Treatment of Depression Flashcards
MDD
Major Depressive Disorder
Diagnosis of MDD
- at least 5 out of 9 symptoms (In.S.A.D.C.A.G.E.S)
- must have In & D
- for most of the same 2 week period
- causing significant distress or functional impairment
- symptoms are not drug-induced / secondary to other medical conditions
Goal of therapy
- Hamilton Rating Scale =< 7
- Remission of symptoms / symptoms free
- Treatment adherence
- Suicide prevention
Non-pharmacological therapy (4)
- Sleep hygiene
- Psychotherapy
- cannot monotherapy in moderate-severe MDD - Electroconvulsive Treatment (ECT) (more severe & refractory MDD)
- Repetitive Transcranial Magnetic Stimulation (rTMS) (less invasive)
Pharmacological therapy + Adjunctives
- Anti-depressants
- SSRI, SNRI, Mirtazapine (NaSSA) & Bupropion
> Agomelatine & Vortioxetine
> TCA
> MAOi - Adjunctive medications
- anxiolytics
- hypnotics
- short course, PRN
- only if needed
Duration of antidepressant treatment
Acute phase
- 4-8 weeks (max 12 weeks)
Continuation phase
- 4-9 months
Total duration : at least 6-12 months
Duration for physical symptoms treatment (eg poor sleep)
1-2 weeks
Duration for mood symptoms treatment
> 6 weeks
- due to downregulation of pre-synaptic autoreceptors to prevent negative feedback regulation of neurotransmitter secretion into synaptic space
- leads to disinhibition & promotion of neurotransmitter release
Efficacy among antidepressants
All have similar efficacy for uncomplicated first episode of MDD
Duloxetine
SNRI
Also indicated for :
- diabetic peripheral neuropathy
- fibromyalgia
- chronic musculoskeletal pain
All serotonergic agents (SSRI, SSRI, TCA, SMS) ADR
- GI effects
2. SD
Venlafaxine ADR
- worsens HTN
Mirtazapine ADR
- sedation
- weight gain (due to increased appetite)
Mirtazapine benefit
Reduce SD
Bupropion CI
- history of seizures
- psychosis
- eating disorders
Bupropion benefit
No SD effect cos NDRI (no serotonergic effects)
TCAs ADR (6)
- Anticholinergic (dry mouth, blurred vision, constipation)
- Sedation
- Orthostatic hypotension
- Arrhythmias
- Seizures
- Fatal on overdose
Counselling point for all antidepressants to =<24y/o
Suicidality association
Minimal CYP interactions (5)
MEVDV
- Mirtazapine
- Escitalopram
- Venlafaxine
- Desvenlafaxine
- Vortioxetine
Significant PD interactions
- Serotonin Syndrome (RDTSMCCD)
- multiple serotonergic agents used tgt - CNS depression
Discontinuation of antidepressant
- taper dose gradually over 4 weeks
- 10-25% every 1-2 weeks
- if used daily for >=2months
Withdrawal syndrome of antidepressants
FINISH
Flu-like symptoms (fatigue, muscle aches, headaches)
Insomnia
N/V
Imbalance (dizziness)
Sensory (paresthesia, electric shock sensations)
Hyperarousal (anxiety, agitation)
Lifetime prevalence of MDD
5.8%
Correlation with MDD
Physical illness & mental illness
Risk factors for suicide in a general population (6)
- Poor
- Lonely
- Elderly
- Man
- Physical & mental illnesses
- Previous attempts
3 independent predictors of suicide
- Coexisting physical illness
- Delusion
- History of attempted suicide with using highly lethal means
Theory for depression
Monoamine theory
- decrease neurotransmitters in the brain
- NE, 5-HT and dopamine
Secondary causes of depression (3)
- Medical conditions
- CVD
- endocrine disorders - Drug induced / iatrogenic
- Psychological disorders
General assessments prior to diagnosis and treatment (2)
1. Psychiatric history eg maniac or hypomaniac episodes 2. Mental state exam (MSE) - assess for suicidal/homicidal ideations and risks - reassess on every interview
SSRI examples (6)
- Fluoxetine
- Fluvoxamine
- Escitalopram
- Citalopram
- Sertraline
- Paroxetine
SNRI examples (3)
- Venlafaxine (worsens HTN)
- Desvenlafaxine
- Duloxetine
Function of presynaptic autoreceptors
- negative feedback regulation
- down-regulation of presynaptic autoreceptors lead to disinhibition of the release of neurotransmitters into synaptic space
Antidepressants with long half life
- Vortioxetine
- 66h (2-3 days) - Fluoxetine
- 4-6 days
Less concern about withdrawal symptoms (FINISH)
MAOi ADR
- hypertensive crisis
Hypnotics
Benzodiazepines
- diazepam
- lorazepam
- 2-4 weeks, short course, PRN
Switching methods (2)
- Cross-titration
- recommended if daily use of serotonergic agents to non-serotonergic agents (cos need to taper dose gradually) to prevent serotonergic withdrawal syndrome
- careful of serotonergic syndrome - Direct switch
- complete washout required for MAOi
Advice for patients taking alcohol and antidepressants
- space apart 4-6h
eg benzodiazepines & opioids = increased mortality
Benzodiazepines discontinuation
- gradual discontinuation of long-term high dose use
DDI (4)
- Fluvoxamine
- CYP1A2 inhibitor
- CYP2C19 inhibitor - Fluoxetine & Paroxetine
- CYP2D6 inhibitor - Bupropion
- CYP2D6 inhibitor - Grapefruit juice
- CYP3A4 inhibitor
Augmentation of antidepressants
- add 2nd antidepressants with another MOA eg Mirtazapine (NDRI)
Adjunctive SGAs (3)
- Aripiprazole
- Brexpiprazole
- Quetiapine XR
Treatment resistant depression
- no response to 2 adequate trials of antidepressants
Treatment resistant depression management (2)
- Electroconvulsant Therapy (ECT)
- more invasive
- refractory & more severe cases - Repetitive Transcranial Magnetic Stimulation (rTMS)
Antidepressants with short half life (2)
- Paroxetine
2. Venlafaxine