The use of lamotrigine for seizures and psychiatric disorder and its effects on challenging behavior.
Keywords: intellectual disability, anticonvulsant, lamotrigine, behavior, psychiatric, seizure, bipolar
For many years management of challenging behavior in people with developmental disabilities has relied heavily on treatment with neuroleptics. Some of their side-effects, such as cognitive dulling or movement disorders, are particularly problematic for people with developmental disabilities. Although the new or second and third generation antipsychotics are much better tolerated, their long term effects in terms of movement disorders are not well known, and many of them cause weight-gain and metabolic disorders. Thus, these medicines are difficult to choose as a first-line agent, unless one is dealing with a treatment-resistant bipolar disorder or schizophrenia. Drugs from another class that have shown benefit for aggressive behavior, regardless of etiology, as well as posttraumatic stress disorder, and mood disorders are the anticonvulsants. Of these, (20) valproate has been the most studied. In (14,21) addition to being an effective mood stabilizer in the treatment of bipolar disorder, it has been (4,6,9,15) shown to be effective for the treatment of aggression (12,19) and self-injurious behavior (19) regardless of etiology in people with intellectual disabilities. There was also a report of divalproex being used in individuals with autism spectrum disorder resulting in a significant improvement in both core symptoms of autism as well as challenging behaviors. (11)
Lamotrigine is a fairly new anticonvulsant, which was FDA-approved for the treatment of seizures in 1994, and for treatment of bipolar disorder in 2003. It is thought to work by blocking voltage-sensitive sodium and calcium channels, thereby stabilizing the neuronal membrane and also to affect serotonin receptors. (10,21) Its favorable side-effect profile with little to no negative effects on cognition, (1,13,16,23) in addition to its favorable effect on weight, (3) should make lamotrigine a particularly good choice for patients with intellectual disability. Occasionally lamotrigine can be activating, and can cause agitation; other adverse events that have been reported include dizziness, ataxia, nausea and tremor. A serious rash leading to Stevens-Johnson syndrome led to its black box warning, but this condition is rare when one initiates the drug at a very low dose and increases it very slowly.
There have been several published studies concerning the use of lamotrigine for people with developmental disabilities. In most of these reports, lamotrigine was used for the treatment of seizures. (2,5,7,17) These reports noted little in terms of cognitive dulling effects and indicated that some of the individuals seemed more alert, more attentive, and had improved mood. There is one case study of its successful use for challenging behavior in a patient with traumatic brain injury. (18) Two studies investigated the use of lamotrigine for both seizures as well as challenging behavior disorders in individuals with developmental disabilities: one described seven individuals with Lennox-Gastaut syndrome and intellectual disability, (8) and the other addressed girls with Rett syndrome. (22) The latter notes that with 100,000 children having been treated with lamotrigine overall, an improvement in mood, alertness and general well-being was frequently noted. Another advantage of lamotrigine is that unlike valproate which can cause weight-gain, lamotrigine tends to have a negative or neutral effect on appetite.
The purpose of the present study was to investigate the efficacy of lamotrigine in reducing challenging behavior and to assess its side-effects. This study is a retrospective chart review of patients who were treated with lamotrigine. The reason for treatment was prescribed, its effects on challenging behavior, seizures, and side-effects were noted.
Approval for this study was obtained from the state and facility Human Rights Board; in addition, consent was obtained from the conservators of individuals for whom we decided to provide more details in the form of case summaries.
The facility is a large developmental center. An interdisciplinary team system follows all residents. Services provided also include day and recreational services. Behavioral data is collected on all residents. For residents with challenging behavior, individually detailed behavioral data is kept.
The pharmacy staff identified 31 individuals for whom lamotrigine was prescribed during the period of September 2005 and March of 2006. (Tables 1 and 2 present demographic and clinical data.) The majority of individuals had an Axis I psychiatric diagnosis. Aggression was present in 22 individuals; SIB in 11 individuals; agitation in 11 individuals, and one person had pica. Seizures were present in 15 individuals. (Table 3)
Behavioral data for these individuals was examined including target challenging behavior and any current pharmacotherapy. (Table 2) The graphs indicated the target behaviors and the frequency (and sometimes intensity) of those behaviors, and most target behaviors listed consisted of aggression, agitation or self-injurious behavior. Occasionally a mood scale was also used. The graphs also indicated the pharmacotherapy prescribed for the individuals as well as the doses. The graphs described this information over time so the analyst could see how changes in doses of medications were correlated between those changes and changes in the frequency or intensity of target behaviors. This data was analyzed to determine if there was a relationship between the lamotrigine dose and the increase, or reduction of target behaviors pre- and posttreatment. If there were no behavioral changes, this was also noted. With this information, we could determine how many individuals had a decrease in target behaviors that correlated with the administration of lamotrigine. If lamotrigine was prescribed for seizures, the seizure record in the chart was reviewed to determine if there was a reduction in seizures. (Table 3)
Approximately 71% of individuals showed a positive change of a decrease in challenging behavior or increase in functioning; 27% showed no change and 16% had adverse side-effects. Because many of the individuals treated with lamotrigine were non-verbal, side-effects such as headache were difficult to ascertain, and often few specifics were given, other than that there was an increase in agitation or other challenging behaviors. Lamotrigine was discontinued in one individual because of a rash, and in another because of increased agitation and mania-like symptoms.
Table 3 lists other anticonvulsants used to treat seizure disorders and also notes how seizure activity was affected by the addition of lamotrigine. It should be noted that of the 11 individuals with "no change" in seizure activity after the introduction of lamotrigine, five had no seizures in the year preceding the study, and remained free of seizures, whereas three others remained at three or less seizures per year. In other words, 8 of 11 individuals with no change in seizure frequency had good seizure control to start with.
The use of a medication that is less likely to cause sedation or other cognitive side-effects, and is effective for mood regulation as well as seizures seems of particular benefit for people with developmental disabilities. This chart review of 31 individuals with intellectual disability treated with lamotrigine for a seizure disorder and/or psychiatric disorders found that lamotrigine was associated with a decrease in challenging behavior. The benefit/risk ratio was quite impressive. Few individuals had serious side-effects and lamotrigine needed to be discontinued in only two people.
This study has several limitations. It was not a controlled prospective study and based on historical data; therefore, we were not able to consider all the variables that might have influenced the individual's behavior, including decreases in other anticonvulsant medications. We report only the 31 individuals treated with lamotrigine with no control group. Many participants also had a seizure disorder complicating interpretation of the results. In addition, many individuals were treated with multiple medications. Behavioral data was specific to that developed here at our facility and published rating scales were not used. In addition, due to the severity of the intellectual disability of our individuals, verbal self-report was not available.
Several studies have looked at the use of lamotrigine for seizure disorders in the developmentally disabled population. We were (2,5,17) not able to locate studies assessing lamotrigine and challenging behavior, so this may be the first study on this subject. The findings of this study are consistent with those of the earlier studies concerning treatment of seizure disorders. We noticed a wide spread of laboratory levels which seemed independent of doses given. Unfortunately, only 20 out of the 31 participants did have lamotrigine levels in their charts. As expected, levels of individuals who received the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital or diphenylhydantoin tended to be lower than those receiving valproic acid. (2,10,24)
This study suggests that lamotrigine is well-tolerated in people with developmental disabilities and is effective for seizures as well as having a positive effect on challenging behavior. Further prospective research using rigorous scientific methodology is needed to determine its usefulness in treating seizures, psychiatric disorders, and addressing challenging behavior for people with intellectual disability.
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Dagmar Hoheneck, M.D.  & Barbara Bachmeier, PYS.D. 
 Sonoma Developmental Center, Eldridge, CA
 Napa State Hospital, Napa, CA
CORRESPONDENCE: Dagmar Hoheneck, M.D., Staff Psychiatrist, Sonoma Developmental Center, P.O. Box 1493, Eldridge, CA 95431; tel.: 707-938-6854; Dagmar.email@example.com.
TABLE 1. PARTICIPANTS TREATED WITH LAMOTRIGINE AND DSM-IV DIAGNOSES FOR AXIS I, II, AND III Participant DSM-IV Axis I 1 Intermittent explosive disorder 2 Intermittent explosive disorder; autism 3 Generalized anxiety disorder; autism 4 Post-traumatic stress disorder 5 Major depressive disorder; autism 6 PTSD; autism 7 Depressive disorder NOS 8 Intermittent explosive disorder; autism 9 Bipolar disorder, mixed 10 Bipolar disorder 11 Bipolar disorder 12 PTSD 13 PTSD 14 Depressive disorder NOS 15 Congenital Rubella syndrome 16 PTSD; pervasive development disorder NOS 17 PTSD; autism; severe 18 Generalized anxiety disorder 19 Depressive disorder NOS 20 No diagnosis 21 Cyclothymic disorder 22 Dysthymic disorder 23 PTSD 24 Cyclothymic disorder 25 Intermittent explosive disorder 26 No diagnosis 27 PTSD 28 Autism; OCD NOS 29 Bipolar disorder 30 No diagnosis 31 Bipolar disorder Participant DSM-IV Axis II DSM-IV Axis III 1 Profound ID Post-natal encephalitis 2 Severe ID Epilepsy 3 Severe ID Epilepsy 4 Severe ID Epilepsy 5 Severe ID 6 Severe ID Epilepsy 7 Severe ID Epilepsy 8 Severe ID Epilepsy 9 Moderate ID Epilepsy 10 Severe ID 11 Moderate ID 12 Moderate ID 13 Moderate ID 14 Severe ID Epilepsy 15 Severe ID 16 Severe ID Epilepsy 17 Severe ID 18 Severe ID Epilepsy 19 Severe ID Epilepsy 20 Severe ID Post-natal encephalitis, epilepsy 21 Severe ID 22 Moderate ID Epilepsy 23 Moderate ID 24 Severe ID 25 Severe ID Epilepsy 26 Profound ID Down syndrome; deaf, epilepsy 27 Severe ID Post-natal encephalitis 28 Severe ID Epilepsy 29 Severe ID 30 Profound ID Epilepsy 31 Profound ID TABLE 2. DEMOGRAPHIC DATA, CHALLENGING BEHAVIOR, SEIZURES, DOSAGE LEVEL OF LAMOTRIGINE, LABORATORY LEVEL, REPORTED SIDE-EFFECTS, AND ASSESSMENT OF POSITIVE BEHAVIORAL CHANGE OR NO CHANGE M/F Age Behavior Seizures Dose Lab Level 1 M 43 A/AGG no 200mg 1.3 2 M 38 A/AGG no 600mg 6.6 3 M 47 A/SIB yes 200mg 5.2 4 F 20 A/SIB yes 200mg 10 5 F 49 A/SIB no 225mg 2.7 6 M 29 A yes 200mg 3.1 7 M 43 A/SIB yes 250mg 6.3 8 M 37 AGG/SIB yes 50mg Not noted 9 F 31 A/AGG yes 225mg 9.5 10 M 34 A/AGG no 275mg 7.8 11 M 56 AGG no 400mg 2.5 12 F 47 AGG/SIB no 200mg 10.3 13 F 21 AGG/SIB no 250mg 5.8 14 M 40 AGG yes 450mg .7after d/c 15 F 40 AGG/SIB no 600mg 7.7 16 M 40 SIB yes 200mg Not noted 17 M 40 SIB no 200mg 10.3 18 M 45 AGG yes 100mg Not noted 19 F 48 AGG yes 500mg 3.2 20 F 48 AGG yes 250mg 11.1 21 F 58 AGG no 325mg 1.6 22 M 43 AGG yes 100mg Not noted 23 F 51 AGG no 50mg Not Noted 24 F 46 AGG no 75mg 4 25 F 45 AGG yes 175mg Not noted 26 F 56 AGG/SIB yes 175mg Not noted 27 M 43 A/AGG no 150mg Not noted 28 M 31 AGG yes 200mg Not noted 29 M 48 A/AGG no 300mg Not noted 30 F 48 Pica yes 250mg 4 31 M 41 AGG no 50mg 8.6 Positive No M/F Side-Effect Change Change 1 M None X 2 M None X 3 M None X 4 F None X 5 F None X 6 M None X 7 M None X 8 M None X 9 F None X 10 M None X 11 M None X 12 F None X 13 F None X 14 M Unsure X 15 F None X 16 M None X 17 M None X 18 M None X 19 F None X 20 F None X 21 F None X 22 M Possible/rash X 23 F Possible psychosis X 24 F Possible/rash X 25 F Possible/rash X 26 F None X 27 M None X 28 M None X 29 M None X 30 F None X 31 M None X Key: A = agitation; AGG = aggression; SIB = self-injurious behavior TABLE 3. PARTICIPANTS AND SEIZURE ACTIVITY, MEDICATION, LAMOTRIGINE (LMT) LEVEL, INCREASE, DECREASE OR NO CHANGE IN SEIZURE ACTIVITY LMT No Participant Age Medication Level Increase Decrease Change 1 43 1.3 2 38 6.6 3 47 VPA 5.2 X 4 20 VPA, CLZP 10 X 5 49 2.7 6 29 CBZ, CLZP 3.1 X 7 43 VPA 6.3 X 8 37 VPA, CBZ, CLZP X 9 31 VPA 9.5 X 10 34 7.8 11 56 2.5 12 47 VPA 10.3 13 21 5.8 14 40 LEV, CLZP, ZON 15 40 7.7 16 40 VPA, CBZ X 17 40 10.3 18 45 X 19 48 OXC 3.2 X 20 48 LEV, TOP, VPA 11.1 X 21 58 1.6 22 43 PB, GAB X 23 51 24 46 4 25 45 LEV, PB X 26 56 CBZ X 27 43 28 31 VPA X 29 48 30 48 PHT 4 X 31 41 8.6 Key: CBZ = Carbamazepine LEV = Levetiracetam OXC = Oxcarbazepine CLZP = Clonazepam PB = Phenobarbital VPA = Valproate GAB = Gabapentin PHT = Phenytoin ZON = Zonisamide TOP = Topiramaye
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|Author:||Hoheneck, Dagmar; Bachmeier, Barbara|
|Publication:||Mental Health Aspects of Developmental Disabilities|
|Date:||Oct 1, 2008|
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