antidepressants and mood stabilizers

Question 1

Recognize the different classes of antidepressants and discuss the general ideas about mechanism of action.

Answer 1

• SSRIs: block 5HT pre-synaptic reuptake pump
• SNRIs: block NE and 5-HT reuptake pumps
• Mirtazapine: blocks 5-HT2A, 5-HT2C, 5-HT3, a-2-adrenergic receptors
• Buproprion: increases whole-body NE, weakly blocks reuptake of DA
• Trazodone and nefazodone: most potent action is blockade of post-synaptic 5-HT2. Block reuptake of 5-HT and NE.
• Tricyclics: block reuptake of 5-HT and NE, (and, to lesser extent, DA), as well as H1, muscarinic cholinergic receptors and a-1.
• MAOIs: irreversibly inhibit MAO-A and MAO-B, increasing levels of 5-HT and NE.
• Vilazodone, a new antidepressant, is an SSRI + 5HT1A partial agonist.
• Generally, there is no “right” antidepressant. Clinicians must consider the risks and benefits of each drug and select accordingly.

Question 2

Describe the general timeline of response to antidepressants

Answer 2

4-16 week delay
Electroconvulsive Therapy (ECT) is the only approved treatment for depression that produces more rapid response.

Question 3

Discuss issues around treatment of bipolar disorder, and that different phases require different medications

Answer 3

Bipolar always requires medication on top of psychotherapy

Question 4

Describe basic medication strategies for treating bipolar mania and depression.

Answer 4

For bipolar depression there is no effective medication strategy
There are 2 fad approved drugs but rarely effective and can make depression worse, quetiapine or fluoxetine + Olanzapine
For bipolar mania- all atypical antipsychotics should be effective + lithium, carbamazepine, divalproex

Question 5

SSRI

Answer 5

• 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 5

SNRI

Answer 5

• 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 6

TCAs

Answer 6

• Pluses: Time-tested, very effective, more effective in severe depression, can monitor blood levels. Newer TCAs (secondary amines such as desipramine and nortriptyline) have fewer side effects than older TCAs (tertiary amines, such as imipramine and amitryptyline)
• Minuses: Hypotension, orthostasis, anticholinergic side effects, weight gain, sexual side effects, dangerous in overdose (10 day supply can be lethal)

Question 7

MAOis

Answer 7

• 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 8

Bupropion

Answer 8

• 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

Mirtazipine

Answer 9

• Pluses: Helpful with insomnia, rapid anti-anxiety effect, low incidence of sexual side effects
• Minuses: Daytime somnolence, weight gain