Antidepressants and Mood Stabilizers (Schneck)

Question 1

How long does it take for antidepressants to work?

Answer 1

weeks (even though SSRIs and SNRIs almost immediately block reuptake of serotonin and NE (downstream changes take time))
4-16 weeks

Question 2

Mechanism of antidepressant efficacy

Answer 2

• 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

Question 3

What is the only approved tx for depression that produces a more rapid response?

Answer 3

ECT

Question 4

Response rates to antidepressants

Answer 4

first 8 weeks: 67%

only about 1/3 achieve remission w/ SSRI

Question 5

Newer meds

Answer 5

There are currently no adequately powered randomized, controlled clinical trials comparing newer medications

Question 6

SSRIs

Answer 6

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

Question 7

SNRIs

Answer 7

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”)

Question 8

Bupropion

Answer 8

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)

Question 9

trazodone

Answer 9

most potent action is blockade of post-syn 5HT2. Block reuptake of 5HT and NE
-Mixed Serotonin Reuptake Blocker / Receptor Antagonist

Question 10

TCADs

Answer 10

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

Question 11

MAOIs

Answer 11

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

Question 12

Other strategies for tx

Answer 12

Vagal Nerve Stimulators
DBS
Transcranial Magnetic Stimulation (alter trimonoamine circuits)

Question 13

Tx of bipolar disorder– problem?

Answer 13

• 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

Question 14

Treatment of ___ in bipolar disorder is effective, of_____ is difficult

Answer 14

• tx of mania is effective

- tx of bipolar depression is difficult: 2 tx approved: quetiapine and Olanzapine+fluoxetine

Question 15

Which class of drugs are anti-manic?

Answer 15

ATYPICAL antipsychotics

as well as lithium, divalproex, carbamazepine

Question 16

Lithium (mania)

Answer 16

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

Question 17

Divalproex sodium (mania)

Answer 17

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

Question 18

Atypical antipsychotics (mania tx)

Answer 18

• 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?

Question 19

Bipolar depression study problem

Answer 19

No large, randomized, adequately controlled and powered studies have shown that antidepressants are effective in the treatment of bipolar depression

Question 20

Best tx for bipolar depression

Answer 20

quetiapine>lithium

antidepressants in bipolar disrder is controversial and not well proven

Question 21

med for prevention of future episodes for bipolar?

Answer 21

Lithium: best established

Lithium +divalproex: many SEs but good

Question 22

Clinical trial evidence for antidepressant efficacy?

Answer 22

ALL FDA approved antidepressants have comparable response rates in placebo controlled, double blind clinical trials

Question 23

What is the major benefit of Bupropion?

Answer 23

No sexual side effects

weight neutral