Printer Friendly

The use of lamotrigine for seizures and psychiatric disorder and its effects on challenging behavior.

This is a retrospective chart review of a group of adults with developmental disabilities and seizures, and/or psychiatric and behavioral disorders treated with lamotrigine. All patients were residents of a large facility. Each was treated with the anticonvulsant lamotrigine during a specific nine month period, either for psychiatric disorder or seizures. Challenging behavior and side-effects were studied comparing pretreatment and posttreatment data. We identified 31 patients who had been treated with lamotrigine and of those, 22 showed an improvement in challenging behavior, seven showed no change, and five had side-effects that led to discontinuation in two patients. The results suggest that lamotrigine is a well-tolerated anticonvulsant and that it has other therapeutic effects on challenging behaviors.

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.

METHOD

Participants

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)

Data

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)

RESULTS

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.

DISCUSSION

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.

REFERENCES

(1.) Besag FM. Behavioural effects of the new anticonvulsants. Drug Saf 2001;24:513-536.

(2.) Besag FM. Lamotrigine in the treatment of epilepsy in people with intellectual disability. J Intellect Disabil Res 1998;42:50-56.

(3.) Biton V, Mirza W, Montouris G, et al. Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Neurology 2001;56:172-177.

(4.) Bowden CL, Calabrese JR, Sachs G, et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry 2003;60:392-400.

(5.) Buchanan N. The efficacy of lamotrigine on seizure control in 34 children, adolescents and young adults with intellectual and physical disability. Seizure 1995;4:233-236.

(6.) Calabrese JR, Bowden CL, McElroy SL, et al. Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. Am J Psychiatry 1999; 156:1019-1023.

(7.) Coppola G, Pascotto A. Lamotrigine as add-on drug in children and adolescents with refractory epilepsy and mental delay: An open trial. Brain Dev 1997; 19:398-402.

(8.) Ettinger AB, Weisbrot, DM, Saracco J, et al. Positive and negative psychotropic effects of lamotrigine in patients with epilepsy and mental retardation. Epilepsia 1998;39:874-877.

(9.) Ghaemi SN, Gaughan S. Novel anticonvulsants: A new generation of mood stabilizers. Harv Rev Psychiatry 2000;8:1-7.

(10.) Goldsmith DR, Wagstaff AJ, Ibbotson T, Perry CM. Spotlight on lamotrigine in bipolar disorder. CNS Drugs 2004;18:63-67.

(11.) Hollander E, Dolgoff-Kaspar R, Cartwright C, et al. An open trial of divalproex sodium in autism spectrum disorders. J Clin Psychiatry 2001; 62:530-534.

(12.) Lindenmayer JP, Kotsaftis A. Use of sodium valproate in violent and aggressive behaviors: A critical review. J Clin Psychiatry 2000;61:232238.

(13.) Loring DW. Cognitive side effects of antiepileptic drugs in children. Psychiatric Times 2005;22:1-7.

(14.) Lott AD, McElroy SL, Keys MA. Valproate in the treatment of behavioral agitation in elderly patients with dementia. J Neuropsychiatry Clin Neurosci 1995;7:314-319.

(15.) Marangell LB, Martinez JM, Ketter TA, et al. Lamotrigine treatment of bipolar disorder: Data from the first 500 patients in STEP-BD. Bipolar Disord 2004;6:139-143

(16.) Meador KJ, Loring DW, Ray PG, et al. Differential cognitive and behavioral effects of carbamazepine and lamotrigine. Neurology 2001;56:1177-1182.

(17.) Motte J, Trevathan E, Arvidsson JF, et al. Lamictal Lennox-Gastaut Study Group: Lamotrigine for generalized seizures associated with the LennoxGastaut syndrome. N Engl J Med 1997;337:18071812.

(18.) Pachet A, Friesen S, Winkelaar D, Gray S. Beneficial behavioural effects of lamotrigine in traumatic brain injury. Brain Inj 2003;17:715722.

(19.) Ruedrich S, Swales TP, Fossaceca C, et al. Effect of divalproex sodium on aggression and self-injurious behaviour in adults with intellectual disability: A retrospective review. J Intellect Disabil Res 1999; 43:105-111.

(20.) Stein D, Lerer B, Stahl S. Evidence-Based Psychopharmacology. Cambridge: Cambridge University Press, 2005.

(21.) Steiner H. Handbook of Mental Health Interventions in Children and Adolescents. An Integrated Developmental Approach. San Francisco, CA: Jossey-Bass, 2004.

(22.) Stenbom Y, Tonnby B, Hagberg B. Lamotrigine in Rett syndrome: Treatment experience from a pilot study. Eur Child Adolesc Psychiatry 1998;7:4952.

(23.) Wong ICK, Mawer GE, Sander JWAS. Adverse event monitoring in lamotrigine patients: A pharmacoepidemiologic study in the United Kingdom. Epilepsia 2001;42:237-244.

(24.) Zerjav-Lacombe S, Tabarsa E. Lamotrigine: A review of clinical studies in bipolar disorders. Can J Psychiatry 2001;46:328-333.

Dagmar Hoheneck, M.D. [1] & Barbara Bachmeier, PYS.D. [2]

[1] Sonoma Developmental Center, Eldridge, CA

[2] 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.hoheneck@sonoma.dds.ca.gov.
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
COPYRIGHT 2008 Psych-Media of North Carolina, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2008 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Hoheneck, Dagmar; Bachmeier, Barbara
Publication:Mental Health Aspects of Developmental Disabilities
Article Type:Report
Geographic Code:1USA
Date:Oct 1, 2008
Words:3061
Previous Article:Identifying symptoms of psychiatric disorders in people with autism and intellectual disability: an empirical conceptual analysis.
Next Article:Effects of Fixed-Time Release (FTR) fading on implementation of physical restraint.
Topics:

Terms of use | Privacy policy | Copyright © 2020 Farlex, Inc. | Feedback | For webmasters