Mefloquine Long Half-Life is Associated with Sustained Psychiatric Side Effects: A Case Report

Background: Psychiatric side effects of mefloquine, an antimalarial drug, are well known (agitation, depression and suicidal ideation, psychosis with paranoia and hallucinations). Case Presentation: We report the case of a 30-year-old man without psychiatric antecedents, who developed acute psychosis and depression with suicidal ideation after five weeks of treatment with mefloquine. The symptomatology decreased rapidly a few days later, under antipsychotic drug (olanzapine) and benzodiazepines (lorazepam) and the treatment doses were diminished after one week. However, three weeks later, the same symptomatology reappeared and the treatment doses of both psychotropic drugs had to be increased once again. The antidepressant escitalopram was also introduced. Three months were necessary to definitively suppress the psychotropic drugs. Plasma mefloquine clearance was monitored by a validated liquid-chromatography mass-spectrometric method and confirmed the very long half-life of the drug, which is estimated at 14.5 days. Conclusions: The pathophysiological mechanisms of these psychiatric side effects probably involve a toxic limbic encephalopathy. Mefloquine is highly lipophilic and may accumulate in the limbic system. In conclusion, due to the very long half-life of mefloquine, psychiatric symptoms can persist for weeks, necessitating an appropriate psychotropic treatment. Chronic symptoms resulting from permanent neurotoxicity may also occur.