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 (PMs) 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, 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;
OB: Use during pregnancy only if potential maternal benefit outweighs risk to fetus;
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 and orthostatic hypotension. 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

GI: constipation, dry mouth, hepatitis, paralytic ileus

GU: ↓libido, urinary retention

Hemat: blood dyscrasias

Metab: ↑appetite, weight gain

Neuro: drowsiness, fatigue

Interactions ⬆ ⬇

Drug-drug:

Desipramine is metabolized in the liver by the CYP2D6 isoenzyme and its action may be affected by drugs that compete for metabolism or alter the activity of this enzyme including other antidepressants, phenothiazines, carbamazepine, class 1C antiarrthythmics (propafenone or flecainide); when used concurrently dose ↓ of one or the other or both may be necessary. Concurrent use of other drugs that inhibit the activity of the enzyme, including cimetidine, quinidine, amiodarone, and ritonavir, may result in ↑ effects.
May cause hypotension, tachycardia, and potentially fatal reactions when used with MAO inhibitors (avoid concurrent use—discontinue 2 wk prior to).
Concurrent use with SSRIs may result in ↑ toxicity and should be avoided (fluoxetine should be stopped 5 wk before).
Concurrent use with clonidine may result in hypertensive crisis and should be avoided.
Phenytoin may ↓ levels and effectiveness; ↑ doses of desipramine may be required to treat depression.
Concurrent use with levodopa may result in delayed/↓ absorption of levodopa or hypertension.
Blood levels and effects may be ↓ by rifampin, carbamazepine, and barbiturates.
Concurrent use with moxifloxacin↑ risk of adverse cardiovascular reactions.
↑CNS depression with other CNS depressants including alcohol, antihistamines, clonidine, opioid analgesics, and sedative/hypnotics.
Barbiturates may alter blood levels and effects.
Adrenergic and anticholinergic side effects may be ↑ with other agents having these properties.
Hormonal contraceptives↑ levels and may cause toxicity.
Cigarette smoking may ↑ metabolism and alter effects.

Drug-Natural Products:

Concomitant use of 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 BMI initially and periodically during therapy.
Refer as appropriate for nutrition/weight management and medical management.
Monitor BP and pulse prior to and during initial therapy. Notify health care professional of decreases in BP (10–20 mm Hg) or sudden increase in pulse rate. Monitor ECG prior to and periodically during therapy in patients taking high doses or with a history of cardiovascular disease.
Depression: Monitor mental status (orientation, mood, behavior) frequently. Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient.
Assess mental status and mood changes, especially during initial few mo of therapy and during dose changes. Risk may be increased in children, adolescents, and adults ≤24 yrs. Inform health care professional if patient demonstrates significant increase in signs of depression (depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, suicide attempt or suicidal ideation). Restrict amount of drug available to patient.
Pain: Assess intensity, quality, and location of pain periodically during therapy.

Lab Test Considerations:

Assess leukocyte and differential blood counts, liver function, and serum glucose periodically. May cause an ↑ serum bilirubin and alkaline phosphatase. May cause bone marrow depression. Serum glucose may be ↑ or ↓.
Serum levels may be monitored in patients who fail to respond to usual therapeutic dose.
Assess fasting blood glucose and cholesterol levels for overweight/obese individuals.

Implementation ⬆ ⬇

Do not confuse despiramine with disopyramide.
- Begin dose increases at bedtime due to sedation. Dose titration is a slow process; may take wks to mos. May give entire dose at bedtime.
When discontinuing, taper to avoid withdrawal effects. Reduce dose by half for 3 days then reduce again by half 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 ⬆ ⬇

Instruct patient to take desipramine 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 at least 2 wk. Abrupt discontinuation may cause nausea; vomiting; diarrhea; headache; trouble sleeping, with vivid dreams; and irritability; decrease dose gradually. Instruct patient to read the Medication Guide prior to starting and with each Rx refill in case of changes.
May cause drowsiness and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to drug is known.
Orthostatic hypotension, sedation, and confusion are common during early therapy, especially in the elderly. Protect patient from falls. 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 professional 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 professional if urinary retention, dry mouth, or constipation persists. Sugarless candy or gum may diminish dry mouth, and an increase in fluids or bulk may prevent constipation. If symptoms persist, dose reduction or discontinuation may be necessary. Consult health care professional if dry mouth persists for more than 2 wk.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Inform patient of need to monitor dietary intake. Increase in appetite may lead to undesired weight gain.
Alert patient that medication may turn urine blue-green in color.
Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Enroll pregnant patients in National Pregnancy Registry for Antidepressants at 1-844-405-6185 or http://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants to monitor pregnancy outcomes in women exposed to antidepressants; enroll as early as possible.
Therapy for depression is usually prolonged. Emphasize the importance of follow-up exams to monitor effectiveness and side effects and to improve coping skills.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇