Treatment of Depression Flashcards
Etiology & Pathophysiology of Depression
- Biological
- -> Hormonal influences: Increase cortisol
- -> Monoamine hypothesis: Decrease in neurotransmitters in brain (NE, 5-HT, DA)
- Psychological
- Psychosocial
- Genetics
- Medical disorders
- -> Endocrine disorders: Hypothyroidism, Bidirectional association between depression & T2DM in women
- -> Neurological & Malignancy: -ve impact on mood
- -> Deficiency states
- -> Infections
- -> Metabolic disorders
- -> CVS (Depression as rf for poor diagnosis among pts with ACS)
- Psychiatric disorders
- -> Alcoholism (CNS Depressant: will eventually cause depression)
- -> Anxiety disorders
- -> Eating disorders
- -> Schizophrenia
- Drug-induced
DSM-5 Diagnostic Criteria for major depressive disorder
Criteria: At least 5 symptoms during same 2-week period
- One of the symptom has to be depressed mood/ lost of interest
“In.SAD.CAGES”
I: Decreased interest*
S(leep): Insomnia
A(petite): Decreased appetite/weight loss
D: Depressed mood*
C(oncentration): Impaired conc & decision making
A(ctivity): Psychomotor retardation/agitation
G: Guilt/ unworthiness
E(nergy): Decreased energy/fatigue
S: Suicidal thoughts or attempts
- Symptoms cause significant depression/impairment
- Not caused by underlying medical condition/substance
General Assessments of Depression
- Hx of present illness, Psychiatric hx, Substance use hx, Complete medical & medication hx, family social forensic developmental & occupational hx
- Phy & neurological exam
- Labs & other investigation (To exclude general medical conditions or substance-induce symptoms)
- Mental state exam (MSE)
- -> Assess for suicidal/homicidal ideation & risks
- -> Reassess MSE on every interview
Psychiatric rating scales
Clinician-rated: Hamilton rating scale for depression
(HAM-D) “Gold standard”
Self-rated: Screening -> PHQ-2
Assessment tool -> PHQ-9
(Proceed if pt ans ‘yes’ to either qn in PHQ-2)
Geriatric depression scale: 15-item short form
30-item long form
Non-pharmacological treatment of Depression
- Sleep hygiene
- Psychotherapy
- Neurostimulation:
Electroconvulsive treatment (ECT) - for severe refractory
cases
Repetitive Transcranial magnetic stimulation (rTMS)
Pharmacological treatment of Depression
Mod-severe depression, certain anxiety disorders & dysthmia:
Antidepressants +/- Adjunctive meds
- Choice based on target symptoms, comorb conditions, DDI, prior response, preference
1st line: SSRI/SNRI/Mirtazapine (subsidised)
Buproprion
SSRI, SNRI, NaSSA, Buproprion > Agomelatine > Vortioxetine > TCA > MAOIs
Phases of Depression Treatment
Acute phase:
- Adequate trial = adequate dose + duration (4-8wks)
- Delayed onset due to down-regulation of pre-synaptic autoreceptors*
- Phy symptoms may improve in ~1-2wks
- Mood symptoms in ~4-6wks
Continuation phase:
- Continue for at least 4-9 mths after acute phase treatment
=> Total = 6-12mths
Longer-term Maintenance Therapy:
- Consider if high risks, >= 2 episodes MDD & geriatric MDD
Why are TCAs not favoured & the exception when it is still used?
- Toxicity in overdose, strong anticholinergic, sedative, orthostatic hypotension effects, conductance abnormalities….
Exception:
Clomipramine for OCD (when SSRIs fail)
Note:
Amitriptyline & Clomipramine - Max: 300mg
Which antidepressants have long t1/2 so there’s < worry of antidepressant withdrawal syndrome?
Fluoxetine (SSRI): 4-6days
Vortioxetine (SMS): 66hrs
Buproprion
SSRIs
[Compare between options, SE & Additional notes]
Options:
- Fluoxetine (20mg OM, Max: 80mg): long t 1/2
- Fluvoxamine: > sedative
- Esticalopram/Citaprolam: More $ & Qtc prolongation
(high doses, elderly women) but less DDI
- Sertraline: Much safer
- Paroxetine: Most anticholinergic, sedating, increase wt,
short t1/s (withdrawal)
Side Effects:
GI (5-HT3) & Sexual dysfunction (5-HT2)
Initial jitters!!!
Insomnia (fluoxetine)
Hyponatremia (SIADH) - Cramps, muscle twitching
Bleeding risk; EPSE
SNRIs
[Compare between options, SE & Additional notes]
Options:
- Venlafaxine: Has box warning for uncontrolled BP
- Desvenlafaxine (50mg/day)
- Duloxetine: Also indicated for Diabetic peripheral neuropathy, fibromyalgia, chronic muscoskeletal pain
Side Effects (As for SSRIs):
- Increase BP
- Urinary hesitation (Dulox)
NaSSA: Mirtazapine
[MOA, SE & Additional notes]
MOA:
Aims straight for the presynaptic membrane, alpha2-adrenoreceptor antagonist, increases 5-HT & NE, 5HT2,3 & H1 antagonism
Side Effects:
- Somnolence
- Increases appetite -> Weight gain
Note:
- Reverses sexual dysfunction of SSRI & SNRI
Dose: 15-45mg
NDRI: Buproprion
[MOA, SE & Additional notes]
MOA:
Blocks re-uptake of DA & NE
Side effects: *Seizures *Not suitable for eating d/o/seizures/psychosis Insomnia Psychosis
Note:
- Decreases sexual dysfunction of SSRI & SNRI
- Smoking cessation aid
Use of Moclobemide
Reversible MAOI-A
Use (Rare, 2nd/3rd line):
- Atypical depression
- Social phobia
Pointers to note for Agomelatine
Increases LFT
- Check at baseline & at week 3, 6, 12, 24
Pointers to note for Trazodone
- Very sedating
- Rare SE: Priapism (painful penile erection)
Adjunctive medications for Depression
1) Benzodiazepines (eg. Lorazepam, Diazepam)
- SE: Sedation, drowsiness, amnesia, muscle weakness
- Note: Limit to 2 weeks PRN, lowest effective dose
2) Z-Hypnotics (eg. Zolpidem, Zopiclone)
- Causes sedation
- SE: Taste disorders (zopiclone), complex sleep disorders eg. sleep walking
- Note: Half dose of Zolpidem for females (6.25mg alt day)
3) Antihistamine (eg. Promethazine/Hydroxyzine)
- SE: Sedation, anticholinergic (dry mouth, constipation)
Therapeutic lifestyle/behavioural changes for Depression
- Sleep hygiene
- Exercise
- Relaxation techniques
- Others, as appropriate
DDI with antidepressants
1) St john’s wort
- Significant DDI, not to be used concomitantly
2) 2x Serotonergic Agents -> Serotonin syndrome
- SSRIs increase risks of bleeding (Higher risk in elderly on NSAIDs, Warfarin, Steroids -> Consider to + PPI/ Stop 2 weeks b/f surgery if high bleeding risks)
- Increases CNS depressants effects with Alcohol/other antidepressants
- “Do not take med at the same time as alcohol, separate them 4-6hrs apart”
3) Benzodiazepines + Opioids = Increased mortality
- CNS depression, avoid if possible
Special populations & other considerations to consider in Depression
1) Pregnancy
- Nortripyline in late pregnancy
2) Breastfeeding
- Sertraline/ Mirtazapine
3) Elderly
- Avoid TCAs, anticholinergic, CNS, hypotensive or other cardiac SE
- SIADH (mostly for SSRIs, lesser risk for Agomelatine, Mirtazapine, Buproprion)
- -> Monitor serum Na+ at baseline, 2nd, 4th week thn 3mthly
4) Children & Young Adult
- Association to suicidality in pts <= 24yo, require counselling to patients
Which antidepressants have fewer CYP interactions?
- Mirtazapine
- Esticalopram
- Venlafaxine
- Desvenlafaxine
- Vortioxetine
Managing partial/no response
Switching
- When ineffective/intolerable to adequate dose in 1-4wks
- Gradual tampering when switching from serotonergic -> non-serotoninergic agent
- Wash-out period is necessary for MAOIs
Augmentation
- Combine by adding a 2nd antidepressant: Mirtazapine, Quetiapine XR, Aripriprazole, Brexipiprazole
Treatment-Resistant Depression
- Neurostimulation: ECT, rTMS
- Symbyax oral capsule
- Spravato nasal spray as adjunct to SSRI/SNRI treatment
Antidepressant Discontinuation Syndrome
- Worse with abrupt discontinuation syndrome
- -> Esp with short t1/2 antidepressants: Paroxetine, Venlafaxine
Symptoms: FINISH
- Flu-like symptoms (fatigue, MA, HA)
- Insomnia
- Nausea
- Imbalance (dizziness)
- Sensory (‘electric shock’ sensations)
- Hyperarousal (anxiety, agitation)
Patient Counselling for Depression
- May take a couple of weeks to help with symptoms of low mood/poor sleep/appetite, at least a couple of mths to help with anxiety
- Do not take same time as alcohol (4-6h apart)
- To contact Dr asap if you feel your condition worsening/ feeling suicidal/ agitated/ bothersome & persistent side effects
Possible Side Effects:
- Drowsy
- Insomnia
- Dizzy/light-headedness
- Stomach upset
- Changes in sexual dysfunction (can be reversed & treated if it occurs)
How to discontinue antidepressants?
Taper over 4 weeks
