moclobemide moclobemide moclobemide, sold under the brand names amira, aurorix, clobemix, depnil and manerix among others, is a reversible inhibitor of monoamine oxidase a (rima) 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 uk and australia (tga approved in december 2000). 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 initially, aurorix was also marketed by roche in south africa, but was withdrawn after its patent rights expired and cipla medpro's depnil and pharma dynamic's clorix became available at half the cost. moclobemideclinical datatrade namesamira, aurorix, clobemix, depnil, manerix, othersahfs/drugs.commicromedex detailed consumer informationpregnancycategory au: b3 routes ofadministrationby mouthatc coden06ag02 (who) legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) pharmacokinetic databioavailability55-95% (increases with repeat administration)protein binding50%metabolismliverelimination half-life1-2 hours, 4 hours (elderly)excretionkidney, faecal (<5%)identifiers iupac name 4-chloro-n-(2-morpholin-4-ylethyl)benzamide cas number71320-77-9 ypubchem cid4235iuphar/bps7428drugbankdb01171 ychemspider4087 yuniipj0y7azb63keggd02561 ychebichebi:83531 nchemblchembl86304 ycomptox dashboard (epa)dtxsid9040554 echa infocard100.163.935 chemical and physical dataformulac13h17cln2o2molar mass268.74 g·mol−13d model (jsmol)interactive image smiles clc1ccc(cc1)c(=o)nccn2ccocc2 inchi inchi=1s/c13h17cln2o2/c14-12-3-1-11(2-4-12)13(17)15-5-6-16-7-9-18-10-8-16/h1-4h,5-10h2,(h,15,17) ykey:yhxiswvbgdmdlq-uhfffaoysa-n y ny (what is this?) (verify) 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 (maois), 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. medical uses reversible selective maois such as moclobemide are widely 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 very good safety profile and very low incidence of side effects moclobemide is likely to have a high level of acceptability by individuals suffering from depression. higher doses (>450 mg/day) 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. psychotic depression, unipolar endogenous depression, melancholic depression, retarded depression, agitated depression and neurotic depression all respond to moclobemide, as does atypical depression. unipolar endogenous depression is reported to have the best response to moclobemide therapy. individuals suffering from depression who are given moclobemide are twice as likely to improve on moclobemide than on placebo. a concern of antidepressant adverse effects is sexual dysfunction; however, moclobemide has actually been found to increase libido and also improve impaired erection, ejaculation and orgasm. cardiovascular toxicity is a concern with antidepressants such as tricyclic antidepressants as well as the irreversible maois; when cardiovascular toxicity is a concern, ssris or the reversible maois such as moclobemide are an option as they lack or have a significantly reduced level of cardiovascular toxicity in terms of adverse effect as well as in overdose. the effectiveness of moclobemide in agitated depression is equivalent to that of imipramine and sedative antidepressants such as amitriptyline, mianserin and maprotiline. the therapeutic response in agitated depressive individuals is similar to that seen in non-agitated depression; however, a past history of use of antidepressants reduces the chance of successful therapeutic response. the addition of a benzodiazepine to moclobemide therapy has not been found to be of benefit in this population group. moclobemide causes less side effects than imipramine and it has better tolerability compared to tcas. bipolar depression. while not generally recommended as a monotherapy for bipolar depression (as with all antidepressants) in one clinical trial it appeared (although statistical significance at the p=0.05 was not reached) as though moclobemide was equally effective as imipramine at reducing depressive symptoms, but had a significantly lower risk of causing a manic switch. this is in line with recent findings that maois as a class are superior to other antidepressants (in terms of both their relatively low rate of manic switching and their efficacy) in the treatment of bipolar depression. 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 (>300 mg/d) 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. moclobemide 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. migraine. moclobemide has been reported to be effective in the treatment of migraine and chronic tension headache. 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. moclobemide may also have benefit for some patients with parkinson's disease by extending and enhancing the effects of l-dopa. 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 (tcas) and selective serotonin reuptake inhibitors (ssris), 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 (dst) and plasma and urine methoxyhydroxyphenylglycol (mhpg) test can be used to estimate who is likely to respond to moclobemide antidepressant therapy. pregnancy and lactation the doses of moclobemide in breast milk are very low (0.06% of moclobemide being recovered in breast milk) 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 (scopolamine) induced cognitive impairments thus making moclobemide a good choice in the depression in the elderly and those with dementia. adverse effects 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. side effects of moclobemide are exceptionally 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 (dizziness upon standing) 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 (>1% incidence) adverse effects nausea dry mouth constipation diarrhoea insomnia dizziness anxiety restlessness uncommon/rare (<1%) 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 (dysuria, polyuria, tenesmus) 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. contraindications avoid use in: confusional states bipolar disorder (although it seems less likely than imipramine to cause a manic switch) phaeochromocytoma and caution is recommended in: agitated/excited patients thyrotoxicosis interactions drug moclobemide has fewer interactions than irreversible maois. cimetidine however, causes a significant rise in moclobemide levels and therefore if the combination is used, lower doses of moclobemide have been recommended. there is little increase in the effects of alcohol when combined with moclobemide and, in