L9-10 Depression Flashcards
What is the first-line treatment option for mild depression?
psychosocial treatments (watch your own thoughts, healthy coping mechanisms)
What are the treatment options for moderate and severe depression?
pharmacological and psychological treatments (down to molecules, receptors, anatomy)
What is the lifetime prevalence of MDD?
5.8%
Among persons with a mental illness,
50.6% also had a chronic physical illness
Suicide in general population - general risk factors:
A poor, elderly, lonely, man, with physical/mental comorbidities and previous attempts
Biological etiology and pathophysiology of depression
- hormonal influences: incr cortisol scretion (major stress hormone)
- monamine hypothesis: decr neurotransmitter in brain eg. NE, 5-HT, DA
What are the secondary causes for depression?
medical disorders:
- endocrine disorder eg hypothyroidism
- deficiency states
- infections
- metabolic disorders
- cv
- neurological
- malignancy
psychiatric disorders
drug-induced:
- alc/stimulants withdrawal
DSM-5 diagnostic criteria for MDD
- IN.SAD.CAGES, at least 5 sx during same 2 week period + change from previous functioning
^ one of the sx must be D - sx cause significant distress or impairment in social, occupational, or other important areas of functioning
- not caused by an underlying medical condition or substance ie. intoxication/withdrawal
Why is it important the evaluate for any history of maniac/hypomaniac episodes prior to diagnosis and treatment of MDD?
Antidepressants may cause ‘maniac switch’ in patients with underlying bipolar disorder
What is the MSE used for?
For accurate diagnosis: assess for suicidal/homicidal ideations and risks
- appearance, speech, mood, thought process, insight, judgement
- reassessed on every interview to evaluate efficacy and tolerability
What are the general evaluations required prior to diagnosis and treatment?
- hx of present illness
- psychiatric illness
- substance use hx
- complete medical hx and medication hx
- family, social, forensic, developmental and occupational hx
- physical and neurological exam
- MSE
- labs and other investigations
Why is it important to exclude general medical conditions or substance-induced sx eg psychosis//depression/mania/anxiety/insomnia ?
Before starting on antidepressants
- chronic commitment, >= 6 months
- comes with SE
Escitalopram
2C19 substrate
Sertraline
2C19 substrate
Paroxetine
2D6 substrate
What is the therapy goal for MDD tx?
remission, sx free
Difference between PHQ-2 and PHQ-9
2: screening instrument
- if patient has a positive response to either question (little interest or pleasure in doing things/feeling down, depressed or hopeless over the past 2 weeks),
a. consider administering the PHQ9 or asking the patient more questions about possible depression
- a negative response to both questions is considered a ‘negative’ result for depression screening
When are non-pharmacologicals used?
- monotherapy in mild depression
- in combination with antidepressants for moderate-severe depression
Examples of non-pharmacological tx of MDD
sleep hygiene, psychotherapy, neurostimulation ie ECT, rTMS
Dysthymia
milder, but persistent (over 2 years) form of depression
antidepressant effectiveness
all kinda have equal efficacy - select based on target sx, comorbid conditions, ddi, prior response, preference
first line antidepressant monotherapy
usually SSRI, SNRI, mirtazapine (subsidised)
- or bupropion (non-subsidised)
mirtazapine
NaSSA
- a2 adrenergic autoreceptors antagonist
- 5-HT2 receptor antagonist
bupropion
NDRI
If immediate relief of insomnia required,
short course of sleeping pills can be given
- antidepressants work very slowly, few weeks
adequate trial =
adequate dose (lowest dose in licensed dose regimen?) + duration (4-8 weeks according to APA guidelines 2010, max 12 weeks)
2 phases of treatment
acute phase: trial
continuation phase
Why does it take weeks for physical and mood sx to improve?
acute phase treatment: delayed onset due to down-regulation of pre-synaptic autoreceptors
SSRI work within
a day, inhibition of serotonin reuptake
How long does physical sx take to improve?
1-2 weeks
How long does mood sx take to improve?
4-6 weeks
SSRI
fluoxetine, fluvoxamine, escitalopram
SNRI
venlafaxine, duloxetine
NaSSA
mirtazapine
presynaptic autoreceptors
regulate synthesis and release of neurotransmitters
MDD: TCA
amitriptyline, clomipramine, dothiepin, imipramine, nortriptyline
MDD: SSRI
fluoxetine, fluvoxamine, escitalopram, citalopram, paroxetine, sertraline
MDD: SNRI
venlafaxine, desvenlafaxine, duloxetine
MDD: SMS
vortioxetine
MDD: NaSSA
mirtazapine
MDD: RIMA
moclobemide
MDD: others
bupropion, trazodone, agomelatine
why has TCA fallen out of favour?
- anticholinergic effecs, bad for elderly!!!
- a1-adrenoceptor blockade: sedation
- proconvulsant: seizures
- heart arrhythmia, sudden cardiac death
longer acting antidepressants
- fluoxetine: 4-6 days elimination half life, active metabolite can last a week+ too
- vortioxetine: 66hr elimination half life
^ hence, less worried about antidepressant discontinuation syndrome
how to manage partial/no response?
switching, augmentation, treatment-resistant depression (neurostimulation, symbyax oral capsule or spravato nasal spray)
association to suicidality in patients =< ___ years old?
24, suicidality and antidepressants in children and young adults - require counselling to patients and caregivers for close monitoring and regular review
clinically significant ddi
- serotonergic agent + serotonergic agent = serotonin syndrome
- SSRIs incr risk of bleeding by at least 2 folds - nsaids, warfarin, steroids, surgery
- incr cns depressant effects - alcohol and cns depressants / benzo+opioids
- anticholinergic agents
high dose serotonergic meds eg.
- triptans
- sibutramine
- opioids (tramadol, fentanyl, pethidine), dextromethorphan
- linezolid, ritonavir
what class of drugs cannnot be used with benzodiazepines
opioids = incr mortality due to cns depression
=- sleeping pill + painkiller
antidepressants with fewer CYP interactions
mirtazapine, escitalopram, venlafaxine, desvenlafaxine, vortioxene, sertraline (but some 2d6 interactions at high doses)
must benzodiazepines discontinuation be done gradually?
yes, for long-term and high-dose use
how long does antidepressants take to help sx of low mood, poor sleep and appetite?
a couple of weeks
how long does antidepressants take to help w anxiety?
a couple of months
sexual dysfunction SE less likely with
mirtazapine, bupropion, agomelatine
duloxetine also indicated for
diabetic peripheral neuropathy, fibromyalgia and chronic musculoskeletal pain
all antidepressants are
similar in efficacy for uncomplicated first ep MDD
