Curses, Madness, and Mefloquine
Curses, Madness, and Mefloquine
Curses, Madness, and Mefloquine
the differential diagnosis was narrowed to drug-induced to access the biomedical health care system.6 This pattern
psychosis versus new-onset bipolar illness. Ms. A was is particularly true in cases of psychiatric disorders, which
treated with divalproex sodium, haloperidol, and benztro- are believed by many to be caused by curses and therefore
pine, but she had minimal change in her symptoms. Six to require a spiritual cure. In Ms. A’s case, this course of
days later, she was transferred to a tertiary care hospital action led to a delay in the initiation of appropriate medical
closer to her home in another Midwestern city for contin- care, which likely did not affect her outcome but may have
ued care. On admission, she had psychomotor restlessness, affected the outcome if her condition had had an infectious
akathisia, and emotional lability. She was distressed by the or vasculitis etiology. On arrival in the United States, her
persistent delusions and hallucinations, and she indicated husband was briefly held by the police, on the basis of the
that she wanted them to stop. Her mood was not elevated. prevailing belief that an agitated woman who was afraid of
Her sleep and appetite were severely disturbed. The results her husband was likely to have been harmed by him. The
of a physical examination were remarkable for tachycardia, patient and her family had not been informed about the po-
old mosquito bites, and mild right upper quadrant tender- tential side effects of mefloquine. At the 2-year follow-up,
ness. Haloperidol, divalproex sodium, and benztropine her husband was still clinging to the belief that her symp-
were discontinued, and risperidone and lorazepam were in- toms were caused by witchcraft, while the patient only fog-
stituted in their place. A medical workup was further pur- gily remembered the events that had happened 2 years ago.
sued. The results of a magnetic resonance imaging scan of Risk factors for psychosis associated with the use of
the brain and magnetic resonance angiography were un- mefloquine that have been reported in the published case
remarkable. An EEG showed diffuse cerebral dysfunction. reports include dosage, a family or personal past history of
Although her liver transaminase concentrations remained neuropsychiatric disease, previous exposure to mefloquine,
elevated, she had negative serological tests for hepatitis A, use of psychotropic drugs within the last 2 months, con-
B, and C, and her blood count and thyroid functioning tests comitant use of alcohol and other medications, and female
were normal. Her potassium level of 2.9 was low, and this gender;7 Ms. A had some of these risk factors.
deficit was corrected by intravenous infusion of potassium Mefloquine appears to be a noncompetitive inhibitor
chloride. An ultrasound of the right upper quadrant showed of both acetylcholinesterase and butyrylcholinesterase, and
mild fatty infiltration of the liver with small gallbladder this process is thought to explain some of its CNS effects.8
stones but no other abnormalities. Spinal fluid analysis was The general incidence of severe neuropsychiatric events
unremarkable. A malaria smear was negative. A urine test has been estimated to be 1 in 8,000 mefloquine users,
for pregnancy was negative. equivalent to 1 in 215 therapeutic users or 1 in 10,000–
An infectious diseases consultant concurred that Ms. 15,000 prophylactic users.4 This rate is similar to the rate
A’s symptoms were most likely secondary to mefloquine of similar side effects described with chloroquine use.5
and suggested finishing her prophylactic course with doxy- Psychotic symptoms generally resolve promptly with dis-
cycline. She was hospitalized for 6 days, and by discharge continuation of the drug, although reports of symptoms
she had only mild referential and paranoid thinking, with persisting for as long as a year or more have been pub-
no other psychotic symptoms. She was discharged home lished.9–11
with a prescription for 1 mg of risperidone twice daily. At Until the past decade, most CNS side effects were be-
follow-up 4 weeks later, she had no residual symptoms, lieved to be minor and few in number. The accumulating
and the antipsychotic was stopped. She was symptom free data suggest that earlier estimates were conservative. In a
at 2-year follow-up. recent randomized, controlled trial in a heterogeneous
group of nonimmune Western travelers, the incidence rate
of neuropsychiatric side effects was 33%, with 6% of pa-
tients seeking medical advice.12 A recent review of 516
Discussion reports in the literature published between 1976 and 2000
suggested that a transient hepatocellular injury was possi-
bly the mechanism for the mefloquine-induced symptoms.
Ms. A’s symptoms were initially attributed to witchcraft, It is known that elevated transaminase concentrations are
consistent with prevailing local beliefs. Spiritual healing is commonly found in mefloquine users.7 Other agents that
a parallel health care system in Nigeria, and many patients are metabolized by the liver, including oral contraceptives
are first taken to spiritual healers before an attempt is made and alcohol, were found to be present in half of the patients
with psychiatric side effects. One of the earliest reports of and reports in the press of “mefloquine survivors.”16 The
suicidal ideation described a healthy Canadian who became manufacturer Roche has recently strengthened its label
psychotic and suicidal when he drank half a bottle of warning to include a statement that suicides have been re-
whisky with his dose of mefloquine and whose symptoms ported among users of mefloquine, although the company
resolved after he stopped drinking the alcohol.13 It is in- emphasizes that no relationship to drug administration has
teresting to note that his colleague, who drank the remain- been confirmed.2 The warning label recommends that pa-
ing half-bottle of whisky but who was not taking an anti- tients with active depression or a history of major psychi-
malarial, never developed psychiatric symptoms. Ms. A atric disorders, such as anxiety disorders, psychotic disor-
was taking an oral contraceptive and had a persistent rise ders, or depressive disorders, not take the drug for
in her transaminase concentrations that is consistent with prophylaxis. The company also warns that if symptoms of
the aforementioned hepatocellular injury hypothesis. acute anxiety, depression, restlessness, or confusion occur,
Given that the symptoms of hepatocellular injury are non- the medicine should be stopped, as such symptoms could
specific, a prospective trial testing this hypothesis would constitute a prodrome to a more serious event.2 As yet, it
be needed before this hypothesis can be widely accepted. cannot be reliably predicted which patients may develop
Mefloquine has recently received media attention be- serious psychiatric symptoms while taking mefloquine,
cause of a postulated link to suicide and homicide, includ- thus limiting the effectiveness of these recommendations.
ing the murders and suicides committed in the summer of
2002 by soldiers at Fort Bragg, N.C., who had taken me- The authors thank Aminat B. Kukoyi, Pharm.D., for
floquine.14,15 There are several antimefloquine web sites her contributions to this report.
References
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