TaperCommunityimipramine
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial antidepressant treatment.
Imipramine is the prototype tricyclic antidepressant, FDA-approved for major depression and pediatric enuresis (bedwetting). Largely displaced by SSRIs but still used for treatment-resistant depression, panic disorder, and chronic pain.
10mg, 25mg, 50mg tablets; 75mg, 100mg, 125mg, 150mg capsules
Tablets: 10mg, 25mg, 50mg; Capsules (pamoate): 75mg, 100mg, 125mg, 150mg
Category C
Inhibits reuptake of both serotonin and norepinephrine at the presynaptic terminal. Also blocks histamine H1, muscarinic, and alpha-1 adrenergic receptors — these "off-target" actions explain most of the side-effect profile.
Slow hyperbolic taper recommended due to anticholinergic rebound. Compounded liquid useful for fine cuts at the low end.
Reduce by smaller proportional steps as the dose gets lower. Cholinergic rebound (sweating, abdominal cramps, malaise) is common and often misread as relapse.
1-3 days after dose reduction
5-10 days
2-6 weeks for most symptoms
Sleep disturbance and emotional reactivity can persist 1-3 months
Toxicity
Highly toxic in overdose — narrow therapeutic index. Cardiac arrhythmias, seizures, anticholinergic toxicity, coma. Even 1-2 weeks of supply can be lethal.
Pharmacokinetics
Well absorbed orally; extensive first-pass metabolism.
Hepatic via CYP1A2, CYP2C19, CYP2D6, CYP3A4 to active desipramine.
Renal (80%) and fecal (20%) as metabolites.
~90%
Browse our map of deprescribing-informed providers worldwide.