Week 7 Antidepressants and Mood Stabilizers

Question 1

What are the general categories of treatment of major depressive disorder?

Answer 1

1. psychotherapy
   - 33% will achieve remission
2. Electroconvulsive therapy (ECT)
   - 50-70% effective in treating acute episode
   - memory loss and headache
   - useful for MDD with psychosis
3. Pharmacotherapy
   - 33% will achieve remission with one antidepressant

Question 2

What is the mechanism of amitriptyline (Elavil), a TCA? Adverse effects? pros?

Answer 2

1. Mechanism: presynaptic NT reuptake inhibition NE/5HT/DA
2. adverse effects:
   - sedation-hisatmine, blockade of alpha 1
   - orthostatic hypotension, blockade of alpha1
   - dry mouth, constipation, cholinergic block
   - weight gain-histamine antagonism
   - cardiotoxicity/heart block, high lethality in overdose
3. pros
   - effective and inexpensive

Question 3

What is the mechanism of fluoxetine (prozac), a SSRI? Adverse effects? pros?

Answer 3

1. mechanism
   -presynaptic 5HT reuptake inhibition
2. adverse effects
   due to 5HT stimulation
   -nausea, diarrhea (5HT3)
   -anorgansmia, delayed ejaculation (5HT2), 30-50% sexual side effects
   -headache (5HT2)
   due to NT reuptake inhibition
   -restlessness, insomnia
   -FDA approved for children and teens
3. pros
   -relatively safe in overdose

Question 4

What is the mechanism of phenelzine (Nardil), a MAOI? Adverse effects? pros?

Answer 4

1. mechanism: inhibits monoamine oxidase, thereby inhibiting breakdown of NT
2. Adverse effects:
   - dizziness, orthostatic hypotension (a1 block)
   - insomnia (NT reuptake inhibition)
   - no aged cheese or wine due to drug interaction
3. pros
   - effective and inexpensive

Question 5

What is the mechanism of Mirtazapine (Remeron)? Adverse effects? pros?

Answer 5

1. mechanism: 5HT2 antagonism (5HT2 inhibits DA and 5HT release), improve pre-synaptic 5HT neurotransmission
2. adverse effects
   - sedation and weight gain (histamine receptor block)
3. pros
   - blocks nausea (5HT3 antagonism)
   - low to no sexual dysfunction
   - low to no nausea or headache
   - increase NE outflow to CNS (a2 antagonism)

Question 6

What is the mechanism of Bupropion (Wellbutrin)? Adverse effects? pros?

Answer 6

1. mechanism: presynaptic NE and DA reuptake inhibition, no 5HT effects
2. adverse effects:
   - insomnia, upset stomach
   - seizure risk
3. Pros
   - low to no sexual dysfunction
   - low to no weight gain
   - helpful for smoking cessation and ADHD

Question 7

What is the mechanism of Lithium (Eskalith, lithobid, eskalith CR)? Uses? Adverse effects?

Answer 7

1. mechanism: NT stabilization, inhibits excitatory neurotransmitters (NE, DA)
   - enhances 5HT to help with depression
   - for acute mania, bipolar depression, well established relapse prevention efficacy
   - therapeutic plasma level: 0.6-1.5 mEq/L
   - renal elimination
   - 1-3 week onset
2. Adverse effects:
   - intentional tremor
   - weight gain
   - polyuria, polydipsia
   - drug interactions: ibuprofen, caffeine

Question 8

What is the mechanism of Valproate (Depakene, Depakote)? Adverse effects? pros?

Answer 8

1. mechanism: facilitates GABA, calming over excited brain areas
   - broad spectrum anticonvulsant activity
   - for acute mania
   - for mixed mania and rapid cycling
   - probably relapse prevention, less established
   - therapeutic plasma level: 50-125 meg/mo
   - wide therapeutic range, less risk of toxicity
   - hepatic elimination
   - 2-7 day onset
2. adverse effects
   - sedation, lethargy
   - weight gain
   - lower risk of intentional tremor
   - drug interaction: aspirin, antacids

Question 9

What are approaches to treating bipolar disorder?

Answer 9

• mood stabilizer mono therapy only 50% effective, need multiple meds for better response
• antipsychotics used as adjuncts to mood stabilizers when psychotic symptoms present
• mood stabilizers taken life long
• discontinue antidepressant if patient switches to mania, and need to maintain mood stabilizer