medical research references
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Matteelli, A., et al. 2005. Mefloquine versus quinine plus sulphalene-pyrimethamine (metakelfin) for treatment of uncomplicated imported falciparum malaria acquired in Africa. Antimicrobial Agents and Chemotherapy 49(2):663-7. PDF REPRINT
Picot, S., et al. 2005. Absence of nucleotide polymorphism in a Plasmodium vivax multidrug resistance gene after failure of mefloquine prophylaxis in French Guyana. Transactions of the Royal Society of Tropical Medicine and Hygiene 99(3):234-7.
van Riemskijk, M.M., et al. 2005. Mefloquine increases the risk of serious psychiatric events during travel abroad : A nationwide case-control study in the Netherlands. Journal of Clinical Psychiatry, Feb 66(2):199-204.
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Cruikshank, S.J., Hopperstad, M., Younger, M., Connors, B.W., Spray, D.C., & Srinivas, M. 2004. Potent block of Cx36 and Cx50 gap junction channels by mefloquine. Proceedings of the National Academy of Science, 101(33): 12364-12369. PDF REPRINT
News in brief. 2004. Danish court rules against Roche. British Medical Journal 28: 364.
Ruebush, T.K., et al. 2004. Modifying national malaria treatment policies in Peru. Journal of Public Health Policy 25(3-4):328-45.
Farooq, U. & R.C. Mahajan. 2004. Drug resistance in malaria. Journal of Vector Borne Disease 41(3-4):45-53.
van Riemsdijk, M.M., Sturkenboom, M.C., Ditters, J.M., Tulen, J.H., Ligthelm, R.J., Overbosch, D., and Stricker, B.H. 2004. Low body mass index is associated with an increased risk of neuropsychiatric adverse events and concentration impairment in women on mefloquine. British Journal of Clinical Pharmacology, 57(4):506-512.
FULL TEXTABSTRACT AIMS: We performed a prospective cohort study to gain more insight into risk factors for neuropsychiatric effects of mefloquine among tourists travelling to tropical areas. METHODS: We enrolled all patients who consulted the Travel Clinic of the Havenziekenhuis & Institute for Tropical Diseases Rotterdam for mefloquine prophylaxis during the period between 1 May 1999 and 7 March 2000. Each patient was followed from baseline (prior to starting mefloquine) up to 3 weeks after starting weekly intake of 250 mg mefloquine. We compared the intraindividual change in scores between baseline and follow-up visit on the Dutch shortened Profile of Mood States, and on the Continuous Performance Test (CPT) which measures sustained attention. RESULTS: The final cohort consisted of 151 subjects with a mean age of 38 years. In this population, a significant impairment of mood state was observed in those with a body mass index (BMI) < or = 20 kg m(-2). Stratification for gender showed that the total mood disturbance in females in the lowest BMI category significantly increased by 8.42 points [95% confidence interval (CI) 3.33, 13.50], whereas BMI did not affect the risk in males. Stratification for history of use of mefloquine showed that the risks were highest in first-time users. Analyses of the CPT showed that reaction time in women with a BMI < or = 20 kg m(-2) increased significantly by 22.5 ms (95% CI 7.80, 37.20), whereas reaction time in men showed a slight and nonsignificant decrease. CONCLUSION: Risk factors for mefloquine-associated neuropsychiatric adverse events and concentration impairment are female gender, low BMI, and first-time use. The frequency of neuropsychiatric effects is highest in women with a BMI < or = 20 kg m(-2).Dow, G.S., Koenig, M.L., Wolf, L., Gerena, L., Lopez-Sanchez, M., Hudson, T.H., and Bhattacharjee, A.K. 2004. The antimalarial potential of 4-quinolinecarbinolamines may be limited due to neurotoxicity and cross-resistance in mefloquine-resistant Plasmodium falciparum strains. Antimicrobial Agents and Chemotherapy, 48(7):2624-2632.
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Pettinelli, F., Pettinelli, M.E., Eldin de Pecoulas, P., Millet, J., Michel, D., Brasseur, P., and Druilhe, P. 2004. Short report: High prevalence of multidrug-resistant Plasmodium falciparum malaria in the French territory of Mayotte. American Journal of Tropical Medicine and Hygiene, 70(6):635-637.
Patten, S.B. & Barbui, C. 2004. Drug-induced depression: a systematic review to inform clinical practice. Psychotherapy and Psychosomatics, 73(4):207-15.
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McArdle, J.J. and L.C. Sellin. 2003. Mefloquine (lariam) increases spontaneous transmitter release from mature and immature motor nerve terminals. FASEB Journal 17 (4): A634-A634, Part 1 Suppl. S.
Meyer, P., N. Combes, P. Corne, and O. Jonquet. 2003. Convulsions and shock during overzealous anti-malarial chemoprophylaxis [in French]. Presse Medicale 32 (9): 408-408.
Wichmann, O., B. Betschart, T. Loscher, H.D. Nothdurft, F.V. Sonnenburg and T. Jelinek. 2003. Prophylaxis failure due to probable mefloquine resistant P-falciparum from Tanzania. Acta Tropica 86 (1): 63-65.
ABSTRACT : We report the case of a 44-year-old German female who travelled to Tanzania for 3 weeks. The patient reported that she never missed a dose of mefloquine during her weekly prophylaxis schedule. Four weeks after returning from Tanzania, the patient presented with fever, headache and myalgia. Only a few trophozoites of Plasmodium falciparum were found in a thick film. Blood levels of mefloquine at that stage were at 1400 ng/ml, thus largely excluding non-compliance and malabsorption. To our knowledge, this is the first case of confirmed prophylaxis failure due to mefloquine resistance in East Africa.Dow, G.S., T.H. Hudson, M. Vahey, and M.L. Koenig. 2003. The acute neurotoxicity of mefloquine may be mediated through a disruption of calcium homeostasis and ER function in vitro. Malaria Journal 2 (1):14.
ABSTRACT CONCLUSIONS: Mefloquine was found to disrupt neuronal calcium homeostasis and induce an ER stress response at physiologically relevant concentrations, effects that may contribute, at least in part, to the neurotoxicity of the drug in vitro.Loefler, I. 2003. Mefloquine and anticoagulant interaction. Journal of Travel Medicine 10 (3): 194-195.
Kofoed, K. and E. Petersen. 2003. The efficacy of chemoprophylaxis against malaria with chloroquine plus proguanil, mefloquine, and atovaquone plus proguanil in travelers from Denmark. Journal of Travel Medicine. 10 (3): 150-154.
Etkin, N.L. 2003. The co-evolution of people, plants, and parasites: biological and cultural adaptations to malaria. Proceedings of the Nutrition Society. 62(2):311-317.
Falchook, G.S., et al. 2003. Postmalaria neurological syndrome after treatment of Plasmodium falciparum malaria in the United States. Clinical Infectious Diseases. 37(2):e22-4.
Garavelli, P.L. 2003. [Mefloquine resistance in Plasmodium falciparum malaria]. Recenti Progressi in Medicina. 2003 Jul-Aug;94(7-8):343. [in Italian.]
Schlagenhauf, P., et al. 2003. Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study. British Medical Journal. 327(7423):1078. FULL TEXT
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Wooltorton, E. 2002. Mefloquine: contraindicated in patients with mood, psychotic or seizure disorders. Canadian Medical Association Journal 167 (10):1147.
Croft, A.M. and A. Herxheimer. 2002. Tolerability of antimalaria drugs. Clinical Infectious Diseases 2002 May 1; 34(9):1278.
Fuller, S.J., Naraqi, S., and Gilessi, G. 2002. Paranoid psychosis related to mefloquine antimalarial prophylaxis. P N G Medical Journal. 45(3-4):219-221.
Guan J., et al. 2002. Design, synthesis, and evaluation of new chemosensitizers in multi-drug-resistant Plasmodium falciparum. Journal of Medical Chemistry 45(13):2741-2748.
Karle, J.M. and I.L. Karle. 2002. Crystal structure of (-)-mefloquine hydrochloride reveals consistency of configuration with biological activity. Antimicrobial Agents and Chemotherapy 2002 May; 46(5):1529-34.
Martín-Galiano, A.J., et al. 2002. Mefloquine and New Related Compounds Target the F(0) Complex of the F(0)F(1) H(+)-ATPase of Streptococcus pneumoniae. Antimicrobial Agents and Chemotherapy 46(6):1680-1687.
Newton, Paul N., et al. 2002. Murder by Fake Drugs. British Medical Journal 324(7341):800-802
"A countrywide survey in Cambodia in 1999 showed that 60% of 133 drug vendors sampled sold, as the antimalarial mefloquine, tablets that contained the ineffective but much cheaper sulphadoxine-pyrimethamine, obtained from stocks that should have been destroyed, or fakes that contained no drug at all (Rozendaal 2000; Rozendaal 2001)."Rendi-Wagner, P., et al. 2002. Unexpected frequency, duration and spectrum of adverse events after therapeutic dose of mefloquine in healthy adults. Acta Tropica 81(2):167-173.
ABSTRACT: The frequency and spectrum of adverse events associated with the antimalarial therapeutic regimen of mefloquine (MQ) (750 and 500 mg at an interval of 6 h) was assessed in 22 healthy volunteers who were monitored for 21 days following drug administration. An unexpected high frequency of side effects of any grade were reported by all 22 subjects. The most commonly reported symptoms were vertigo (96%), followed by nausea (82%) and headache (73%). Participants suffering from severe (grade 3) vertigo (73%) required bed rest and specific medication for 1 to 4 days. More females than males reported severe adverse reactions. The majority (77.3%) of the participants (f: 8/12, m: 9/10) showed symptom resolution within 3 weeks (510 h) after drug administration. Biochemical and haematological findings stayed within the normal range of values, but showed nevertheless a significant rise of Na, Cl, Ca, bilirubin, GGT and LDH. The unexpectedly high frequency and severity of adverse reactions after normal therapeutic dosage of MQ in healthy subjects may influence future recommendations regarding the use of MQ for stand-by treatment of suspected malaria in travellers.Simpson, J.A., et al. 2002. The influence of body weight on the pharmacokinetics of mefloquine. British Journal of Clinical Pharmacology 53(3):337.
Wongsrichanalai, C., et al. 2002. Epidemiology of drug-resistant malaria. Lancet Infectious Diseases 2(4):209-218.
"By the late 1980s, resistance to sulfadoxine-pyrimethamine and to mefloquine was also prevalent on the Thai-Cambodian and Thai-Myanmar (Thai-Burmese) borders, rendering them established multidrug-resistant (MDR) areas."
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Borruat, F.X., et al. 2001. Prolonged visual illusions induced by mefloquine (Lariam): A case report. Journal of Travel Medicine 8(3):148-149.
Even, C., et al. 2001. Bipolar disorder after mefloquine treatment. Journal of Psychiatry & Neuroscience 26(3):252-253.
Javorsky, D.J., et al. 2001. Cognitive and neuropsychiatric side effects of mefloquine. Journal of Neuropsychiatry and Clinical Neurosciences 13(2):302. PDF REPRINT
Lightbown, I.D., et al. 2001. Potentiation of halofantrine-induced QTc prolongation by mefloquine: Correlation with blood concentrations of halofantrine. British Jounal of Pharmacology 132(1):197-204.
Overbosch, David, et al. 2001. Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: Results from a randomized, double-blind study. Clinical Infectious Diseases 33 (1 Oct):1015-1021.
The frequency of AEs [adverse events] attributed to mefloquine in the present study (42%) is similar to the frequency in 2 previous studies.... Among 1214 British travelers who received mefloquine and who responded to a postal questionnaire... 503 (41%) reported side effects that they attributed to mefloquine (Barrett, et al. 1996). Among 183 British soldiers who responded to a questionnaire 2 weeks after starting prophylaxis with mefloquine, 71 (39%) reported AEs concidered by the investigators to be side effects of mefloquine (Croft, et al. 1997).
Rozendaal, J.A. 2001. Fake antimalaria drugs in Cambodia. Lancet 57:890.
Schwartz, E., et al. 2001. Serious adverse events of mefloquine in relation to blood level and gender. American Journal of Tropical Medicine and Hygiene 65(3):189-192.
Udry, E., et al. 2001. Pulmonary toxicity with mefloquine. European Respiratory Journal 18(5):890-892.
Watt-Smith, S., et al. 2001. Mefloquine-induced trigeminal sensory neuropathy. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 92(2):163-165.
ABSTRACT: Trigeminal sensory neuropathy is an important finding, often indicative of trauma but sometimes related to neoplasia, infections, demyelinating conditions, connective tissue disorders, other disorders, or, occasionally, drugs. This paper reports on a patient with sudden-onset trigeminal sensory neuropathy of the lip that proved to be drug-induced, secondary to the antimalarial drug mefloquine. This appears to be the first report of sensory impairment in the orofacial region from exposure to mefloquine.
X, Nicolas, et al. 2001. [Danger of malaria self-treatment. Acute neurologic toxicity of mefloquine and its combination with pyrimethamine-sulfadoxine] La Presse Medicale30(27):1349-1350.
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Abell, L. 2000. Health advice for travelers. New England Journal of Medicine 343(14):1045-1046.
Brenier-Pinchart, M.P., et al. 2000. [Glucose-6-phosphate dehydrogenase deficiency and hemoglobinuric biliary fever after taking mefloquine] La Presse Medicale 29(3):142.
Gotsman, I., et al. 2000. Mefloquine-induced acute hepatitis. Pharmacotherapy 20(12):1517-1519.
Havaldar, P.V. and K.D. Mogale. 2000. Mefloquine-induced psychosis. Pediatric Infectious Disease Journal 19(2):166-167.
Kollaritsch, H., et al. 2000. Mefloquine concentration profiles during prophylactic dose regimes. Wiener Klinische Wochenscrift 112:441-447.
Lebain, P., et al. 2000. [Neuropsychiatric symptoms in preventive antimalarial treatment with mefloquine: Apropos of 2 cases] Encephale 26(4):67-70.
ABSTRACT: Two observations of severe neuropsychiatric reactions occurring during chemoprophylaxis with mefloquine are reported. The first case regards a 43 years old woman who developed a severe depression with visual and auditive hallucinations and a paranoid delusion. She was treated by clomipramine and risperidone. The second case concerns a 55 years old man who developed an acute psychosis with confusion. He was treated with halopridol during a short time. He presented twice an acute psychosis during a chemoprophylaxis with mefloquine. Several cases of neuropsychiatric side effects with mefloquine chemoprophylaxis or treatment have been described. Authors estimate that one of 250 therapeutic users has severe neuropsychiatric reactions, compared with one of 10,000 to 15,000 in the prophylaxis users. Disorders could last from 15 minutes to several weeks. Women and patients with personal or familial antecedents of psychiatric disorders are more frequently concerned. Alcohol and the association with other antimalarial drugs (like quinine) are two other risk factors. Therefore, some advices may be suggested regarding the use of mefloquine for malaria prophylaxis and treatment.
Mangalvedhekar, S.S., et al. 2000. Convulsions in non-epileptics due to mefloquine-fluoroquinolone co-administration. National Medical Journal of India 13(1):47.
Micheo, C., C. Arias, and A. Rovira. 2000. Adverse effects and compliance with mefloquine or chloroquine plus proguanil malaria chemoprophylaxis. Abstract No 83. Second European Conference on Travel Medicine, Venice, Italy.
Peterson, E., T. Ronne, A. Ronn, I. Bygbjerg & S.O. Larsen. 2000. Reported side effects to chloroquine, chloroquine plus proguanil, and mefloquine as chemoprophylaxis against malaria in Danish travelers. Journal of Travel Medicine 7:79-84.
Potasman, I., et al. 2000. Neuropsychiatric problems in 2,500 long-term young travelers to the tropics. Journal of Travel Medicine 7(1):5-9.
Rozendaal, J. 2000. Fake antimalarials circulating in Cambodia. Bulletin Mehong Malaria Forum 7:62-8.
Schiemann, R., et al. 2000. Seizures after antimalarial medication in previously healthy persons. Journal of Travel Medicine 7(3):155-156.
[No author cited.] 2000. Pregnancy and mefloquine prevention of malaria. Prescrire Internationa 9(50):180-181.
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Bygbjerg, I.C. and A.M. Rønn. 1999. [Long-lasting neuropsychiatric side-effects following mefloquine prophylaxis. A case after six weeks of initiating and lasting six months] (in Danish) Ugeskrift for Laeger 161(10):1422-1423.
ABSTRACT: Neuropsychiatric side-effects from mefloquine are well known. When used for prophylaxis, the side-effects have been claimed to be relatively rare, mild and transient, most often arising within two to three weeks, and in patients with a previous history of neuropsychiatric disorders. We here describe a case of severe neuropsychiatric side-effects arising six weeks after initiating mefloquine prophylaxis, requiring repeated hospitalization, and not resolving completely after six months, in a previously healthy 30 year-old female.
Fusetti, M., et al. 1999. [Mefloquine and ototoxicity: a report of 3 cases] (in Italian) La Clinica Terapeutica 150(5): 379-382.
ABSTRACT: We report these cases of high-frequency sensorineural hearing loss and tinnitus, following malaria prophylaxis with mefloquine (Lariam). Only one patient had partial remission of hearing loss after suspension of the treatment. In the remaining two cases the symptomatology remained unchanged. None of the patients reported improvement of tinnitus. Our experience suggests that a routine audiologic evaluation, before and after prophylactic use of antimalarial drugs, is important to monitor potential hearing deficit.
Javorsky, D. and Tremont, G. 1999. Cognitive and neuropsychiatric side effects of the antimalarial drug mefloquine: A case study. Archives of Clinical Neuropsychology. 14(8):649-50. FULL TEXT
Krüger, E., et al. 1999. [Acute paranoid hallucinatory psychosis following mefloquine prophylaxis (Lariam)] (in German) Psychiatrische Praxis 26(5): 252-254.
Minei-Rachmilewitz, T. 1999. [Neuropsychiatric side effects of malarial prophylaxis with mefloquine (Lariam)] (in Hebrew) Harefuah 137(1-2):25-27.
Schlagenhauf, P. 1999. Mefloquine for malaria chemoprophylaxis 1992-1998: A review. Journal of Travel Medicine 6(2):122-133.
Smith, H.R., et al. 1999. Dermatological adverse effects with the antimalarial drug mefloquine: A review of 74 published case reports [FULL TEXT PDF REPRINT]. Clinical & Experimental Dermatology 24(4):249-254.
Voskuil, P.H. 1999. Convulsions during prophylactic use of mefloquine] (in Dutch). Nederlands Tijdschrift Voor Geneeskunde 143(5):273-274.
[author not cited]. 1999. Canadian soldiers used as 'guinea pigs'? CMAJ: Canadian Medical Association Journal 160(13):1814.
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Bregani, E.R., et al. 1998. Mefloquine-induced grand mal seizure in tubercular meningitis. Panminerva Medica 40(4):345-346.
Davis, T.M. 1998. Adverse effects of antimalarial prophylactic drugs: an important consideration in the risk-benefit equation. Annals of Pharmacotherapy 32(10):1104-1106.
Heeringa, M., et al. 1998. [Convulsions during prophylactic use of mefloquine] (in Dutch). Nederlands Tijdschrift voor Geneeskunde 142(45):2477-2480.
"The practising physician should be aware of the possible occurrence of rare neuropsychiatric adverse events like convulsions during the prophylactic use of mefloquine."
Jensen, J.J. 1998. [Mefloquine: Neuropsychiatric adverse effects are often severe and persistent long after withdrawal of the drug] (in Danish). Ugeskrift for Laeger 160(16): 2413.
Leutscher, P.D. [We are driving in circles around malaria prophylaxis] (in Danish). Ugeskrift for Laeger 160(33):4781-4782.
Lysack, J.T., et al. 1998. A severe adverse reaction to mefloquine and chloroquine prophylaxis. Australian Family Physician 27(12):1119-1120.
ABSTRACT: A 23 year old man with no history of neurological or psychiatric illness ingested three weekly 228 mg doses of mefloquine base (250 mg salt) as malaria prophylaxis while in India. He experienced an increasingly severe adverse reaction after each dose, including symptoms of paranoia, hallucinations, and suicidal ideation. The man discontinued mefloquine and continued malaria prophylaxis with chloroquine. Shortly after the first 300 mg dose of chloroquine base (500 mg chloroquine phosphate salt), symptoms acutely intensified and became debilitating. Severe symptoms persisted for 12 months following the discontinuation of both antimalarial drugs.
Potasman, I. and H. Seligmann. 1998. A unique case of mefloquine-induced psoriasis. Journal of Travel Medicine 5(3):156.
Rønn, A.M., et al. 1998. Neuropsychiatric manifestations after mefloquine therapy for Plasmodium falciparum malaria: Comparing a retrospective and a prospective study. [FULL TEXT PDF REPRINT] Tropical Medicine & International Health 3(2):83-88.
[Author not named]. 1998. Mefloquine and malaria prophylaxis. Drug Therapy Bulletin 36(3):20-22.
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Clattenburg, R.N. and C.L. Donnelly. 1997. Case study: Neuropsychiatric symptoms associated with the antimalarial agent mefloquine. Journal of the American Academy of Child and Adolescent Psychiatry 36(11):1606-1608.
ABSTRACT: The development of acute neuropsychiatric symptoms in a 10-year-old boy subsequent to his return from travel abroad in Africa, where he had taken the antimalarial agent mefloquine (Lariam), is reported. A 4-week course of cognitive-behavioral therapy was used to effectively treat this substance-induced anxiety disorder, which had been caused by treatment with mefloquine. A review of the literature about adverse neuropsychiatric effects of mefloquine and the differential diagnosis of malaria is provided. In an age in which international travel is occurring with increasing frequency, it is important to obtain travel histories, including exposure to prophylactic medication, when patients present with acute-onset psychiatric symptoms.Corominas, N., et al. 1997. [Adverse effects associated with antimalarial chemoprophylaxis] (in Spanish). Medicina Clinica (Barcelona) 108(20):772-775.
"Mefloquine presents an outstanding neuropsychiatric toxicity and is worse tolerated in low weight patients."
Croft, Ashley and Paul Garner. 1997. Mefloquine to prevent malaria: A systematic review of trials. British Medical Journal 315(7120):1412 (29 November 1997).
Croft, A.M., et al. 1997. Side effects of mefloquine prophylaxis for malaria: An independent randomized controlled trial. Transactions of the Royal Society of Tropical Medical Hygiene 91:199-203.
Ingram, R.J. and R.B. Ellis-Pegler. 1997. Malaria, mefloquine and the mind. New Zealand Medical Journal 110(1042):137-138.
Laffitte, E. 1997. [Convulsions and mefloquine prophylaxis] (in French). Medecine Tropicale : Revue du Corps de Sante Colonial (Marseilles) 57(3):307.
McBride, S.R., et al. 1997. Fatal toxic epidermal necrolysis associated with mefloquine antimalarial prophylaxis. Lancet 349(9045):101.
Patten, Scot B. and Edgar J. Love. 1997. Drug-Induced Depression. Psychotherapy and Psychosomoatics 66:63-73.
Ravera, M. 1997. Severe adverse reaction to prophylactic use of mefloquine in nonimmune travelers in Hoima District, Uganda. Journal of Travel Medicine 4(3):153-154.
Richter, J., et al. 1997. Aberrant atrioventricular conduction triggered by antimalarial prophylaxis with mefloquine. Lancet 349(9045):101-102.
van Riemsdijk, M.M., et al. 1997. Spontaneous reports of psychiatric adverse effects to mefloquine in the Netherlands. British Journal of Clinical Pharmacology 44(1):105-106.
van Riemsdijk, M.M., et al. 1997. Neuro-psychiatric effects of antimalarials. European Journal of Clinical Pharmacology 52(1):1-6.
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Barrett, P.J., P.D. Emmins, P.D. Clarke and D.J. Bradley. 1996. Comparison of adverse events associated with use of mefloquine and combination of chloroquine and proguanil as antimalarial prophylaxis: postal and telephone survey of travellers. British Medical Journal 313:13 (31 August 1996) [on-line reprint: Is Mefloquine Safe? ]
Behrens, R. 1996. Adverse events associated with mefloquine. Explaining about possible adverse events may reduce problems. British Medical Journal 313(7071):1553-1554.
Clarke, Paul. 1996. Temporarily disabling neuropsychiatric side effects after taking the anti-malarial drug mefloquine (lariam) are more common than previously thought. British Medical Journal 313(7056), 31 August 1996.
Corbett, E.L., et al. 1996. Adverse events associated with mefloquine. Study in returned travellers confirms authors' findings. British Medical Journal 313(7071):1552.
Croft, A.M. and M.J. World 1996. Neuropsychiatric reactions with mefloquine chemoprophylaxis. Lancet 347(8997):326.
Dyer, C. 1996. Legal aid won for malaria drug case. British Medical Journal 313(7058):643.
Fonteyne, W., A. Bauwens and L. Jordaens. 1996. Atrial flutter with 1:1 conduction after administration of the anti-malarial drug mefloquine. Clinical Cardiology 19:967.
Meszaros, K. 1996. Acute psychosis caused by mefloquine prophylaxis? Canadian Journal of Psychiatry 41(3):196.
Meszaros, K. and Kasper, S. 1996. [Psychopathological phenomena in long-term follow-up of acute psychosis after preventive mefloquinine (Lariam) administration] (in German) Der Nervenarzt 67(5):404-406.
ABSTRACT: There are some reports about neuropsychiatric side effects associated with the intake of the antimalarial drug mefloquine. We report a long-term observation of a patient suffering for his first time on an acute psychosis under mefloquine prophylaxis. Mefloquine's role as a drug possibly inducing psychosis and the influence of vulnerability therefore will be discussed.
Phillips, M. 1996. Adverse events associated with mefloquine. Women may be more susceptible to adverse events. British Medical Journal 313(7071):1552-1553.
Phillips, M.A. and R.B. Kass. 1996. User acceptability patterns for mefloquine and doxycycline malaria chemoprophylasis. Journal of Tropical Medicine 3:40-45.
Piening, R.B. and S.A. Young. 1996. Mefloquine-induced psychosis. Annals of Emergency Medicine 27(6):792-793.
Ruff, T. 1996. Mefloquine - A brief review. Australian Family Physician 25(5):793.
Traer-Clark, L. 1996. Adverse events associated with mefloquine. Manufacturer should also give incidence of 'severe' adverse events. British Medical Journal 313(7071):1553.
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Assan, R., et al. 1995. Mefloquine-associated hypoglycaemia in a cachectic AIDS patient. Diabetes/Metabolism 21(1):54-58.
ABSTRACT EXERPT : Clinicians who manage cachectic patients, particularly those with protracted diarrhoea and/or receiving anti-malarial drugs including mefloquine, should be aware of the risk of severe hypoglycaemia.Hessen-Soderman, A.C., et al. 1995. Mefloquine prophylaxis and hearing, postural control, and vestibular functions. Journal of Travel Medicine 2(2):66-69.
Hollweg, M. 1995. [Mefloquine-induced psychoses--problems in etiologic classification based on 2 case reports] (in German). Psychiatr Prax 22(1):33-36.
Lench, P. 1995. Malaria prophylaxis. Psychological problems after mefloquine and chloroquine. British Medical Journal 311(6998):192.
Pous, E., et al. 1995. Mefloquine-induced grand mal seizure during malaria chemoprophylaxis in a non-epileptic subject. Transactions of the Royal Society of Tropical Medicine and Hygiene 89(4):434.
Sowumi, A. 1995. Acute psychosis after mefloquine. Report of six cases. Trop Geogr Med. 47(4):179-80.
ABSTRACT: A self-limiting psychosis characterized by acute onset of visual and auditory hallucinations and poor sleep developed in six adults between 8 and 24 hours after oral administration of 750-1500 mg of the antimalarial mefloquine. All patients had no personal or family history of psychosis and were neurologically and mentally normal before mefloquine ingestion. These cases illustrate that acute psychotic symptoms may occur in patients treated with mefloquine.
Whittes, R.C. and R. Sanginur. 1995. Adverse reaction to mefloquine associated with ethanol injestion. Canadian Medical Association Journal 152:515-517.
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Benardo, M. and E. Parellada. 1994. [Mefloquine and severe psychiatric disorder] (in Spanish). Medicina Clinica (Barcelona) 102(15):596.
Grupp, D., et al. 1994. Neuropsychiatric disturbances after malaria prophylaxis with mefloquine. (in German) Aktuell Neurologie 21:134-136.
A 36 year old man developed neuropsychiatric symptoms after a single dose of mefloquine, which still persisted 18 months later. A causal relationship between the symptomatology of the patient and mefloquine intake appears possible.
Hennequin, C., et al. 1994. Severe psychiatric side effects observed during prophylaxis and treatment with mefloquine. Archives of Internal Medicine 154:2360-2362.
Rønn, A.M. and I.C. Bygbjerg. 1994. [Acute brain syndrome after mefloquine treatment] (in Danish). Ugeskrift for Laeger 156(41): 6044-5.
ABSTRACT: It is known that the antimalarial drug mefloquine may cause neurological side-effects. Only few cases of encephalitis ascribed to mefloquine treatment have been reported. We here describe a 34 year-old female patient with symptoms of acute brain syndrome. The patient was initially treated with mefloquine for infection with P. falciparum. She was rehospitalized 12 days after mefloquine treatment with fever, nausea, dizziness and headache. Her condition worsened and her temperature rose and 15 days after treatment she had generalized convulsions and went into a coma. The EEG was severely abnormal. The patient was discharged 37 days after mefloquine treatment, but it was two months before the EEG was normal and the patient in her usual condition.
Ruff, T.A., et al. 1994. Seizure associated with mefloquine for malaria prophylaxis. Medical Journal of Australia 161(7):453.
Sowumi, A. 1994. Acute psychosis after mefloquine: a case report. East Afrian Medical Journal 71(12):818-819.
ABSTRACT: A self-limiting psychosis characterized by visual and auditory hallucinations and isomnia occurred in a 17-year old male after mefloquine administration for presumed chloroquine resistant falciparum malaria. The attending physician failed to recognise the association between mefloquine and psychosis.Speich, R. and A. Haller. 1994. Central anticholinergic syndrome with the antimalarial drug mefloquine. New England Journal of Medicine 331(1):57-58.
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Gascón, J., et al. 1993. [Severe neuropsychiatric reaction following mefloquine use] (in Spanish). Medicina Clinica (Barcelona) 101(13):515-516.
Marsepoil, T., et al. 1993. [Encephalopathy and memory disorders during treatments with mefloquine] (in French). La Revue de Medecine Interne 14(8):788-791.
Ries, S. 1993. [Cerebral spasm during malaria prophylaxis with mefloquine] (in German). Deutsche medizinische Wochenschrift 118(51-52):1911-1912.
Sowumi, A., et al. 1003. Neuropsychiatric side effects of mefloquine in Africans. Transactions of the Royal Society of Tropical Medicine and Hygiene 87(4):462-463.
Steffen, R., E. Fuchs and J. Schildkhect. 1993. Mefloquine compared with other malaria chemoprophylactic regimens in tourists visiting East Africa. Lancet 341:1299-1303).
1 9 9 2
Bern, J.L., et al. 1992. Mefloquine prophylaxis: An overview of spontaneous reports of severe psychiatric reactions and convulsions. Journal of Tropical Medicine and Hygiene 95(3):167-79.
Brasseur, P., et al. 1992. Multi-drug resistant falciparum malaria in Cameroon 1987-88. American Journal of Tropical Medicine and Hygene 46:8-14.
Bunnag, D., et al. 1992. Fansimef for prophylaxis of malaria: a double-blind randomized placebo controlled trial. Southeast Asian Journal of Tropical Medicine and Public Health 23(4):777-782.
Caillon, E., et al. 1992. Acute depressive symptoms after mefloquine treatment. American Journal of Psychiatry 149(5):712.
Folkerts, H. and H. Kuhs. 1992. [Psychotic episode caused by prevention of malaria with mefloquine. A case report] (in German). Der Nervenarzt 63(5):300-302.
ABSTRACT: We report on a 41 year old woman, who after 750 mg mefloquine, a newer antimalarial agent, developed a psychosis with dizziness, confusion and delusions. The symptoms were more intensive and remained longer than hitherto reported in the literature. A total of 23 patients are known to have had psychiatric adverse effects under mefloquine. Psychotic episodes are undoubtedly though rarely associated with the intake of mefloquine.
1 9 9 1 & Before
Besser, R. and G. Krämer. 1991. [Suspected convulsive side-effect of mefloquine (Lariam)] (in German). Der Nervenarzt 62(12):760-761.
De Gennes, C. 1991. [Panic attack after therapeutic administration of mefloquine] (in French). Ann. Med. Interne (Paris) 142(8):631.
Singh, K., et al. 1991. Seizures after mefloquine. Annals of Internal Medicine 114(11): 994.
Weinke, T., et al. 1991. Neuropsychiatric side effects after the use of mefloquine. American Journal of Tropical Medicine and Hygiene 45(1):86-91.
ABSTRACT: This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.
Gascón, J., et al. 1990. [Side-effects of the antimalarial mefloquine. Presentation of 20 cases] (in Spanish). Medicina Clinica (Barcelona) 95(7): 277.
Rodor, F., et al. 1990. [Recurrent psychiatric manifestations during malaria prevention with mefloquine. A case report] (in French). Therapie 45(5):433-434.
ABSTRACT: The authors report the case of a 22 years old woman without psychiatric antecedent who started a prophylaxis with mefloquine for a journey in a chloroquino resistant area. The first tablet induced an acute psychiatric syndrome which lasted five days; the second tablet induced the recidive of the psychiatric data and a suicide attempt by drowning.
Stürchler, D., et al. 1990. Neuropsychiatric side effects of mefloquine. New England Journal of Medicine 322(24):1752-1753.
Björkman, A. 1989. Acute psychosis following mefloquine prophylaxis. Lancet 2(8667):865.
Hellgren, U. and L. Rombo. 1989. [Neurologic side effects of mefloquine. Implications for prevention and self administration] (in Swedish). Lakartidningen 86(52):4592.
Patchen, L.C., et al. 1989. Neurologic reactions after a theraputic dose of mefloquine. New England Medical Journal 321(20):1415-1416.
Rouveix, B. 1989. Mefloquine and an acute brain syndrome. Annals of Internal Medicine 110(7): 577-578.
Stuiver, P.C., et al. 1989. Acute psychosis after mefloquine. Lancet 2(8657):282.
Bernard, J. 1987. [Toxic encephalopathy caused by mefloquine?] (in French). La Presse Medicale 16(33):1654-1655.
Stuby, K., et al. 1983. [A case of chloroquine-resistant tropical malaria from eastern Africa (Kenya)]. Schweizerische Medizinische Wochenschrift 113(7):258-260. [in German].
PLEASE NOTE - This bibliography highlights the adverse effects of mefloquine; it is not a comprehensive review of the literature.
Specific search engines exist for medical and scientific literature databases. PubMed is one freely-available database.
Hettena, Seth. 2005. Worry spreads over GI drug side effects. The Las Vegas Sun. 23 Feb 2005.
* Lawton, Wendy. 2004. Malaria drug blocks brain conduits, a boon for neuroscience research. Medical News Today. 7 Aug 2004. [ see Cruikshank et al. 2004 above for research article reference. ]
United Press International's investigative series on Lariam. (March 2002 and on-going).
Shapiro, Joseph. 2004. Illness Troubles Troops Back from Iraq. National Public Radio (NPR), Weekend Edition Saturday, 24 July 2004.
Leher, Brian. 2004. Interview with Andrew Pogany, The Brian Lehrer Show, WNYC radio, June 15, 2004.
News in brief. 2004. Danish court rules against Roche. British Medical Journal 28: 364.
Benjamin, Mark & Dan Olmsted. 2004. VA alerts doctors to malaria-drug concerns. United Press International. 24 July 2004.
Benjamin, Mark & Dan Olmsted. 2004. Exclusive: Army surrenders to 'coward' GI. United Press International. 15 July 2004.
16 July 2004. U.S. Senator Diane Feinstein Press Release. Senator Feinstein urges HHS to evaluate safety of Lariam use by Americans overseas.
Kelley, Eileen. 2004. Soldiers blame ills on drug. The Denver Post. 11 June 2004.
Benjamin, Mark & Dan Olmsted. 2004. Malaria-drug diagnosis for 'coward' GI. United Press International. 4 June 2004.
Werner, Erica. 2004. Concerns growing about anti-malarial drug given to U.S. troops. SFgate.com / San Francisco Chronicale (Associated Press). 3 June 2004.
Jontz, Sandra. 2004. 7 servicemembers 'likely' ill from malaria drug. Stars and Stripes (Pacific Edition), 30 May 2004.
Benjamin, Mark & Dan Olmsted. 2004. Drug causing GIs permanent brain damage. United Press International. 26 May 2004.
INSIGHT with Jonathan Mann. 2004. Harmful Side Effects of Lariam [PDF transcript]. CNN International. 26 May 2004.
24 May 2004. U.S. Senator Diane Feinstein Press Release. Senator Feinstein urges Secretary Powell to reassess Lariam use by State Department employees.
2004. [Author not cited] Editorial/Opinion: Drug used in malaria fight deserves closer scrutiny. USA Today 8 March 2004.
Benjamin, Mark & Dan Olmsted. 2004. Pentagon eyes malaria drug in suicides. United Press International. 25 February 2004.
[Author not cited]. 2004. FDA requires warnings on anti-malaria drug Lariam. Consumer Report. 69(1):45.
Benjamin, Mark & Dan Olmsted. 2004. Army won't review medication in suicides. United Press International. 29 January 2004.
Krug, Laura L. 2003. Graduate's Death Prompts Scrutiny of Common Malaria Drug. The Harvard Crimson Online. 1 August 2003.
Benjamin, Mark and Dan Olmsted. 2003. Malaria Drug Warning Follows Problems. UPI International. 10 July 2003.
60 Minutes II. 29 January 2003, The Dark Side of Lariam. CBS News.
Fifth Estate [1-hour program]. 16 October 2002. The Nightmare Drug. CBC TV, Canada.
Honigsbaum, Mark. 2002. It's not a benign drug - it has ruined my life. The Guardian, 24 October 2002.
Fuhrmans, Vanessa. 2002. Malaria Pill's Side Effects Raise Issues About Safety. The Wall Street Journal Online, 4 September 2002.
[Author not cited.] 2002. Lariam's Legacy. Consumer Reports. March 2002.
United Press International (UPI). 2002. Anti-malaria drug Lariam and suicide. International Desk, 21 May 2002:
"WASHINGTON, May 21 (UPI) - Mounting evidence suggests the anti-malaria drug Lariam - prescribed to Peace Corps volunteers, travelers and U.S. soldiers - has triggered mental problems so severe that in a small percentage of users it has led to suicide. Lariam - also known as mefloquine - is a product of Hoffmann-La Roche, a giant Swiss pharmaceutical company with U.S. headquarters in Nutley, N.J. Lariam has been prescribed to more than 22 million people worldwide since 1985. It was cleared for use in the United States in 1989. Some health experts charge that neither patients nor doctors in the United States are being adequately warned about the risk of suicide from taking Lariam, which is prescribed by U.S. doctors 1,000 times every day."Benjamin, Mark and Dan Olmsted. 2002. Suicides, Attempts from FDA Database. UPI Washington Politics & Policy Desk. 21 May 2002.
Benjamin, Mark and Dan Olmsted. 2002. UPI Investigates: Lariam and Sucicide. UPI Washington Bureau. 21 May 2002.
Benjamin, Mark and Dan Olmsted. 2002. Lawmaker Slams Drug Company on Suicides. UPI: Washington Politics & Policy Desk, 24 May 2002.
Benjamin, Mark and Dan Olmsted. 2002. UPI Investigates: Lariam and Peace Corps. UPI: Washington Politics & Policy Desk, 30 July 2002.
Benjamin, Mark and Dan Olmsted. 2002. Lariam Connection to Bragg Killings? UPI: Washington Politics & Policy Desk, 7 July 2002.
Benjamin, Mark and Dan Olmsted. 2002. Experts Question Fort Bragg Investigation. UPI: Washington Politics & Policy Desk, 8 August 2002.
Benjamin, Mark and Dan Olmsted. 2002. Army Eyes Malaria Drug in Bragg Killings. UPI: Washington Politics & Policy Desk, 9 August 2002.
Marsha, Linda. 2001. When Good Drugs Do Harm. The Los Angeles Times. 8 January 2001.
Lariam Action USA. 2001. Press Release: Neuropsychiatric Side Effects Confirmed by Latest Lariam Research. February 2001.
Torassa, Ulysses. 2001. Paring Anti-Malaria Drugs Could Be Fatal Combination. The San Francisco Chronicle. 18 March 2001, page T6.
Donald, Lisa. 2001. How Far Can You Rely on the Professionals? The Daily Telegraph (London). 24 March 2001, page 4.
[Author not named]. 2001. I Risked My Health to Stop Getting Sick. Sun Herald (Sydney). 25 March 2001, Travel section, page 70.
Weaver, Carolyn. 2001. Unintended Damage. Voice of America webcast. 7 April 2001.
Torassa, Ulysses. 2001. A New Complaint Against Lariam: Bad Business Deals. San Francisco Chronica. 8 April 2001, Travel section, page T10.
Rowlands, Barbara. 2001. A Better Pill for Preventing Malaria. The Daily Telegraph (London). 27 April 2001, page 20.
News Now. 2001. Science Segment on Lariam. Voice of America. 17 May 2001.
Sheftell, Jason. 2001. The Nightmare Drug. GEAR Magazine. May 2001.
Sunderland, Alan. 2000. Lariam - A Bad Trip. Insight television show. SBS TV, Australia (17 Feb).
Sutton, Russell. 2000. The Problems with Lariam. aPieceOfUs e-'zine. Issue 8 (22 Mar).
SBS TV Australia. 2000. Insight program: "Lariam: A Bad Trip" (17 February).
Borcover, Al. 2000. Travelers' Dilemma: Take Anti-Malaria Drugs, But Get All of the Facts First, Chicago Tribune (14 June).
Dawood, Richard. 2000. Malaria: Why You Are Denied the Drugs that Could Save Your Life, The Telegraph (13 March).
Harris, Paul. 2000. British Troops Risk Brain Damage from Malaria Pill. The Observer. 10 September 2000, page 6.
Stuttaford, Thomas (Dr.). 2000. Better Ways to Treat Malaria. The Times (London). 21 September 2000.
Epstein, Keith. 2000. The Lariam Files. The Washington Post. 10 October 2000, page Z12.
O'Connor, Alison. 1999. I Was Told It Was Only Media Hype. The Irish Times (1 February 1999).
O'Connor, Alison. 1999. The Malaria Dilemma. The Irish Times (1 February 1999).
Winokur, Scott. 1998. Some Find Malaria Drug Worse Than the Disease. San Francisco Examiner May 17, 1998.
Lewon, Dennis. 1999. Malaria's Not So Magic Bullet. Escape Magazine (July 1999), page 16.
Cummins, John (Member of Canadian Parliment). 1998. "Military Brass Covers Up Drug Problem" (letter), Ottawa Citizen (25 June), page A14.
Cummins, John (M.P.). 1998. "Auditor General to Probe Mefloquine Use by Canadian Forces", 9 December News Release.
Winokur, Scott. 1998. Malaria Drug Called Worse Than Disease, San Francisco Examiner (17 May).
Parris, Matthew. 1998. I Think I'd Rather Have Malaria, Times [London] Weekend (4 April).
Laurance, Jeremy. 1997. Fears over malaria drug after girl dies The Times, 27 January 1997.
Stuttaford, Thomas (M.D.). 1997. Acure that can be lethal The Times, 30 January 1997.
Williamson, Nigel. 1996. Victims of malaria pill start legal fight The Times, 6 February 1996.
Ransdell, Eric. 1997. Lariam's Sting Outside Magazine, September issue, page 110.
CTV Network Canada. 1997. W5 Series: "Mefloquine Nightmare" (14 October). [purchase video].
Duffy, Andrew & Mike Blanchfield. 1997. Military probes malaria drug: MP says drug linked to Somalia incidents. The Ottawa Citizen. 16 April 1997.
Wade, Betsy. 1997. Warding off malaria. New York Times, 20 April 1997.
Cole, Lance. 1997. Lariam [Letter to the Editor]. New York Times, 18 May 1997.
Dawood, Richard. 1997. The lariam effect: outcry over malaria drug. Condé Nast Traveler, page 20.
1996. Adverse reactions. Nursing Times (12 June 1996) 92(24):16-17.
Thompson, Clare. 1996. Malaria pill stands accused. New Scientist (27 April 1996).
Dyer, Clare. 1996. Legal aid won for malaria drug case British Medical Journal 313(7508), 14 Sept 1996.
Nutt, Kathleen. 1996. War veteran: I was crippled by malaria pill. Western Daily Press, 29 March 1996, page 1-2.
1996. My deathly fear, by malaria pill 'victim'. Western Daily Press, 7 June 1996.
Williamson, Nigel. 1996. Patients say GPs failed to outline malaria drug risks The Times, 27 January 1996.
To Lariam or not to Lariam Sheldon Johnston, Australia
Malaria prophylaxis British Medical Journal
Current Views on Malaria Prophylaxis review by Dr. A. Goldman
Mefloquine and neuropsychiatric reactions (DH Circ. No. 216/96)
The Lariam Debate? by Joanna
Die Mefloquin-Kontroverse (text Deutsch; many links are in English)
Chromtech - mefloquine the chemical structure of mefloquine
Lariam Use Survey
Lariam Discussion on-line discussion forum
Dr. Manuel Pattaroyo discusses the discovery of an anti-malaria vaccine
Bednets for Malaria Control in Benin
Mefloquine/Lariam Side Effects |Deutsche Christoph Harmann, Germany
Lariamed Ernst Boere, the Netherlands
The Manufacturer's (Roche) Lariam Product Information (for U.S. only, not complete information)
MK's InfoBahn Off-Ramps Africa, malaria, neurology links
Research Guide (tips on how to find information)
Lariam Action USA
64 El Pavo Real Circle
San Rafael, CA 94903-3521 USA
Phone: 415.492.8424 (leave message)
Lariam Action UK
Lariam Info UK
Mefloquine Action IRELAND
138 Dublin Road
Lariam Victims in DENMARK
founded 21 March 1999
Hanne Meister, spokeswoman
Phone: +45 39641972
Lariam Action SWITZERLAND
See Humberto's Personal Page (en français)
Lariam Action AUSTRALIA
Medical Products Reporting Program
U.S. Food and Drug Administration
5600 Fishers Lane
Rockville, MD 27052-9787 USA
800.332.1088 to request a copy of the Adverse Reaction and
Product Problem Reporting Form for U.S. consumers
If you have suffered an adverse reaction to lariam, please call the toll-free FDA number above and fill out an Adverse Reaction Form. This is the only formal mechanism by which individuals can inform the U.S. FDA of potentially serious problems related to approved drugs.
NOTE: The FDA's definition of "disability" is "...if the adverse event resulted in a significant, persistent or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities and/or quality of life."
Internationally, law suits have been filed in Ireland, Canada, Denmark, and the United States.
A class action (with approximately 300 members) was started against Hoffmann-La Roche in 1996 by the former law firm of Larence Tucketts. After three years nothing was adjudicated in terms of liability on the part of Roche. The class action was officially withdrawn in 1999, due in large part to the increasing financial burden on the class members.
Individual lawsuits have been filed in several different states against Hoffmann-La Roche. The U.S. Plaintiffs allege that "the manufacturer failed to warn them (and the rest of the public) of the true frequency, severity and duration of the serious side effects associated with Lariam."
For more information, contact:Susan Rose, Attorney at Law
Silver Spring, MD
E-mail : email@example.com
"Danish court rules against Roche: A Danish court has ruled that Roche, the manufacturer of the antimalarial drug mefloquine (Lariam), failed to issue patient information leaflets with the drug in Denmark, despite instructions from the government that it must do so. A traveller who experienced severe mental disturbances after taking two tablets successfully argued that neither he nor his doctor were aware of the side effects. The court ordered Roche to pay Kr10 700 (£980; $1820; €1440) in compensation."
-- News in brief. 2004. British Medical Journal 28: 364.