Antidepressants and Mood Stabilizers (Schneck) Flashcards
How long does it take for antidepressants to work?
weeks (even though SSRIs and SNRIs almost immediately block reuptake of serotonin and NE (downstream changes take time))
4-16 weeks
Mechanism of antidepressant efficacy
- unclear
- may alter expression of BDNF
- ALL pharm treatments target neurotransmitter systems (NE, 5-HT, DA) and boost synaptic action
- all are monoamine based
- modest efficacy
- slow onset
- tolerability issues
What is the only approved tx for depression that produces a more rapid response?
ECT
Response rates to antidepressants
first 8 weeks: 67%
only about 1/3 achieve remission w/ SSRI
Newer meds
There are currently no adequately powered randomized, controlled clinical trials comparing newer medications
SSRIs
block 5HT2A pre-synaptic reuptake pump
- Pluses: Safe, effective, multiple indications: Generalized Anxiety Disorder, social anxiety, panic, Obsessive Compulsive Disorder, Post Traumatic Stress Disorder, Premenstrual Dysphoric Disorder
- Minuses: Diarrhea, nausea, jitteriness/anxiety, sexual side effects, drug interactions: P450 inhibition
SNRIs
block NE and 5HT reuptake pumps
- Pluses: Some evidence more effective than SSRIs, safe, better tolerated than TCAs, multiple indications
- Minuses: Sexual side effects, sweating, increased diastolic blood pressure, withdrawal syndrome (flu-like, “electric shocks”)
Bupropion
increases whole body NE, weakly blocks reuptake of DA
- Pluses: No sexual side effects, weight neutral, activating.
- Minuses: Increased anxiety, jitteriness, ineffective in panic disorder, insomnia, higher seizure risk (***contraindicated in eating disorder patients and those with seizure disorder)
trazodone
most potent action is blockade of post-syn 5HT2. Block reuptake of 5HT and NE
-Mixed Serotonin Reuptake Blocker / Receptor Antagonist
TCADs
block reuptake of 5-HT and NE, (and, to lesser extent, DA), as well as H1, muscarinic cholinergic receptors and alpha1.
Pluses: Time-tested, very effective, more effective in severe depression, can monitor blood levels
Minuses: Hypotension, orthostasis, anticholinergic side effects, weight gain, sexual side effects, dangerous in overdose
MAOIs
irreversibly inhibit MAO-A and MAO-B increasing levels of 5HT and NE
- Pluses: Can be very effective in non-responsive patients, especially atypical depression, time-tested.
- Minuses: Hypotension, orthostasis, dry mouth, constipation, urinary retention, sexual side effects, weight gain, **hypertensive crisis–Tyramine reaction
Other strategies for tx
Vagal Nerve Stimulators
DBS
Transcranial Magnetic Stimulation (alter trimonoamine circuits)
Tx of bipolar disorder– problem?
- more complex than treating unipolar depression
- have to treat different phases of the illness
- an ideal drug: anti-manic, anti-depressive and prevent future episodes. Few drugs truly work in all three phases
Treatment of ___ in bipolar disorder is effective, of_____ is difficult
- tx of mania is effective
- tx of bipolar depression is difficult: 2 tx approved: quetiapine and Olanzapine+fluoxetine
Which class of drugs are anti-manic?
ATYPICAL antipsychotics
as well as lithium, divalproex, carbamazepine
Lithium (mania)
effects on glycogen synthase kinase 3 beta and PKC
- Pluses: Best studied, best proven drug, effective anti-manic, reasonable preventative agent, some antidepressant effect, anti-suicidal properties, neuro-regenerative effects, cheap.
- Minuses: Tremor, nausea, diarrhea, taste, thirst, cognitive dulling, *narrow therapeutic window (0.6-1.2 mEq/l), toxic/lethal in overdose, renal effects, decreased urine concentration, *diabetes insipidus, *hypothyroidism
Divalproex sodium (mania)
Mech of action: inhibiton of GABA transamination
-bipolar
- Pluses: Individualized treatment (based on weight), rapid loading (20-30 mg/kg), safe and effective.
- Minuses: Not proven as preventative agent, weight gain, sedation, not effective in bipolar depression
Atypical antipsychotics (mania tx)
- Pluses: All are anti-manic, reasonably safe & effective, different routes of administration (injection, dissolvable tabs), rapid dose titration
- Minuses: Weight gain, risk of metabolic effects/diabetes, risk of increased cholesterol/lipids, expensive, are they any better than typical antipsychotics?
Bipolar depression study problem
No large, randomized, adequately controlled and powered studies have shown that antidepressants are effective in the treatment of bipolar depression
Best tx for bipolar depression
quetiapine>lithium
antidepressants in bipolar disrder is controversial and not well proven
med for prevention of future episodes for bipolar?
Lithium: best established
Lithium +divalproex: many SEs but good
Clinical trial evidence for antidepressant efficacy?
ALL FDA approved antidepressants have comparable response rates in placebo controlled, double blind clinical trials
What is the major benefit of Bupropion?
No sexual side effects
weight neutral
