Pharmacotherapy

Note: Combining behavioral therapy with pharmacotherapy is significantly more effective than either alone.

  • First-Line Agents:
    • Varenicline:
      • MOA: α4β2 nicotinic acetylcholine receptor partial agonist; reduces craving and withdrawal while blocking nicotine binding.
      • Efficacy: Most effective monotherapy for smoking cessation.
      • Adverse Effects: Nausea, insomnia, vivid/abnormal dreams.
      • Clinical Pearl: Black box warning for neuropsychiatric events removed by FDA; safe in stable psychiatric pts, but monitor for mood changes/suicidality.
    • Bupropion SR:
      • MOA: Norepinephrine-dopamine reuptake inhibitor (NDRI).
      • Key Benefits: Minimizes post-cessation weight gain; excellent for pts with co-morbid major depressive disorder (MDD).
      • Contraindications:
        • Seizure disorders (lowers seizure threshold).
        • Current or prior diagnosis of bulimia or anorexia nervosa.
        • Abrupt withdrawal from alcohol, benzodiazepines, or barbiturates.
        • Use of MAO inhibitors within 14 days.
      • Adverse Effects: Insomnia, dry mouth, headache, agitation.
    • Nicotine Replacement Therapy (NRT):
      • Options: Transdermal patch (long-acting); gum, lozenge, nasal spray, inhaler (short-acting).
      • Combination NRT (e.g., patch + gum/lozenge) is superior to monotherapy NRT and roughly equal in efficacy to varenicline.
      • Precautions: Caution in acute coronary syndrome (<2 weeks post-MI), serious arrhythmias, or severe angina.
  • Second-Line Agents (used if first-line fails, contraindicated, or unavailable):
    • Nortriptyline (TCA).
    • Clonidine (α2-adrenergic agonist).