Mania Associated With Mefloquine Prophylaxis

Abstract

Values are expressed as mean T SD, t tests, P values (week 24: responders only). Covance laboratory upper limit of normal range for adolescents: males 16.1 Kg/L, females 29.0 Kg/L. LOCF indicates last observations carried forward; NA, not applied.

Behavioral effects of mefloquine in tail suspension and light/dark tests

“…Moreover, a decrease in immobility was seen in the tail suspension test with the highest dose, further suggesting the occurrence of an altered emotional state; lower doses, however, had no effect on immobility. This study provides converging evidence consistent with case reports of emotionally disinhibited behavior associated with mefloquine exposure (Yelmo et al 2010 ; Piening and Young 1996 ).…”

“…Of relevance to the current work is the association of mefloquine with both depression and mania, both of which have been identified in case studies (Yelmo et al 2010 ; Caillon et al 1992 ; Javorsky et al 2001 ; Whitworth and Aichhorn 2005 ; Piening and Young 1996 ). It is possible that mefloquine’s stimulatory effects—through antagonism of adenosine receptors (Alisky et al 2006 ; Shepherd 1988 ) or other mechanisms—could produce manic-like behavior within a short time after administration.…”

“…It is possible that mefloquine’s stimulatory effects—through antagonism of adenosine receptors (Alisky et al 2006 ; Shepherd 1988 ) or other mechanisms—could produce manic-like behavior within a short time after administration. Moreover, due to mefloquine’s long-half life in the body, continued stimulation of adenosine receptors over the course of many days could continuously interfere with sleep, leading to symptoms of depressed mood rather than mania; indeed, insomnia is one of the most common adverse effects reported (Yelmo et al 2010 ).…”

“…Mefloquine was developed at the Walter Reed Army Institute of Research in the 1970’s and had been marketed under the trade name Lariam, among others (Nevin 2012b ). Due to its long half-life in the body (Yelmo et al 2010 ), allowing for weekly rather than daily treatment, and its efficacy against chloroquine-resistant forms of the disease (Nevin 2012b ), mefloquine was employed widely among travelers to areas where malaria infection was likely (Nevin 2012b ; Petersen et al 2000 ; van Riemsdijk et al 1997 , 2005 ; Phillips and Kass 1996 ) including members of the U.S. military deployed overseas to such areas as Iraq and Afghanistan (Nevin 2010 ; Peterson et al 2011 ; Vuurman et al 1996 ).…”

“…Initially it was believed that side effects were rare (1 in every 10,000 cases; Choo 1996 ). Yet, numerous case studies of travelers with (Wittes and Saginur 1995 ; Even et al 2001 ; Peterson et al 2011 ) and without complicating factors such as a prior history of psychiatric difficulties (Nevin 2012a ; Yelmo et al 2010 ) suggest that exposure to prophylactic regimens of mefloquine or higher treatment doses are associated with side effects, including insomnia (Yelmo et al 2010 ), depression (Caillon et al 1992 ; Javorsky et al 2001 , Whitworth and Aichhorn 2005 ), manic behavior and/or bipolar disorder (Piening and Young 1996 ; Yelmo et al 2010 ), mental confusion and concentration difficulties (Javorsky et al 2001 ; Nevin 2012a ; Tor et al 2006 ), and memory impairment (Javorsky et al 2001 ; Nevin 2012a ). Especially troubling are reports of symptoms indicative of mania and confusional psychoses, including symptoms of insomnia, elevated mood and energy, disinhibition in social interactions, delusions and hallucinations (Björkman 1989 ; Javorsky et al 2001 ; Kukoyi and Carney 2003 ; Peterson et al 2011 ; Piening and Young 1996 ; Stuiver et al 1989 ; Tor et al 2006 ), which have been shown to respond to treatment with antipsychotics (Piening and Young 1996 ; Tor et al 2006 ).…”