IMIPRAMINE HYDROCHLORIDE
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Tricyclic antidepressant that inhibits the reuptake of norepinephrine and serotonin at presynaptic neuronal membranes, increasing their synaptic concentrations. Also has anticholinergic, antihistaminergic, and alpha-1 adrenergic blocking effects.
| Metabolism | Primarily hepatic via CYP1A2, CYP2D6, CYP3A4; active metabolite desipramine; also glucuronidation. |
| Excretion | Renal (70% as metabolites, <5% unchanged), biliary/fecal (30%) |
| Half-life | Terminal half-life 11-25 hours (mean ~20 h); clinical context: steady-state achieved in ~1 week, dosing adjustment needed in hepatic impairment |
| Protein binding | 90-95% bound to alpha1-acid glycoprotein, albumin, and lipoproteins |
| Volume of Distribution | 10-20 L/kg (mean 15 L/kg); clinical meaning: extensive tissue distribution, large Vd indicates slow elimination |
| Bioavailability | Oral: 20-70% due to extensive first-pass metabolism (mean ~40%); IM: not available; IV: not available |
| Onset of Action | Oral: 2-4 weeks for antidepressant effect; IV: not applicable |
| Duration of Action | Variable; anticholinergic effects persist for hours after single dose; antidepressant effect requires steady-state levels |
Initial 75 mg/day orally in divided doses, increase to 150-200 mg/day; maximum 300 mg/day. For maintenance, 50-150 mg/day orally.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: reduce dose by 50%. GFR <30 mL/min: use with caution, reduce dose by 75% or consider alternative. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated or reduce dose by 75% with close monitoring. |
| Pediatric use | For enuresis: age 6-12 years, 25 mg/day orally; >12 years, 50 mg/day. For depression: not recommended under 12 years; age 12-18, start 25-50 mg/day, max 100 mg/day. |
| Geriatric use | Initial 30-40 mg/day orally, increase slowly; maximum 100 mg/day. Monitor for orthostatic hypotension, sedation, and anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause serotonin syndrome and hyperpyrexia Strong anticholinergic effects may occur with other drugs Increased risk of suicide in children and young adults.
| Breastfeeding | Enters breast milk; M/P ratio approximately 0.5. Avoid breastfeeding due to potential for infant adverse effects (irritability, sedation, poor feeding). |
| Teratogenic Risk | First trimester: Limited human data; animal studies show embryotoxicity. Second and third trimesters: Associated with neonatal withdrawal (irritability, tachypnea, poor feeding) and anticholinergic effects (ileus, urinary retention). Avoid in third trimester unless benefits outweigh risks. |
■ FDA Black Box Warning
Suicidality and Antidepressant Drugs: Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. Monitor closely for worsening or emergence of suicidal thoughts and behaviors.
| Common Effects | enuresis |
| Serious Effects |
["Hypersensitivity to imipramine or any tricyclic antidepressant","Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI therapy","Recent myocardial infarction","Angle-closure glaucoma","Concurrent use with linezolid or intravenous methylene blue"]
| Precautions | ["Clinical worsening and suicide risk","Activation of mania/hypomania","Increased intraocular pressure in narrow-angle glaucoma","Urinary retention","Cardiovascular effects (QT prolongation, arrhythmias, orthostatic hypotension)","Seizure threshold lowering","Serotonin syndrome with concurrent serotonergic drugs","Bone marrow suppression","Discontinuation syndrome with abrupt cessation"] |
Loading safety data…
| Fetal Monitoring |
| Maternal: ECG (QTc prolongation risk), serum drug levels, blood pressure, mood assessment. Fetal/neonatal: Observational monitoring for withdrawal and anticholinergic effects. |
| Fertility Effects | May impair fertility in both sexes via hyperprolactinemia and sexual dysfunction; reversible upon discontinuation. |