Desipramine

Today's med: Desipramine  (des IP ra meen) (brand name: Norpramin)

Drug Class: Antidepressant, Tricyclic (secondary amine)

Other Drugs in this class: Imipramine, Nortriptyline, Amitriptyline,Doxepin, Clomipramine, 

Trimipramine, Protriptyline, Amoxapine,Amitriptyline hydrochloride, Doxepin hydrochloride, Nortriptyline Hydrochloride, Imipramine hydrochloride, Clomipramine hydrochloride,Chlordiazepoxide/Amitriptyline, Imipramine Pamoate, Trimipramine Maleate, Perphenazine/Amitriptyline, Desipramine hydrochloride,Protriptyline hydrochloride

Indications: Treatment of depression

Use: Unlabeled

Analgesic adjunct in chronic pain; peripheral neuropathies (including diabetic neuropathy); attention-deficit/hyperactivity disorder (ADHD); depression in children ≤12 years of age

Contraindications: Hypersensitivity to desipramine, drugs of similar chemical class, or any component of the formulation; use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either desipramine or the MAO inhibitor); initiation of desipramine in a patient receiving linezolid or intravenous methylene blue; use in a patient during the acute recovery phase of MI

Action: Traditionally believed to increase the synaptic concentration of norepinephrine (and to a lesser extent, serotonin) in the central nervous system by inhibition of its reuptake by the presynaptic neuronal membrane. However, additional receptor effects have been found including desensitization of adenyl cyclase, down regulation of beta-adrenergic receptors, and down regulation of serotonin receptors.

Adverse Effects: Cardiovascular: Arrhythmias, edema, flushing, heart block, hyper-/hypotension, MI, palpitation, stroke, tachycardia

Central nervous system: Agitation, anxiety, ataxia, confusion, delusions, disorientation, dizziness, drowsiness, EEG alterations, exacerbation of psychosis, extrapyramidal symptoms, fatigue, fever, hallucinations, headache, hypomania, incoordination, insomnia, neuroleptic malignant syndrome, nightmares, restlessness, seizure, suicidal thinking and behavior

Dermatologic: Alopecia, itching, petechiae, photosensitivity, skin rash, urticaria

Endocrine & metabolic: Breast enlargement, galactorrhea, gynecomastia, hyper-/hypoglycemia, impotence, libido changes, SIADH

Gastrointestinal: Abdominal cramps, anorexia, black tongue, constipation, diarrhea, epigastric distress, nausea, parotid edema, paralytic ileus, stomatitis, sublingual adenitis, unpleasant taste, vomiting, weight gain/loss, xerostomia

Genitourinary: Micturition delayed, nocturia, painful ejaculation, polyuria, testicular edema, urinary retention

Hematologic: Agranulocytosis, eosinophilia, purpura, thrombocytopenia

Hepatic: Alkaline phosphatase increased, cholestatic jaundice, hepatitis, liver enzymes increased

Neuromuscular & skeletal: Falling, numbness, paresthesia of extremities, peripheral neuropathy, tingling, tremor, weakness

Ocular: Blurred vision, disturbances of accommodation, intraocular pressure increased, mydriasis

Otic: Tinnitus

Miscellaneous: Allergic reaction, diaphoresis (excessive), withdrawal symptoms

Warnings: 

Major psychiatric warnings:

• Suicidal thinking/behavior: [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription.Desipramine is FDA approved for the treatment of depression in adolescents.

• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with extreme caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by this agent is low relative to other antidepressants.

• Hematologic effects: TCAs may rarely cause bone marrow suppression; monitor for any signs of infection and obtain CBC if symptoms (eg, fever, sore throat) evident.

• Orthostatic hypotension: May cause orthostatic hypotension (risk is moderate relative to other antidepressants); use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).

• Sedation: May cause sedation, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). The degree of sedation is low-moderate relative to other antidepressants.

• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John’s wort, tryptophan) or agents that impair metabolism of serotonin (eg, MOA inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

Lab Test Interferences

Increased glucose; decreased glucose has also been reported. May interfere with urine detection of amphetamines/methamphetamines (false-positive).

Standard Dosing: Oral: Children 6-12 years: Depression (unlabeled use): 1-3 mg/kg/day in divided doses; monitor carefully with doses >3 mg/kg/day; maximum dose: 5 mg/kg/day.

Adolescents: Depression: Initial dose: Start at the lower range and increase based on tolerance and response to 100 mg/day in divided or single dose; usual maintenance dose: 25-100 mg/day, but doses up to 150 mg/day may be necessary in severely depressed patients

Adults:

Depression: Initial dose: Start at the lower range and increase based on tolerance and response; usual maintenance dose: 100-200 mg/day, but doses up to 300 mg/day may be necessary in severely depressed patients

Neuropathic pain (unlabeled use): Initial: 10-25 mg/day; increase dose every 3 days as necessary until the desired effect is obtained; usual effective dose: 50-150 mg/day (maximum dose: 150 mg/day)

Elderly: Depression: Initial dose: Start at the lower range and increase based on tolerance and response to 100 mg/day in as single or divided doses; usual maintenance dose: 25-100 mg/day, but doses up to 150 mg/day may be necessary in severely depressed patients

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of desipramine.

Allow 14 days to elapse between discontinuing desipramine and initiation of an MAO inhibitor intended to treat psychiatric disorders.

Drug interactions: http://www.drugs.com/drug-interactions/desipramine.html

A total of 945 drugs (5496 brand and generic names) are known to interact with desipramine.

• 250 major drug interactions (1727 brand and generic names)
• 632 moderate drug interactions (3276 brand and generic names)
• 63 minor drug interactions (493 brand and generic names)

Show all medications in the database that may interact with desipramine.

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Consider therapy modification

CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions:Tamoxifen. Monitor therapy

Des IP ramine to raise Epinephrine...