Imipramine (Tofranil)

Class

Tricyclic antidepressant (TCA)

Mechanism

Inhibits reuptake of norepinephrine and serotonin; also has significant antagonism at muscarinic, histamine H1, and alpha-1 adrenergic receptors.

FDA-Approved Use

Major depressive disorder (MDD), childhood enuresis

Off-Label Use

Panic disorder, neuropathic pain, post-traumatic stress disorder (PTSD), augmentation in treatment-resistant depression

Formulation

Oral tablets

Titration

Start at 25–50 mg p.o. daily, given at bedtime or in divided doses; titrate gradually based on response and tolerability

Dose Range

75–200 mg/day for adults (lower pediatric dosing for enuresis, age-dependent)

Kinetics

Metabolized by CYP2D6 and CYP2C19; active metabolite (desipramine); half-life ~11–25 hours

Common AEs

Dry mouth, constipation, urinary retention, blurred vision, dizziness, sedation, weight gain

Serious/Rare AEs

Cardiac conduction abnormalities, orthostatic hypotension, seizures, delirium, overdose toxicity

Monitoring

Baseline ECG for patients over age 40 or with cardiac history; monitor for orthostasis, anticholinergic burden, and suicidal ideation

Black Box Warning

Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults

Considerations

Use with caution in patients with dementia, post-stroke cognitive impairment, or traumatic brain injury (TBI) due to heightened risk of confusion, delirium, and falls from anticholinergic and hypotensive effects. ECG screening is recommended prior to initiation in adults over 40 or those with cardiac risk factors.