tenth of that of irreversible MAOIs. In order to minimize this potentiation, postprandial administration (taken after meals) of moclobemide is recommended. The combined use of moclobemide and selegiline requires dietary restrictions as the combination can lead to increased sensitivity to the pressor effect of foods containing tyramine. While moclobemide or the irreversible MAO-B selective inhibitor selegiline taken alone has very little pressor effect, and requires no dietary restriction, the combination of selegiline with moclobemide leads to a significant enhancement of the pressor effect and such a combination requires dietary restriction of foods containing high amounts of tyramine. The combination of moclobemide and a reversible MAO-B inhibitor requires tyramine dietary restrictions. Overdose Moclobemide is considered to be less toxic in overdose compared to older antidepressants, such as the tricyclic antidepressants and the irreversible and non-selective MAOIs, making it a safer antidepressant in the elderly or people with physical disorders. Of 18 people who overdosed on moclobemide during clinical trials, all recovered fully and moclobemide was judged to be safe for inpatient as well as outpatient use. Intoxications with moclobemide as single agent are usually mild; however, when combined with tricyclic or SSRI antidepressants the overdose is much more toxic and potentially fatal. Moclobemide, is preferred by doctors for patients who are at risk of suicide, due to moclobemide's low toxicity in overdose. Patients with mixed intoxications (e.g. with other CNS active drugs) may show severe or life-threatening symptoms and should be hospitalized. Treatment is largely symptomatic and should be aimed at maintenance of the vital functions. Withdrawal and tolerance Withdrawal symptoms appear to be very rare with moclobemide compared to other antidepressants; a single report of relatively mild flu-like symptoms persisting for 7 days after rapid reduction of high dose moclobemide therapy has been reported in one patient. Withdrawal of moclobemide causes a rebound in REM sleep. Moclobemide does not seem to prevent withdrawal symptoms from serotonin reuptake inhibitors. Discontinuation of moclobemide is recommended to be done gradually to minimise side effects (e.g. rapid return of condition being treated and/or the appearance of withdrawal symptoms). Tolerance to the therapeutic effects has been reported in a small number of users of MAOIs including moclobemide. Pharmacology Moclobemide is a benzamide, derivative of morpholine, which acts pharmacologically as a selective, reversible inhibitor of monoamine oxidase-A (RIMA), a type of monoamine oxidase inhibitor (MAOI), and increases levels of norepinephrine (noradrenaline), dopamine, and especially serotonin in