Cognitive-Behavioral Therapy for PANDAS-Related Obsessive-Compulsive Disorder: Findings From a Preliminary Waitlist Controlled Open Trial

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1 Cognitive-Behavioral Therapy for PANDAS-Related Obsessive-Compulsive Disorder: Findings From a Preliminary Waitlist Controlled Open Trial ERIC A. STORCH, PH.D., TANYA K. MURPHY, M.D., GARY R. GEFFKEN, PH.D., GISELLE MANN, PH.D., MPH, JENNIFER ADKINS, PH.D., LISA J. MERLO, PH.D., DANNY DUKE, B.A., MELISSA MUNSON, B.A., ZOE SWAINE, B.A., AND WAYNE K. GOODMAN, M.D. ABSTRACT Objective: To provide preliminary estimates of the effectiveness of cognitive-behavioral therapy (CBT) in treating pediatric obsessive-compulsive disorder (OCD) of the pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) subtype. Method: Seven children with OCD of the PANDAS subtype (range 9-13 years) were treated in a 3-week intensive CBT program conducted at a university clinic. Six of seven children were taking selective serotonin reuptake inhibitor medication(s) upon presentation. Assessments were conducted at four time points: baseline, pretreatment approximately 4 weeks later, posttreatment, and 3-month follow-up. Raters were blind to the nature of the study treatment. Results: Six of seven participants were classified as treatment responders (much or very much improved) at posttreatment, and three of six remained responders at follow-up. Clinician severity ratings, as measured by the Children's Yale-Brown Obsessive-Compulsive Scale and Anxiety Disorder Interview Schedule for DSM-IVChild Interview Schedule- Parent version, decreased significantly following intervention, with effect sizes of 3.38 and 2.29, respectively. Self-reported general anxiety and depression symptoms were not significantly reduced. Conclusions: This study provides preliminary support for CBT in treating the PANDAS subtype of pediatric OCD. This approach is also considered a safe and.minimally invasive treatment approach. J. Am. Acad. Child Adolesc. Psychiatry, 2006;45(10): Key Words: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, obsessive-compulsive disorder, cognitivebehavioral therapy. Pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) are defined by the following diagnostic criteria: presence of obsessivecompulsive disorder (OCD) and/or tic disorder, prepubertal onset of symptoms, symptom severity that is episodic in nature, and association with group A streptococcal (GAS) infections (Murphy and Pichichero, 2002; Swedo et al., 1998). Although the exact prevalence Accepted May 8, Drs. Storch, Murphy, Goeen, Mann, and Goodman, Ms. Munson, Ms. Swaine, and Mr. Duke are with the DepartmentofPsychiatry anddrs. Storch and Gefken are with the Department fpediatrics, UniversiVy offlorida, Gainesville. Funding for this study came from the Children's Mira&de Network. Reprint requests to Dr. EricA. Storch, Department ofpychiatry, Universiýy of FloridA, Box , Gainesville, FL 32610; e-maik estorch@pschiatry.ufledu /06/ by the American Academy of Child and Adolescent Psychiatry. DOI: chi aO of PANDAS subtype of OCD remains unknown (March, 2004), symptoms have a sudden onset characterized by an episodic course with symptom recurrences experienced by approximately 50% of patients (Murphy and Pichichero, 2002). To date, the efficacy of several pharmacologic treatments have been supported for PANDAS-related OCD symptoms (e.g., intravenous immunoglobulin and plasma exchange [Perlmutter et al., 19993). For example, Perlmutter et al. (1999) found intravenous immunoglobulin and plasma exchange to be associated with 45 % and 58% reductions on the Yale-Brown Obsessive- CompulsiVe Scale (Y-BOCS; Murphy et al, 2006) at 1 month after treatment. At 1 year, 58% and 70% reductions on the Y-BOCS were found, and 82% of children "much" or "very much" improved relative to baseline. Although encouraging, both procedures are J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 45:10, OCTOBER

2 STORCH ET AL. marked by adverse side effects (e.g., dizziness, nausea, and perioral tingling for plasma exchange; nausea, vomiting, and headache for intravenous immunoglobulin), and these findings suggest that many youths experience residual symptoms at 1 month following treatment. Thus, investigation into alternative treatment approaches that may be less invasive and/or have good efficacy is warranted. Others have investigated antibiotic prophylaxis. Garvey et al. (1999) randomized 37 children with PANDAS to either 4 months of twice-daily oral 250 mg penicillin V followed by 4 months of placebo or vice versa. Findings did not support the efficacy of penicillin prophylaxis because there were an equal number of infections in both the active and placebo phases and no significant change in obsessive-compulsive symptom severity between phases. Using a 12-month parallel design comparing penicillin and azithromycin, Snider et al. (2005) examined antibiotic prophylaxis in decreasing streptococcal infections and neuropsychiatric symptom exacerbations relative to the baseline year before study entry. Twenty-three children with the PANDAS subtype were administered penicillin or azithromycin for 12 months. Subjects randomized to penicillin had a mean of 2.1 (± 1.0) neuropsychiatric exacerbations and a mean of 1.9 (± 1.2) streptococcal infections the year before being placed on antibiotic prophylaxis. Overall, antibiotic prophylaxis was effective, with an overall reduction in neuropsychiatric symptom exacerbations and GAS infections when compared with the year before study efitry. In a case series (Murphy and Pichichero 2002), those with new-onset OCD and documented GAS streptococcus showed rapid resolution in symptoms when the active GAS infection was treated. However, the benefits of prophylactic antibiotics on symptom course have not been definitively determined and once the GAS infection has cleared, acute antibiotic treatment is not clinically indicated. Very little acute intervention for PANDAS-related OCD has been examined. Following the lead of.adult findings, recent data highlight the strong efficacy of cognitive-behavioral therapy (CBT) for pediatric OCD. For example, the Pediatric OCD Treatment StudyTeam (2004) demonstrated that OCD symptoms were more likely to diminish in patients receiving CBT alone or in combination with sertraline, whereas Barrett et al. (2004, 2005) found marked immediate and sustained improvements associated with individual and group cognitive-behavioral family-based therapy. Given the efficacy of CBT for pediatric OCD, together with the need for less invasive treatments for PANDAS-related symptoms, CBT may be a viable approach to treating PANDAS symptoms. Only one known report has examined this. Storch et al. (2004c) reported on the effectiveness of CBT for the treatment of rapidonset pediatric OCD of the PANDAS phenotype in a 6-year-old boy. During a 1-week intensive CBT protocol, marked symptom reductions measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS; Scahill et al., 1997) were found (pretreatment of 34, posttreatment of 8); treatment gains were maintained for 1 year. In this study, we contribute to the literature by examining the efficacy of CBT for a sample of pediatric patients with OCD of the PANDAS subtype. To help control for certain nonspecific factors such as the passage of time, repeated assessments, and enrolling in a clinical trial, we employed a waidist open trial in which 4 weeks preceded CBT treatment. We predicted that CBT but not the waitlist would be associated with decreased OCD symptom severity and improved psychosocial functioning. METHOD Participants Participants were seven children (four boys; mean age, 11.1 ± 1.4; range 9-13 years) identified as meeting criteria for the PANDAS subtype (Table 1 for demographic information and clinical characteristics, and Table 2 for principal symptoms). Using all of the Characteristics TABLE 1 Baseline Demographic and Clinical Characteristics Gender 4 boys/3 girls Ethnicity 6 white, 1 Hispanic Age, yr (mean ± SD) 11.1 ± 1.4 yr Family income $94,571 ± $42,480 Treatment history' Medication alone 2 Psychotherapy alone I Medication and psychotherapy 4 Psychiatric comorbidity Generalized anxiety disorder 3 Tourette's disorder or tics 3 Major depression 2 Attention-deficit/hyperactivity disorder 2 Oppositional defiant disorder 2 a At the baseline assessment, three children were taking sertraline alone, one child was taking paroxetine, one child was taking fluoxetine, and one child was taking both fluoxetine and fluvoxamine. 1172

3 CBT FOR PANDAS Subject TABLE 2 Principal Obsessions and Compulsions Targeted in Treatment Age/Gender 10-yr-old girl 10-yr-old boy 12-yr-old boy 11-yr-old girl 13-yr-old boy 9-yr-old boy 11-vr-old airl Primary Obsessions Aggressive thoughts Somatic Contamination feats Aggressive thoughts Sexual thoughts Aggressive thoughts Magical thoughts Aggressive thoughts Somatic fears?rimary Compulsions Repeating Counting Washing/deaning Washing/deariing available clinical information, PANDAS diagnosis was determined by the second author (T.K.M.) in conjunction with the first and final authors (E.A.S. and W.K.G.), and based largely on the criteria of new-onset or dramatic symptom exacerbation of OCD that was temporally associated with a GAS infection (e.g., GAS temporally preceded symptom onset or exacerbation). All of the children had an exacerbation or symptom onset within several weeks of GAS exposure, infection, or sore throat and fever (but no culture conducted). In all of the children, there was a history of dramatic onset or recent, clinically significant flare ups. Six had a history of dramatic symptom exacerbations followed by periods of reduced symptoms since OCD onset (based on parent report); the symptom duration of the seventh child was not long enough to determine this. Upon evaluation, all of the children had abnormal neurological signs/ symptoms. The most common presentations included motor overflow, pronator drift, deterioration in school performance, clumsiness, handwriting deterioration, and compulsive/frequent urination. Based on parental recall, the age at onset of PANDAS symptoms was 6.5 ± 3.2 years (range 3-12 years).at the time of the study, all of the children were prepubescent. Other inclusion criteria were (1) a primary diagnosis of OCD at baseline derived from the Anxiety Disorder Interview Schedule for DSM-IV-Child Interview Schedule- Parent version (ADIS-IV-P; Silverman and Albano, 199), with a clinical severity rating of 24; (2) CY-BOCS total score >16; (3) stable on any psychotropic medication for at least 8 weeks before study entry; (4) between the ages of 8 and 17 years; and (5) had at least one parent available to accompany the child to all of the treatment sessions. Children were excluded from the study if they met any of the following criteria: (1) psychosis, pervasive developmental disorder, bipolar. disorder, or current suicidality measured by the ADIS-IV-P and all available clinical information; (2) principal diagnosis other than OCD; or (3) a positive diagnosis in the caregivef of mental retardation, psychosis, or other psychiatric disorders or conditions that would limit their ability to understand CBT (based on clinical interview). Patients with comorbid psychiatric diagnoses or taking psychotropic medications were not excluded. Six of the youths were taking one or more selective serotonin reuptake inhibitor (SSRI) medication upon presentation (Table 1 for a specific listing of medication). All but one family that was approached by the first author agreed to participate, but these subjects were a minority of the patients 6eing followed for PANDAS. Although all of the families of children who were followed for PANDAS-related OCD were informed that CBT was an option, only the eight (including the family that did not consent) expressed interest in being contacted about the study. Among the remaining families, reasons for not being contacted included not meeting exclusion criteria (e.g., the child had a principal diagnosis other than OCD, unwilling to keep. medication stable during the course of the trial), not interested in receiving intensive CBT, or already in psychotherapy. Measures ADIS-IV-P. The ADIS-V-P (Silverman and Albano, 1996) is a dinician-rated, structured diagnostic instrument that assesses for the 1173

4 STORCH ET AL. presence of anxiety and mood disorders and screens for additional disorders including externalizing behavior disorders, psychotic, and eating disorders. Severity ratings for each diagnosis (range 0-8) are used to categorize all positive diagnoses. Excellent interrater agreement has been reported for anxiety disorders (intraclass correlation coefficients JICCs] = ; Wood et al., 2002), and Silverman et al. (2001) found the 7- to 14-day test-retest reliability to range from adequate to excellent across anxiety disorder diagnoses (K = for child interview, for parent interview, and for combined diagnoses). The ADIS-IV-P also has shown sensitivity to treatment effects in studies of children with anxiety disorders (Kendall et al., 1997). CY-BOCS. The CY-BOCS (Scahill et al., 1997) is a 10-item semistnuctured measure of obsession and compulsion severity rated over the previous week on a 5-point Likert scale. Obsession and Compulsion Severity scores are derived by summing the applicable five items; a total score is derived by summing all 10 scale items. In this study, the CY-BOCS was administered to both the child and parent(s) jointly, given that many youths underestimate their symptoms. The CY-BOCS has high internal consistency (a = ; Scahill et al., 1997; Storch et al., 2004a), good to excellent interrater agreement (ICCs = ; Scahill et al., 1997), and good 6-week test-retest stability (ICC = 0.79; Storch et al., 2004a). The CY-BOCS is treatment sensitive (e.g., Geller et al., 2003; Pediatric OCD Treatment Study Team, 2004) and has shown stronger associations with other measures of obsessive thinking and compulsive symptoms than with measures of general anxiety, depression, tic severity, aggression, or ADHD (Scahill et al., 1997; Storch et al., 2004a). CGI-S. The CGI-S (National Institute of Mental Health, 1985) is a 7-point clinician rating of severity of psychopathology. Severity ratings range from 0 (no illness) to 6 (extremely severe). In children with OCD (Storch et al., 2004c), the CGI-S correlated strongly with the CY-BOCS total score (r = 0.75) and modestly with the Tourette's Disorder Scale-Parent Rated total score (TODS-PR; r = 0.60; Shydle et al., 2003). The CGI-S is widely used and shown to be sensitive to treatment effects (e.g., March et al., 1998; Pliszka et al., 2000; Riddle et al., 1992). CGI-1 The CGI (Guy, 1976) is a 7-point rating of treatment response anchored by 1 (very much improved) and.7 (very much worse). Youths receiving a score of very much improved and much improved were defined a priori as treatment responders. TODS-PR The TODS-PR (Shytle et al., 2003) is a 15-item parent-rated scale designed to measure a broad range of symptoms common to Tourette's disorder and OCD, including tics, obsessions, compulsions, inattention, hyperactivity, aggression, and mood disturbances. Support for the convergent and divergent validity of the TODS-PR total score has been reported (Shyde et al., 2003; Storch et al., 2004b). Multidimensional Anxiety Scale for Children-I 0 (MASC-I 0). The MASC-10 (March, 1997) is a 10-item self-report questionnaire derived from the full version that assesses symptoms of general, social, and separation anxiety in children and adolescents on a 4-point Likert scale. The MASC-10 internal consistency is adequate (a =.68; March, 1997). Three-month test-retest reliability was high (r = 0.83; Marc, 1997). The MASC-10 correlates highly with the psychometrically sound fulil version (r = 0.90; March et al., 1997, 1999). Children's Depression Inventory (CDI). The CDI (Kovacs, 1992) is a 27-item self-report measure that assesses the presence and severity of cognitive, affective, or behavioral symptoms of depression during the previous 2 weeks. The CDI has adequate internal consistency and differentiates between depressed and nondepressed youths (Carlson and Cantwell, 1979). In addition, the CDI has good test-retest reliability (r = 0.87) and construct validity as determined by high correlations with similar depression measures and through factor analysis (Craighead et al., 1998; Kovacs, 1992). Procedures At the initial session, which included an unstructured clinical interview by the first author (E.A.S.) about current symptoms, written consent and assent were obtained. Thereafter, an independent doctoral-level research assistant (supervised by the first author) who was blinded to the nature of any treatment offered performed all of the diagnostic interviews and ratings. Participants were assessed at baseline (4 weeks before start of treatment), immediately before the first CBT session, 1 to 2 days following the final session, and 3 months after treatment with self-report scales, parent-rated scales, and independent assessor ratings. Children were allowed up to four booster CBT sessions after treatment, depending on their needs. Psychotropic medications remained stable throughout treatment and the follow-up period. The University of Florida Institutional Review Board approved all study procedures. The first author, who has extensive experience in assessment and treatment of OCD, trained all raters. ADIS-IV-P training consisted of (1) observation of three interviews conducted by experienced raters, (2) administration of two interviews under direct supervision, and (3) matching the principal diagnosis of three interviews with the first author. Final diagnoses were derived using the Leckman et al. (1982) best-estimate procedure in which all of the available information was used (e.g., unstructured clinical interview, ADIS-IV-P, CY-BOCS). CY-BOCS training consisted of steps 1 and 2 above. To examine interrater reliability, the first author readministered the CY- BOCS to three children at baseline and three different children at the pretreatment assessment; kappa was excellent for the total score (K =.97). CBT. All patients received 14 ninety-minute CBT sessions over 3 weeks according to the manual by Lewin et al. (2005). This manual describes an adaptation of the Pediatric OCD Treatment Study Team (2004) protocol for use in an intensive format. This intervention indudes psychoeducation, cognitive training, and exposure and response prevention. Maladaptive parent-child interactions (e.g., accommodation) and the developmental needs of the youngster are incorporated into each treatment plan. Given the young age of patients, sessions included both a parent and the child to ensure optimal in-session effort, to improve understanding of treatment principles and homework assignments, and to address any problematic parent-child relationships (e.g., accommodation). Therapists were clinical psychology postdoctoral fellows or interns experienced in CBT for pediatric OCD. The first author supervised all of the cases and supervised dinicians daily. The attendance rate was 99% (97/98 possible sessions) across participants. Consistent with others (e.g., Tolin et al., 2004), the first author assigned a treatment fidelity rating on a 6-point scale (0 = poor fidelity, 5 = excellent fidelity) for each child's treatment based on a comparison to the manual (mean = 4.7, SD = 0.5). Data Analysis Examination of the interviewer, parent, and self-rated data at baseline, pretreatment, and postrreatment was examined and demonstrated nonnormal distributions. Therefore, nonparametric analyses were used when appropriate. A comparison of baseline to preassessment scores across the outcome measures revealed no significant differences for any of the seven children. Given this, the most recent 1174

5 CBT FOR PANDAS 30- o 25- S 20 S15- = Subjects [ CYBOCS - P.1 13 CYBOCS - PoIt a] CYBOCS ý Fol11w-p Fig.1 Mean Children's Yale-Brown Obsessive-Compulsive Scale scores for subjects across the study period. time point (preassessment) was used for subsequent analyses. The CY-BOCS, CGI-S, ADIS-1V-P Severity scale, TODS-PR, MASC, and CDI results were analyzed using Wilcoxon signed,rank test (twosided) comparing pretreatment and posttreatment and pretreatment and 3-month follow-up time points. Because of the preliminary nature of this study, no correction for family-wise error rate was conducted. Dichotomous diagnostic outcomes were reviewed using both descriptive and graphical methods. To determine the degree of longer-term gain, both the posttreatment and follow-up were graphically compared to pretreatment. To examine degree of relapse, the follow-up assessment was also graphically compared with posttreatment (Fig. 1). To further evaluate the clinical relevance of the findings, independent of sample size, the standardized difference between means was calculated as a measure of effect size. The fbllowing formula was used for this analysis (Cohen's d = M1 - M-21sp.lje, where Spoole = O[(sl 2 + 2]rY = dlo(d 2, 4) (Cohen, 1988). RESULTS All of the children completed treatment. One child was lost during the follow-up period because the family moved and no forwarding information was available. Data on this individual were included in the analyses up to the point of dropout. Primary Outcomes The primary treatment response was monitored using several outcome measures, including the CY-BOCS total score, CGI-S, ADIS -Severity rating, CGI, and remission status. All of the participants responded well, demonstrating a significant positive group change on all primary outcome indices (Table 3) for means, SDs, inferential statistics, and effect sizes. CY-BOCS. A Wilcoxon signed rank test indicated that the children demonstrated significantly lower CY- BOCS scores at the posttreatment assessment relative to pretreatment (T(7) = -2.37, p.018). This difference was maintained at follow-up (T(6) = -2.20,.p =.028). CGI-S. The group as a whole demonstrated a positive treatment response on the CGI-S, with an average pretreatment rating of 4.3 ± 1.0 and posttreatment rating of 1.4 ± 1.0, (T(7) = ,p =.017). Correspondingly, all seven children demonstrated a greater than two-grade improvement on this scale at the posttreatment assessment point. At posttreatment, illness severity on the CGI-S was classified as "no illness!' for one child (subject 5), "slight" for three (subjects 3, 6, and 7), "mild" for two (subjects 1 and 2), and "moderate" for one child (subject 4). This improvement was sustained to follow-up (T(6) = -1.90, p =.059), with illness severity classified as "slight" for two children (subjects 2 and 6), "moderate" for three (subjects 1, 3, and 5), and "severe" for one child (subject 4). ADIS-XV-P Severity Rating. A comparison of ADIS-. NV-P severity ratings demonstrated a significant improvement from pretreatment at both the posttreatment TABLE 3 Means, SDs, p Values, and Effect Sizes for Outcome Measures Baseline Pretreatment Posttreatment p Value Effect Sizea 3-Mo Follow-up p Value Scale Mean (SD) Mean (SD) Mean (SD) (Posttreatment) Cohen's d Mean (SD) (Follow-up) CY-BOCS 28.0 (4.6) 31.4 (5.9) 10.0 (6.7) ( ) 14.5 (8.6).028 ADIS-P 6.4 (1.1) 6.4 (1.1) 2.4 (2.2) ( ) 3.5 (1.5).027 CGI-S 3.7 (0.8) 4.3 (1.0) 1.4 (1.0) ( ) 3.0 (1.3).059 CGI-I (0.8) (1.2) N/A TODS-PR 41.0 (29.5) 64.3 (18.3) 41.8 (29.8) ( ) 39.8 (23.2).043 MASC (6.5) 13.0 (5.4) 15.1 (11.3) NS (.196) ( ) N/A N/A CDI 7.0 (5.3) 7.5 (5.5) 6.4 (4.3) N4S (.498) 0.22 ( ) N/A N/A 2 2 Note: Effect size (Cohen's d= M, -M2/Spooled, where s 1,,ooI, 6[(s 1 + s 2 )/ 2 ]ry, d/o(d 2 + 4); CY-BOCS = Children's Yale-Brown Obsessive-Compulsive Inventory; ADIS-P = Anxiety Disorders Interview Schedule for DSM-I11 Parent Version Severity rating; CGI-S = Clinical Global Impressions-Severity rating; CGI-1 = Clinical Global Impressions-Improvement; TODS = Tourette's Disorder Scale-Parent Rated; MASC-10 = Multidimensional Anxiety Scale for Children-10-item version; CDI Children's Depression Inventory; NS = not significant; N/A = not available. a Effect size was calculated based on pre- and posttreatment differences. 1175

6 STORCH ET AL. (T(7) = -2.38, p =.018) and follow-up assessments (T(6) = -2.21,p =.013). CGI-J. At posttreatment, 86% (6 of 7; subjects 1, 2, 3, 5, 6, and 7) of the children were considered treatment responders on the CGI. Fifty percent (3 of 6; subjects 2, 3, and 6) were classified as responders at follow-up. Remission Status. At posttreatment, 71% (5 of 7; subjects 2, 3, 5, 6, and 7) of children were classified as not having an OCD diagnosis on the ADIS-P. At follow-up, 50% (3 of 6; subjects 2, 3, and 6) of children remained diagnosis free. Secondary Outcomes TODS-PR. A comparison of pre- to posttreatment TODS-PR scores demonstrated a significant treatment response (T(7) = -2.03, p =.042). Again, this effect was demonstrated at the follow-up assessment (T(6) -2.02, p =.043). CDI and AMSC-1O. Scores on the CDI and MASC-10 were not significantly different from those at pretreatment or at the posttreatment assessments (CDI: T(7) -1.29, p = 0.196; MASC-10: T(7) -0.68, p 0.498). DISCUSSION PANDAS-related OCD is an autoimmune disorder characterized by symptom exacerbations following a streptococcal infection. Although several pharmacological treatments have been tested for reducing symptoms, each has limitations including invasiveness, side effects, and delayed and incomplete treatment response. Furthermore, some data (Murphy et al., 2006) indicate high rates of behavior activation in the PANDAS subtype following SSRI use. Upon initiating this study, we believed that CBT, an intervention with excellent support in non-pandas pediatric OCD (Barrett et al., 2004; De Hann et al., 1998; Pediatric OCD Treatment Study Team, 2004), may have utility as a safe and effective treatment for OCD symptoms of the PANDAS subtype. With the exception of one case report (Storch et al., c), this has not been tested. Accordingly, we present,a waitlist controlled open trial of intensive CBT for seven children with PANDASrelated OCD. Overall, children showed significantly better ratings at posttreatment and follow-up on the CY-BOCS with a large effect size exceeding that of the Pediatric OCD Treatment Study Team (2004). On the CY-BOCS, symptom reductions of 68% and 46% were found at posttreatment and follow-up, respectively, figures that correspond favorably with those of the Pediatric OCD Treatment Study Team (2004). Seventy-one percent (subjects 2, 3, 5, 6, and7) and 50% (subjects 2, 3, and6) of youths were diagnosis free at posttreatment and followup, respectively. Eighty-six percent (subjects 1, 2, 3, 5, 6, and 7) and 50% (subjects 2, 3, and 6) were rated as much improved or very much improved at posttreatment and follow-up, respectively. Subjects 1, 4, and 5 experienced partial or full relapses at follow-up as evidenced by increased ratings on instruments. However, it is notable that follow-up CY-BOCS scores remained below pretreatment levels for two of these youths. Reductions in self-reported anxiety and depression were not found, which may be a function of the treatment protocol (e.g., focuses more on OCD symptoms than depression, 3-week duration) or relatively low symptom endorsement on each measure at the baseline assessment. It is relevant to note that two children fully relapsed (subjects 4 and 5) and one child (subject 1) partially relapsed during the follow-up period after successful acute treatment. This may reflect the episodic nature of the PANDAS subtype. Although it is not possible to empirically determine response predictors given the small sample size, both children who relapsed had comorbid oppositional behavior and at least one parent with clinically significant anxiety. For others who did not relapse, it is possible that treatment may serve as a prophylaxis against future exacerbations in a manner similar to findings in the depression literature (Paykel et al., 2005). For example, CBT may enhance the ability of parents and children in dealing with new and existing symptoms by promoting adaptive behaviors (e.g., exposure and response prevention exercises, cognitive restructuring) and minimizing reinforcing or accommodating behaviors. Limitations Although the results are promising, several limitations must be noted. First, although we partially controlled for time with a waitlist period, the waitlist was relatively short in duration because of the ethical constraints of withholding treatment. A randomized, controlled design would have been preferable; however, given the relatively 1176

7 CBT FOR PANDAS low base rates of PANDAS and the preliminary nature of this study, obtaining an adequate sample size for parallel groups would have been difficult and perhaps premature without additional supporting data. Second, some have suggested that PANDAS be diagnosedonly after the presence of episodes of symptom exacerbations and remission that correspond to rising and falling titers (e.g., Snider and Swedo, 2004). Given this,, a significant limitation is that -PANDAS was diagnosed without benefit of longitudinal laboratory data. On balance, the diagnostic criteria for PANDAS are currently uncertain (Kurlan, 2004), and withholding treatment while attempting to document temporal relations was not feasible. Some data (e.g., Murphy et al., 2004) also stiggest that many children with a PANDAS course have persistently elevated titers and that after streptococcal infections, titers may remain elevated for 6 months to 1 year., Third, our small sample of treatment-seeking youths may not be representative of all children with PANDAS. The small sample size also precludes informative and reliable analyses of response predictors. Fourth, our modest follow-up period may not have been long enough to detect actual symptom fluctuations. Given the episodic course of PANDAS, it is possible that some of these cases would have remitted naturally without treatment. However, it seems reasonable that CBT accelerated symptom remission given that symptoms remained stable over the waitlist and then rapidly decreased following time-limited treatment. Fifth, six of seven children were taking one or more SSRI medication upon treatment presentation. Although all of the children were stable on medication during CBT and follow-up, their positive results may be attributable to combined treatment rather than CBT alone. Finally, our treatment program differed from standard outpatient CBT in that families were seen daily for 3 weeks. On balance, this approach has been shown to have comparable efficacy to standard weekly treatment in both adults (Abramowitz et al., 2003) and children (Franklin et al., 1998; Storch et al., 2005). Clinical Implications A cognitive-behavioral intervention for OCD symptoms in the PANDAS subtype demonstrated promising preliminary treatment effects. Such an approach may be less invasive and less expensive than pharmacological approaches such as SSRI or antibiotic use. One theory is that most cases of OCD are biologically triggered, but environmental factors such as avoidance and parental accommodation may help maintain the OCD into a chronic state. CBT in the early phases of illness onset may "short circuit" the potential of a chronic illness. Although CBT may not prevent future episodes of GAS-triggered OCD exacerbations, CBT gives the family and child the skills needed to allow for exacerbations to be of a diminished severity and duration. Future study in larger, controlled settings is warranted. Disclosure: Dr. Storch has received grant support from the Obsessive- Compulive Foundation and Genentech, Incorporated Dr. Murphy has received grant support from Bristol-Myers Squibb and Pediamed Pharmaceutical. The other authors have nofinancial relationships to disclose. REFERENCES Abramowitz JS, Foa EB, Franklin ME (2003), Exposure and ritual prevention for obsessive-compulsive disorder: effects of intensive versus twice-weekly sessions. J Consult Clin Psychol 71: Barrett P, Healy-Farrell L, March JS (2004), Cognitive behavioral family treatment of childhood obsessive-compulsive disorder: a controlled trial. 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Although others have examined the effects of the accumulation of risk factors, this methodology has not been applied to child health. Objective: We tested 4 social risk factors (poverty, minority race/ethnicity, low parental education, and not living with both biological parents) to assess whether they have cumulative effects on child health and examined whether access to health care reduced health disparities. Design: We analyzed data on children <18 years from the 1994 and 1995 National Health Interview Survey Disability Supplement. Of the 4 risk factors, 3 (poverty, low parental education, and single-parent household) were consistently associated with child health. These were summed, generating the Social Disadvantage Index (range: 0-3). Results: A total of 43.6% of children had no social disadvantages, 30.8% had 1, 15.6% had 2, and, 10.0% had all 3. Compared with those with no social disadvantages, the odds ratios (ORs) of being in "good, fair, or poor health" (versus "excellent or very good") were 1.95 for 1 risk, 3.22 for 2 risks, and 4.06 for 3 risks. ORs of having a chronic condition increased from 1.25 (1 risk) to 1.60 (2 risks) to 2.11 (3 risks). ORs for activity limitation were 1.51 (1 risk) to 2.14 (2 risks) and 2.88 (3 risks). Controlling for health insurance did not affect these findings, Conclusions: The accumulation of social disadvantage among children was strongly associated with poorer child health and having insurance did not reduce the observed health disparities. Pediatrics 2006;117:

9 COPYRIGHT INFORMATION TITLE: Cognitive-Behavioral Therapy for PANDAS-Related Obsessive-Compulsive Di SOURCE: Journal of the American Academy of Child and Adolescent Psychiatry 45 no10 O 2006 PAGE(S): WN: The magazine publisher is the copyright holder of this article and it is reproduced with permission. Further reproduction of this article in violation of the copyright is prohibited. Copyright The H.W. Wilson Company. All rights reserved.