Psychosis mefloquine

While its detailed mechanism of action is unknown, it is an effective blood schizonticide that is, it acts against the form of the parasite responsible for chnical symptoms. Orally administered mefloquine is well absorbed and has an absorption half-hfe of about 2 hours the elimination half-hfe is 2 to 3 weeks. Among its side effects are vertigo, visual alterations, vomiting, and such CNS disturbances as psychosis, hallucinations, confusion, anxiety, and depression. It should not be used concurrently with compounds known to alter cardiac conduction or prophylactically in patients operating dangerous machinery. It should not used to treat severe malaria, as there is no intravenous formulation. 

Weekly dosing with mefloquine for chemoprophylaxis may cause nausea, vomiting, dizziness, sleep and behavioral disturbances, epigastric pain, diarrhea, abdominal pain, headache, rash, and dizziness. Neuropsychiatric toxicities have received a good deal of publicity, but despite frequent anecdotal reports of seizures and psychosis, a number of controlled studies have found the frequency of serious adverse effects from mefloquine to be no higher than that with other common antimalarial chemoprophylactic regimens. Leukocytosis, thrombocytopenia, and aminotransferase elevations have been reported. 

The latter adverse effects are more common with the higher dosages required for treatment. These effects may be lessened by administering the drug in two doses separated by 6-8 hours. The incidence of neuropsychiatric symptoms appears to be about ten times more common than with chemoprophylactic dosing, with widely varying frequencies of up to about 50% being reported. Serious neuropsychiatric toxicities (depression, confusion, acute psychosis, or seizures) have been reported in less than one in 1000 treatments, but some authorities believe that these toxicities are actually more common. Mefloquine can also alter cardiac conduction, and arrhythmias and bradycardia have been reported. 

In a prospective, double-blind, randomized, placebo-controlled study in 119 healthy volunteers (mean age 35 years), who took either atovaquone 250 mg/day + chlor-oguanide 100 mg/day or mefloquine 250 mg/week, depression, anger, and fatigue occurred during the use of mefloquine but not atovaquone + chloroguanide (510). Mefloquine can also cause psychosis. 

In another major review the risk of depression, psychosis, a panic attack, or a suicide attempt during current or previous use of mefloquine was compared with the risk during the use of proguanil and/or chloroquine or doxy-cycline (513). The study population (n = 35 370) was aged 17-79 years (45% men). There was no evidence that the risk of depression was increased during or after the use of mefloquine, but psychoses and panic attacks were more frequent in current users of mefloquine than in those using other antimalarial drugs. 

Havaldar PV, Mogale KD. Mefloquine-induced psychosis. Pediatr Infect Dis J 2000 19(2) 166-7. 

Mefloquine does not normally appear to interact with alcohol, although excessive alcohol may possibly contribute to its adverse effects on the liver. An isolated report describes two incidents of severe psychosis and depression in a man taking mefloquine who drank large quantities of alcohol. 

Nervous system The literature on mefloquine neurotoxicity has been reviewed [9 ]. Nausea, dizziness, sleep disturbances, anxiety, and psychosis have been reported. Female patients and patients with a low body mass index are at greater risk. 

Fever and malaria can induce a psychosis, but in this case, fever was an unlikely cause, as fever-induced psychosis is usually polymorphic and associated with some alteration of consciousness and orientation, which were absent there was also no past history of an altered mental state after febrile illnesses. Falciparum malaria leading to psychiatric sequelae usually presents with cerebral malaria, which has well-defined neurological signs. Antimalarial drugs such as chloroquine, mefloquine, and quinine can cause psychoses, and given substantial evidence of neurotoxicity after exposure to artemisinin compounds. 

Thapa R, Biswas B. Childhood mefloquine-induced mania and psychosis a case report. J Child Neurol 2009 24(8) 1008-9. 

Mawson A. Mefloquine use, psychosis, and violence a retinoid toxicity hypothesis. Med Sci Monit Int Med J Exp Chn Res 2013 19 579-83. Nevin RL. Limbic encephalopathy and central vestibulopathy caused by mefloquine a case report. Travel Med Infect Dis 2012 10 144r-51. Nevin RL. Mefloquine gap junction blockade and risk of pregnancy loss. Biol Reprod 2012 87(3) 65,1-9. 

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