Moclobemide (Manerix)

Moclobemide is an antidepressant that works differently from SSRIs, SNRIs and tricyclic antidepressants. Instead of blocking a neurotransmitter transporter, moclobemide temporarily and reversibly inhibits an enzyme called:

Monoamine Oxidase-A — MAO-A

MAO-A normally helps break down several neurotransmitters, particularly:

Serotonin

Norepinephrine

and:

Dopamine

By inhibiting MAO-A, moclobemide slows the breakdown of these neurotransmitters and increases their availability for signaling.

A simplified mechanism is:

1. Moclobemide
2. Reversibly inhibits MAO-A
3. Breakdown of serotonin + norepinephrine + dopamine decreases
4. More monoamine neurotransmitters remain available
5. Neurotransmitter receptors and neural networks adapt
6. Depressive symptoms may improve

The current Canadian product monograph describes moclobemide as a short-acting reversible inhibitor of MAO-A. At a 300 mg dose, MAO-A inhibition is estimated at approximately 80%, compared with about 20–30% inhibition of MAO-B, and the MAO-A inhibition is reversible and generally lasts no more than about 24 hours.

What You Need to Know About Moclobemide

Moclobemide is an unusual antidepressant because it belongs to the broader monoamine oxidase inhibitor family but differs substantially from older irreversible MAO inhibitors.

Traditional MAOIs such as phenelzine and tranylcypromine bind more persistently to monoamine oxidase.

Moclobemide instead:

Preferentially inhibits MAO-A

and:

Does so reversibly

This generally gives moclobemide a different:

• Drug-interaction profile
• Food-interaction profile
• Duration of enzyme inhibition
• Tolerability profile However, moclobemide still has important and potentially serious interactions, particularly with serotonergic medications and some sympathomimetic drugs.

Is Moclobemide Available in Canada?

Yes.

Health Canada currently lists generic MOCLOBEMIDE from AA Pharma as marketed in 100 mg, 150 mg and 300 mg tablets. The Manerix 300 mg product is also currently listed as marketed, while the Manerix 150 mg product was moved to dormant status in July 2026.

For patient-facing content, Manerix remains the best-known brand name, although generic moclobemide is widely relevant in Canada.

What Is Moclobemide Used For?

In Canada, moclobemide is indicated for:

Major Depressive Disorder — MDD

in adults.

It is not indicated for patients under 18 years of age because safety and effectiveness have not been established in the pediatric population.

Depression symptoms may include:

• Persistent low mood
• Loss of pleasure or interest
• Low motivation
• Fatigue
• Difficulty concentrating
• Sleep disturbance
• Appetite changes
• Anxiety
• Negative or repetitive thinking
• Difficulty functioning at work or home Moclobemide does not treat depression simply by correcting a single “chemical imbalance.” Its effect is better understood as changing monoamine signaling across multiple brain systems.

How Does Moclobemide Work?

Monoamine oxidase is an enzyme that helps break down neurotransmitters.

Two main forms are:

MAO-A

and:

MAO-B

MAO-A is particularly important for metabolism of:

• Serotonin
• Norepinephrine
• Dopamine Moclobemide preferentially inhibits:

MAO-A

Therefore:

• Serotonin
• Norepinephrine
• Dopamine Normally: MAO-A helps metabolize them

With moclobemide:

1. MAO-A is inhibited
2. Monoamine breakdown decreases
3. Serotonin, norepinephrine and dopamine availability increases

The Canadian monograph identifies reduced deamination of these three neurotransmitters as the likely basis of moclobemide’s antidepressant activity.

Is Moclobemide an MAOI?

Yes, but more specifically it is a:

RIMA — Reversible Inhibitor of Monoamine Oxidase-A

This distinction matters.

Older MAOIs can produce prolonged inhibition of MAO because the enzyme must be regenerated after irreversible inhibition.

Moclobemide binds reversibly.

Therefore:

1. Moclobemide present
2. MAO-A inhibited

but when drug concentrations decline:

MAO-A activity can recover relatively quickly

Its Canadian monograph describes MAO-A inhibition as short-lasting and reversible.

How Is Moclobemide Different from SSRIs?

An SSRI such as:

• Escitalopram
• Sertraline
• Fluoxetine primarily blocks:

SERT — Serotonin Transporter

Therefore:

1. SSRI
2. Serotonin reuptake decreases
3. Serotonin availability increases

Moclobemide works earlier in the metabolic pathway:

1. Moclobemide
2. MAO-A inhibited
3. Serotonin breakdown decreases

• Norepinephrine breakdown decreases
• Dopamine breakdown decreases Therefore, moclobemide has a broader monoamine mechanism than an SSRI.

How Is Moclobemide Different From an SNRI?

SNRIs such as duloxetine or levomilnacipran primarily inhibit:

SERT + NET

Moclobemide does not directly inhibit these transporters.

Instead:

1. Moclobemide
2. MAO-A inhibition
3. Less serotonin + norepinephrine + dopamine metabolism

Thus, both treatments can increase serotonin and norepinephrine signaling, but through completely different mechanisms.

Does Moclobemide Increase Dopamine?

Yes, indirectly.

Moclobemide does not stimulate dopamine receptors or block the dopamine transporter.

Instead:

1. Dopamine
2. Normally metabolized partly by:

MAO-A

1. Moclobemide inhibits MAO-A:
2. Dopamine breakdown decreases
3. Dopamine availability may increase

The magnitude and clinical importance of this effect vary by brain region.

This dopaminergic component may help distinguish moclobemide from strongly serotonin-focused antidepressants.

Does Moclobemide Increase Norepinephrine?

Yes.

Norepinephrine is an important MAO-A substrate.

Therefore:

1. Moclobemide
2. MAO-A inhibition
3. Norepinephrine metabolism decreases
4. Norepinephrine signaling may increase

Norepinephrine contributes to:

• Energy

• Alertness

• Attention

• Motivation

• Stress response This may contribute to antidepressant benefit, but excessive noradrenergic activation can also contribute to:

• Anxiety

• Restlessness

• Insomnia

• Palpitations in susceptible individuals.

Does Moclobemide Increase Serotonin?

Yes.

Serotonin is also metabolized by MAO-A.

Therefore:

1. Moclobemide
2. MAO-A inhibited
3. Serotonin breakdown decreases
4. Serotonin availability increases

This serotonin effect is important therapeutically but also explains why moclobemide has potentially dangerous interactions with other strongly serotonergic medications.

What Are the Common Side Effects of Moclobemide?

Common or recognized side effects include:

• Insomnia or sleep disturbance
• Dizziness
• Nausea
• Headache
• Dry mouth
• Anxiety
• Restlessness or nervousness
• Tremor
• Sleepiness
• Fatigue
• Weakness
• Sweating
• Changes in appetite
• Gastrointestinal discomfort
• Constipation or diarrhea
• Palpitations in some patients
• Changes in blood pressure The current Canadian patient information specifically identifies insomnia, dizziness, nausea and headache as common effects and also lists sleepiness, fatigue, anxiety, weakness, dry mouth, sweating and appetite changes.

Can Moclobemide Cause Insomnia?

Yes.

Because moclobemide can increase:

Norepinephrine

and:

Dopamine

signaling, it can feel activating in some patients.

Possible effects include:

• Difficulty falling asleep
• Restlessness
• Nervousness
• Increased alertness For this reason, timing of the second daily dose may sometimes matter clinically.

Patients should follow the prescribed schedule rather than independently moving doses.

Can Moclobemide Cause Anxiety or Activation?

Yes.

Some patients experience:

• Increased anxiety
• Restlessness
• Agitation
• Irritability
• Tremor
• Insomnia particularly when treatment begins or the dose changes.

These effects may reflect increased:

Noradrenergic and dopaminergic signaling

before the nervous system fully adapts.

Severe or unusual activation should be assessed clinically.

Can Moclobemide Cause Mania or Hypomania?

Potentially.

Like other antidepressants, moclobemide can produce:

• Hypomanic symptoms
• Excitation
• Irritability in susceptible patients. These effects are listed among less-common psychiatric adverse reactions in Canadian product information.

Patients with possible bipolar disorder should therefore be assessed carefully before antidepressant treatment.

Can Moclobemide Cause Serotonin Syndrome?

Yes.

Serotonin syndrome is one of the most important moclobemide safety concerns.

Because moclobemide reduces serotonin breakdown, combining it with medications that substantially increase serotonin can produce excessive serotonergic activity.

Possible symptoms include:

• Agitation
• Confusion
• Sweating
• Fever
• Rapid heart rate
• Tremor
• Muscle twitching
• Hyperreflexia
• Muscle rigidity
• Diarrhea
• Nausea or vomiting The Canadian monograph describes serotonin syndrome as potentially life-threatening and specifically identifies neuromuscular excitation, autonomic stimulation and mental-status changes.

Can Moclobemide Be Taken With an SSRI?

Under the current Canadian product monograph:

No.

Concurrent use with SSRIs is contraindicated.

Examples include:

• Escitalopram
• Citalopram
• Sertraline
• Fluoxetine
• Fluvoxamine
• Paroxetine Combining them can produce excessive serotonin signaling and increase the risk of:

Serotonin syndrome

Can Moclobemide Be Taken With an SNRI?

The Canadian product monograph also contraindicates combination with:

SNRIs

such as:

• Venlafaxine
• Desvenlafaxine
• Duloxetine
• Levomilnacipran because of potentially dangerous monoamine and serotonin accumulation.

Can Moclobemide Be Taken with Bupropion?

Under the current Canadian product monograph:

No.

Concomitant use with:

Bupropion

is listed as contraindicated.

This is particularly relevant because bupropion increases catecholaminergic signaling and is commonly used as an antidepressant.

Can Moclobemide Be Taken with Tramadol?

No.

The current Canadian monograph contraindicates:

Tramadol

with moclobemide.

Tramadol has serotonergic and noradrenergic activity in addition to its opioid effects, creating a risk of serious toxicity when combined with an MAO inhibitor.

Can Moclobemide Be Taken with Meperidine?

No.

Meperidine — pethidine

is contraindicated with moclobemide because severe and potentially fatal reactions have historically occurred when opioid drugs with relevant serotonergic properties are combined with MAO inhibition.

Other opioids should also be evaluated carefully rather than assumed to be safe.

Can Moclobemide Be Taken with Dextromethorphan?

No.

Dextromethorphan is found in many:

Cough and cold medications

and can affect serotonin signaling.

The Canadian product monograph specifically states that moclobemide should not be co-administered with dextromethorphan because severe central nervous system reactions have been reported.

This is an important over-the-counter interaction for patients to know.

Can Moclobemide Be Taken with Triptans?

Not under current Canadian labeling.

Migraine medications such as:

• Sumatriptan
• Rizatriptan
• Other triptans are contraindicated with moclobemide because MAO inhibition can increase exposure to some triptans and potentially increase serotonergic toxicity.

Moclobemide and Stimulants or Decongestants

Moclobemide can interact with:

Sympathomimetic medications including compounds related to:

• Amphetamine
• Ephedrine
• Some decongestants
• Some cold and allergy preparations
• Some weight-loss products The Canadian monograph advises avoiding sympathomimetic amines because moclobemide may potentiate their cardiovascular effects.

This interaction may increase:

• Heart rate
• Blood pressure
• Palpitations
• Headache
• Cardiovascular stress

Can Moclobemide Be Taken with Selegiline?

No.

Selegiline is primarily an:

MAO-B inhibitor

at lower doses.

Combining it with moclobemide can substantially increase overall MAO inhibition and sensitivity to tyramine.

The Canadian product monograph lists:

Moclobemide + selegiline

as contraindicated.

Can Moclobemide Be Taken with Linezolid?

No.

Linezolid

is an antibiotic that also reversibly inhibits monoamine oxidase.

Current Canadian moclobemide labeling contraindicates the combination because the total degree of MAO inhibition could become dangerous.

What About Thioridazine?

The combination is contraindicated.

Moclobemide can inhibit:

CYP2D6

which can reduce thioridazine metabolism.

Higher thioridazine concentrations can increase:

QT prolongation

and potentially serious ventricular arrhythmias.

The Canadian monograph specifically identifies this interaction.

Does Moclobemide Interact with Food?

Yes, but considerably less than traditional irreversible MAO inhibitors.

The main concern is:

Tyramine

Tyramine is found in some:

• Aged cheeses
• Fermented foods
• Yeast extracts
• Aged or cured products Normally MAO helps metabolize tyramine.

With very strong MAO inhibition:

1. Tyramine absorbed
2. Norepinephrine release can increase sharply
3. Blood pressure can rise dramatically

This is the basis of the classic:

“Cheese reaction”

associated with traditional MAO inhibitors.

Does Moclobemide Require a Strict MAOI Diet?

Generally:

No strict tyramine-free diet is required under current Canadian labeling.

Because moclobemide is selective and reversible, its tyramine interaction is substantially less pronounced than that of traditional irreversible MAOIs.

Canadian product information states that special dietary restrictions are not required, but very large amounts of strongly tyramine-rich foods should still be avoided. Examples specifically given are more than approximately 200 g of strong cheese or 70 g of Marmite yeast extract.

This should not be interpreted as a challenge to determine a “safe maximum” amount of tyramine. Individual sensitivity varies.

Why Should Moclobemide Be Taken After Meals?

This is a specific Canadian dosing instruction.

The interaction between tyramine and moclobemide is smaller when moclobemide is taken:

After a meal

rather than shortly before tyramine exposure.

Therefore, Canadian labeling states that moclobemide should:

Always be taken after meals.

This is unusual among antidepressants and is important patient information.

What Are Symptoms of a Tyramine-Related Hypertensive Reaction?

Patients should seek prompt medical attention for sudden symptoms such as:

• Severe throbbing headache, particularly at the back of the head
• Neck stiffness
• Palpitations
• Very rapid or unusually slow heartbeat
• Significant blood-pressure symptoms
• Other sudden unusual cardiovascular symptoms These warning symptoms are specifically highlighted in the Canadian product monograph.

Moclobemide and Alcohol

Excessive alcohol consumption should be avoided.

The Canadian monograph notes that interaction studies were performed only at relatively modest blood-alcohol concentrations and that high levels of alcohol were not adequately studied.

Alcohol may also:

• Worsen depression
• Increase dizziness
• Impair coordination
• Increase sedation
• Complicate medication adherence

Moclobemide and Cimetidine

Cimetidine is an important pharmacokinetic interaction.

The Canadian monograph states that:

Cimetidine approximately doubles moclobemide exposure

and that a:

50% reduction in moclobemide dose may be necessary

when they are used together.

The mechanism is reduced hepatic metabolism of moclobemide.

Moclobemide and Omeprazole

Moclobemide and omeprazole can interact through:

CYP2C19

Moclobemide inhibits CYP2C19 and can increase exposure to drugs metabolized by this enzyme.

Interestingly, omeprazole can also increase moclobemide exposure. In CYP2C19 normal metabolizers, Canadian data describe approximately a two-fold increase in moclobemide AUC with omeprazole and a similar increase in omeprazole exposure caused by moclobemide.

This is an example of a potentially bidirectional drug interaction.

Switching Between Moclobemide and Other Antidepressants

Switching requires particular care because residual antidepressant activity can interact with MAO inhibition.

The Canadian monograph recommends allowing approximately:

4–5 half-lives of the previous serotonergic antidepressant and any active metabolites

before starting moclobemide.

For:

Fluoxetine

at least:

5 weeks

should pass between stopping fluoxetine and starting moclobemide because fluoxetine and norfluoxetine remain in the body for a long time.

Because washout requirements depend on the specific drug, switching should be directed by the prescriber or pharmacist rather than calculated by the patient.

Moclobemide Dosage

The current Canadian recommended starting dose is:

300 mg per day

usually given as:

150 mg twice daily

The dose may be increased gradually according to response and tolerability to:

600 mg per day maximum

usually:

300 mg twice daily

The initial 300 mg/day dose should generally not be increased during the first week, because moclobemide bioavailability increases during repeated dosing and rapid dose escalation does not shorten the delay before antidepressant response.

These are product-label ranges, not individualized prescribing instructions.

How Should Moclobemide Be Taken?

According to the current Canadian monograph:

Take moclobemide after meals

and:

Swallow the tablet whole with water.

The AA Pharma patient information advises that the tablets should not be split, crushed, chewed or dissolved.

Patients should follow the instructions for their exact prescribed product.

How Long Does Moclobemide Take to Work?

Some patients may notice changes within:

Days

but full antidepressant benefit can require:

Several weeks

The Canadian patient information specifically notes that moclobemide may take from a few days to several weeks to become fully effective.

Increasing the dose rapidly does not necessarily make the antidepressant effect appear sooner and may increase side effects.

How Long Does Moclobemide Stay in the Body?

Moclobemide has a relatively short elimination half-life.

After a single therapeutic dose, the Canadian monograph reports an elimination half-life of approximately:

1.5 hours

although the half-life increases somewhat at higher doses because moclobemide shows nonlinear pharmacokinetics.

A short plasma half-life does not mean the medication should be stopped or switched without medical supervision.

Moclobemide and Liver Function

The liver is important for moclobemide clearance.

In patients with severe hepatic impairment, the Canadian monograph recommends reducing the daily dose to approximately:

One-third to one-half of the standard dose.

In patients with cirrhosis, a pharmacokinetic study described approximately:

• 3-fold higher peak concentrations
• A longer half-life
• About 4-fold lower clearance following a single dose.

This makes liver function an important determinant of moclobemide exposure.

Moclobemide and Kidney Function

Renal impairment appears to affect moclobemide less dramatically than liver impairment.

Single-dose data did not show major changes in moclobemide pharmacokinetics in renal impairment, although multiple-dose data are limited.

Canadian labeling therefore states that:

A routine dose adjustment may not be required solely from single-dose renal data

but advises caution because repeated-dose studies in renal dysfunction are limited.

Does Moclobemide Need to Be Tapered?

The current Canadian monograph does not provide a universal stepwise taper schedule.

However, antidepressant treatment should generally not be stopped simply because the person begins to feel better. Canadian patient information specifically advises discussing treatment duration with the physician rather than discontinuing independently.

When discontinuation is planned, the approach should be individualized according to:

• Current dose
• Duration of therapy
• Depression history
• Previous discontinuation symptoms
• Planned replacement medication
• Required antidepressant washout periods This is particularly important with moclobemide because switching to or from serotonergic medications can involve serious interactions.

Moclobemide and Suicide Risk

As with all antidepressant treatment, patients should be monitored for:

• Worsening depression

• New agitation

• Significant behavioural change

• Self-harm thoughts

• Suicidal thoughts particularly:

• Early in treatment

• During dose changes The Canadian monograph recommends careful monitoring for suicidality and behavioural or emotional changes in patients receiving antidepressant medication.

Can Moclobemide Cause Angle-Closure Glaucoma?

Rarely, antidepressant-induced pupil dilation can trigger:

Acute angle-closure glaucoma

in someone with anatomically narrow drainage angles.

Symptoms such as:

• Eye pain
• Sudden visual change
• Eye redness
• Swelling around the eye require urgent medical assessment.

Moclobemide and Pregnancy

The current Canadian monograph states that safety during pregnancy has not been adequately established and moclobemide is generally not recommended during pregnancy unless the expected benefit clearly outweighs the potential risk.

Treatment decisions should consider both:

Medication risk

and:

Risk from untreated depression.

Medication should not be stopped abruptly because pregnancy is discovered without discussing treatment with the prescriber.

Moclobemide and Breastfeeding

Small amounts of moclobemide can pass into breast milk.

Canadian labeling therefore recommends using it during breastfeeding only when the anticipated benefit to the mother outweighs the potential risk to the infant.

Frequently Asked Questions About Moclobemide

Is Moclobemide the Same as Manerix?

Manerix is the best-known brand name for moclobemide.

Health Canada currently lists Manerix 300 mg as marketed; generic moclobemide tablets are also marketed in Canada.

Is Moclobemide an Antidepressant?

Yes.

Moclobemide is approved in Canada for:

Major depressive disorder in adults.

Is Moclobemide an MAOI?

Yes.

More specifically, it is a:

Reversible MAO-A inhibitor — RIMA.

It differs from older irreversible MAOIs because its enzyme inhibition is reversible and shorter acting.

Does Moclobemide Increase Serotonin?

Yes, indirectly.

It inhibits MAO-A, reducing serotonin breakdown.

Does Moclobemide Increase Norepinephrine?

Yes.

Norepinephrine is also metabolized by MAO-A, so moclobemide reduces its degradation.

Does Moclobemide Increase Dopamine?

Yes, indirectly.

MAO-A contributes to dopamine metabolism, so reversible MAO-A inhibition can increase dopamine availability.

Is Moclobemide an SSRI?

No.

Moclobemide inhibits:

MAO-A

rather than:

SERT.

Does Moclobemide Have Fewer Food Restrictions Than Traditional MAOIs?

Yes.

Current Canadian labeling does not require a strict tyramine-free diet, although extremely large amounts of highly tyramine-rich foods should still be avoided and moclobemide should be taken after meals.

Can I Eat Cheese While Taking Moclobemide?

Ordinary dietary quantities are generally not prohibited under Canadian labeling.

However, excessive amounts of strongly aged cheese should be avoided. The product monograph specifically uses more than 200 g of strong cheese as an example of an excessive amount.

Should Moclobemide Be Taken with Food?

It should be taken:

After meals

according to current Canadian product information.

Can Moclobemide Be Taken with Fluoxetine?

No.

The combination is contraindicated.

Furthermore, because fluoxetine has a very long half-life, Canadian labeling requires at least:

5 weeks

between stopping fluoxetine and starting moclobemide.

Can Moclobemide Be Taken with Escitalopram or Sertraline?

Not concurrently under current Canadian labeling.

SSRIs are contraindicated with moclobemide because of serotonin-toxicity risk.

Can Moclobemide Be Taken with Bupropion?

No under the current Canadian product monograph.

The combination is listed as contraindicated.

Can Moclobemide Be Taken with Tramadol?

No.

Tramadol is contraindicated because of the risk of serious monoaminergic and serotonergic toxicity.

Can Moclobemide Be Taken with Cough Medicine?

Some cough medicines contain:

Dextromethorphan

which should not be taken with moclobemide.

Patients should therefore check non-prescription cough and cold medications with a pharmacist.

Does Moclobemide Cause Weight Gain?

Weight gain is not generally among moclobemide’s most characteristic adverse effects.

Appetite can either increase or decrease in some patients.

Long-term weight response varies by patient, depression recovery, diet and other medications.

Does Moclobemide Cause Sexual Side Effects?

Sexual dysfunction can occur with many antidepressants, but it has historically been less prominent with moclobemide than with strongly serotonergic reuptake inhibitors.

That does not mean sexual side effects are impossible.

Individual response remains important.

Does Moclobemide Cause Sleepiness?

It can, although:

Insomnia

is also common.

Some patients find moclobemide activating, while others experience:

• Somnolence
• Fatigue
• Sedation The clinical effect varies.

Which CYP Enzymes Metabolize Moclobemide?

CYP2C19 and CYP2D6 both contribute to metabolic variability.

CYP2C19 appears particularly relevant in pharmacokinetic studies.

Does CYP2C19 Poor Metabolizer Status Require a Lower Moclobemide Dose?

There is no established CPIC or DPWG genotype-based dose recommendation.

Reduced CYP2C19 activity can increase moclobemide exposure, but the available data have not been converted into a validated prescribing algorithm.

Does CYP2D6 Poor Metabolizer Status Require a Dose Adjustment?

No established genotype-based adjustment currently exists.

CYP2D6 contributes to moclobemide metabolism, but it is only one of several pathways.

Can Genetics Predict Whether Moclobemide Will Work?

Not reliably enough for routine individual prescribing.

Potentially relevant genes include:

• MAOA
• CYP2C19
• CYP2D6
• SLC6A4
• SLC6A2
• SLC6A3
• HTR1A
• HTR2A
• HTR2C
• COMT but there is currently no validated multigene or single-gene moclobemide efficacy algorithm recognized by CPIC or DPWG.

References

• [https://health-products.canada.ca/dpd-bdpp/info?code=13256&lang=eng&lang=eng)
• [https://health-products.canada.ca/dpd-bdpp/search-fast-recherche-rapide?lang=eng&no=0122658003&no=0122658003)
• https://pdf.hres.ca/dpd_pm/00071479.PDF
• https://pubmed.ncbi.nlm.nih.gov/7781267/