Antidepressants, Anti-Manic drugs, & Mood Stabilizers Flashcards
How long does it take for antidepressants to work
4-16 week delay; likely downstream changes caused by blockade of neurotransmitters
mechanism of antidepressants
unclear; may ultimately alter expression of brain-derived neurotrophic factor (BDNF) which increases neural growth (specifically hippocampal volume)
proportion of pts achieving remission
67% of those treated initially with SSRI
response rate to different drugs
all FDA approved antidepressants have similar response-rates in placebo-controlled double blind clinical trials
Types of Antidepressants
SSRI, SNRI, TCA, MAOI
SSRI mechanism
block 5HT pre-synaptic reuptake pump
SNRI
block NE and 5HT reuptake pumps
Bupropion
NDRI– increases whole body NE, weakly blocks reuptake of DA
Trazodone (and defazodone)
mixed serotonin reuptake blocker/alpha1 antagonist
most potent action = block of post-synaptic 5HT2
block reuptake of 5HT and NE
Tricyclics Mechanism
block reuptake of 5HT and NE (and DA to lesser extent), as well as H1, muscarinic cholinergic receptors, and alpha-1
MAOI mech
irreversibly inhibit MAO-A and MAO-B, increasing levels of 5HT and NE
TCAs
Plus: very effective, can monitor blood levels
Minuses: hypotension, orthostasis, anticholinergic effects, weight gain, sexual dysfunction, dangerous in OD (10 day supply can be lethal)
MAOIs
Plus: can be effective in non-respiratory pts, including atypical depression,
Minus: Hypotension, orthostasis, dry mouth, constipation, urinary retention, sexual side effects, weight gain, hypertensive crisis–Tyramine reaction (beef chees)
SSRI
Plus: Safe, effective, multiple indications (GAD, social anxiety, panicm OCD, PTSD, Premenstrual dysphoric disorder)
Minus: diarrhea, nausea, jitteriness/anxiety, sexual side effects, drug interactions: P450 inhibition
Bupropion
NDRI (Wellbutrin)
Pluses: NO Sexual side effects, weight gain, activating
Minus: increased anxiety, jitteriness, ineffetive in panic disorder, insomnia, higher seizure risk (contraindicated in eating disorder and those with seizure disorder)
Mirtazapine
Plus: helpful with insomnia, rapid anti-anxiety effect, low incidence of sexual side effects
Minus: daytime somnolence, weight gain
Other strategies
Vagal nerve stimulators (VNS), Deep brain stimulation (DBS), Transcranial Magnetic Stimulation(TMS)
These still rely on altering monoamines as primary mechanism of action, and efficacy and cost/benefit ratio still unclear
TMS emerging as more promising with depression
Which is more complex to treat– bipolar disorder or unipolar depression
bipolar disorder
Ideal bipolar drug
antimanic, anti-depressive, prevent future episodes— few drugs truly work in all three phases
Mania vs depression in BD–which is easier to treat
Mania
Antimanic agents
ALL atypical antipsychotics, lithium, divalproex, carbamazepine)
Lithium
Pluses: best studied, best proven effective antimanic with some antidepressant effect
Minuses: narrow therapeutic window, lethal in OD, decreased urine concentration, diabetes insipidus, hypothroidism
Divalproex sodium
Pluses: rapid loading, safe and effective, individualized treatment based on weight
Minuses: Not proven as preventative agent, weight gain, sedation, not effective in bipolar depression
Atypical antipsychotics
Pluses: All are antimanic, reasonably safe/effective, different routes, rapid dose titration
Minuses: weight gain, risk of metabolic effects/diabetes, risk of increased cholesterol/lipids, expensive, are they better than typical antipsychotics?
Prevention of future episodes
Lithium has best established evidence (Lithium + divalproex also good preventative combo, though higher side effect burden)
Other: aripiprazole, olanzapine, lamotrigine
Bipolar depression treatment
no large random adequately controlled and powered studies have shown antidepressants effective in treating bipolar depression (some evidence antidepressants worsen course of bipolar disorder)
Best treatments for bipolar depression
quetiapine, lamotrigine, olanzapine/fluoxetine combo, lithium
