DESIPRAMINE HYDROCHLORIDE
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Inhibits reuptake of norepinephrine and serotonin at presynaptic neuronal membrane, increasing their concentrations in the synaptic cleft.
| Metabolism | Hepatic, primarily via CYP2D6 isoenzyme; active metabolite 2-hydroxydesipramine. |
| Excretion | Renal excretion of metabolites accounts for approximately 70%; fecal elimination ~30%. Unchanged drug <5% in urine. |
| Half-life | Terminal half-life 12–30 hours (mean ~22 hours); extensive interindividual variability due to CYP2D6 polymorphism. |
| Protein binding | 92% bound primarily to alpha-1-acid glycoprotein (AAG) and albumin. |
| Volume of Distribution | 20–60 L/kg (mean ~42 L/kg); extensive tissue distribution including brain. |
| Bioavailability | Oral ~60% (range 30–70%) due to first-pass metabolism. |
| Onset of Action | Oral: antidepressant effect 1–3 weeks; therapeutic plasma levels achieved in 3–5 days. |
| Duration of Action | Antidepressant effect persists for several days after discontinuation; single dose effects last ~24 hours. |
| Molecular Weight | 266.38 |
Oral: Initial 25-75 mg/day in divided doses; increase gradually to 100-200 mg/day, maximum 300 mg/day. Usual maintenance: 100-200 mg/day single or divided doses.
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment. GFR 10-50 mL/min: reduce dose by 25-50%. GFR <10 mL/min: reduce dose by 50-75%. |
| Liver impairment | Child-Pugh Class A: reduce dose by 25-50%. Child-Pugh Class B: reduce dose by 50-75%. Child-Pugh Class C: avoid use or use with extreme caution, maximum 100 mg/day. |
| Pediatric use | Adolescents: 25-50 mg/day initially, increase to 100-200 mg/day. Children (6-12 years): 1-3 mg/kg/day in divided doses, maximum 5 mg/kg/day or 150 mg/day. Not recommended for children <6 years. |
| Geriatric use | Initial 10-25 mg/day, increase by 10-25 mg/week; maximum 150 mg/day. Monitor for anticholinergic effects and orthostatic hypotension. |
| 1st trimester | Limited studies; potential risk of congenital malformations (cardiac defects) based on some epidemiological data. Use only if benefit outweighs risk. |
| 2nd trimester | May be associated with preterm birth and low birth weight; monitor for maternal and fetal effects. |
| 3rd trimester | Neonatal withdrawal symptoms (irritability, respiratory distress) and anticholinergic effects possible. Avoid near term. |
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.
| Placental transfer | Desipramine crosses the placenta with cord blood concentrations approximately 50-70% of maternal plasma levels. |
| Breastfeeding | Desipramine is excreted into breast milk in low levels. Case reports suggest low infant exposure; monitor infant for drowsiness, feeding difficulties, and weight gain. Consider risk-benefit. |
■ FDA Black Box Warning
Suicidality and antidepressant drugs: Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Common Effects | Dry mouth |
| Serious Effects |
Hypersensitivity to desipramine or other tricyclic antidepressantsRecent myocardial infarctionConcomitant use of MAOIs (risk of hypertensive crisis)Narrow-angle glaucomaSevere hepatic impairment
| Precautions | Activation of mania/hypomania, Seizures, Cardiovascular effects (QT prolongation, arrhythmias, orthostatic hypotension), Serotonin syndrome (especially with MAOIs), Anticholinergic effects (urinary retention, narrow-angle glaucoma), Bone marrow suppression |
| Food/Dietary | Avoid alcohol; may increase CNS depression. Grapefruit juice may alter metabolism; limit intake. High-tyramine foods (aged cheese, cured meats, soy products) may cause hypertensive crisis if used with MAOIs; desipramine alone has low risk but caution. Take with food if GI upset occurs. |
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| Lactation Rating | L2 (Possibly Safe) |
| Teratogenic Risk | First trimester: Limited data, but associated with cardiovascular malformations (e.g., VSD) in some studies; risk appears low. Second and third trimesters: Risk of neonatal withdrawal syndrome (irritability, respiratory distress) and anticholinergic effects (e.g., urinary retention, constipation). No clear teratogenicity. |
| Fetal Monitoring | Maternal: ECG for QT prolongation (especially at doses >200 mg/day), liver function tests, serum drug levels if toxicity suspected. Fetal/neonatal: Monitor for withdrawal symptoms (e.g., jitteriness, tachypnea) for 48 hours after delivery. Consider fetal echocardiography if first-trimester exposure. |
| Fertility Effects | May cause hyperprolactinemia in females (rare with desipramine), leading to menstrual irregularities and anovulation. In males, possible erectile dysfunction and delayed ejaculation; no evidence of permanent infertility. |
| Clinical Pearls | Desipramine, a secondary amine TCA, is less sedating than amitriptyline but still has anticholinergic effects. Monitor for orthostatic hypotension, QTc prolongation, and seizures at high doses. Therapeutic drug monitoring is useful; target plasma concentration 125-300 ng/mL. Onset of antidepressant effect takes 2-4 weeks. Avoid in recent MI, narrow-angle glaucoma, or with MAOIs within 14 days. |
| Patient Advice | Take exactly as prescribed; do not adjust dose without consulting your doctor. · It may take 2-4 weeks to feel the full benefit; do not stop abruptly to avoid withdrawal symptoms. · Avoid alcohol and other CNS depressants; they can increase dizziness and drowsiness. · Rise slowly from sitting or lying to prevent falls due to low blood pressure. · Report signs of serotonin syndrome (agitation, hallucinations, fever, fast heart rate) immediately. · Inform your doctor of all medications, including OTC and herbal products. · Do not drive or operate heavy machinery until you know how this medication affects you. · Store at room temperature away from moisture and heat. |