Elmood

Approved Indications:

• Major Depressive Disorder (MDD): Treatment of major depressive episodes in adults.
• Treatment-Resistant Depression: Used as an adjunct or alternative in patients not responding adequately to conventional antidepressants.
• Off-label / Emerging Uses:
• Management of depressive symptoms in bipolar disorder (with caution).
• Investigational use in certain neuropsychiatric conditions such as pseudobulbar affect.
• Cough suppression is not an approved indication for this combination despite dextromethorphan's antitussive properties, as formulation and dosing differ.

Adults:

• Initial dose: Typically 45 mg dextromethorphan hydrobromide / 105 mg bupropion hydrochloride administered orally twice daily.
• Dose adjustments: May increase after 3 days based on tolerability and clinical response.
• Maximum recommended dose: 45 mg/105 mg twice daily.
• Duration: Continued as clinically indicated; evaluate efficacy after 6–8 weeks.

Pediatrics:

• Safety and efficacy not established in patients under 18 years; use not recommended.

Elderly:

• No specific dose adjustment generally required; monitor for increased sensitivity to side effects.

Renal/Hepatic Impairment:

• Moderate to severe hepatic impairment: Use with caution; bupropion metabolism affected, risk of accumulation.
• Renal impairment: No dosage adjustment generally required, but monitor clinical response.

Administration:

• Oral administration with or without food.
• Take at consistent times each day to maintain steady drug levels.
• Avoid abrupt discontinuation; taper if stopping.

This combination leverages two pharmacologic actions. Dextromethorphan is a low-affinity, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 receptor agonist, and serotonin-norepinephrine reuptake inhibitor (SNRI) at higher concentrations, which contributes to modulation of glutamatergic neurotransmission implicated in depression. Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI) that increases synaptic concentrations of norepinephrine and dopamine, enhancing mood and cognitive function. Additionally, bupropion inhibits the CYP2D6 enzyme, increasing dextromethorphan plasma levels, potentiating its effects. Together, they produce synergistic antidepressant effects through modulation of multiple neurotransmitter systems.

• Absorption: Both components are well absorbed orally; peak plasma concentrations occur within 3–4 hours.
• Distribution: Widely distributed; bupropion is highly protein bound (~84%).
• Metabolism: Bupropion extensively metabolized by CYP2B6 into active metabolites; inhibits CYP2D6, slowing dextromethorphan metabolism.
• Half-life: Bupropion ~21 hours; dextromethorphan ~3–4 hours but prolonged due to CYP2D6 inhibition.
• Elimination: Primarily renal excretion of metabolites.

• Pregnancy: Category C. Animal studies show adverse effects; no adequate human studies. Use only if benefits justify risks.
• Lactation: Both drugs excreted in breast milk in low amounts; caution advised. Monitor infant for adverse effects.

• Primary Class: Antidepressant combination.
• Subclass: NMDA receptor modulator (dextromethorphan) + norepinephrine-dopamine reuptake inhibitor (bupropion).

• Known hypersensitivity to dextromethorphan, bupropion, or excipients.
• Seizure disorders or history of seizures.
• Current or prior diagnosis of bulimia or anorexia nervosa.
• Use of monoamine oxidase inhibitors (MAOIs) within 14 days.
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.
• Concurrent use of other bupropion-containing products.

• Increased risk of seizures, especially at higher doses or in predisposed individuals.
• Risk of serotonin syndrome when combined with serotonergic agents.
• Monitor for worsening depression, suicidal ideation, especially in younger adults.
• Caution in patients with hypertension or cardiovascular disease.
• Avoid abrupt discontinuation to prevent withdrawal symptoms.
• Potential for increased blood pressure and tachycardia; monitor vital signs.
• CYP2D6 poor metabolizers may experience increased dextromethorphan effects and side effects.

Common:

• Insomnia
• Dry mouth
• Dizziness
• Headache
• Anxiety or agitation
• Nausea

Serious/Rare:

• Seizures
• Hypertension
• Serotonin syndrome
• Allergic reactions (rash, angioedema)
• Suicidal thoughts or behavior

• CYP2D6 substrates: Increased plasma concentrations due to CYP2D6 inhibition by bupropion.
• MAOIs: Risk of hypertensive crisis and serotonin syndrome; contraindicated.
• Other serotonergic drugs: Increased risk of serotonin syndrome.
• Drugs lowering seizure threshold: Increased seizure risk (e.g., antipsychotics, tramadol).
• Alcohol: May increase neuropsychiatric adverse effects; avoid.
• CNS depressants: Additive sedation or CNS effects.

• FDA approval emphasizes use in adults with major depressive disorder, especially treatment-resistant cases.
• Updated warnings on seizure risk and serotonin syndrome.
• Recommendations for careful dose titration and monitoring in clinical guidelines.
• Ongoing studies evaluating broader neuropsychiatric indications.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Store out of reach of children.
• Do not freeze.