Moclobemide

Usage

• Moclobemide is prescribed for the treatment of major depressive episodes and social anxiety disorder (social phobia).
• Pharmacological Classification: Moclobemide is a reversible inhibitor of monoamine oxidase A (RIMA), a type of antidepressant.
• Mechanism of Action: Moclobemide reversibly inhibits the enzyme monoamine oxidase A (MAO-A), which is responsible for breaking down neurotransmitters like serotonin, norepinephrine, and dopamine in the brain. This inhibition leads to increased levels of these neurotransmitters, which are believed to play a crucial role in mood regulation. Moclobemide’s selectivity for MAO-A and the reversibility of its inhibition minimizes the risk of the “cheese effect” (hypertensive crisis) often associated with older, irreversible MAO inhibitors.

Alternate Names

• No commonly used alternate names for the generic drug itself.
• Brand Names: Aurorix, Manerix.

How It Works

• Pharmacodynamics: Moclobemide primarily exerts its antidepressant effect by increasing the synaptic concentrations of serotonin, norepinephrine, and dopamine. It achieves this by reversibly inhibiting MAO-A, preventing the breakdown of these neurotransmitters. This leads to enhanced neurotransmission and improved mood.

• Pharmacokinetics:

  • Absorption: Moclobemide is well-absorbed after oral administration. Its bioavailability increases during the first week of treatment. Food may enhance its absorption.
  • Metabolism: Moclobemide undergoes extensive hepatic metabolism primarily via CYP2C19, producing several metabolites, most of which are inactive.
  • Elimination: Primarily renal excretion. A small amount is excreted in breast milk.

• Mode of Action: Moclobemide binds reversibly to MAO-A. This is in contrast to the older, irreversible MAO inhibitors, which permanently bind to the enzyme. This reversible binding reduces the risk of tyramine-induced hypertensive crisis.

• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Moclobemide’s primary mechanism is reversible MAO-A inhibition, leading to increased serotonin, norepinephrine, and dopamine levels in the synaptic cleft.

• Elimination Pathways: Primarily renal excretion of metabolites. Some hepatic metabolism occurs via CYP2C19.

Dosage

Standard Dosage

Adults:

• Depression: Initial dose: 300 mg/day, given in two divided doses after meals. The dose can be gradually increased up to a maximum of 600 mg/day, based on the patient’s response, after the first week of treatment.
• Social Anxiety Disorder: Initial dose: 300 mg/day. Increase to 600 mg/day, given in two divided doses, after 3 days.
• Note: The dose should not be increased during the first week of treatment due to increasing bioavailability during this period.

Children:

• Not recommended for use in children due to lack of clinical data.

Special Cases:

• Elderly Patients: No dose adjustment is generally necessary.
• Patients with Renal Impairment: No dose adjustment is usually needed. However, exercise caution due to limited multiple-dose studies in this population.
• Patients with Hepatic Dysfunction: Reduce the daily dose to half or one-third for severe hepatic impairment.
• Patients with Comorbid Conditions: Caution is advised in patients with bipolar disorder, schizophrenia, suicidal tendencies, thyrotoxicosis, or pheochromocytoma.

Clinical Use Cases

• Moclobemide’s clinical use is specifically focused on the treatment of major depressive episodes and social anxiety disorder. It’s not typically used in settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations.

Dosage Adjustments

• Dose adjustments should be made based on individual patient response and tolerability.
• Consider renal and hepatic function and potential drug interactions.
• Monitor for clinical worsening, suicidal thoughts, and unusual changes in behavior, especially during early treatment and after dose changes.

Side Effects

Common Side Effects

• Nausea, vomiting, dry mouth, constipation, dizziness, insomnia, nervousness, headache, changes in appetite, tingling or numbness in the hands or feet, low blood pressure.

Rare but Serious Side Effects

• Serotonin syndrome (confusion, fever, convulsions, ataxia, hyperreflexia, myoclonus, diarrhea), mania or hypomania, suicidal ideation, seizures, irregular heartbeat, vision changes, confusion, delusions, severe fatigue, loss of consciousness, hallucinations, memory disturbances, disorientation, increased depression.

Long-Term Effects

• While information on specific long-term side effects is limited, it’s important to monitor patients for potential adverse events during prolonged use.

Adverse Drug Reactions (ADR)

• Serotonin syndrome, manic switch, suicidal ideation, seizures, severe allergic reactions.

Contraindications

• Hypersensitivity to moclobemide.
• Acute confusional states.
• Phaeochromocytoma.
• Concomitant use with selegiline, linezolid, triptans, pethidine, tramadol, bupropion, dextromethorphan, and other serotonergic antidepressants (including tricyclics and SSRIs).

Drug Interactions

• CYP450 Interactions: Moclobemide is primarily metabolized by CYP2C19 and inhibits this enzyme. It can affect the metabolism of drugs that are substrates of CYP2C19.
• Clinically Significant Drug Interactions:
  • Selegiline, linezolid, triptans, pethidine, tramadol, bupropion, dextromethorphan: Contraindicated due to risk of serotonin syndrome or hypertensive crisis.
  • Cimetidine: Can increase moclobemide plasma levels; dose reduction may be necessary.
  • Other serotonergic drugs (e.g., SSRIs, SNRIs, tricyclic antidepressants): Increased risk of serotonin syndrome.
  • Opioids: Increased risk of serotonin syndrome; dose adjustment may be necessary.
  • Tyramine-containing foods: While the “cheese effect” is less pronounced with moclobemide than older MAOIs, caution is advised, especially with high tyramine intake.
  • Alcohol: No clinically significant interaction noted, but caution is advisable.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Safety in human pregnancy has not been established. Use only if the potential benefits outweigh the risks.
• Breastfeeding: Small amounts of moclobemide are excreted in breast milk. Not recommended during breastfeeding unless the benefits clearly outweigh the risks.

Drug Profile Summary

• Mechanism of Action: Reversible inhibition of MAO-A.
• Side Effects: Nausea, vomiting, dry mouth, insomnia, dizziness, serotonin syndrome (rare).
• Contraindications: Hypersensitivity, concomitant use with certain drugs (e.g., selegiline, SSRIs).
• Drug Interactions: Cimetidine, other serotonergic drugs, opioids.
• Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
• Dosage: 300-600mg/day (adults), divided doses. Adjust for hepatic impairment.
• Monitoring Parameters: Monitor for mood changes, suicidal ideation, signs of serotonin syndrome, blood pressure.

Popular Combinations

• No established “popular combinations” exist. Moclobemide is typically used as monotherapy. Combining it with other serotonergic antidepressants or MAOIs is contraindicated.

Precautions

• General Precautions: Screen for allergies, drug interactions, and contraindications before initiating treatment.
• Specific Populations: As described in the “Dosage” section.
• Lifestyle Considerations: Caution patients about potential interactions with tyramine-containing foods, alcohol, and other medications.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Moclobemide?

A: Initial dose is 300 mg/day, divided into two doses, taken after meals. This can be titrated up to 600 mg/day, if necessary, after the first week. Dosage should be adjusted for hepatic impairment. It is not recommended for children.

Q2: What are the common side effects of Moclobemide?

A: Common side effects include nausea, vomiting, dry mouth, constipation, dizziness, insomnia, nervousness, headache, and changes in appetite.

Q3: How does Moclobemide compare to other antidepressants like SSRIs?

A: Moclobemide is an RIMA, while SSRIs inhibit serotonin reuptake. Moclobemide is associated with a lower risk of sexual dysfunction compared to SSRIs.

Q4: What are the serious side effects to watch out for?

A: Serotonin syndrome, mania/hypomania, suicidal thoughts, seizures, irregular heartbeat, and severe allergic reactions.

Q5: Can Moclobemide be used during pregnancy or breastfeeding?

A: Its safety during pregnancy and breastfeeding hasn’t been fully established. Use only if the potential benefits outweigh the potential risks to the fetus or infant.

Q6: How long does it take for Moclobemide to start working?

A: It may take 1-3 weeks or even up to 4-6 weeks to see a significant improvement in depressive symptoms.

Q7: What should I do if I miss a dose?

A: Take the missed dose as soon as you remember. If it’s almost time for your next dose, skip the missed dose and take the next dose as scheduled. Do not double up on doses.

Q8: Does Moclobemide interact with any foods?

A: While less pronounced than older MAOIs, Moclobemide can interact with tyramine-rich foods. Caution patients about limiting intake of aged cheese, cured meats, fermented products, etc.

Q9: Can Moclobemide be used to treat other conditions besides depression and social anxiety?

A: While sometimes explored in research for other uses, it’s not currently clinically indicated for other conditions. Its primary clinical use is restricted to major depression and social anxiety disorder.

Q10: Should Moclobemide be discontinued abruptly?

A: No, it is generally recommended to taper the dose gradually when discontinuing Moclobemide to reduce the risk of withdrawal symptoms. Consult with a physician for guidance on tapering.