Elmood45 mg+105 mg

Elmood is an oral combination product containing dextromethorphan (an NMDA receptor antagonist and sigma-1 receptor agonist) and bupropion (which here also acts as a CYP2D6 inhibitor to raise dextromethorphan exposure). It represents a non-monoaminergic mechanism distinct from traditional antidepressants.

Established/FDA-Approved Uses

• Major depressive disorder (MDD) in adults
• Agitation associated with dementia due to Alzheimer's disease in adults (as scheduled, ongoing treatment; Elmood is not indicated for as-needed/"prn" use in this population)

Elmood has not been shown to be effective, and is not indicated, for anxiety disorders, cough suppression, or any use in patients under 18 years of age. It should be prescribed only for its approved indications, under medical supervision.

Each extended-release tablet of Dextromethorphan + Bupropion contains a fixed-dose combination of dextromethorphan hydrobromide and bupropion hydrochloride, most commonly available as a 45 mg/105 mg (dextromethorphan/bupropion) strength tablet. Exact strengths and available dosage forms may vary by manufacturer and market; only the studied and approved fixed-dose combination should be used.

Elmood is a fixed-dose oral combination of dextromethorphan (an NMDA receptor antagonist and sigma-1 receptor agonist) and bupropion (an aminoketone that inhibits the CYP2D6 enzyme, increasing and prolonging dextromethorphan exposure). Together these components produce a glutamatergic, non-monoaminergic antidepressant effect that is mechanistically distinct from SSRIs, SNRIs, and other traditional antidepressants. Elmood is supplied as an extended-release tablet taken by mouth and carries a boxed warning regarding suicidal thoughts and behavior.

Elmood belongs to a novel antidepressant class combining an NMDA receptor antagonist/sigma-1 receptor agonist (dextromethorphan) with an aminoketone norepinephrine-dopamine reuptake inhibitor that also serves as a CYP2D6 inhibitor (bupropion). It is classified as a non-monoaminergic antidepressant, mechanistically distinct from SSRIs, SNRIs, and tricyclic antidepressants.

Pharmacodynamics

The dextromethorphan component of Dextromethorphan + Bupropion acts as an NMDA receptor antagonist and sigma-1 receptor agonist, effects thought to underlie its rapid-acting antidepressant activity. The bupropion component independently contributes antidepressant activity as a norepinephrine-dopamine reuptake inhibitor, and importantly inhibits the CYP2D6 enzyme, which markedly increases plasma exposure and prolongs the half-life of dextromethorphan, allowing sustained NMDA/sigma-1 activity at lower dextromethorphan doses than would otherwise be required.

Pharmacokinetics

• Absorption: Both components are absorbed after oral dosing; the extended-release formulation of Dextromethorphan + Bupropion provides a controlled release profile.
• Metabolism: Dextromethorphan is primarily metabolized via CYP2D6, which bupropion inhibits, substantially raising dextromethorphan levels; bupropion itself is extensively hepatically metabolized to active metabolites (including hydroxybupropion).
• Elimination: Metabolites of both components are eliminated mainly via the kidneys; poor CYP2D6 metabolizers and patients on strong CYP2D6 inhibitors achieve higher dextromethorphan exposure and require dose limitation.

Elmood tablets should be swallowed whole with a glass of water; do not crush, divide, or chew the tablet, as this may cause more rapid release of the medication and increase the risk of adverse effects. It may be taken with or without food. When dosed twice daily, doses should be separated by at least 8 hours, and the second daily dose should be timed to reduce the risk of insomnia. See Dosage and Administration for full titration schedules.

Elmood has clinically significant interactions with the following:

Side effects of Elmood reported in clinical studies include:

Common

• Dizziness
• Headache
• Diarrhea
• Somnolence
• Dry mouth
• Sexual dysfunction
• Hyperhidrosis (excessive sweating)
• Dyspepsia
• Insomnia, anxiety, or agitation (bupropion-related activation)

Less Common

• Tremor
• Nausea, decreased appetite
• Blurred vision
• Palpitations

Rare/Serious

• Seizures (dose-dependent - see Precautions and Warnings)
• Suicidal thoughts or behavior, especially in patients under 25 years old
• Serotonin syndrome
• New or worsening psychosis, mania, hallucinations, delusions, or paranoia
• Marked increase in blood pressure
• Angle-closure glaucoma
• Hyponatremia

Patients should seek prompt medical attention for a seizure, chest pain, signs of an allergic reaction, confusion, hallucinations, or thoughts of self-harm.

Pregnancy

Elmood is not recommended during pregnancy. Animal reproduction studies with the components of Elmood have shown evidence of developmental toxicity, including fetal malformations and embryo-fetal loss, at doses relevant to human exposure. Elmood should be used during pregnancy only if the potential benefit to the mother clearly justifies the potential risk to the fetus, and only under close medical supervision; a physician should always be consulted before use in pregnancy or if pregnancy occurs during treatment.

Lactation

The bupropion component of Elmood is known to pass into human breast milk. Breastfeeding is not recommended during treatment with Elmood and for a short period after discontinuation, given the potential for adverse effects in a nursing infant. A physician should be consulted to weigh the benefits of treatment against potential infant exposure and to discuss alternatives.

Boxed Warning - Suicidal Thoughts and Behavior

Antidepressants, including Elmood, increase the risk of suicidal thinking and behavior in children, adolescents, and young adults, particularly during the first months of treatment or after dose changes. Elmood is not approved for use in patients under 18 years of age. All patients on Elmood should be monitored closely for clinical worsening, unusual changes in behavior, or emergence of suicidal thoughts, especially early in treatment.

Seizure Risk

The bupropion component of Elmood is associated with a dose-dependent risk of seizure. Risk is increased at higher doses, in patients with predisposing factors, and with concurrent use of other drugs that lower seizure threshold or with abrupt discontinuation of alcohol or sedative-hypnotics (see Contraindications and Interactions).

Serotonin Syndrome

Because dextromethorphan has serotonergic activity, concurrent use of Elmood with other serotonergic drugs (SSRIs, SNRIs, triptans, and others) or MAOIs can cause a potentially life-threatening serotonin syndrome, with symptoms such as agitation, hallucination, tachycardia, hyperthermia, tremor, and incoordination. Discontinue immediately and seek medical care if this is suspected.

Dissociative and Psychoactive Effects

Elmood can cause dizziness and dissociative or psychoactive effects, including new or worsening mania, hypomania, hallucinations, delusions, or paranoia, particularly at treatment initiation or after a dose increase. Patients should avoid driving or operating hazardous machinery until they know how Elmood affects them.

Blood Pressure

Elmood can cause or worsen hypertension. Blood pressure should be assessed before starting treatment and monitored periodically during treatment.

Angle-Closure Glaucoma and Hyponatremia

Pupillary dilation associated with the bupropion component can precipitate an attack in patients with anatomically narrow angles who lack a protective iridectomy. Hyponatremia has also been reported rarely with antidepressants of this general type.

CYP2D6-Mediated Drug Interactions

The mechanism of Elmood relies in part on CYP2D6 inhibition by its bupropion component; concurrent strong CYP2D6 inhibitors or known CYP2D6 poor-metabolizer status significantly raise dextromethorphan exposure and require dose limitation (see Dosage and Administration and Interactions).

Overdose of Elmood may cause seizures, hallucinations, agitation, tachycardia, tremor, loss of consciousness, and cardiac conduction disturbances (including arrhythmias associated with the bupropion component), among other effects. There is no specific antidote for Elmood overdose.

If overdose of Elmood is suspected, seek immediate medical attention or contact emergency services/a poison control center right away. Overdose should be managed in a monitored medical setting with supportive and symptomatic care by trained personnel; do not attempt any specific treatment at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric Patients

Elmood is not approved for use in children or adolescents; see Pediatric Uses for full detail, including the boxed warning on suicidal thoughts and behavior in this age group.

Elderly/Geriatric Patients

Patients treated for agitation associated with Alzheimer's disease dementia with Elmood are typically elderly; use general antidepressant precautions, start at the lower end of dosing where applicable, and monitor closely for adverse effects, falls, and changes in renal function.

Renal Impairment

Dose of Elmood is reduced to once daily in moderate renal impairment; use in severe renal impairment or end-stage renal disease is not recommended (not adequately studied).

Hepatic Impairment

Use of Elmood is not recommended in moderate-to-severe hepatic impairment because of significantly increased exposure to the bupropion component.

Pregnancy and Lactation

See Pregnancy and Lactation section for full details.

The need for continued treatment with Elmood should be reassessed periodically by the prescribing physician, weighing ongoing benefit against risks such as seizure and suicidality. There is no fixed maximum duration, but treatment should not be continued beyond what is clinically necessary, and Elmood should not be stopped abruptly without medical guidance, as antidepressant discontinuation can cause withdrawal-type symptoms.

Dextromethorphan + Bupropion combines an NMDA receptor antagonist/sigma-1 receptor agonist (dextromethorphan) with an aminoketone norepinephrine-dopamine reuptake inhibitor and CYP2D6 inhibitor (bupropion), together forming a non-monoaminergic antidepressant class distinct from SSRIs, SNRIs, and tricyclic antidepressants.

Dextromethorphan + Bupropion works through the combined action of dextromethorphan (NMDA receptor antagonism and sigma-1 receptor agonism, contributing glutamatergic antidepressant effects) and bupropion, which both contributes independent antidepressant activity and inhibits the CYP2D6 enzyme, increasing and prolonging dextromethorphan exposure so that its central effects are sustained at lower doses. See Pharmacology for full detail.

The safety and efficacy of Elmood in children and adolescents have not been established, and it is not approved for use in patients under 18 years of age. As with other antidepressants, Elmood carries a boxed warning for increased risk of suicidal thinking and behavior in children, adolescents, and young adults; it should never be used in pediatric patients outside of this approved population without explicit medical direction.