LEITERS TO THE EDITOR
Clomipramine for Comorbid Conditions To the Editor: We wish to describe the successful pharmacological treatment of a girl with comorbid obsessive-compulsive disorder (OCD), attentiondeficit hyperactivity disorder (ADHD), and trichotillomania with the tricyclic antidepressant (TCA), clomipramine (Anafranil", CMI). OCD has a reported prevalence of 0.3% in children, with appro ximately 1% to 2% of children and adolescents reporting significant obsessive-compulsive symptoms (Flament et al., 1988). ADHD is a disorder that is thought to co-occur in up to 10% of children and adolescents referred for OCD (Swedo et aI., 1989). Likewise, an estimated 3.5% of children and adolescents who present with ADHD may have comorbid OCD (Biederman et aI., pers . commun.). Pharmacotherapy for the treatment of comorbid OCD plus ADHD in children and adolescents has not been well described. One strategy for the treatment of children and adolescents with this comorbidity might rely on agents that are effective in both disorders. Available medication treatments generally employed for OCD in children and adolescents have included the use of CMI (Flament et aI., 1985) and fluoxetine (Riddle et aI., 1990). Although the pharmacological treatment of ADHD has relied predominately on the use of stimulants, CMI has also been reported to .be effective (Garfinkel et aI., 1983). Therefore, CMI would appear to be an effective intervention for comorbid OCD plus ADHD. B. S. is a 12-year-old girl who was referred for obsessional thoughts and behavioral problems at school. She had a 6-year history of "being obsessed with hair." As a result , she would shave her body hair, pull out her scalp hair and eyebrows, and worry constantly about the length of her pet's fur. She also had contaminant fears, but denied "checking," hand washing, or other OCD symptoms. Additionally, the patient had marked difficulty with school performance, and her history revealed symptoms consistent with a diagnosis of ADHD, including marked inattention, distractibility, impulsivity, and motoric hyperactivity. Her past medical history was remarkable for severe eczema, which was treated with hydroxyzine and Benadryl'", neither of which were reported to have affected her behavioral symptoms. One year of individual psychotherapy had little effect on her symptoms. The patient met DSM-lll-R criteria for OCD , ADHD, and trichotillomania. Before treatment, she had a score of 28 (severe range) on a Yale Brown Obsessive-Compulsive Scale (YBOCS), and a parent checklist indicated nine of 14 DSM-lll-R symptoms for ADHD. Psychological testing revealed a low average IQ without specific learning disorders. B. S. was treated initially with fluoxetine up to 80 mg daily for 6 months with no effect on her OCD or ADHD symptoms. The fluoxe tine was changed to CMI , which was titrated up to 250 mg nightl y (5.5 mg/kg). At this dose, the electrocardiogram was unchanged from baseline, and a combined serum level of 366 nglml (CMI = 35 ngl ml; n-desmelhylCMI = 331 nglml) was achieved. There was excellent resolution of her hair pulling with regrowth of scalp hair and eyebrows as well as diminished obsession about her hair and contaminant fears. While the patient was receiving CMI, a YBOCS score of I I (mild range) was obtained and there was a reduction in the number of ADHD symptoms (three of 14). In addition, there was marked improvement in school performance. Follow-up at 6 months revealed persistent reduction in all symptoms. Although this patient failed to respond to 80 mg of fluoxetine, she experienced symptom reduction while receiv ing 5.5 mg/kg daily of CMI. To our knowledge, this is the first demonstrated case of the efficacy of CMI in the treatment of comorbid OCD , ADHD, and trichotillomania. Although serotonin has been hypothesized to be involved in the pathogenesis of OCD, there is little evidence of the role of serotonin in ADHD (Zametkin and Rapoport, 1987). In contrast, both doparnin- . ergic and noradrenergic systems have been implicated in the patho-
J. Am. Acad. Child Adolesc. Psychiatry, 31:1, January 1992
physiology of ADHD (Zametkin and Rapoport, 1987). CMI and its desmethyl metabolite affect both serotoninergic and noradrenergic neuronal systems (Flament et aI., 1985) and likewise appears to reduce both OCD and ADHD symptoms. In conclusion, CMI may be helpful in treating patients with OCD, ADHD, and trichotillomania, a comorbidity that may require agents affecting both noradrenergic and serotoninergic systems. Timothy E. Wilens, M.D. Ronald Steingard, M .D. Joseph Biederman, M.D. Pediatric Psychopharmacology Clinic Massachusetts General Hospital Boston , Massachusetts REFERENCES
Flament, M. F., Rapoport, J. L., Berg, C. J., Sceery, W ., Kilts, C., Mellstrom, B. & Linnoila, M. (1985), Clomipramine treatment of childhood obsessive-compulsive disorder. Arch. Gen. Psychiatry, 42:977-983. - - Whitaker, A. , Rapoport, J. et ai. (1988), Obsessive-compulsive disorder in adolescence: an epidemiological study . J. Am. Acad. Child Adolesc. Psychiatry, 27:764-771. Garfinkel, B. D., Wender, P. H., Sloman, L. & O'Neill, I. (1983), Tricyclic antidepressants and methylphenidate treatment of attention deficit disorder in children. J. Am. Acad. Child Adolesc. Psychiatry, 2:343-348. Riddle, M . A, Hardin, M. T., King , R., Scahill, L. & Woolston, J. C. (1990), Fluoxetine treatment of children and adolescents with Tourette's and obsessive-compulsive disorder: preliminary clinical experience. J. Am. Acad. Child Adolesc. Psychiatry, 29:45-48. Swedo, S. E., Rapoport, J. L., Leonard, H., Lenane, M. & Cheslow, D. (1989) , Obsessive-compulsive disorder in children and adolescents. Arch. Gen. Psychiatry, 46:335-341. Zametkin, A. J. & Rapoport, J. L. (1987), Neurobiology of attention deficit disorder with hyperactivity: where have we come in 50 years? J. Am. Acad. Child Adolesc. Psychiatry, 26:676--686.
ADHD and Research Methodology To the Editor: Klorman and his coworkers (1990) are to be congratulated on their study of the effectiveness of methylphenidate in adolescents with attention deficit disorder. Studies of this calibre are to be welcomed in an area where misconceptions on the part of the lay public and many clinic ians still abound . Although subsidiary to the study's primary findings , the section dealing with teacher-derived behavioral data, using the Conners and other rating scales, contained points of both methodological and substantive interest. Behavioral ratings of two or more teachers were examined for reliability by calculating the appropriate concordance index, the intraclass correlation coefficients (R1) . Values in the range of 0.3 to 0.4 were obtained, which were statistically significant and described as "acceptable." The p-values associated with coefficients of concordance or correlation are of no help, however, in judging the quantitative significance of such indices. They are, in fact, relevant only where an hypothesis of no association between the measures is being tested . On the other hand, statisticians have cited values for kappa (the index of concordance for categorical data corresponding to R 1 for dimensional data) of 0.61 or greater as showing "substantial" agreement (Landis and Koch, 1977) and values for R 1 of 0.75 as indicating "high" concordance (Burdock et aI., 1963). How do these assertions affect our interpretation of lhe relatively low levels of concordance found by Klorman et al? R 1 is maximized if variance resulting from differences among sub-
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Clomipramine for Comorbid Conditions To the Editor: We wish to describe the successful pharmacological treatment of a girl with comorbid obsessive-compulsive disorder (OCD), attentiondeficit hyperactivity disorder (ADHD), and trichotillomania with the tricyclic antidepressant (TCA), clomipramine (Anafranil", CMI). OCD has a reported prevalence of 0.3% in children, with appro ximately 1% to 2% of children and adolescents reporting significant obsessive-compulsive symptoms (Flament et al., 1988). ADHD is a disorder that is thought to co-occur in up to 10% of children and adolescents referred for OCD (Swedo et aI., 1989). Likewise, an estimated 3.5% of children and adolescents who present with ADHD may have comorbid OCD (Biederman et aI., pers . commun.). Pharmacotherapy for the treatment of comorbid OCD plus ADHD in children and adolescents has not been well described. One strategy for the treatment of children and adolescents with this comorbidity might rely on agents that are effective in both disorders. Available medication treatments generally employed for OCD in children and adolescents have included the use of CMI (Flament et aI., 1985) and fluoxetine (Riddle et aI., 1990). Although the pharmacological treatment of ADHD has relied predominately on the use of stimulants, CMI has also been reported to .be effective (Garfinkel et aI., 1983). Therefore, CMI would appear to be an effective intervention for comorbid OCD plus ADHD. B. S. is a 12-year-old girl who was referred for obsessional thoughts and behavioral problems at school. She had a 6-year history of "being obsessed with hair." As a result , she would shave her body hair, pull out her scalp hair and eyebrows, and worry constantly about the length of her pet's fur. She also had contaminant fears, but denied "checking," hand washing, or other OCD symptoms. Additionally, the patient had marked difficulty with school performance, and her history revealed symptoms consistent with a diagnosis of ADHD, including marked inattention, distractibility, impulsivity, and motoric hyperactivity. Her past medical history was remarkable for severe eczema, which was treated with hydroxyzine and Benadryl'", neither of which were reported to have affected her behavioral symptoms. One year of individual psychotherapy had little effect on her symptoms. The patient met DSM-lll-R criteria for OCD , ADHD, and trichotillomania. Before treatment, she had a score of 28 (severe range) on a Yale Brown Obsessive-Compulsive Scale (YBOCS), and a parent checklist indicated nine of 14 DSM-lll-R symptoms for ADHD. Psychological testing revealed a low average IQ without specific learning disorders. B. S. was treated initially with fluoxetine up to 80 mg daily for 6 months with no effect on her OCD or ADHD symptoms. The fluoxe tine was changed to CMI , which was titrated up to 250 mg nightl y (5.5 mg/kg). At this dose, the electrocardiogram was unchanged from baseline, and a combined serum level of 366 nglml (CMI = 35 ngl ml; n-desmelhylCMI = 331 nglml) was achieved. There was excellent resolution of her hair pulling with regrowth of scalp hair and eyebrows as well as diminished obsession about her hair and contaminant fears. While the patient was receiving CMI, a YBOCS score of I I (mild range) was obtained and there was a reduction in the number of ADHD symptoms (three of 14). In addition, there was marked improvement in school performance. Follow-up at 6 months revealed persistent reduction in all symptoms. Although this patient failed to respond to 80 mg of fluoxetine, she experienced symptom reduction while receiv ing 5.5 mg/kg daily of CMI. To our knowledge, this is the first demonstrated case of the efficacy of CMI in the treatment of comorbid OCD , ADHD, and trichotillomania. Although serotonin has been hypothesized to be involved in the pathogenesis of OCD, there is little evidence of the role of serotonin in ADHD (Zametkin and Rapoport, 1987). In contrast, both doparnin- . ergic and noradrenergic systems have been implicated in the patho-
J. Am. Acad. Child Adolesc. Psychiatry, 31:1, January 1992
physiology of ADHD (Zametkin and Rapoport, 1987). CMI and its desmethyl metabolite affect both serotoninergic and noradrenergic neuronal systems (Flament et aI., 1985) and likewise appears to reduce both OCD and ADHD symptoms. In conclusion, CMI may be helpful in treating patients with OCD, ADHD, and trichotillomania, a comorbidity that may require agents affecting both noradrenergic and serotoninergic systems. Timothy E. Wilens, M.D. Ronald Steingard, M .D. Joseph Biederman, M.D. Pediatric Psychopharmacology Clinic Massachusetts General Hospital Boston , Massachusetts REFERENCES
Flament, M. F., Rapoport, J. L., Berg, C. J., Sceery, W ., Kilts, C., Mellstrom, B. & Linnoila, M. (1985), Clomipramine treatment of childhood obsessive-compulsive disorder. Arch. Gen. Psychiatry, 42:977-983. - - Whitaker, A. , Rapoport, J. et ai. (1988), Obsessive-compulsive disorder in adolescence: an epidemiological study . J. Am. Acad. Child Adolesc. Psychiatry, 27:764-771. Garfinkel, B. D., Wender, P. H., Sloman, L. & O'Neill, I. (1983), Tricyclic antidepressants and methylphenidate treatment of attention deficit disorder in children. J. Am. Acad. Child Adolesc. Psychiatry, 2:343-348. Riddle, M . A, Hardin, M. T., King , R., Scahill, L. & Woolston, J. C. (1990), Fluoxetine treatment of children and adolescents with Tourette's and obsessive-compulsive disorder: preliminary clinical experience. J. Am. Acad. Child Adolesc. Psychiatry, 29:45-48. Swedo, S. E., Rapoport, J. L., Leonard, H., Lenane, M. & Cheslow, D. (1989) , Obsessive-compulsive disorder in children and adolescents. Arch. Gen. Psychiatry, 46:335-341. Zametkin, A. J. & Rapoport, J. L. (1987), Neurobiology of attention deficit disorder with hyperactivity: where have we come in 50 years? J. Am. Acad. Child Adolesc. Psychiatry, 26:676--686.
ADHD and Research Methodology To the Editor: Klorman and his coworkers (1990) are to be congratulated on their study of the effectiveness of methylphenidate in adolescents with attention deficit disorder. Studies of this calibre are to be welcomed in an area where misconceptions on the part of the lay public and many clinic ians still abound . Although subsidiary to the study's primary findings , the section dealing with teacher-derived behavioral data, using the Conners and other rating scales, contained points of both methodological and substantive interest. Behavioral ratings of two or more teachers were examined for reliability by calculating the appropriate concordance index, the intraclass correlation coefficients (R1) . Values in the range of 0.3 to 0.4 were obtained, which were statistically significant and described as "acceptable." The p-values associated with coefficients of concordance or correlation are of no help, however, in judging the quantitative significance of such indices. They are, in fact, relevant only where an hypothesis of no association between the measures is being tested . On the other hand, statisticians have cited values for kappa (the index of concordance for categorical data corresponding to R 1 for dimensional data) of 0.61 or greater as showing "substantial" agreement (Landis and Koch, 1977) and values for R 1 of 0.75 as indicating "high" concordance (Burdock et aI., 1963). How do these assertions affect our interpretation of lhe relatively low levels of concordance found by Klorman et al? R 1 is maximized if variance resulting from differences among sub-
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