Usage
- Reboxetine is prescribed for the treatment of major depressive disorder (MDD), also known as major depression. It is effective in both the acute treatment of depressive episodes and maintaining clinical improvement to prevent relapse in patients who have responded initially.
- Pharmacological Classification: Reboxetine is a selective norepinephrine reuptake inhibitor (SNRI).
- Mechanism of Action: Reboxetine works primarily by inhibiting the reuptake of norepinephrine (noradrenaline) at the presynaptic nerve terminals, which leads to increased levels of norepinephrine in the synaptic cleft, thereby enhancing noradrenergic neurotransmission in the brain. This increase in norepinephrine activity is thought to be the primary mechanism responsible for its antidepressant effects. It may also increase dopamine in the prefrontal cortex due to inhibition of norepinephrine reuptake pumps which inactivate dopamine in that region.
Alternate Names
- Reboxetine mesilate (mesylate) is the salt form used in the medication.
- Brand Names: Edronax®
How It Works
- Pharmacodynamics: Reboxetine’s primary effect is to enhance noradrenergic neurotransmission. This can lead to improved mood, increased energy levels, and better concentration in individuals with depression.
- Pharmacokinetics:
- Absorption: Reboxetine is well-absorbed after oral administration, with an absolute bioavailability of at least 60%. Peak plasma levels are reached approximately 2 hours after dosing. Food does not significantly affect absorption.
- Distribution: Reboxetine distributes widely throughout the body, with high plasma protein binding (97% in young adults, 92% in elderly). It has a volume of distribution similar to total body water.
- Metabolism: Primarily metabolized in the liver via CYP3A4.
- Elimination: Elimination half-life is around 13 hours, allowing for twice-daily dosing. Excreted primarily in the urine as metabolites.
- Mode of Action: Reboxetine binds selectively to the norepinephrine transporter, blocking the reuptake of norepinephrine from the synaptic cleft. This results in increased extracellular concentrations of norepinephrine, enhancing its effects on postsynaptic receptors. Reboxetine does not significantly bind to other receptors or transporters, such as serotonin, dopamine, histamine, muscarinic cholinergic, or alpha-adrenergic receptors. It does not inhibit monoamine oxidase (MAO) enzymes. Elimination is predominantly renal, with around 55% excreted in the urine as unchanged drug in those with renal insufficiency.
Dosage
Standard Dosage
Adults:
- Initial: 4 mg twice daily (8 mg/day) orally.
- Maintenance: After 3-4 weeks, the dose can be increased to 10 mg/day (maximum 12 mg/day) based on individual response and tolerability.
Children:
- Reboxetine is not recommended for use in children and adolescents under 18 years of age due to lack of safety and efficacy data.
Special Cases:
- Elderly Patients: Initial: 2 mg twice daily (4 mg/day) orally. May increase to 6 mg/day after 3 weeks based on response and tolerability. Elderly patients are more sensitive to the effects of reboxetine and may require lower doses. Close monitoring is recommended.
- Patients with Renal Impairment: Initial: 2 mg twice daily. The dose may be increased based on individual response and tolerability.
- Patients with Hepatic Dysfunction: Initial: 2 mg twice daily. The dose may be increased based on individual response and tolerability. Close monitoring for adverse effects is recommended.
- Patients with Comorbid Conditions: Caution is advised in patients with seizure disorders, bipolar disorder, suicidal ideation, cardiovascular disease (including hypertension, recent MI, unstable heart disease, and heart failure), hyperthyroidism, urinary retention, prostatic hypertrophy, narrow-angle glaucoma, and conditions predisposing to hypotension. Dose adjustments and close monitoring may be necessary.
Clinical Use Cases
Reboxetine is not indicated for the following clinical scenarios:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations (e.g., status epilepticus, cardiac arrest)
Dosage Adjustments
- Dose adjustments should be based on individual patient response and tolerability. Close monitoring is recommended, particularly in patients with renal or hepatic impairment, elderly patients, and those with comorbid medical conditions.
Side Effects
Common Side Effects:
- Insomnia, sweating, constipation, dry mouth, dizziness, nausea, headache, tachycardia, increased blood pressure, urinary retention, blurred vision (accommodation disorder), decreased appetite, vertigo.
Rare but Serious Side Effects:
- Suicidal thoughts and behavior, worsening of depression, mania/hypomania, seizures, orthostatic hypotension, serotonin syndrome (with concomitant serotonergic agents), severe allergic reactions, withdrawal syndrome upon abrupt discontinuation.
Long-Term Effects:
- The long-term effects of reboxetine are not fully understood. Potential long-term side effects may include sexual dysfunction, weight gain, and sleep disturbances.
Adverse Drug Reactions (ADR):
- Clinically significant ADRs include suicidal thoughts/behavior, mania/hypomania, serotonin syndrome, seizures, and severe allergic reactions.
Contraindications
- Hypersensitivity to reboxetine.
- Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 2 weeks of stopping MAOIs.
- Patients with narrow-angle glaucoma (relative contraindication due to weak mydriatic effect).
- Seizure disorders (relative contraindication; caution and close monitoring required).
- Pregnancy and lactation (relative contraindication; potential risks to fetus/infant should be weighed against potential benefits to mother).
Drug Interactions
- MAOIs: Concomitant use contraindicated due to risk of serotonin syndrome.
- CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin, fluvoxamine): May increase reboxetine plasma levels; dose adjustments may be needed.
- CYP3A4 Inducers (e.g., phenobarbital, carbamazepine, phenytoin, rifampicin): May decrease reboxetine serum levels; dose adjustments may be needed.
- Serotonergic Drugs (e.g., SSRIs, tricyclic antidepressants): Concomitant use should be avoided where possible due to increased risk of serotonin syndrome.
- Antihypertensive Agents: May exacerbate orthostatic hypotension.
- Ergot Derivatives: May increase blood pressure.
- Potassium-Depleting Diuretics: May cause hypokalemia.
- Alcohol: Though reboxetine does not seem to potentiate the effects of alcohol on cognitive function in healthy volunteers, it is generally advisable to avoid alcohol during treatment with antidepressants.
Pregnancy and Breastfeeding
- Reboxetine’s Pregnancy Safety Category is not clearly established. Limited data suggest a potential risk to the fetus.
- Reboxetine’s excretion into breast milk is unknown. It is generally recommended to avoid its use during breastfeeding due to potential risk to the infant.
- Alternative safer options should be considered during pregnancy and lactation.
Drug Profile Summary
- Mechanism of Action: Selective norepinephrine reuptake inhibitor.
- Side Effects: Insomnia, sweating, constipation, dry mouth, dizziness, nausea, headache, sexual dysfunction, weight changes. Serious but rare: Suicidal thoughts, mania/hypomania, seizures, serotonin syndrome.
- Contraindications: Hypersensitivity, concurrent MAOI use, narrow-angle glaucoma, seizure disorders.
- Drug Interactions: MAOIs, CYP3A4 inhibitors/inducers, serotonergic drugs, antihypertensives.
- Pregnancy & Breastfeeding: Not recommended due to potential risks.
- Dosage: Adults: 4 mg BID initially, may increase to 10 mg/day. Elderly: 2 mg BID initially, may increase to 6 mg/day. Renal/hepatic impairment: Start 2 mg BID.
- Monitoring Parameters: Monitor for mood changes, suicidal ideation, blood pressure, heart rate, and adverse effects. Liver function tests and renal function tests may be considered, particularly in patients with pre-existing hepatic or renal impairment.
Popular Combinations
While reboxetine is often used as monotherapy, it can be combined with other medications for enhanced effects in some instances. For example, it may be used in conjunction with mood stabilizers in patients with treatment-resistant depression or bipolar disorder. Combining reboxetine with other antidepressants, especially SSRIs, has shown some promise in improving treatment response in cases where individual antidepressants are insufficient. However, combining with serotonergic drugs should generally be avoided due to an increased risk of serotonin syndrome, and close monitoring is needed when concomitant use is unavoidable.
Precautions
- General Precautions: Assess for history of allergies, metabolic disorders, cardiovascular, renal and hepatic dysfunction prior to starting treatment. Monitor blood pressure and heart rate, especially during initial dose titration. Monitor for suicidal ideation. Avoid abrupt discontinuation to minimize withdrawal symptoms. Electrolyte levels should be monitored, especially potassium levels in patients taking concomitant potassium-depleting diuretics.
- Specific Populations:
- Pregnant Women: Use only if potential benefit outweighs the risk to the fetus.
- Breastfeeding Mothers: Avoid use.
- Children & Elderly: Not recommended for children. Elderly patients require lower doses and close monitoring.
- Lifestyle Considerations: Advise patients to avoid alcohol. Smoking may affect reboxetine metabolism. Caution patients about potential for dizziness and advise against driving or operating machinery until effects are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Reboxetine?
A: Adults: Initial dose is 4 mg twice daily, which can be increased to 10 mg/day after 3-4 weeks if needed. Maximum dose is 12 mg/day. Elderly: Initial dose is 2 mg twice daily, which can be increased to 6 mg/day. Patients with renal or hepatic impairment: Start with 2 mg twice daily. Children: Not recommended.
Q2: How long does it take for Reboxetine to work?
A: The onset of clinical effect is typically seen after 2-4 weeks of treatment. It may take several weeks to achieve the full therapeutic benefit.
Q3: What are the most common side effects of Reboxetine?
A: Common side effects include insomnia, sweating, constipation, dry mouth, dizziness, nausea, urinary difficulties, blurred vision, and decreased appetite.
Q4: Is Reboxetine safe to use during pregnancy or breastfeeding?
A: Reboxetine is generally not recommended for use during pregnancy or breastfeeding due to potential risks to the fetus or infant. Consult a specialist for guidance.
Q5: Can Reboxetine be taken with other antidepressants?
A: Combining Reboxetine with other antidepressants, particularly serotonergic agents, should be done with extreme caution and close monitoring due to the risk of serotonin syndrome.
Q6: What should I do if I miss a dose of Reboxetine?
A: If you miss a dose, take it as soon as you remember. If it’s almost time for your next dose, skip the missed dose and take your next dose at the regular time. Do not double the dose.
Q7: Does Reboxetine interact with any other medications?
A: Yes, Reboxetine can interact with several medications, including MAOIs, CYP3A4 inhibitors/inducers, certain antihypertensives, and ergot derivatives. It is essential to inform your doctor about all other medications you are taking.
Q8: Can Reboxetine cause withdrawal symptoms if stopped suddenly?
A: Yes, abrupt discontinuation of Reboxetine can lead to withdrawal symptoms, such as dizziness, nausea, headache, anxiety, and irritability. It is important to taper the dose gradually under medical supervision.
Q9: Can Reboxetine be used to treat anxiety disorders?
A: While Reboxetine is primarily indicated for depression, some studies suggest it may be beneficial in treating certain anxiety disorders, particularly those co-occurring with depression. However, it is not a first-line treatment for anxiety disorders.
