We present a case involving a fatality due to the combined ingestion of two different types of antidepressants. A 41-year-old Caucasian male, with a history of depression and suicide attempts, was found deceased at home. Multiple containers of medication, the MAO-inhibitor moclobemide (Aurorix), the SSRI citalopram (Cipramil), and the benzodiazepine lormetazepam (Noctamid) as active substance, as well as a bottle of whiskey were present at the scene. The autopsy findings were unremarkable, but systematic toxicological analysis (EMIT, radioimmunoassay, high-performance liquid chromatography-diode-array detection [HPLC-DAD], gas chromatography-nitrogen-phosphorus detection, and gas chromatography-mass spectrometry) revealed the following: ethanol (0.23 g/L blood, 0.67 g/L urine), lormetazepam (1.65 microg/mL urine), cotinine (0.63 microg/mL blood, 5.08 microg/mL urine), caffeine (1.20 microg/mL urine), moclobemide (and metabolites), and citalopram (and metabolite). There upon, we developed a new liquid chromatographic separation with optimized DAD, preceded by an automated solid-phase extraction, for the quantitation of the previously mentioned antidepressive drugs. The results obtained for blood and urine, respectively, were as follows: Ro 12-5637 (moclobemide N´-oxide) not detected and 424 microg/mL; Ro 12-8095 (3-keto-moclobemide) 2.26 microg/mL and 49.7 microg/mL; moclobemide 5.62 microg/mL and 204 microg/mL; desmethylcitalopram 0.42 microg/mL and 1.22 microg/mL; and citalopram 4.47 microg/mL and 19.7 microg/mL. The cause of death was attributed to the synergistic toxicity of moclobemide and citalopram, both antidepressants, which, by intentional or accidental combined ingestion, can produce a potentially lethal hyperserotoninergic state. Based on the history of the case and pharmacology of the drugs involved, the forensic pathologists ruled that the cause of death was multiple drug intoxication, resulting in a fatal ´serotonin syndrome,´ and that the manner of death was suicide

The use of monoamine oxidase inhibitors (MAOIs) in the treatment of depression has been bedeviled by reports of potentially dangerous or even fatal interactions with dietary amines and other drugs together with reports of more conventional toxicity to organs such as the liver. As a result, these otherwise very important and useful drugs have not been employed clinically as much as their effectiveness as antidepressants would indicate. Many of these unwanted actions were due partially or entirely to the fact that the older MAOIs all inhibited MAO irreversibly. The introduction of reversible inhibitors of monoamine oxidase-A (RIMAs) has greatly reduced both the number and severity of these interactions and, in particular, the risk of hypertensive crises following the ingestion of tyramine (the ´cheese effect´). Potential interactions may remain with inhibitors of the uptake of 5-hydroxytryptamine, including pethidine and rapid release formulations of nasal decongestant amines. Potential interactions between RIMAs and other drugs that compete for the same metabolic pathways may still occur but should only result in changes in duration of action

Combinations of monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) are discussed with regard to general toxicity, drug interactions, animal studies, clinical reports, efficacy of combination therapy and usage conditions. Although MAOI-TCA combinations are usually considered contraindicated, informed opinion has shifted to cautious recommendation for the combination. Only refractory patients in whom less hazardous treatment has failed should be considered for combination therapy. The preferred dosage regimen is administration of the MAOI t.i.d. during the day and the entire TCA dose at bedtime. Patients should be informed of the immediate need for medical advice should side effects occur. It is concluded that the simultaneous administration of these agents is potentially efficacious and safe is carefully monitored and controlled

Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses

Monoamine oxidase inhibitors (MAOIs) are medicines with potential for therapeutic gains, but they may also have adverse consequences. The risk: benefit ratio is assessed and, in appropriately selected cases, efficacy should outweigh disadvantages. Hypotension is the most prominent side-effect; yet the primary concern in the MAOI-treated person is to prevent co-exposure to substances with indirectly-acting sympathomimetic properties. Such co-utilisations from certain foods or drugs can result in dangerous hypertensive and hyperpyretic crises. A responsible individual should be involved in the administration of these drugs. The patient and family must fully understand the self-discretionary diet avoidance rules, which stress abstinence from high-tyramine foods. Drug prohibitions also emphasise elimination of indirect action sympathomimetics, but all pharmaceutical applications are always strictly controlled by the well informed physician who prescribes MAOIs. Treatment of the hypertensive crisis is urgent and includes alpha-blockade. Overdoses require supportive therapies and may necessitate acidification of the urine

Serotonin syndrome with moclobemide-fluoxetine combination

Sertraline and isocarboxazid cause a serotonin syndrome