Lamotrigine improves aggression in patients with temporal lobe epilepsy
Research highlights
► The BAQ was used to evaluate aggression in patients with TLE. ► Comparison with 115 healthy subjects, the 21 patients with TLE had higher BAQ scores. ► Lamotrigine improved the patient’s BAQ scores. ► Anger, the affective factor of aggression in the BAQ, was especially improved.
Introduction
Aggression is a personality characteristic and is related to antisocial behavior, though its significance in patients with TLE is a highly controversial issue [1]. According to a previous review [2], patients with TLE are more aggressive than those with other types of epilepsy. However, a problem encountered when studying aggression is its phenomenological and neurobiological heterogeneity, leading to difficulties in assessment and classification [1]. Nevertheless, one line of studies of aggression has consistently recognized at least two subtypes, impulsive and premeditated [1], [3], [4], [5]. Impulsive aggression is typically described as an emotionally charged aggressive response characterized by loss of behavioral control, with behavior that is less structured and defensive [1]. In contrast, premeditated aggression is considered to be displayed in a predatory, goal-directed, and controlled aggressive manner that is usually instrumental in nature [1]. Behavior associated with this type is well structured and purposeful and performed in an emotionally calm state [1]. Stanford et al. suggested that antiepileptic drugs may be applicable to the treatment of impulsive aggression [6]. In recent years, these drugs have become increasing popular for the management of emotional disturbances in patients with psychiatric disorders.
In the present study, we targeted patients with TLE who showed aggression and evaluated the effects of lamotrigine (LTG) on this symptom using the Buss–Perry Aggression Questionnaire (BAQ), a self-rating scale designed for assessing aggression. The BAQ is based on a four-factor model consisting of instrumental, motor, emotional, and cognitive components, which enables phenomenological analysis of aggression in patients with TLE [7], [8], [9].
Lamotrigine is a broad-spectrum antiepileptic drug applicable to partial as well as generalized epilepsy, although it may also have unique psychotropic actions. Many authors have indicated that LTG has antidepressant effects in patients with epilepsy [10], [11], [12], [13], [14], [15]. Furthermore, Labiner et al. suggested that adjunctive LTG improves Anger–Hostility subscale scores of the Profile of Mood States (POMS) significantly more robustly when compared with levetiracetam in patients with partial seizures [16]. Emotional disturbances are major obstacles to improving quality of life in patients with TLE. Therefore, it would be beneficial if LTG could contribute to stabilization of aggression.
Section snippets
Subjects
We enrolled 23 adult patients with TLE (10 males, 13 females), who were diagnosed based on the 1989 International League Against Epilepsy classification. They were either in- or outpatients of the Department of Neuropsychiatry of Aichi Medical University Hospital, and were selected based on the following criteria: (1) seizures that failed to respond to at least one antiepileptic drug and newly given LTG as an adjunct treatment; (2) age ≥ 20 years; (3) no active psychotic state; (4) neither
Comparison of BAQ scores between patients with TLE and control subjects in Table 2
The patient group obtained a significantly a higher Total score as well as higher scores on three subscales—Physical Aggression, Anger, and Hostility—as compared with the control subjects (P = 0.003, 0.025, 0, and 0.008, respectively).
Comparison of patients’ BAQ scores between baseline and endpoint
We also compared the baseline and endpoint BAQ scores of the patients with TLE, as outlined in Table 3. BAQ Total score was significantly improved by the endpoint (P = 0.002). However, of the four BAQ subscales, only the Anger score was significantly improved at the
Discussion
According to a previous review, patients with TLE are more aggressive than those with other types of epilepsy [2]. In general, interictal depression is the most common emotional disturbance seen in patients with TLE, and it frequently accompanies aggressive moods ranging from irritability to explosive anger or rage [18], [19]. Blumer et al. highlighted the characteristic association between interictal depression and anger in patients with epilepsy and designated this dysphoric type of mood
Acknowledgment
The authors express their thanks to Dr. Chiaki Matsudaira for dedicated cooperation.
References (28)
- et al.
Subtypes of aggression and their relevance to child psychiatry [review]
J Am Acad Child Adolesc Psychiatry
(1997) Psychometric evaluation on the Japanese adaptation of the Aggression Questionnaire
Behav Res Ther
(2001)- et al.
Effect of lamotrigine on depressive symptoms in adult patients with epilepsy
Epilepsy Behav
(2007) - et al.
Lamotrigine in patients with epilepsy and comorbid depressive symptoms
Epilepsy Behav
(2007) - et al.
Improved mood states with lamotrigine in patients with epilepsy
Epilepsy Behav
(2004) - et al.
Lamotrigine monotherapy improves depressive symptoms in epilepsy: a double-blind comparison with valproate
Epilepsy Behav
(2001) - et al.
Improvement in depression associated with partial epilepsy in patients treated with lamotrigine
Epilepsy Behav
(2002) - et al.
Violence and postictal psychosis: a comparison of postictal psychosis, interictal psychosis, and postictal confusion
Epilepsy Behav
(2010) - et al.
Depression in epilepsy: a common but often unrecognized comorbid malady
Epilepsy Behav
(2000) - et al.
Lamotrigine as a promising approach to borderline personality: an open case series without concurrent DSM-IV major mood disorder
J Affect Disord
(1998)
Borderline personality disorder in patients with bipolar disorder and response to lamotrigine
J Affect Disord
Affective aggression in patients with temporal lobe epilepsy: a quantitative MRI study of the amygdala
Brain
Temporal lobe epilepsy and aggression
J Nerv Ment Dis
Brain research and violent behavior: a summary and evaluation of the status of biomedical research on brain and aggressive violent behavior—clinical studies
Arch Neurol
Cited by (15)
Differences in aggression as psychiatric side effect of levetiracetam and perampanel in patients with epilepsy
2022, Epilepsy and BehaviorCitation Excerpt :In a study of PER conducted by Goji et al. [8], scores for the Verbal Aggression and Physical subscales were increased. In two other reports that presented findings showing the aggression-ameliorating effects of lamotrigine [5,20], subjectively felt aggression, that is, anger, was primarily improved, while objectively observed aggression, that is, verbal and physical aggression did not show such change. Furthermore, Mori et al. demonstrated that anger is a salient feature of depression appearing in PWE in comparison with depression in patients without a prior history of central nervous system disease [20].
Insomnia symptoms and obesity are associated with aggression independent of depression in patients with epilepsy
2020, SeizureCitation Excerpt :In addition, in a recent study, Chen et al. [5] attributed levetiracetam to more aggressive behavior, and lamotrigine to less aggressive behavior. Kato et al. [39] also found that lamotrigine improved aggression in patients with temporal lobe epilepsy. This was particularly notable with respect to anger, which represents the emotional component of aggression in the AQ.
The effect of perampanel on aggression and depression in patients with epilepsy: A short-term prospective study
2019, SeizureCitation Excerpt :Our findings showed that predatory and instrumental aggression, i.e., aggression that is easily noticeable, was augmented in patients given PER. In contrast, Kato et al. found impulsive aggression to be the main component ameliorated by lamotrigine administration in PWE [23]. There is no doubt that aggression is a composite of multiple heterogeneous components, and different antiepileptic drugs seem to exert either a negative or positive influence on the different components of aggression in a manner independent of each other.
Causative factors and phenomenology of depression in EPILEPSY—A review
2017, International Journal of EpilepsyCitation Excerpt :From a pharmaco-therapeutic perspective, this presumed similarity has resulted in the widespread belief in the efficacy of antidepressants in epilepsy patients. Mood stabilizers such as lamotrigine (LTG) has significant effect on moods in epileptic patients in at least 11 studies, including 3 randomized control investigations.134–143 Interestingly, Labiner et al. (2009) recently revealed that the effects of LTG on mood primarily affect anger or hostility rather than depression itself.142
Anger with murderous impulse induced by lamotrigine
2014, General Hospital PsychiatryCitation Excerpt :The US Food and Drug Administration has issued an alert regarding suicidality and antiepileptic drugs (AEDs) [7], but there is no such alert been made regarding aggression, anger or hostility toward people and AEDs. In patients with partial epilepsy, LTG has, if anything, been reported to improve aggression, anger and hostility [8,9]. There is a report noting that 15% of patients with epilepsy treated with LTG manifested self-reported anger, while 5% of the patients with epilepsy not taking AED manifested it, but LTG had the lowest frequency of self-reported anger among the AEDs [10].