desipramine

Absorption: Well absorbed from the GI tract.

Distribution: Widely distributed.

Protein Binding: 90–92%.

Metabolism/Excretion: Mostly metabolized by the liver by the CYP2D6 isoenzyme; one metabolite is pharmacologically active (2-hydroxydesipramine);the CYP2D6 enzyme system exhibits genetic polymorphism; ∼7% of population may be poor metabolizers and may have significantly ↑ desipramine concentrations and an ↑ risk of adverse effects. Small amounts enter breast milk.

Half-Life: 12–27 hr.

Time/Action Profile ⬆ ⬇

(antidepressant effect)

ROUTE	ONSET	PEAK	DURATION
PO	2–3 wk	2–6 wk	days–wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Angle-closure glaucoma;
Recent MI, HF, or known history of QTc interval prolongation.

Use Cautiously in:

Pre-existing cardiovascular disease;
Family history of sudden death, cardiac arrhythmias, or conduction disturbances;
Prostatic hyperplasia (↑ susceptibility to urinary retention);
History of seizures (threshold may be ↓; seizures may precede the development of cardiac arrhythmias or death);
May ↑ risk of suicide attempt/ideation, especially during early treatment or dose adjustment; risk may be greater in children or adolescents;
Hypovolemia or dehydration (↑ risk of syndrome of inappropriate antidiuretic hormone secretion [SIADH]);
OB: Use during pregnancy only if potential maternal benefit outweighs potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit outweighs risk to infant;
Pedi: Children <12 yr (safety not established);
Geri: Appears on Beers list. ↑ risk of adverse reactions in older adults, including falls secondary to sedative and anticholinergic effects, orthostatic hypotension, and SIADH. Avoid use in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, ARRHYTHMIAS, ECG changes

Derm: photosensitivity

EENT: blurred vision, dry eyes

Endo: changes in blood glucose, gynecomastia

F and E: hyponatremia, SIADH

GI: constipation, dry mouth, hepatitis, paralytic ileus

GU: ↓libido, urinary retention

Hemat: blood dyscrasias

Metab: ↑appetite, weight gain

Neuro: drowsiness, fatigue, SUICIDAL THOUGHTS/BEHAVIORS

Interactions ⬆ ⬇

Drug-drug:

CYP2D6 inhibitors, including cimetidine, quinidine, amiodarone, and ritonavir, may ↑ levels and risk of toxicity.
May cause hypotension, tachycardia, and potentially fatal reactions when used with MAO inhibitors; avoid concurrent use; discontinue 2 wk before starting desipramine.
SSRIs may result in ↑ toxicity; avoid concurrent use. Fluoxetine should be stopped 5 wk before starting desipramine.
Clonidine may ↑ risk of hypertensive crisis; avoid concurrent use.
Phenytoin may ↓ levels and effectiveness; ↑ doses of desipramine may be required.
Levodopa may ↑ risk of extrapyramidal reactions and hypertension.
Rifampin, carbamazepine, barbiturates, and cigarette smoking may ↓ levels and effectiveness.
Concurrent use with moxifloxacin may ↑ risk of adverse cardiovascular reactions.
↑CNS depression with other CNS depressants, including alcohol, antihistamines, clonidine, opioid analgesics, and sedative/hypnotics.
Adrenergic and anticholinergic side effects may be ↑ with other agents having these properties.
Hormonal contraceptives may ↑ levels and risk of toxicity.
Diuretics may ↑ risk of SIADH.

Drug-Natural Products:

Kava-kava, valerian, or chamomile can ↑ CNS depression.
↑anticholinergic effects with jimson weed and scopolia.

Route/Dosage ⬆ ⬇

PO (Adults ): 100–200 mg/day as a single dose or in divided doses (up to 300 mg/day).
PO Geriatric Patients ): 25–50 mg/day in divided doses (up to 150 mg/day).
PO (Children >12 yr): 25–50 mg/day in divided doses; may ↑ as needed up to 100 mg/day.
PO (Children 6–12 yr): 10–30 mg/day (1–5 mg/kg/day) in divided doses.

Availability ⬆ ⬇

(Generic available)

Tablets: 10 mg; 25 mg; 50 mg; 75 mg; 100 mg; 150 mg

Assessment ⬆ ⬇

Monitor for weight gain. Obtain weight and body mass index initially; at 3, 6, and 12 mo; and then yearly in all patients and if receiving combination therapy.
Monitor BP and HR at baseline, with significant dose ↑, and every 3–6 mo once stabilized. Notify health care provider of ↓ in BP (by 10–20 mm Hg) or sudden ↑ in HR. Monitor ECG prior to and periodically during therapy in patients taking high doses or with a history of cardiovascular disease.
Assess for signs and symptoms of serotonin syndrome (confusion, delirium, agitation, coma, dilated pupils, tachycardia, hyperthermia, shivering, hyperreflexia, muscle rigidity, hypertension, vomiting, diarrhea, seizures). ↑ risk of serotonin syndrome with concurrent use of other serotonergic drugs (SSRIs, SNRIs, triptans); monitoring recommended; discontinuation may be required.
Assess for signs and symptoms of SIADH (hyponatremia, headache, muscle cramps or weakness, tremors).
Depression: Monitor mental status (orientation, mood behavior) frequently.
Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be ↑ in children, adolescents, and adults ≤24 yr. After starting therapy, children, adolescents, and young adults should be seen by health care provider at least weekly for 4 wk, every 3 wk for next 4 wk, and on advice of health care provider thereafter.
Pain: Assess intensity, quality, and location of pain periodically during therapy.

Lab Test Considerations:

Assess CBC with differential, liver function, and serum glucose periodically. May ↑ serum bilirubin and alkaline phosphatase. May cause bone marrow depression. Serum glucose may be ↑ or ↓.
Assess sodium level at baseline and after 3–4 wk in high-risk patients (>65 yr, previous history of antidepressant-induced hyponatremia, ↓ body weight, concurrent use of thiazides or other hyponatremia-inducing agents).
Serum levels may be monitored in patients who fail to respond to usual therapeutic dose; therapeutic reference range is 100–300 ng/mL when used as an antidepressant.
Assess fasting blood glucose and cholesterol levels for overweight/obese individuals.

Implementation ⬆ ⬇

Do not confuse despiramine with disopyramide.
- Begin dose ↑ at bedtime due to sedation. Dose titration is a slow process; may take wk to mo. May give entire dose at bedtime.
When discontinuing, taper to avoid withdrawal effects. ↓ dose by 50% for 3 days; then ↓ again by 50% for 3 days; then discontinue. May require 2–4 wk to discontinue.
PO: Administer medication with or immediately after a meal to minimize gastric upset. Tablet may be crushed and given with food or fluids.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of desipramine. Instruct patient to take as directed. Take missed doses as soon as possible unless almost time for next dose; if regimen is a single dose at bedtime, do not take in the morning because of side effects. Advise patient that drug effects may not be noticed for ≥2 wk. Abrupt discontinuation may cause nausea; vomiting; diarrhea; headache; trouble sleeping, with vivid dreams; and irritability; ↓ dose gradually. Instruct patient to read the Medication Guide prior to starting and with each Rx refill in case of changes.
Therapy for depression is usually prolonged. Emphasize the importance of follow-up exams to monitor effectiveness and side effects and to improve coping skills.
May cause drowsiness and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to drug is known.
Orthostatic hypotension, SIADH, sedation, and confusion are common during early therapy, especially in older adults. Protect patient from falls and advise patient to make position changes slowly. Institute fall precautions. Advise patient to make position changes slowly.
Advise patient to avoid alcohol or other CNS depressant drugs, including opioids, during and for 3–7 days after therapy has been discontinued.
Advise patient, family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care provider immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior occur.
Instruct patient to notify health care provider if urinary retention, dry mouth, or constipation persists. Sugarless candy or gum may diminish dry mouth, and an ↑ in fluids or bulk may prevent constipation. If symptoms persist, dose ↓ or discontinuation may be necessary. Consult health care provider if dry mouth persists for >2 wk.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Inform patient of need to monitor dietary intake. ↑ in appetite may lead to undesired weight gain. Refer as appropriate for nutrition/weight management and medical management.
Alert patient that medication may turn urine blue-green in color.
Advise patient to notify health care provider of medication regimen prior to treatment or surgery.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Enroll pregnant patients in National Pregnancy Registry for Antidepressants by calling 1-844-405-6185 or visiting https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants to monitor outcomes in women exposed to antidepressants.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇