Moclobemide


Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A drug primarily used to treat depression and social anxiety. It is not approved for use in the United States, but is approved in other Western countries such as Canada, the United Kingdom and Australia. It is produced by affiliates of the Hoffmann–La Roche pharmaceutical company. Initially, Aurorix was also marketed by Roche in South Africa, but was withdrawn after its patent rights expired and Cipla Medpro's Depnil and Pharma Dynamic's Clorix became available at half the cost.
No significant rise in blood pressure occurs when moclobemide is combined with amines such as tyramine-containing foods or pressor amine drugs, unlike with the older irreversible and non-selective monoamine oxidase inhibitors, which cause a severe rise in blood pressure with such combination. Due to the lack of anticholinergic, cardiovascular, cognitive and psychomotor impairments moclobemide is advantageous in the elderly as well as those with cardiovascular disease.
Moclobemide was first introduced for medical use in 1989.

Medical uses

Psychiatric disorders

Reversible selective MAOIs such as moclobemide are underprescribed due to the misconception that the side effect profiles are analogous to that of the irreversible and non-selective MAOIs. MAOIs such as moclobemide are reported to have a relatively fast onset of action compared to other antidepressant drug classes, and have good long-term tolerability in terms of side effects.
Tolerance does not seem to occur; research has found that moclobemide retains its beneficial therapeutic properties in depression for at least a year.
  • Unipolar depression – Moclobemide has demonstrated effectiveness and efficacy in the treatment and management of major depressive disorder, with both endogenous and non-endogenous depression responding; in addition moclobemide has a fast onset of action compared to other antidepressants and is significantly more tolerable than the tricyclic antidepressants. Due to a good safety profile and low incidence of side effects moclobemide is likely to have a high level of acceptability by individuals suffering from depression. Higher doses may be more effective in severe depression, while patients treated with a lower dose tend to respond less well than those treated with tricyclic antidepressants.
  • Dysthymia – moclobemide has been found to be effective in the treatment and management of this depressive disorder.
  • Social phobia – Moclobemide has been found to be effective for the treatment of social anxiety disorder in both short and long-term placebo controlled clinical trials. Moclobemide is effective but not as effective as the irreversible MAOIs in the treatment of social phobia. Maximal benefits can take 8–12 weeks to manifest. There is a high risk of treatment failure if there is co-morbid alcohol use disorder, however. The Australian Medicines Handbook lists social phobia as an accepted but not a licensed indication. The use of moclobemide in the treatment of social anxiety disorder has given mixed results with a tendency of response at higher doses compared with placebo.
  • Smoking cessation – Moclobemide has been tested in heavy dependent smokers against placebo based on the theory that tobacco smoking could be a form of self-medicating of major depression, and moclobemide could therefore help increase abstinence rates due to moclobemide mimicking the MAO-A inhibiting effects of tobacco smoke. A 2023 Cochrane review found only one 1995 trial studying the effects of moclobemide on smoking cessation, it was administered for 3 months and then stopped; at 6 months follow-up it was found those who had taken moclobemide for 3 months had a much higher successful quit rate than those in the placebo group. However, at 12-month follow-up the difference between the placebo group and the moclobemide group was no longer significant.
  • Panic disorder – moclobemide is useful in the treatment and management of panic disorder. Panic disorder is mentioned as an accepted but unlicensed indication in the Australian Medicines Handbook.
  • ADHD – Two small studies assessing the benefit of moclobemide in people with attention deficit disorder found that moclobemide produced favourable results.
  • Fibromyalgia – moclobemide has been found to improve pain and functioning in this group of people.
Similar to other MAOIs, reversible MAOIs such as moclobemide may also be effective in a range of other psychiatric disorders. Menopausal flushing may also respond to moclobemide.
In efficacy studies for the treatment of major depressive disorder, moclobemide has been found to be significantly more effective than placebo, as effective as the tricyclic antidepressants and selective serotonin reuptake inhibitors, and somewhat less effective than the older, irreversible MAOIs phenelzine and tranylcypromine. In terms of tolerability, however, moclobemide was found to be comparable to the SSRIs and better tolerated than the TCAs and older MAOIs. There is some evidence that moclobemide on its own or in combination with other antidepressants such as SSRIs is also effective for treatment resistant depression and that the combination can be administered without the development of serotonin syndrome; however, further research is needed before such a combination can be recommended. Follow-up studies show that ongoing use of antidepressants leads to continuing improvement in depression over time; and also have demonstrated that moclobemide retains its therapeutic efficacy as an antidepressant for at least a year. This long-term efficacy is equivalent to that seen with other antidepressant classes.
People on irreversible MAOIs have to discontinue these antidepressants two weeks before general anesthesia, however, the use of moclobemide, due to its reversible nature, would allow such patients to possibly continue antidepressant therapy.
A dexamethasone suppression test and plasma and urine methoxyhydroxyphenylglycol test can be used to estimate who is likely to respond to moclobemide antidepressant therapy.

Combination with psychedelics

Moclobemide has been used as a component of "pharmahuasca", in which the serotonergic psychedelic dimethyltryptamine is combined with a synthetically produced or pharmaceutical monoamine oxidase inhibitor rather than with naturally sourced harmala alkaloids. This inhibits the metabolism of DMT and allows it to become orally active and to have a much longer duration than it would otherwise.

Special populations

Pregnancy and lactation

The doses of moclobemide in breast milk are very low and therefore it has been concluded that moclobemide is unlikely to have any adverse effect on a suckling baby.

Children

Use in children is not recommended as there is insufficient data to assess safety and efficacy in these patients.

Elderly

Reversible MAOIs such as moclobemide may have advantages in the treatment of depression associated with Alzheimer's disease due to its effect on noradrenaline. Cognitive impairments have been found to improve in people with dementia when depression is treated with moclobemide. Due to its superior safety profile, moclobemide has been recommended as a first line agent for the treatment of depression in the elderly. Due to the side effect profile of moclobemide, it may be a better option for this sub group of people than other antidepressants. Research has found evidence that moclobemide may be able to counter anti-cholinergic induced cognitive impairments thus making moclobemide a good choice in the depression in the elderly and those with dementia.

Contraindications

Avoid use in:
and caution is recommended in:
The incidence of adverse events is not correlated with age; however, adverse events occur more often in females than in males. Moclobemide is regarded as a generally safe antidepressant and due to its favorable side effect profile, it can be considered a first-line therapeutic antidepressant. The rate of incidence of side effects of moclobemide is low, with insomnia, headache and dizziness being the most commonly reported side effects in the initial stages of therapy with moclobemide. Moclobemide, even at high doses of 600 mg, does not impair the ability to drive a motor vehicle. The tolerability of moclobemide is similar in women and men and it is also well tolerated in the elderly. Moclobemide has been found to be superior to tricyclic and irreversible MAOI antidepressants in terms of side effects, as it does not cause anticholinergic, sedative or cardiovascular adverse effects.
Unlike the irreversible MAOIs there is no evidence of liver toxicity with moclobemide. Moclobemide has a similar efficacy profile compared to other antidepressants while being superior to the classic MAOIs and the tricyclics in terms of tolerance and safety profile. Moclobemide has little effect on psychomotor functions. Other side effects include nausea, insomnia, tremor and lightheadedness; orthostatic hypotension is uncommon even among the elderly. Behavioural toxicity or other impairments relating to everyday living does not occur with moclobemide, except that in doses of 400 mg or higher peripheral reaction time may be impaired. Peripheral oedema has been associated with moclobemide.
Some of the side effects are transient and disappear within 2 weeks of treatment. Serious fatigue, headache, restlessness, nervousness and sleep disturbances have been described as side effects from moclobemide therapy. A paradoxical worsening of depression has been reported in some individuals in several studies, and reports of suicide or suicidal ideation have been reported as a rare adverse effect of moclobemide. Overall, antidepressants decrease the risk of suicide. Moclobemide is believed to have only small proconvulsant effects; however, rarely seizures may occur. Hypertension has been reported to occur very rarely with moclobemide therapy.
Moclobemide is relatively well tolerated. The following are the potential adverse effects and their respective incidences:
;Common adverse effects
  • Nausea
  • Dry mouth
  • Constipation
  • Diarrhea
  • Insomnia
  • Dizziness
  • Anxiety
  • Restlessness
;Uncommon/Rare adverse effects
  • Difficulties falling asleep
  • Nightmares and vivid dreams
  • Hallucinations
  • Memory disturbances
  • Confusion
  • Disorientation
  • Delusions
  • Increased depression
  • Excitation/irritability
  • Hypomania
  • Mania
  • Aggressive behaviour
  • Apathy
  • Tension
  • Suicidal ideation
  • Suicidal behaviour
  • Migraine
  • Extrapyramidal effects
  • Tinnitus
  • Paraesthesia
  • Dysarthria
  • Heartburn
  • Gastritis
  • Tympany
  • Indigestion
  • Hypertension
  • Bradycardia
  • Extrasystoles
  • Angina/chest pain
  • Phlebetic symptoms
  • Flushing
  • Exanthema/rash
  • Allergic skin reaction
  • Itching
  • Gingivitis
  • Stomatitis
  • Dry skin
  • Conjunctivitis
  • Pruritus
  • Urticaria
  • Disturbances of micturition
  • Metrorrhagia
  • Prolonged menstruation
  • General malaise
  • Skeletal/muscular pain
  • Altered taste sensations
  • Hot flushes/cold sensation
  • Photopsia
  • Dyspnoea
  • Visual disturbances
  • Increased hepatic enzymes without associated clinical sequelae.