Imipramine
Tofranil
Tricyclic AntidepressantGeneric availableTDM data
Clinical Pharmacology The mechanism of action of imipramine hydrochloride is not definitely known. However, it does not act primarily by stimulation of the central nervous system. The clinical effect is hypothesized as being due to potentiation of adrenergic synapses by blocking uptake of norepinephrine at nerve endings. The mode of action of the drug in controlling childhood enuresis is thought to be apart from its antidepressant effect.
Compare Imipramine →FDA-Approved Indications
- Depression (adults)
- Childhood enuresis — temporary adjunctive therapy (6+ years)
Common Off-Label Uses
- Panic disorder
- Neuropathic pain
- Chronic pain
- ADHD
What Sets This Drug Apart
- Prototypical first-generation TCA; historically the most widely prescribed antidepressant before SSRIs
- Only TCA with FDA-labeled indication for enuresis in children aged 6+ — mechanism is multifactorial (anticholinergic, sleep architecture, bladder tone)
- Extensive first-pass metabolism to active metabolite desipramine (noradrenergic); at steady state, plasma is a mixture of serotonergic parent and noradrenergic metabolite
- Off-label evidence for panic disorder; anticholinergic and orthostatic burden limits use as first-line for any indication
- Multiple CYP substrate (2D6, 2C19, 1A2, 3A4) — extensive drug interaction potential similar to amitriptyline
Boxed Warning
Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality)