The incidence of adverse events is not correlated with age; however, adverse events occur more often in females than in males.<unk>  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<unk>  are exceptionally low, with insomnia, headache and dizziness being the most commonly reported side effects in the initial stages of therapy with<unk> .<unk> , even at high doses of 600 mg, does not impair the ability to drive a motor vehicle. The tolerability of<unk>  is similar in women and men and it is also well tolerated in the elderly.<unk>  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<unk> .<unk>  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.<unk>  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<unk> , except that in doses of 400 mg or higher peripheral reaction time may be impaired. Peripheral oedema has been associated with<unk> . 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<unk>  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<unk> . Overall, antidepressants decrease the risk of suicide.<unk>  is believed to have only small proconvulsant effects; however, rarely seizures may occur. Hypertension has been reported to occur very rarely with<unk>  therapy.<unk>  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/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 * Meteorism * 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<unk>  has fewer interactions than irreversible MAOIs. Cimetidine, however, causes a significant rise in<unk>  levels and therefore if the combination is used, lower doses of<unk>  have been recommended. There is little increase in the effects of alcohol when combined with<unk>  and, in fact,<unk>  causes a reduction in alcohol-related impairments.<unk>  also interacts with pethidine/meperidine, and dextropropoxyphene. Ephedrine in combination with<unk>  increases the risk of cardiovascular adverse effects.<unk>  is also likely to interact with warfarin. The combination of<unk>  with prescription or over the counter sympathomimetic drugs is not recommended due to the potential of significant drug interactions. Serotonin syndrome has been reported when<unk>  has been taken in combination with other serotonin enhancing drugs; however, due to<unk> 's reversible MAO inhibition, serotonin syndrome is significantly less likely to occur with<unk>  than with older irreversible MAOIs. Serotonin syndrome has been reported when trazodone was abruptly replaced with<unk> . Taking at the same time or starting<unk>  too soon after discontinuing clomipramine, or other serotonin reuptake inhibitors, such as SSRIs may result in the development of a serotonin syndrome. SNRIs, such as venlafaxine in combination with<unk>  have also been associated with serotonin syndrome. Cimetidine, causes a doubling of the blood plasma levels of<unk> . Blood plasma levels of trimipramine and maprotiline and possibly other tricyclic antidepressants increase when used in combination with<unk>  and may require dosage adjustments if the combination is used for treatment resistant depression. The elimination of zolmitriptan is reduced by<unk>  and if the combination is used, a dosage reduction of zolmitriptan is recommended.<unk>  reduces the metabolism of dextromethorphan.<unk>  may decrease metabolism of diazepam, omeprazole, proguanil, propranolol, and others due to inhibition of CYP2C19. ;Dietary Irreversible MAOIs can cause unpleasant and occasionally dangerous side effects such as a hypertensive crises after intake of food or drink containing indirectly acting sympathomimetic amines such as tyramine. This is sometimes referred to as the 'cheese effect'. These side effects are due to irreversible inhibition of MAO in the gut and vasomotor neurones. However, the reversible MAOI antidepressants such as<unk>  have a very different side effect profile in this regard. The reversible binding to MAO-A by<unk>  allows amines such as tyramine to displace<unk>  from MAO-A allowing its metabolism and removing the risk of a hypertensive crisis that occurs with irreversible MAO inhibition. Of 2300 people in multiple clinical trials who were treated with<unk>  in doses up to 600 mg with no dietary restrictions, none experienced a tyramine-mediated hypertensive reaction. As the pressor effect of<unk>  is so low, dietary restrictions are not necessary in people eating a normal diet, in contrast to irreversible MAOIs. However, some rare cheeses that have a high tyramine level may possibly cause a pressor effect and require caution. The potentiation of the pressor effect of tyramine by<unk>  is only one seventh to one tenth of that of irreversible MAOIs. In order to minimize this potentiation, postprandial administration (taken after meals) of<unk>  is recommended. The combined use of<unk>  and selegiline requires dietary restrictions as the combination can lead to increased sensitivity to the pressor effect of foods containing tyramine. While<unk>  or the irreversible MAO-B selective inhibitor selegiline taken alone has very little pressor effect, and requires no dietary restriction, the combination of seligiline with<unk>  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<unk>  and a reversible MAO-B inhibitor requires tyramine dietary restrictions. Overdose<unk>  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<unk>  during clinical trials, all recovered fully and<unk>  was judged to be safe for inpatient as well as outpatient use. Intoxications with<unk>  as single agent are usually mild; however, when combined with tricyclic or SSRI antidepressants the overdose is much more toxic and potentially fatal.<unk> , is preferred by doctors for patients who are at risk of suicide, due to<unk> '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<unk>  compared to other antidepressants; a single report of relatively mild flu-like symptoms persisting for 7 days after rapid reduction of high dose<unk>  therapy has been reported in one patient. Withdrawal of<unk>  causes a rebound in REM sleep.<unk>  does not seem to prevent withdrawal symptoms from serotonin reuptake inhibitors. Discontinuation of<unk>  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<unk> .
Moclobemide
Torasemide
Altretamine
Bumetanide
Yohimbine
Brimonidine
Clonidine
Amiloride