Topiramate Plus Quetiapine Cut Cannabis Use in Bipolar Teens

TORONTO – Topiramate in combination with quetiapine was well tolerated in adolescents who had bipolar disorder and reported frequent cannabis use, based on a 75-patient study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Concurrent substance use is a barrier to treating adolescents with bipolar disorder, said Dr. Melissa DelBello of the University of Cincinnati. Topiramate is approved by the Food and Drug Administration as an antiepileptic drug for children as young as age 2 years. Topiramate has been shown to reduce drug cravings, but is not approved for that indication, she added.

The researchers recruited adolescents, aged 12-21 years, who met criteria for bipolar disorder, had a Young Mania Rating Scale (YMRS) score of at least 20, and were using cannabis an average of at least twice a week for the 28 days before entering the study. In a previous study, Dr. DelBello and her colleagues found that topiramate was effective for reducing mania symptoms in adolescents (J. Am. Acad. Child Adolesc. Psychiatry 2005; 44:539-47).

The 75 teens were randomized to a maximum of 800 mg of quetiapine and placebo or to quetiapine and a minimum dose of 75 mg of topiramate twice daily that was increased gradually to 150 mg twice daily by day 21 of treatment.

At baseline, the average number of joints smoked per week was 14 in the quetiapine and placebo group and 11 in the quetiapine and topiramate group.

After 16 weeks of treatment, the average weekly use dropped to four joints in the quetiapine and placebo group and to 0.4 joints in the quetiapine and topiramate group. The difference was statistically significant.

On average, teens in the quetiapine and topiramate group used cannabis 1 day per week, and teens in the quetiapine and placebo group used cannabis 2 days per week, Dr. DelBello said.

Over the 16-week study, scores on the YMRS improved significantly from baseline, with an average drop of –14 with quetiapine and topiramate and –16 with quetiapine and placebo. Scores on the Childhood Rating Depression Scale-Revised (CRDS-R) also improved significantly from baseline to 16 weeks in both groups.

The presence of conduct disorder and ADHD were significant predictors of reduction in cannabis use while taking topiramate, said Dr. DelBello. Teens given topiramate showed significant improvement in general scores on the Marijuana Craving Questionnaire, compared with teens given placebo.

The groups did not differ in laboratory measures or vital signs, but excitement and pallor occurred in 26% of the topiramate group and in 16% of the placebo group.

Eleven serious events occurred during the study; five occurred in the topiramate group (two cases of suicidal ideation with intent and three cases of mania) and six occurred in the placebo group (four cases of mania, one suicide attempt, and one pregnancy).

The study was limited by a lack of data on cognition, Dr. DelBello noted. The neurobiological effects of topiramate and its effects when combined with other medications and used in different mood states need further study.

Dr. DelBello has received research support and/or served as a consultant, advisory board member, or speakers’ bureau member for multiple companies including Schering-Plough, Merck, Bristol-Myers Squibb Somerset, Lilly, and Pfizer.

TORONTO – Topiramate in combination with quetiapine was well tolerated in adolescents who had bipolar disorder and reported frequent cannabis use, based on a 75-patient study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Concurrent substance use is a barrier to treating adolescents with bipolar disorder, said Dr. Melissa DelBello of the University of Cincinnati. Topiramate is approved by the Food and Drug Administration as an antiepileptic drug for children as young as age 2 years. Topiramate has been shown to reduce drug cravings, but is not approved for that indication, she added.

The researchers recruited adolescents, aged 12-21 years, who met criteria for bipolar disorder, had a Young Mania Rating Scale (YMRS) score of at least 20, and were using cannabis an average of at least twice a week for the 28 days before entering the study. In a previous study, Dr. DelBello and her colleagues found that topiramate was effective for reducing mania symptoms in adolescents (J. Am. Acad. Child Adolesc. Psychiatry 2005; 44:539-47).

The 75 teens were randomized to a maximum of 800 mg of quetiapine and placebo or to quetiapine and a minimum dose of 75 mg of topiramate twice daily that was increased gradually to 150 mg twice daily by day 21 of treatment.

At baseline, the average number of joints smoked per week was 14 in the quetiapine and placebo group and 11 in the quetiapine and topiramate group.

After 16 weeks of treatment, the average weekly use dropped to four joints in the quetiapine and placebo group and to 0.4 joints in the quetiapine and topiramate group. The difference was statistically significant.

On average, teens in the quetiapine and topiramate group used cannabis 1 day per week, and teens in the quetiapine and placebo group used cannabis 2 days per week, Dr. DelBello said.

Over the 16-week study, scores on the YMRS improved significantly from baseline, with an average drop of –14 with quetiapine and topiramate and –16 with quetiapine and placebo. Scores on the Childhood Rating Depression Scale-Revised (CRDS-R) also improved significantly from baseline to 16 weeks in both groups.

The presence of conduct disorder and ADHD were significant predictors of reduction in cannabis use while taking topiramate, said Dr. DelBello. Teens given topiramate showed significant improvement in general scores on the Marijuana Craving Questionnaire, compared with teens given placebo.

The groups did not differ in laboratory measures or vital signs, but excitement and pallor occurred in 26% of the topiramate group and in 16% of the placebo group.

Eleven serious events occurred during the study; five occurred in the topiramate group (two cases of suicidal ideation with intent and three cases of mania) and six occurred in the placebo group (four cases of mania, one suicide attempt, and one pregnancy).

The study was limited by a lack of data on cognition, Dr. DelBello noted. The neurobiological effects of topiramate and its effects when combined with other medications and used in different mood states need further study.

Dr. DelBello has received research support and/or served as a consultant, advisory board member, or speakers’ bureau member for multiple companies including Schering-Plough, Merck, Bristol-Myers Squibb Somerset, Lilly, and Pfizer.

TORONTO – Topiramate in combination with quetiapine was well tolerated in adolescents who had bipolar disorder and reported frequent cannabis use, based on a 75-patient study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Concurrent substance use is a barrier to treating adolescents with bipolar disorder, said Dr. Melissa DelBello of the University of Cincinnati. Topiramate is approved by the Food and Drug Administration as an antiepileptic drug for children as young as age 2 years. Topiramate has been shown to reduce drug cravings, but is not approved for that indication, she added.

The researchers recruited adolescents, aged 12-21 years, who met criteria for bipolar disorder, had a Young Mania Rating Scale (YMRS) score of at least 20, and were using cannabis an average of at least twice a week for the 28 days before entering the study. In a previous study, Dr. DelBello and her colleagues found that topiramate was effective for reducing mania symptoms in adolescents (J. Am. Acad. Child Adolesc. Psychiatry 2005; 44:539-47).

The 75 teens were randomized to a maximum of 800 mg of quetiapine and placebo or to quetiapine and a minimum dose of 75 mg of topiramate twice daily that was increased gradually to 150 mg twice daily by day 21 of treatment.

At baseline, the average number of joints smoked per week was 14 in the quetiapine and placebo group and 11 in the quetiapine and topiramate group.

After 16 weeks of treatment, the average weekly use dropped to four joints in the quetiapine and placebo group and to 0.4 joints in the quetiapine and topiramate group. The difference was statistically significant.

On average, teens in the quetiapine and topiramate group used cannabis 1 day per week, and teens in the quetiapine and placebo group used cannabis 2 days per week, Dr. DelBello said.

Over the 16-week study, scores on the YMRS improved significantly from baseline, with an average drop of –14 with quetiapine and topiramate and –16 with quetiapine and placebo. Scores on the Childhood Rating Depression Scale-Revised (CRDS-R) also improved significantly from baseline to 16 weeks in both groups.

The presence of conduct disorder and ADHD were significant predictors of reduction in cannabis use while taking topiramate, said Dr. DelBello. Teens given topiramate showed significant improvement in general scores on the Marijuana Craving Questionnaire, compared with teens given placebo.

The groups did not differ in laboratory measures or vital signs, but excitement and pallor occurred in 26% of the topiramate group and in 16% of the placebo group.

Eleven serious events occurred during the study; five occurred in the topiramate group (two cases of suicidal ideation with intent and three cases of mania) and six occurred in the placebo group (four cases of mania, one suicide attempt, and one pregnancy).

The study was limited by a lack of data on cognition, Dr. DelBello noted. The neurobiological effects of topiramate and its effects when combined with other medications and used in different mood states need further study.

Dr. DelBello has received research support and/or served as a consultant, advisory board member, or speakers’ bureau member for multiple companies including Schering-Plough, Merck, Bristol-Myers Squibb Somerset, Lilly, and Pfizer.