depression Flashcards
what are the components of a suicide inquiry
ideation
- frequency, intensity, duration
suicide plan
- timing, location, lethality, access to means, preparatory acts
intent
- extent to which patient expects to carry out the plan and believes to be lethal/ self injurious
explore ambivalence
what are some helplines
- IMH’s mental helpline (6389-2222)
- Samaritan’s of SG (1800-221-4444)
what are the etiology of MDD
biological
- hormonal (increased secretion of stress hormone cortisol)
- monoamine hypothesis (decreased neurotransmitters in brain - NE, 5HT, DA)
psychological
- loss
- negative self-evaluation
psychosocial
- isolation
- lack of social support
genetics
- FMHx
- polymorphism in S allele of SERT gene (S/S more vulnerable)
medical
- medical conditions (endocrine, infection, neurological, CVD, deficiency, metabolic, malignancy)
- psychiatric (alcoholism, anxiety, ED, schizophrenia)
pharmacologicals (drug-induced)
- lipid soluble BB
- psychotropics (BZP, ASMs)
- withdrawal from alcohol
- corticosteroids (systemic)
- interferon beta 1a
- isotretinoin
what is the presentation and diagnostic criteria of MDD based on DSM5
at least 5 of the following over 2w
- In terest loss
- S leep (insomnia/ hypersomnia)
- A ppetite decreased
- D epressed mood (or irritability in children)
- C oncentration difficulties
- A ctivity level decreased
- G uilt/ worthlessness
- E nergy decreased
- S uicidal thoughts
what are the differentials for MDD
- adjustment disorder (within 3m onset of stressor but once stressor terminates, sx does not persist for additional 6m)
- acute stress disorder
(within 1m of traumatic event and last 3d to 1m) - dementia (stepwise/ insidious onset, progressive course, clear consciousness until later stages, poor short and long term memory)
- delirium
(acute onset, variable course, impaired consciousness, poor memory) - substance induced withdrawal/ intoxication (acute onset, rapid course lasting 24-72hrs, continuum of unimpaired to impaired consciousness, intact memory)
comparison to depression - cyclical onset, diurnal variation, generally unimpaired consciousness, intact memory)
what are the general assessments of MDD
- history of presenting illness
- psychiatric hx
- substance use hx
- complete medical and medication hx (drug allergy, s/e, effectiveness, other OTC/ supplements/ non-oral)
- family, social, developmental, occupational hx
- physical and neurological exam
- mental state exam
- labs and other investigations
- labs like vital signs, weight and BMI, U/E/Cr, FBC, LFTs, TFTs, ECG, FBG, lipid, urine toxicology
- other investigations like folate, vitB12 and pregnancy as indicated
identify significance of obtaining a few of the baseline labs
- weight bc extreme weight may indicate fluid congestion
- ECG to rule out cardiac abnorm
- FBG and lipid as some antidepressants and antipsychotics can increase these
- FBC to check for infection
list psychiatric rating scales used for MDD and their scoring
clinician-rated
- hamilton rating scale for depression (HAM-D)
*gold standard
self-rated
- PHQ2
- continue to PHQ9 if any of the two questions is positive response
scoring based on PHQ9
- minimal sx if 1-4
- mild if 5-9
- moderate if 10-14
- moderately-severe if 15-19
- severe if 20 or more
*start antidepressant if score 10 and above
what are the goals of therapy for MDD
symptom free
what are the non-pharmacological management for MDD
lifestyle/ behavioral changes
- good sleep hygiene to improve mood, appetite, energy and concentration
- relaxation techniques
- exercise
nutritional
- vitB12 (meat, poultry, fish, eggs, dairy products)
- L-methylfolate (leafy green vege, legumes, citrus fruits)
- vitD (fatty fish)
- SAMe
- omega-3 fatty acids (fatty fish)
- 5-hydroxytryptophan (lean protein like chicken and tofu, nuts and seeds, legumes, dairy, wholegrains like oats and brownrice)
herbal
- st john’s wort
*significant DDI with antidepressants
neurostimulation
- ECT
- rTMS
psychotherapy
*not as mono therapy in moderate to severe
light therapy for SAD
describe the chemical transmission at the synapse
precursors are transported by blood to the brain –> converted into NT via enzymatic processes –> stored in synaptic vesicles or released on demand –> released into the synaptic cleft in response to an action potential –> diffuse across the synaptic cleft and interact with receptors on the postsynaptic neurons –> induce events relating to downstream signal transduction cascade, leading to various physiological effects –> transmission ends by (i) enzymatic breakdown of NT (ii) NT reuptake (iii) presynaptic autoreceptors that regulate synthesis and release based on a negative feedback mechanism
list the classes of antidepressants and examples in each of the classes
tricyclic antidepressants (TCAs)
- amitriptyline
- nortriptyline
- clomipramine
- imipramine
- dothiepine
selective serotonin reuptake inhibitor (SSRI)
- fluoxetine
- fluvoxamine
- sertraline
- paroxetine
- escitalopram
- citalopram
selective norepinephrine reuptake inhibitor (SNRI)
- duloxetine
- venlafaxine
- desvenlafaxine
Noradrenergic and specific serotoninergic antidepressant (NaSSA)
- mirtazapine
serotonin modulator and stimulators (SMS)
- vortioxetine
reversible inhibitor of monoamine oxidase A (RIMA)
- meclobemide
melatonin receptor agonist
- agomelatine
norepinephrine dopamine reuptake inhibitor (NDRI)
- bupropion
serotonin antagonist and reuptake inhibitor (SARI)
- trazodone
list the additional indications for each antidepressant where relavant
amitriptyline
- depression
- neuropathic pain
- migraine prophylaxis
nortriptyline
- depression
- neuropathic pain
clomipramine
- depression
- OCD
fluoxetine
- depression
- OCD
- bulimia
fluvoxamine
- depression
- OCD
escitalopram
- depression
- anxiety
citalopram
- depression
- PD
sertraline
- depression
- OCD
- PD
paroxetine
- depression
- anxiety
duloxetine
- depression
- GAD
- DM neuropathy
- chronic MSK pain
- stress UI
venlafaxine
- depression
- GAD
bupropion
- depression
- smoking cessation
mirtazapine
- depression
what are the major adverse effects of concern to various antidepressants
- anticholinergic s/e
- sedation
- orthostatic hypotension
- seizures
- cardiac abnormalities
- sexual s/e
which antidepressants are likely to cause anticholinergic s/e
- TCAs (tertiary amines > secondary amines)
- paroxetine (+)
- venlafaxine (+)
- duloxetine (+)
- mirtazapine (+)
- bupropion (+)
which antidepressants are likely to cause sedation
- TCAs (tertiary amines > secondary amines)
- paroxetine (+)
- venlafaxine (+)
- trazadone (++++)
- mirtazapine (++)
- agomelatine (+)
which antidepressants are likely to cause orthostatic hypotension
- TCAs (tertiary amines > secondary amines)
- duloxetine (+)
- mirtazapine (++)
- trazodone (+++)
which antidepressants are likely to cause seizures
- TCAs (tertiary amines > secondary amines)
- trazodone (++)
- bupropion (++++)
- fluoxetine (++)
- fluvoxamine (++)
- paroxetine (++)
- sertraline (++)
which antidepressants are likely to cause cardiac abnormalities
- TCA
- escitalopram (+)
- venlafaxine (+)
- bupropion (+)
- trazodone (+)
which antidepresesants are likely to cause sexual s/e
TCA
SSRI
SNRI
what are the usual dosings for some antidepressants
amitriptyline (to nortriptyline) 50-100mg/d
clomipramine 25-250mg/d
imipramine (to desimipramine) 75-100mg/d
fluoxetine 20-60mg/d
fluvoxamine 50-100mg/d
sertraline 25-50mg/d
paroxetine 12.5-50mg/d
escitalopram 10-20mg/d
venlafaxine (to desvenlafaxine)
- venlafaxine XR 75-225mg/d
- desvenlafaxine ER 50mg/d
duloxetine 30-60mg/d
mirtazapine 15-45mg/d
bupropion 150mg OM x4d f/b 150mg BD
what is the moa of various classes of antidepressants
TCAs
- block reuptake of 5HT and NE
- alpha and H1 antagonism
SSRI
- block reuptake of 5HT
SNRI
- block reuptake of 5HT and NE
NaSSA
- alpha2 antagonist
- increase 5HT and NE levels
- 5HT2 and 5HT3 antagonism (which reverses sexual s/e associated with TCA, SSRI and SNRI)
NDRI
- block reuptake of NE and DA
what are common adjunctive treatments for MDD
- antipsychotics (aripiprazole, brexpiprazole, quetiapine XR)
- esketamine for treatment-resistant depression
- BZP (lorazepam)
- Z-hypnotics (zopiclone, zolpidem)
- antihistamines (promethazine, hydroxyzine)
what are clinically significant ddi for antidepressants?
- serotonergic agent + serotonergic agent = serotonin syndrome
- SSRIs + NSAID/ warfarin/ steroids = increased risk of bleed
- antidepressants + alcohol/CNS depressants = increased CNS depressant effects
- antidepressants + anticholinergics = anticholinergic s/e
what are drugs that are highly serotonergic which concomitant administration can increase risk of serotonin syndrome
- triptans
- opioids (fentanyl, tramadol, pethidine)
- linezolid, ritonavir
- dextromethorphan
- MAOI + serotonergic antidepressant (washout period required)
how is serotonin syndrome presented
mild: insomnia, anxiety, N, D, hypertension, tachycardia, hyper-reflexia
moderate: fever <38degC, tremor, agitation, myoclonus, flushing, diaphoresis
severe: severe hyperthermia, confusion, rigidity, respiratory failure, coma, death
which antidepressants have fewer cyp interactions
- escitalopram
- mirtazapine
- venlafaxine
- desvenlafaxine
- vortioxetine
what are the substrates, inhibitors and inducers of 1A2
substrates
- warfarin R
- theophylline
- amiodarone
- agomelatine
- clozapine
- phenothiazine
inhibitor
- fluvoxamine
- ciprofloxacin
inducer
- CBZ
what are the substrates, inhibitors and inducers of 2C9
substrates
- warfarin S
- sulfonylureas
inhibitors
- amiodarone
- fluconazole
- VPA
inducers
- CBZ
- PHT
- rifampicin
what are the substrates, inhibitors and inducers of 2C19
substrates
- warfarin R
- tolbutamide
inhibitors
- fluvoxamine
- omeprazole
- ticlopidine
- TPM (moderate)
inducer
- CBZ
- PHT
- rifampicin
what are the substrates, inhibitors and inducers of 2D6
substrates
- metoprolol
- tramadol
- oxycodone
- codeine
- desipramine
- risperidone
- olanzapine
- aripiprazole
- brexipiprazole
inhibitors
- fluoxetine
- duloxetine
- paroxetine
- bupropion
what are the substrates, inhibitors and inducers of 3A4
substrates
- simvastatin
- lovastatin
- risperidone
- quetiapine
- aripiprazole
- brexipiprazole
- amlodipine
- nifedipine
- diltiazem
- fentanyl
- ergotamine
- cyclosporine
- tacrolimus
inhibitor
- grapefruit juice
- clarithromycin
- ritonavir
inducer
- st john’s wort
- rifampicin
- PHT
- CBZ
- TPM (moderate)
when do we decide to switch antidepressants
after an adequate trial for 2-4w
what to look out for when switching antidepressants
- if MAOi, washout period necessary
- if from serotonergic agent used daily for past 2m to non-serotonergic, gradual cross tapering to reduce risk of antidepressant discontinuation syndrome
- watch for risk of serotonin syndrome
what is antidepressant discontinuation syndrome and how to prevent this
antidepressant discontinuation syndrome is not withdrawal
patients present with FINISH
F lu-like sx (lethargy, headache, achiness, sweating)
I nsomnia
N ausea
I mbalance (dizziness, light-headedness, vertigo)
S ensory disturbances (burning, tingling)
H yperarousal (agitation, irritability, anxiety, aggression, mania, jerkiness)
presents in 36-72h
will resolve in 1-2w without treatment
prevent by gradually tapering an antidepressant that has been continuously taken for 6-8w or longer by half tablet of lowest strength q1-2w
unnecessary for fluoxetine and bupropion due to long half lives of metabolites
what agents to use to manage MDD in special populations
pregnancy
- nortriptyline in late pregnancy
elderly
- avoid TCAs
- hyponatremia (SIADH) associated with all antidepressants (mostly for SSRIs, possible lower risk with agomelatine, bupropion, mirtazapine) –> monitor serum Na baseline, w2, w4 and q3m
children
- suicidality
comorbidities
- BPH avoid TCA, paroxetine due to ACh effects
- CVD consider sertraline due to antiPLT effect, avoid TCA and escitalopram due to cardiac effects
- chronic pain/ neuropathy consider duloxetine
- DM avoid TCA as may worsen glycemic control
- HTN avoid TCA and SNRI as may increase sympathetic tone
- seizures consider SSRI and SNRI, avoid bupropion and TCA
- tobacco use consider bupropion
