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Letters to the Editor   |    
Drs. Barzman and DelBello Reply
DREW H. BARZMAN; MELISSA P. DelBello
Am J Psychiatry 2007;164:527-528. doi:10.1176/appi.ajp.164.3.527

To the Editor: Although the underlying biology of binge eating disorder, borderline personality disorder, pathological gambling, and disruptive behavior disorders remains largely unknown, our clinical observations, along with randomized controlled data, have shown that topiramate is effective for treating these psychiatric disorders, which are phenomenologically linked by impulse dyscontrol (1–4). Furthermore, following our case report (5), there have been two open-label studies confirming our preliminary finding that topiramate is effective for the treatment of disruptive and impulsive behavior in children and adolescents with psychiatric illnesses (6–7). Additionally, in contrast to the statement by Drs. Kruszewski and Klotz, a review of the literature reveals that the aforementioned disorders may be genotypically related. For example, the G allele of the 5H-T2A receptor gene (1438A/G polymorphism) is associated with both binge eating and borderline personality disorder (8). More strikingly, a specific gene, GABRA2, has been associated with conduct disorder and adult alcohol dependence (9). Finally, topiramate is a novel broad-spectrum anticonvulsant that inhibits glutamate activity at a subtype of glutamate receptors and augments the effects of GABA receptor subtypes (GABAA) (10). Therefore, contrary to the assertion by Drs. Kruszewski and Klotz, topiramate may be effective for impulse control disorders through its effect on glutamate as well as other receptors (11).

We agree that it is important to consider both efficacy and tolerability when prescribing any medication. However, topiramate is generally well tolerated in children and adolescents. In fact, data suggest that topiramate may be better tolerated in children and adolescents than in adults (12); for example, only 14% of 56 children and adolescents experienced paresthesia, and 14% experienced somnolence in a recent double-blind placebo controlled trial of topiramate for pediatric mania (13).

1.McElroy SL, Arnold LM, Shapira NA, Keck PE, Rosenthal NR, Karim MR, Kamin M, Hudson JI: Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial. Am J Psychiatry 2003; 160:255–261
 
2.Johnson BA, Ait-Daoud N, Akhtar FZ, Ma JZ: Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals: a randomized controlled trial. Arch Gen Psychiatry 2004; 61:905–912
 
3.Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, Lawson K, Javors MA, Ma JZ: Oral topiramate for treatment of alcohol dependence: a randomized controlled trial. Lancet 2003; 361:1677–1685
 
4.Dannon PN, Lowengrub K, Gonopolski Y, Musin E, Kotler M: Topiramate versus fluvoxamine in the treatment of pathological gambling: a randomized, blind-rater comparison study. Clin Neuropharmacol 2005; 28:6–10
 
5.Barzman DH, DelBello MP: Topiramate for co-occurring bipolar disorder and disruptive behavior disorders (letters). Am J Psychiatry 2006; 163:1451–1452
 
6.Song DH, Shin WC, Ha EH, Shin YJ, Kim JY, Kim YK: Short-term effects of topiramate on externalizing behaviors in youths with or without mental retardation. American Academy of Child and Adolescent Psychiatry, 53rd Annual Meeting, San Diego, 2006
 
7.Dolengevich SH, Rodriguez SB, Conejo GA, San Sebastian CJ: Efficacy of topiramate in children and adolescent with problems in impulse control: preliminary results. Actas Esp Psiquiatr 2006; 34:280–282
 
8.Nishiguchi N, Matsushita S, Suzuki K, Murayama M, Shirakawa O, Higuchi S: Association between 5HT2A receptor gene promoter region polymorphism and eating disorders in Japanese patients. Biol Psychiatry 2001; 50:123–128
 
9.Dick DM, Bierut L, Hinrichs A, Fox L, Bucholz KK, Kramer J, Kuperman S, Hesselbrock V, Shuckit M, Almasy L, Tischfield J, Porjesz B, Begleiter H, Nurnberger J Jr, Xuei X, Edenberg HJ, Foroud T: The role of GABRA2 in risk for conduct disorder and alcohol and drug dependence. Behav Genet 2006; 36:577–590
 
10.Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE: An overview of the preclinical aspects of topiramate pharmacology, pharmacokinetics and mechanism of action. Epilepsia 2000; 41(suppl1):S3–S9
 
11.Johnson BA: Recent advances in the development of treatments of alcohol and cocaine dependence: focus on topiramate and other modulators of GABA or glutamate function. CNS Drugs 2005; 19:873–896
 
12.Winner P, Pearlman EM, Linder SL, Jordan DM, Fisher AC, Hulihan J, Topiramate Pediatric Migraine Study Investigtors: Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial. Headache 2005; 45:1304–1312
 
13.DelBello MP, Findling RL, Kushner S, Wang D, Olson WH, Capece JA, Fazzio L, Rosenthal NR: A pilot controlled trial of topiramate for mania in children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2005; 44:539–547
 
+

References

+Dr. Barzman has received support (research, consulting fee and/or speaker fees) from AstraZeneca, Pfizer, Eli Lilly, and Jannsen. Dr. DelBello has received support (research, consulting fee, and/or speaker fees) from Abbott Laboratories, AstraZeneca, Eli Lilly, Johnson and Johnson, Shire, Pfizer, Bristol Myers Squibb, and GlaxoSmithKline.

+

References

1.McElroy SL, Arnold LM, Shapira NA, Keck PE, Rosenthal NR, Karim MR, Kamin M, Hudson JI: Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial. Am J Psychiatry 2003; 160:255–261
 
2.Johnson BA, Ait-Daoud N, Akhtar FZ, Ma JZ: Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals: a randomized controlled trial. Arch Gen Psychiatry 2004; 61:905–912
 
3.Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, Lawson K, Javors MA, Ma JZ: Oral topiramate for treatment of alcohol dependence: a randomized controlled trial. Lancet 2003; 361:1677–1685
 
4.Dannon PN, Lowengrub K, Gonopolski Y, Musin E, Kotler M: Topiramate versus fluvoxamine in the treatment of pathological gambling: a randomized, blind-rater comparison study. Clin Neuropharmacol 2005; 28:6–10
 
5.Barzman DH, DelBello MP: Topiramate for co-occurring bipolar disorder and disruptive behavior disorders (letters). Am J Psychiatry 2006; 163:1451–1452
 
6.Song DH, Shin WC, Ha EH, Shin YJ, Kim JY, Kim YK: Short-term effects of topiramate on externalizing behaviors in youths with or without mental retardation. American Academy of Child and Adolescent Psychiatry, 53rd Annual Meeting, San Diego, 2006
 
7.Dolengevich SH, Rodriguez SB, Conejo GA, San Sebastian CJ: Efficacy of topiramate in children and adolescent with problems in impulse control: preliminary results. Actas Esp Psiquiatr 2006; 34:280–282
 
8.Nishiguchi N, Matsushita S, Suzuki K, Murayama M, Shirakawa O, Higuchi S: Association between 5HT2A receptor gene promoter region polymorphism and eating disorders in Japanese patients. Biol Psychiatry 2001; 50:123–128
 
9.Dick DM, Bierut L, Hinrichs A, Fox L, Bucholz KK, Kramer J, Kuperman S, Hesselbrock V, Shuckit M, Almasy L, Tischfield J, Porjesz B, Begleiter H, Nurnberger J Jr, Xuei X, Edenberg HJ, Foroud T: The role of GABRA2 in risk for conduct disorder and alcohol and drug dependence. Behav Genet 2006; 36:577–590
 
10.Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE: An overview of the preclinical aspects of topiramate pharmacology, pharmacokinetics and mechanism of action. Epilepsia 2000; 41(suppl1):S3–S9
 
11.Johnson BA: Recent advances in the development of treatments of alcohol and cocaine dependence: focus on topiramate and other modulators of GABA or glutamate function. CNS Drugs 2005; 19:873–896
 
12.Winner P, Pearlman EM, Linder SL, Jordan DM, Fisher AC, Hulihan J, Topiramate Pediatric Migraine Study Investigtors: Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial. Headache 2005; 45:1304–1312
 
13.DelBello MP, Findling RL, Kushner S, Wang D, Olson WH, Capece JA, Fazzio L, Rosenthal NR: A pilot controlled trial of topiramate for mania in children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2005; 44:539–547
 
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