOT USE IN COMBO WITH SSRI/SNRI
-Pearls: possibly less sexual dysfunction, 2D6 substrate, likely to cause nausea
What is serotonin syndrome?
Medical emergency due to excessive amounts of serotonin in the CNS
-May be caused by OD, combined use of serotonergic meds, or drug interactions
Serotonergic agents
Lithium, Linezolid, serotonin agonists (triptans), fentanyl, serotonergic antidepressants, amphetamines, St. John’s Wort, cocaine, buspirone, dextromethorphan, tramadol, LSD
Treatment for serotonin syndrome
-Stop offending agent and use supportive care
-Potentially could use serotonin blockers (cyproheptadine–has variable efficacy)
-70% of pts recover within 24 hours
Sx of serotonin syndrome
Diarrhea, agitation, diaphoresis, abdominal pain, ataxia, hyperpyrexia, mental status change, labile BP, hyperreflexia, anxiety, confusion, muscle rigidity, myoclonus, nausea, restlessness/hyperactivity, tachycardia, tachypnea, tremor
**Serotonin increases GI peristalsis which causes N/V
Antidepressant withdrawal syndrome
-Occurs from abrupt cessation of antidepressant
-Common with ALL antidepressants (except FLUOXETINE)
-Risk can be minimized by slow dose taper over 1-2 weeks
-Antidepressants with anticholinergic activity should be tapered NO MATTER WHAT
-Symptoms can mimic those of depression (agitation, irritability, GI disturbances, “brain zaps”)
-NOT life-threatening, but extremely uncomfy
Augmentation-atypical antipsychotics (good adjuncts)
Aripiprazole (abilify) - partial agonist
Brexpiprazole - partial agonist
Cariprazine - partial agonist
Quetiapine
Antidepressants for PPD
-Allosteric modulator of alloprenanolone
~Brexanolone: IV only, 60 hour infusion, excessive sedation boxed warning, REMS
~Zuranolone: PO dosing, 14-day dosing, boxed warning for impaired driving (CNS depression)
What to use for tx-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 because can cause BP fluctuations
Overall key counseling points
-Need to continue med for 6-9 months to decrease risk of recurrence
-Abrupt discontinuation can lead to antidepressant withdrawal syndrome
-Possible increase in suicidal thinking in first few weeks of therapy
-NO paroxetine for pregnant women
Non-pharmacological therapy
-Psychotx is the most common (individual or group)
-Mild depression or episodes without psychosis, may use psychotx without drug therapy if they have a hx of response, pt prefers it, med contraindication, or pregnancy
**SSRI have not shown teratogenic effect–better outcome if mom is treated for depression
Other non-pharm options
-Vagus nerve stimulation (VNS)
-Transcranial Magnetic stimulation (TMS)
Steps to manage depression
-Dose optimization
-Switch antidepressant
-Combine antidepressants
-Augmentation
-Esketamine/ECT/VNS/TMS
**Pt-specific so pt can choose which one they try first
