TCAs and other heterocyclics-AE

• Have numerous AEs including weight gain
  • Amoxapine (Ascendin)-active metabolite of Loxapine, can cause EPS and renal failure (rhabodomyolysis) in overdose (OD)
  • Maprotiline (Ludiomil)- rash and seizures

Venlafaxine-AE

• Dose-related increases in diastolic blood pressure
• Lowest protein binding
• Metabolism affected by: CYP2D6

SSRIs-AE

• Lower sedation, anticholinergic and cardiovascular effect
• Biggest problems is sexual dysfunction

Trazodone-AE

• Sedation and priapism

Nefazodone-AE

• Liver failure
• Metabolism affected by: CYP3A4

Bupropion-AE

• Insomnia
• Dose-related seizures

Mirtazapine-AE

• Liver enzymes elevation (monitor LFTs)
• Metabolism affected by: CYP1A2, CYP2D6, and CYP3A4

Fluoxetine-Pharmacokinetics

• Elimination half-life- fluoxetine is days not hours
• Inhibitory potential: CYP2D6, CYP3A4

Antidepressants with active metabolites- Pharmacokinetics

• Fluoxetine/norfluoxetine
• Sertraline/desmethylsertraline
• Amitriptyline/nortriptyline
• Imipramine/desipramine
• Last two are TCA

Sertraline-Pharmacokinetics

• Bioavailibility increases with food

Fluvoxamine-Pharmacokinetics

• Inhibitory potential: CYP1A2

Paroxetine-Pharmacokinetics

• Inhibitory potential: CYP2D6

Drug Interaction-TCAs

• Inhibitors of CYP 1A2, 3A4, and 2D6 may increase TCA concentrations
• Enzyme inducers may decrease TCA concentrations
• Pharmacodynamic:
  • Increased CNS effects (of interacting drug)
  • Peripheral effects (decreased antihypertensive efficacy: clonidine, guanadrel, methyldopa)

Drug Interactions-SSRIs

• Increased TCA concentrations (SSRIs= 2D6, 3A4 inhibitors)
• Warfarin interaction (↑risk of bleeding)
• Fluoxetine (2D6,3A4,2C19 inhibitor) ↑effects/conc. of other CNS active meds 
  • 5 week washout prior to MAOI
• SSRIs have wide therapeutic index
  • When interaction occur, SSRIs increase levels/actions of other drug