Depression Flashcards
DSM-5 Diagnostic criteria for depression (SADiFACES)
5+ of the following AND atleast 1 of the symptoms include either (1) depressed mood or (2) loss of interest/pleasure:
Sad mood almost daily
Anhedonia - loss of pleasure/interest
Diet - incr or decreased appetite, weight loss or sig wt gain
insomnia (or hypersomnia)
Fatigue/loss of energy
Agitation
Concentration low
Esteem low
Suicidality
goals of therapy
- achieve remission
- treat symptoms
- prevent suicide
- restore optimal functioning
- prevent recurrence
Monitoring parameters at baselin
- personal and family history
- previous antidepressant use, alcohol/tobacco/substance use
- physical health, BMI
- pregnancy tst
- LFT
- ECG if pre-existing CVD
- bone density scan
- electrolytes, especially in elderly
monitoring parameters as an ongoing assessment while on drug therapy
suicidal thinking
elevated serum transaminases
hyponatremia (elderly)
hyper or hypotension
which drug classes can cause depression?
oral contraceptives
tretinoin
analgesics
PPIs
antihypertensives
anticonvulsants
sedatives
Types of psychotherapy
CBT
behavioral activation
interpersonal therapy
all considered 1st line or treating depression
What is motivational interviewing?
A type of psychotherapy - improves the patient’s motivation to change problematic behavior. Effective for patients with substance abuse problems + depression. It is mostly effective on the substance abuse.
Forms of non-pharmacological therapy
Exercise/Yoga
Light therapy - 10,000 lux intensity for seasonal depression x 30 mins/day
Novel neurostimulation - not routinely available
How to long to reach minimum therapeutic dose?
the first 2 weeks of treatment, increase if needed within 4-6 weeks
Once starting a new antidepressant, if patients start to experience side effects, within what time frame are they expected to subside?
within 2 weeks
When should clinicians consider SWITCHING within the SAME CLASS of drugs if there are unwanted AEs?
during weeks 3 to 8 if pt is having troublesome side effects even after dose adjustment or adjusting timing of dosing
What is the risk of SSRIs being used in children and young adults?
risk of suicidal ideations, esp during early phase of treatment
Classification of antidepressants based on line of therapy
1st line: SSRIs, bupropion, mirtazapine, SNRIs
2nd line: TCAs, moclobemide (selective MAOai), trazodone
3rd line: non-selective MAOi (phenelzine, tranylcypromine)
Efficacy amongst the first lines of therapy
All are equally effective. Choose best option based on side effect profile or drug interactions
note: escitalopram superior efficacy to citalopram.
6 SSRIs available in canada
escitalo
citalo
sertraline
paroxetine
fluvoxamine
fluoxetine
time to onset of SSRIs
2-4 weeks.
indication of esketamine (intranasal) and administation
for treatment-resistant depression, in combo with SSRI or SNRI. Available only through a controlled distribution program and required HCP to supervise the dose, monitor patient and BP status for atleast 2 hrs after
Common AEs of SSRIs
GI upset/GI bleeding (risk is increased if pt also using NSAID therapy, or history of GI bleed)
sexual dysfunction (impaired desire, arousal, orgasm/ejaculation)
Can sexual dysfunction be reversible with SSRIs?
some reports say it may persist even after d/c
Drug options that don’t have sexual side effects
bupropion
mirtazapine
moclobemide
amongst the SSRIs which drug is the most and least like to cause withdrawal/discontinuation effects?
most = paroxetine (Short T1/2)
least = fluoxetine (long T1/2)
MoA of venlafaxine + AEs
-inhibitory effects on serotonin reuptake @ therapeutic dose.
-doses > 150 mg, inhibits NE reuptake
-6-10% higher rate of remission compared to SSRIs
-AE: dose-related HTN (rare, usually at doses > 225 mg) MONITOR BP if pt has uncontrolled HTN + SSRI AEs
MoA of desvenlafaxine + AEs
active metabolite of venlafaxine, might have less DDIs
AEs: insomnia, somnolence, dizziness, nausea
MoA of duloxetine + AEs
SNRI, can also be used for nerve pain/fibromyalgia
-CYP1A2 substrate (monitor cigarette smokers, my need higher dose)
-isolated cases of liver injury (dont need routine LFTs)
MoA of levomilnacipran (2nd line) + AEs
inhibits NE reuptake > serotonin 2:1
AEs: nausea, headache, dry mouth, hyperhidrosis, constipation, dizziness, increased BP/HR
MoA of bupropion + AEs
-NE and DA reuptake inhibition
lowers seizure threshold - AVOID in pts with epilepsy, caution in pt with head trauma/seizure
reduces appetite - AVOID in anorexia/bulimia pts
MoA of mirtazapine + AEs
-acts of NE and 5HT systems
-sedation, weight gain
MoA of trazodone + AEs
potent post-synaptic serotonin R antagonist, weak reuptake inhibitory effects.
-prescribed at lower doses (50-100 mg), rather than antidepressant doses (300-400 mg/d) due to daytime sedation
-no tolerance developed
MoA of vortioxetine + AEs
-5ht receptor modulation +SERT (transporter) inhibition
-common AE: GI-related, mild-mod nausea (1st week), lower sexual dysfunction
MoA of vilazodone + AEs
5ht reuptake inhibitor, partial agonist at 5ht1a receptor.
-with food.
-titrate to avoid GI upset
-nausea, diarrhea, headache, less sexual AEs
MoA of TCAs and AEs
inhibit the reuptake of NE and serotonin. AEs are anticholinergic because they strongly block muscarinic receptors = dry mouth, blurred vision, constipation, urinary retention, cognitive impairment0
dosing of amitriptyline
25-50 mg per day for nighttime sedation or analgesia
Clomipramine (TCA) indication
favoured in the treatment of OCD
risk of TCA
cardiotoxicity in case of overdose
When are irreversible MAOi used?
reserved for specialized mood disorder clinics.
What are the potentially fatal food interactions with TCAs?
- alcohol - CNS depression
- tyramine-rich foods (aged cheese, fermentd food, cured meat) leading to HTN crisis (rare)
3.caffeine - increases AEs of irritability, restlessness, cardiac arrhythmias - grapefruit - TCA toxicity
signs of TCA toxicity?
- CNS- confusion, hallucinations, agitation, seizures if severe
- Cardiovascular- arrythymias, prolonged QT/TdP, hypotension, tachycardia
- Anticholinergic effects
- Respiratory depression
- Acidosis, electrolyte disturbances
What is an immediate measure to treat TCA toxicity?
ABCs (airway, breathing, circulation)
administer ACTIVATED CHARCOAL if patient presents within 1-2 hours of ingestion
what are dietary restrictions of MAO inhibitors (non-selective/irreversible)?
- aged/fermented foods = high in tyramine and other amines
- alcohol (beer/red wine)
- overripe/spoiled food
avoid meds: decongestants, stimulants, SSRI/SNRI, dextromethorphan, meperidine = serotonin syndrome risk
does moclobemide require dietary restrictions?
no, not when it is prescribed within the recommended dose range
What are the symptoms of hypertensive crisis which can result from tyramine consumption with MAOi?
Severe headache
N/V
stiff neck
rapid HR or palpitations
chest pain
sweating and flushing
T/F - All SSRI/SNRIs are associated with a high risk of sexual dysfunction.
True
Symptoms of serotonin syndrome
(SHIVERS)
Shivering
Hyperreflexia
Increased temperature
Vital sign instability (tachycardia, HTN)
Encephalopathy - confusion/agitation
Restless
Sweating
Which drugs are unlikely to cause serotonin syndrome?
(MAT)
Mirtazapine
Amitriptyline
Trazodone
Which drugs can cause d/c syndrome?
SSRIs or any antidepressants taken 6+ weeks, drugs with shorter half lives (paroxetine, venlafaxine)
Symptoms of discontinuation syndrome
Anxiety
Crying
Headache
Increased dreaming
Insomnia
Irritability
Myoclonus
Nausea
Electric shocks
Tremor
Flulike symptoms
Imbalance
Sensory disturbance
When would the discontinuation syndrome symptoms begin to appear? How long to disappear?
within 1-7 days of stopping the drug. If untreated, symptoms last about 3 days to 3 weeks. If treated, can resolve within 3 days or less.
How to taper dose of antidepressant to prevent withdrawal symptoms
reduce dose by 25% per week, monitor for symptoms re-appearing and taper over 4-6 weeks
If a slow taper is poorly tolerated, what can be used as a substitute?
fluoxetine 10-20 mg PO as one dose. If after several days it hasn’t resolved the d/c symptoms, give another dose of fluoxetine 20 mg if needed (total of 3 doses spread over 7-10 days)
When are atypical antipsychotics used in depression?
2nd gens - approved to treat depression as 2nd line option (XR)
-IR can be used off-label, but has higher sedation
Which antipsychotics are approved as adjuncts to antidepressants in adults with MDD?
Aripiprazole or brexpiprazole if pt doesn’t have adequate response to AD alone
Riseperidone, olanzapine = off label for treatment-resistant depression
After starting antipsychotics for depression, how long to observe response?
within 2 weeks of initiation, monitor for response
Efficacy of St johns wort
monotherapy (potentially) for mild-moderate severity.
lots of DDIs because SJW is a CYP2A4 and Pgp inducer, and risk of serotonin syndrome
Rapid-acting therapies
Ketamine, esketamine - used in TRD, specialty clinics
how long are maintenance antidepressants useed for?
minimum: 9 months after achieving remission from 1st episode.
if at risk for recurrence/other comorbidities, or frequent/recurrent symptoms, minimum 2 years.
When does a patient begin to have treatment-resistant depression?
Failure to respond after 2+ treatments of adequate dose and duration
When do most clinicians switch to a DIFFERENT class of meds?
if no response to first drug at all.
When do most clinicians switch WITHIN the same class of drugs?
If favorable response, but there is persistent unmanageable side effects
Switching from SSRI to SSRI
cross taper method (start new drug at lowest dose and once it reaches lowest effective dose, slowly taper drug 1 until d/c)
NO WASHOUT
Switching from any other antidepressant to MAOi (irreversible or reversible)
washout period: 5 half lives of the first drug or, if clomipramine or imipramine, then 3 weeks)
Switching from moclobemide –> SSRI/SNRI
5 days washout period
Switching from Fluoxetine –> Irreversible MAOi/moclobemide
5 weeks washout
Switching from fluoxetine to SSRI/SNRI
cross tapering, no washout. tapering not generally required but to be on safe side, can do so.
Switching from irreversible MAOi –> SSRI/SNRI
washout: 2 weeks
Switching from SSRI –> moclobemide
- withdraw/reduce 1st drug
- wait 2 weeks
- start moclobemide and titrate up
switching from SSRI –> fluoxetine
cross taper, no washout needed
switching from fluoxetine –> MAOi
WASHOUT: 5 weeks
anytime you switch TO or FROM a MAOi from any drug, the washout period is generally…
2 weeks
(if from fluoxetine = 5 weeks)
When is augmentation indicated (combo tx)?
if a patient tolerates 1st antidepressant @ tx dose, but only has a partial response
OR
mod-severe depression, refractory depression.
Treatment in Pregnancy
1st line - CBT
Drug option: sertraline, escitalopram, citalopram
@ lowest effective dose
2nd line drugs: TCAs, buprop, mirtaz, dulox, fluox, fluvox, desvenla, venla
Risk of antidepressants in pregnancy
SSRIs- not major teratogens
-may have CV malformations, but not enough data to support it. Late pregnancy- risk of pulmonary HTN in baby.
Highest risk SSRIs = paroxetine and fluoxetine
Should clomipramine be used in pregnancy?
ideally use first lines.
can use this only if pt was stable on it pre-pregnancy
drug therapy in breastfeeding
1st line: sertraline, escitalopram, citalopram
2nd line: paroxetine, fluoxetine, nortriptyline
*but generally CBT is first line non-drug tx for post-partum depression
