Ca
Report
Levetiracetam-induced rage and suicidality:Two ca reports and review of literature
Orakwue A.Molokwu ⁎,Birinus A.Ezeala-Adikaibe,Ikenna O.Onwuekwe
Department of Medicine,University of Nigeria Teaching Hospital,Ituku Ozalla,P.M.B.01129Enugu,Nigeria
a b s t r a c t
a r t i c l e i n f o Article history:
Received 5July 2015
Received in revid form 12July 2015Accepted 13July 2015Available online xxxx Keywords:
Levetiracetam-induced rage Kepprage Suicidality
Antiepileptic drug Adver drug reaction Southeast Nigeria
Background:Levetiracetam-induced rage is a rare neurobehavioral adver effect of levetiracetam that is charac-terized by ething rage,uncontrollable anger,fits of fury,depression,violence,and suicidal tendencies.It occurs more in patients with prior mood or psychotic disturbances.No such ca has been reported in Nigeria.
Method:We report two cas of levetiracetam-induced rage.The first patient was a 29-year-old male with a 14-year history of intractable posttraumatic epilepsy.He was initially placed on sodium valproate and phenobarbi-tone and later had phenobarbitone replaced with levetiracetam.Within the first week of initiating levetiracetam,he became aggressive,bursted into fits of fury,and attacked his siblings.Levetiracetam was stopped,and the ething rage cead only to reappear when it was reintroduced;hence,the complete withdrawal of levetirace-tam.Naranjo probability score for adver drug reaction was 8.
Results:The cond patient was a 23-year-old lady who developed ething rage and made veral attempts to kill herlf with a knife following addition of levetiracetam to the clonazepam and carbamazepine that she was taking for treatment-resistant epilepsy.Withdrawal and reintroduction of levetiracetam by the relatives led to cessation and reemergence,respectively,of the rage and suicidal tendencies.Naranjo score was 8.Leveti-racetam was discontinued.
Conclusion:Neuropsychiatric evaluation for prior mood or psychiatric disorders in tho initiating levetiracetam therapy is suggested alongside monitoring for early features of levetiracetam-induced rage by both caregivers and physicians.This will help stem the morbidity and potential mortality associated with this life-threatening ad-ver drug reaction.
©2015The Authors.Published by Elvier Inc.This is an open access article under the CC BY-NC-ND licen
(creativecommons/licens/by-nc-nd/4.0/).
1.Introduction
Epilepsy is a chronic neurologic condition characterized by recurrent izures [1].It is estimated that
鸟类栖息地
about 70million people worldwide are affected with epilepsy [2].Approximately 70–80%of patients with epi-lepsy (PWE)achieve izure control with one or more antiepileptic drugs (AEDs)[3].Unfortunately,20–30%of PWE will continue to have izures despite active treatment and are considered candidates for ep-ilepsy surgery [4].Paucity of facilities for epilepsy surgery has made polytherapy using different AED combinations the only option for this group of patients in most parts of sub-Saharan Africa.Newer AEDs such as levetiracetam have become increasingly available in Nigeria and have helped in achieving izure control in some of the drug-resistant epilepsies.Unfortunately,the association of levetiracetam and an untoward rare neurobehavioral adver effect is increasingly being reported globally.It is characterized by ething rage,文化创新的根基>试论
uncontrollable anger,fits of fury,depression,violence,and suicidal ten-dencies.Levetiracetam-induced rage and suicidality occur more in pa-tients with prior psychiatric disturbance [5,6];we report two cas of levetiracetam-induced rage in which one of the cas had veral sui-cide attempts.2.Ca prentation
The first patient was a 29-year-old male who fell from a two-storey building at 2months of age and subquently developed intractable i-zures and left hemiparesis.His body mass index was 28.4kg/m 2(weight:86kg,height:1.74m).Initially,he took sodium valproate (600mg BD)and phenobarbi
tone (60mg tds).His phenobarbitone was replaced with levetiracetam at a starting do of 250mg twice daily for one week and then escalated to 500mg twice daily for the next four weeks.
Within the first week of taking levetiracetam,he became aggressive,bursted into fits of fury,and attacked his siblings.Levetiracetam was stopped,and the ething rage cead only to reappear when it was reintroduced;hence,the complete withdrawal of levetiracetam.Naranjo score or adver drug reaction probability was ,+1for
Epilepsy &Behavior Ca Reports 4(2015)79–81
中国风壁纸⁎Corresponding author at:Neurology Unit,Department of Medicine,University of Nigeria Teaching Hospital,Ituku Ozalla,P.M.B.01129Enugu,Nigeria.Tel.:+2348035437736.
E-mail address: (O.A.
Molokwu).
dx.doi/10.1016/j.ebcr.2015.07.004如何亲吻
2213-3232/©2015The Authors.Published by Elvier Inc.This is an open access article under the CC BY-NC-ND licen (creativecommons/licens/by-nc-nd/4.0/
).
Contents lists available at ScienceDirect
Epilepsy &Behavior Ca Reports
j o u r na l ho m e p a g e :w w w.e l s e v i e r.c o m /l o c a t e /e b c r
the prence of previous conclusive reports on this adver reaction, +2for appearance of the adver event following initiation of the suspected drug,+1for improvement of the adver event following discontinuation of the suspected drug,+2for reemergence of the reac-tion following readministration of the drug,and+2for the abnce of an alternative explanation for the adver event).
The cond patient was a23-year-old lady who developed ething rage and made veral attempts to kill herlf with a knife after two weeks of initiating adjunctive levetiracetam at a starting do of 250mg twice daily for thefirst week and then500mg twice daily sub-quently.She had been on clonazepam and carbamazepine for treatment-resistant epilepsy.Her body mass index was20.31kg/m2 (weight:52kg,height:1.60m).Withdrawal and reintroduction of leve-tiracetam by the relatives led to cessation and reemergence,respective-ly,of the rage and suicidal tendencies.Naranjo score was8as in thefirst patient.Levetiracetam was discontinued,and the levetiracetam-in-duced rage cead.
3.Discussion
An adver drug reaction(ADR)describes any noxious and unin-tended respon to a drug that occurs at dos normally ud in man for prophylaxis,diagnosis,therapy,or modification of a physiological function[7].Clinically significant ADRs following emergent AEDs can cau rious morbidity and mortality if unrecognized[8].Levetirace-tam is one of the emergent antiepileptic drugs that has become avail-able to patients with epilepsy in sub-Saharan Africa,especially Nigeria. Levetiracetam-induced rage is a rare neuropsychiatric ADR character-ized by ething rage,uncontrollable anger,fits of fury,depression,vio-lence,and suicidal tendencies.Levetiracetam-induced rage occurs more in patients with prior mood or psychiatric disturbance[5,6].
Our multiple cas were patients who were being managed for drug-resistant epilepsy using multiple medications.Levetiracetam was ud to replace phenobarbitone in thefirst patient who was also taking car-bamazepine;levetiracetam was added to carbamazepine and clonaze-pam in the cond patient.In both of the patients,there was reduction in izure frequency despite the ething rage,fits of fury, aggressiveness,and suicidal tendencies(the cond patient).In addi-tion,thefirst patient had no prior mood or psychiatric disturbance though he was overweight and had a history of traumatic brain injury; the cond patient was initially managed for depression and had a normal wei
ght.In both of the patients,the neuropsychiatric features started in thefirst week of commencing levetiracetam and became well established by the cond week of therapy.Thefirst patient had the neuropsychiatric adver effect while on250mg twice daily of levetiracetam;the cond patient was commenced on250mg of levetiracetam twice daily for thefirst week and subquently escalated to500mg twice daily.
Causality asssment describes the evaluation of the likelihood that
a particular treatment is responsible for an obrved adver event
[9].The objective causal asssments are predicated on four basic principles—temporal eligibility,dechallenge and outcome,rechallenge and outcome,and confounding factors[10].The Naranjo algorithm as-ss the probability that an adver event is related to a particular drug therapy bad on a list of weighted questions,which examine fac-tors such as the temporal association of drug administration and event occurrence,alternative caus for the event,drug levels,and previous patient experience with the medication[11].Both of the patients had a Naranjo score of8meaning that it is probable that the neuropsy-chiatric manifestations en in the patients are condary to levetirac-etam intake.
In a cohort of71Korean subjects with drug-resistant epilepsy(DRE) receiving adjunctive levetiracetam,3of them(4.2%)had suicidal ten-dencies which led to the discontinuation of the drug[6].The investiga-tors had argued that forced normalization,a phenomenon whereby depressive or psychotic episodes develop in patients who become izure-free after having suffered from DRE would not explain their finding as only1of their patients who developed suicidal tendency had izure control[12].In another study,4out of517Caucasian pa-tients(0.7%)taking levetiracetam reported suicidal ideation[13].
It is worthy of note that while previous literature associates leveti-racetam-induced rage and suicidal tendencies in patients with prior his-tory of mood or psychiatric disorder[5,6,13,14],newer studies and ca reports have described de novo prentation of levetiracetam-associat-ed rage and suicidality in the abnce of prior history of mood or psychi-atric disorder[15,16].Thefirst patient prented here did not have any prior psychiatric disorder and,thus,supports de novo prentation of levetiracetam-associated rage.
Our cond patient demonstrated an apparent do-dependent rage, aggressiveness,and suicidal tendencies similar to what has been previ-ously documented[15].Thefirst patient,on the other hand,had the as-sociated rage and aggressiveness in a do-independent manner which would sug
gest that patient-related factors may be related to the devel-opment of this adver effect.
Our patients'izures,though reduced in frequency,were not yet controlled with the adjunctive levetiracetam.This implies that forced normalization would also not explain their neuropsychiatric ADR.
From the foregoing,levetiracetam-associated rage,aggressiveness, and suicidal tendencies appear to occur rarely in PWE.Both xes may be affected,the adver effect could be do-dependent or do-independent,and it may occur de novo or on a background of prior psy-chiatric disorder and is not readily explainable by the theory of forced normalization.
The strength of thefindings though germane and worthy of con-sideration pales in significance considering the fact that they are predi-cated on results from only two PWE taking levetiracetam.Nevertheless, a well designed prospective study to determine the prevalence and pre-dictors of levetiracetam-induced rage and suicidality in a large cohort of Nigerian PWE taking levetiracetam is suggested.
4.Conclusion
Neuropsychiatric evaluation for prior mood or psychiatric disorders in tho initiating levetiracetam treatment is suggested alongside con-tinual monitoring for early features of levetiracetam-induced rage and suicidality by both caregivers and physicians.This will help in stemming the adver morbidity and potential mortality associated with this ad-ver effect.
Conflicting interest
早安的情话The authors have no conflict of interest to disclo.
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