Pharmacology of Depression

Question 1

Catecholamine hypothesis of depression

Answer 1

• Initial observation that reserpine depleted brain NE-5HT and induced depression formed the hypothesis of the connection
• additional support came from observation that drugs effective in treating depression shared the common feature of enhancing availability of NE-5HT at postsynaptic receptor (i.e., via block of reuptake, block of metabolism, or increase in release).

Question 2

Limitations of the catecholamine hypothesis

Answer 2

• biogenic amine theory does not totally explain etiology of depression.
• Mood elevating effects take 2-3 weeks for onset, but effects on amines occur immediately and some newer agents have little no effect on amine reuptake.
• Direct evidence in support of the monoamine theory is still largely lacking.

Question 3

Tricyclic antidepressants: MOA, SE, considerations in drug choice

Answer 3

• MOA: Block 5HT reuptake, and NE to some extent
• SE
  • Sedation: lassitude, fatigue, sleepiness.
  • Antimuscarinic effects: blurred vision, dry mouth, urinary hesitancy, fuzzy thinking.
    
    • Higher doses → narrow angle glaucoma aggregation, urinary retention, delirium. …
• Considerations
• Poor SE profile, not commonly used.
• Can give depressed pt easy way to kill self with overdose.

Question 4

Selective Serotonin Reuptake Inhibitors (SSRIs): MOA, SE, considerations in drug choice

Answer 4

• MOA: Block 5HT reuptake
• SE
  
  • Sedative action.
  • Delayed: weight gain, sexual dysfunctin, cognitive blunting.
  • Acute: n/v, activation insomina (common), restlessness.
  • Withdrawal symptoms: Flulike
• Considerations
  
  • Low likelihood of fatality with overdose
  • Inhibits CYP450

Question 5

Buproprion: MOA, SE

Answer 5

• MOA: Block NE/DA reuptake
• SE: tremor, insomnia, anxiety, seizure at high doses

Question 6

Venlafaxine: MOA, SE

Answer 6

• MOA: Block 5HT/NE reuptake
• SE
  
  • HTN, anxiety
  • Rapid appearance of withdrawal symptoms

Question 7

Trazadone: MOA, SE, considerations in drug choice

Answer 7

• MOA: Mixed postsynaptic antag + SRI
• SE
  
  • Drowsiness - major sedative
• Considerations
  
  • OD: minor problems only

Question 8

MAOi’s: MOA, SE, considerations in drug choic

Answer 8

• MOA: Block NE/5HT/DA degredation
• SE
  
  • Postural Hypotension, sedation, CNS stimulatin, liver damage, Seizure + shock + hyperthermia in overdose
• Considerations
  
  • Look out for drug drug interactions - hypertensive crisis.

Question 9

ECT: MOA, SE

Answer 9

• MOA: increases synthesis of NE, 5HT
• SE: memory loss

Question 10

Mood stabilizers: MOA, use

Answer 10

• MOA: blocks VSSC
• Use:
  
  • blocks bipolar strom, supersensitivity and kindling

Question 11

Mood stabilizers (Lithium): MOA, SE, use, considerations in drug choice

Answer 11

• MOA: enhance 5HT, diminish NE and DA
• SE: Fine tremor, GI upset, muscle weakness, weight gain, polyuria, polydipsia
• Use: Effective for ↓ of manic and depressive episodes
• Considerations: Drug drug interactions - diuretics and NSAIDs increase Li plasma levels
  
  • Na⁺ and Li⁺levels are inversely related (compete for absorption)

Question 12

Mood stabilizer examples

Answer 12

• VSSC blocker
  
  • Valproic
  • Carbamazepime
• Lithium