Longitudinal study of insomnia, suicidal ideation, and psychopathology in schizophrenia.

OBJECTIVE: Insomnia is a common comorbidity in schizophrenia. Increasing cross-sectional evidence suggests an association between insomnia and suicidal ideation (SI) and symptom severity in schizophrenia. We investigated longitudinal associations over 3 months between insomnia, suicidal ideation, and symptom severity in a group of patients with chronic schizophrenia. METHOD: We performed a secondary analysis of data from n = 305 participants from the Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy (PROACTIVE) schizophrenia trial using regression models. RESULTS: The prevalence of moderate-to-severe insomnia was 17.7 % at baseline and 13.6 % at 3 months, respectively. The prevalence of SI was 22 % at baseline and 22.5 % at 3 months. After controlling for potential confounders, improved SI from baseline to 3 months was associated with both baseline moderate-to-severe insomnia (OR = 3.81, 95 % CI 1.11-13.12, p = 0.034) and improvement in insomnia (OR = 3.50, 95 % CI 1.23-9.92, p = 0.013). Worsening SI from baseline to 3 months was associated with worsening insomnia (OR = 3.50, 95 % CI 1.23-9.92, p = 0.013), but not baseline insomnia. Improvement in BPRS total score from baseline to 3 months was associated with improvement in insomnia (ß = 0.17, p = 0.029), but not baseline insomnia. CONCLUSION: Insomnia is common in patients with chronic schizophrenia and insomnia showed significant associations with SI and psychopathology. Clinicians should consider insomnia when assessing suicide risk in patients with schizophrenia.

Longitudinal study of inflammation and relapse in schizophrenia.

INTRODUCTION: The clinical course of schizophrenia is often characterized by recurrent relapses. Blood inflammatory markers are altered in acute psychosis, and may be state markers for illness relapse in schizophrenia. Few studies have investigated longitudinal, intra-individual changes in inflammatory markers as a predictor of relapse. In the present study, we explored this association in a relapse prevention trial in patients with schizophrenia. METHODS: We analyzed blood inflammatory markers in 200 subjects, with a mean 11 samples per subject, during the 30 month Preventing Relapse in schizophrenia: Oral Antipsychotics Compared to Injectable: eValuating Efficacy (PROACTIVE) trial. Associations between longitudinal changes in inflammatory markers and relapse were analyzed using a within-subjects design. RESULTS: 70 (35 %) of subjects relapsed during the study period. There were no significant differences in mean inflammatory marker levels based on relapse status (yes/no). Baseline levels of inflammatory markers did not predict incident relapse. Among subjects who relapsed, there was a significant decrease in mean blood IL-6 (n = 38, p = 0.019) and IFN-γ (n = 44, p = 0.012) levels from the visit before the relapse to the visit after relapse. CONCLUSION: Although there was some evidence for inflammation as a potential state marker for acute psychosis, we did not find significant evidence for its utility as a relapse-predictive marker.

Outcomes During and After Early Intervention Services for First-Episode Psychosis: Results Over 5 Years From the RAISE-ETP Site-Randomized Trial.

To examine long-term effects of early intervention services (EIS) for first-episode psychosis, we compared Heinrichs-Carpenter Quality of Life (QLS) and Positive and Negative Syndrome Scale (PANSS) scores and inpatient hospitalization days over 5 years with data from the site-randomized RAISE-ETP trial that compared the EIS NAVIGATE (17 sites; 223 participants) and community care (CC) (17 sites; 181 participants). Inclusion criteria were: age 15-40 years; DSM-IV diagnoses of schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder not otherwise specified; first psychotic episode; antipsychotic medication taken for ≤6 months. NAVIGATE-randomized participants could receive NAVIGATE from their study entry date until NAVIGATE ended when the last-enrolled NAVIGATE participant completed 2 years of treatment. Assessments occurred every 6 months. 61% of participants had assessments conducted ≥2 years; 31% at 5 years. Median follow-up length was CC 30 months and NAVIGATE 38 months. Primary analyses assumed data were not-missing-at-random (NMAR); sensitivity analyses assumed data were missing-at-random (MAR). MAR analyses found no significant treatment-by-time interactions for QLS or PANSS. NMAR analyses revealed that NAVIGATE was associated with a 13.14 (95%CI:6.92,19.37) unit QLS and 7.73 (95%CI:2.98,12.47) unit PANSS better improvement and 2.53 (95%CI:0.59,4.47) fewer inpatient days than CC (all comparisons significant). QLS and PANSS effect sizes were 0.856 and 0.70. NAVIGATE opportunity length (mean 33.8 (SD = 5.1) months) was not associated (P = .72) with QLS outcome; duration of untreated psychosis did not moderate (P = .32) differential QLS outcome. While conclusions are limited by the low rate of five-year follow-up, the data support long-term benefit of NAVIGATE compared to community care.

Comparison of Early Intervention Services vs Treatment as Usual for Early-Phase Psychosis: A Systematic Review, Meta-analysis, and Meta-regression.

Importance: The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal. Objective: To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis. Data Sources: Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017. Study Selection: Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders. Data Extraction and Synthesis: This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses. Main Outcomes and Measures: The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period. Results: Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P < .001), at least 1 psychiatric hospitalization (RR, 0.74; 95% CI, 0.61-0.90; P = .003), involvement in school or work (RR, 1.13; 95% CI, 1.03-1.24; P = .01), total symptom severity (standardized mean difference [SMD], -0.32; 95% CI, -0.47 to -0.17; P < .001), positive symptom severity (SMD, -0.22; 95% CI, -0.32 to -0.11; P < .001), and negative symptom severity (SMD, -0.28; 95% CI, -0.42 to -0.14; P < .001). Superiority of EIS regarding all outcomes was evident at 6, 9 to 12, and 18 to 24 months of treatment (except for general symptom severity and depressive symptom severity at 18-24 months). Conclusions and Relevance: In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.

Predicting relapse in schizophrenia: Is BDNF a plausible biological marker?

Understanding the biological processes that underlie why patients relapse is an issue of fundamental importance to the detection and prevention of relapse in schizophrenia. Brain Derived Neurotrophic Factor (BDNF), a facilitator of brain plasticity, is reduced in patients with schizophrenia. In the present study, we examined whether decreases in plasma BDNF levels could be used as a biological predictor of relapse in schizophrenia. A total of 221 patients were prospectively evaluated for relapse over 30months in the Preventing Relapse in Schizophrenia: Oral Antipsychotics Compared to Injectables: eValuating Efficacy (PROACTIVE) study. Serial blood samples were collected at a maximum of 23 time points during the 30-month trial and BDNF levels were measured in plasma samples by ELISA. Receiver Operating Characteristic (ROC) curve analysis indicated that BDNF was not a significant predictor of relapse, hospitalization or exacerbation. Regardless of treatment group (oral second generation antipsychotic vs. long-acting injectable risperidone microspheres), baseline BDNF value did not differ significantly between those who experienced any of the adverse outcomes and those who did not. While contrary to the study hypothesis, these robust results offer little support for the use of plasma BDNF alone as a biomarker to predict relapse in schizophrenia.

Consistency checks to improve measurement with the Positive and Negative Syndrome Scale (PANSS).

International Society for CNS Clinical Trials and Methodology convened an expert working-group that assembled consistency/inconsistency flags for the Positive and Negative Syndrome Scale (PANSS). Twenty-four flags were identified and divided based on extent to which they represent error (Possibly, Probably, Very probably or definitely). The flags were applied to assessments derived from the NEWMEDS data repository and the CATIE clinical trial data. Almost 40% of ratings had at least one inconsistency flag raised and 10% had two. Application of flags to clinical rating can improve reliability and validity of trials.

Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program.

OBJECTIVE: The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for implementation in the U.S. health care system, with community care on quality of life. METHOD: Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and ≤6 months of antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities. RESULTS: The 223 recipients of NAVIGATE remained in treatment longer, experienced greater improvement in quality of life and psychopathology, and experienced greater involvement in work and school compared with 181 participants in community care. The median duration of untreated psychosis was 74 weeks. NAVIGATE participants with duration of untreated psychosis of <74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in community care. Rates of hospitalization were relatively low compared with other first-episode psychosis clinical trials and did not differ between groups. CONCLUSIONS: Comprehensive care for first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.

Comparison of SGA oral medications and a long-acting injectable SGA: the PROACTIVE study.

Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice, this is not seen in recent randomized clinical trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) relapse prevention study incorporated efficacy and effectiveness features. At 8 US academic centers, 305 patients with schizophrenia or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or physician's choice oral SGAs. Patients were evaluated during the 30-month study by masked, centralized assessors using 2-way video, and monitored biweekly by on-site clinicians and assessors who knew treatment assignment. Relapse was evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group. In contrast, the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores. There were no other between-group differences in symptoms or functional improvement. Despite the advantage for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization. Biweekly monitoring, not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm, may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials.

How can registries contribute to the development and evaluation of CNS therapeutics?

This article is based on the proceedings from a workshop held during the Autumn 2011 International Society for CNS Clinical Trials and Methodology (ISCTM) Conference in Amelia Island, Florida. The goal of the workshop was to establish preliminary steps in determining whether and how patient registries can augment clinical trials in the field of central nervous system therapeutics. Participants in the workshop first defined several different types of registries and then created a list of questions that should be addressed in order to determine how registries might be used. The workshop concluded with discussion on logistical and practical considerations regarding use of patient registries.

Lithium treatment moderate-dose use study (LiTMUS) for bipolar disorder: a randomized comparative effectiveness trial of optimized personalized treatment with and without lithium.

OBJECTIVE: Lithium salts, once the mainstay of therapy for bipolar disorder, have tolerability issues at a higher dosage that often limit adherence. The authors investigated the comparative effectiveness of more tolerable dosages of lithium as part of optimized personalized treatment (OPT). METHOD: The authors randomly assigned 283 bipolar disorder outpatients to 6 months of open, flexible, moderate dosages of lithium plus OPT or to 6 months of OPT alone. The primary outcome measures were the Clinical Global Impression Scale for Bipolar Disorder-Severity (CGI-BP-S) and "necessary clinical adjustments" (medication adjustments per month). Secondary outcome measures included mood symptoms and functioning. The authors also assessed sustained remission (defined as a CGI-BP-S score ≤2 for 2 months) and treatment with second-generation antipsychotics. The authors hypothesized that lithium plus OPT would result in greater clinical improvement and fewer necessary clinical adjustments. RESULTS: The authors observed no statistically significant advantage of lithium plus OPT on CGI-BP-S scores, necessary clinical adjustments, or proportion with sustained remission. Both groups had similar outcomes across secondary clinical and functional measures. Fewer patients in the lithium-plus-OPT group received second-generation antipsychotics compared with the OPT-only group (48.3% and 62.5%, respectively). CONCLUSIONS: In this pragmatic comparative effectiveness study, a moderate but tolerated dosage of lithium plus OPT conferred no symptomatic advantage when compared with OPT alone, but the lithium-plus-OPT group had less exposure to second-generation antipsychotics. Only about one-quarter of patients in both groups achieved sustained remission of symptoms. These findings highlight the persistent and chronic nature of bipolar disorder as well as the magnitude of unmet needs in its treatment.

Blood pressure and heart rate over 10 years in the multimodal treatment study of children with ADHD.

OBJECTIVE: It is unknown whether prolonged childhood exposure to stimulant medication for the treatment of attention deficit hyperactivity disorder (ADHD) increases the risk for developing abnormalities in blood pressure or heart rate. The authors examined the association between stimulant medication and blood pressure and heart rate over 10 years. METHOD: A total of 579 children, ages 7­9, were randomly assigned to 14 months of medication treatment, behavioral therapy, the combination of the two, or usual community treatment. The controlled trial was followed by naturalistic treatment with periodic assessments. Blood pressure and heart rate data were first analyzed with linear regression models based on an intent-to-treat approach, using raw data and the blood pressure categories of prehypertension and hypertension. Currently medicated patients were then compared with never or previously medicated patients. Associations between cumulative stimulant exposure and blood pressure or heart rate were assessed. RESULTS: No treatment effect on either systolic or diastolic blood pressure could be detected. Children who were treated with stimulants had a higher heart rate (mean=84.2 bpm [SD=12.4] on medication alone and mean=84.6 bpm [SD=12.2] on medication plus behavioral therapy) than those who were treated with behavioral therapy alone (mean=79.1 bpm [SD=12.0]) or those who received usual community treatment (mean=78.9 bpm [SD=12.9]) at the end of the 14-month controlled trial, but not thereafter. Stimulant medication did not increase the risk for tachycardia, but greater cumulative stimulant exposure was associated with a higher heart rate at years 3 and 8. CONCLUSIONS: Stimulant treatment did not increase the risk for prehypertension or hypertension over the 10-year period of observation. However, stimulants had a persistent adrenergic effect on heart rate during treatment.

3-year follow-up of the NIMH MTA study.

OBJECTIVE: In the intent-to-treat analysis of the Multimodal Treatment Study of Children With ADHD (MTA), the effects of medication management (MedMgt), behavior therapy (Beh), their combination (Comb), and usual community care (CC) differed at 14 and 24 months due to superiority of treatments that used the MTA medication algorithm (Comb+MedMgt) over those that did not (Beh+CC). This report examines 36-month outcomes, 2 years after treatment by the study ended. METHOD: For primary outcome measures (attention-deficit/hyperactivity disorder [ADHD] and oppositional defiant disorder [ODD] symptoms, social skills, reading scores, impairment, and diagnostic status), mixed-effects regression models and orthogonal contrasts examined 36-month outcomes. RESULTS: At 3 years, 485 of the original 579 subjects (83.8%) participated in the follow-up, now at ages 10 to 13 years, (mean 11.9 years). In contrast to the significant advantage of MedMgt+Comb over Beh+CC for ADHD symptoms at 14 and 24 months, treatment groups did not differ significantly on any measure at 36 months. The percentage of children taking medication >50% of the time changed between 14 and 36 months across the initial treatment groups: Beh significantly increased (14% to 45%), MedMed+Comb significantly decreased (91% to 71%), and CC remained constant (60%-62%). Regardless of their treatment use changes, all of the groups showed symptom improvement over baseline. Notably, initial symptom severity, sex (male), comorbidity, public assistance, and parental psychopathology (ADHD) did not moderate children's 36-month treatment responses, but these factors predicted worse outcomes over 36 months, regardless of original treatment assignment. CONCLUSIONS: By 36 months, the earlier advantage of having had 14 months of the medication algorithm was no longer apparent, possibly due to age-related decline in ADHD symptoms, changes in medication management intensity, starting or stopping medications altogether, or other factors not yet evaluated.

Secondary evaluations of MTA 36-month outcomes: propensity score and growth mixture model analyses.

OBJECTIVE: To evaluate two hypotheses: that self-selection bias contributed to lack of medication advantage at the 36-month assessment of the Multimodal Treatment Study of Children With ADHD (MTA) and that overall improvement over time obscured treatment effects in subgroups with different outcome trajectories. METHOD: Propensity score analyses, using baseline characteristics and severity of attention-deficit/hyperactivity disorder symptoms at follow-up, established five subgroups (quintiles) based on tendency to take medication at the 36-month assessment. Growth mixture model (GMM) analyses were performed to identify subgroups (classes) with different patterns of outcome over time. RESULTS: All five propensity subgroups showed initial advantage of medication that disappeared by the 36-month assessment. GMM analyses identified heterogeneity of trajectories over time and three classes: class 1 (34% of the MTA sample) with initial small improvement followed by gradual improvement that produced significant medication effects; class 2 (52%) with initial large improvement maintained for 3 years and overrepresentation of cases treated with the MTA Medication Algorithm; and class 3 (14%) with initial large improvement followed by deterioration. CONCLUSIONS: We failed to confirm the self-selection hypothesis. We found suggestive evidence of residual but not current benefits of assigned medication in class 2 and small current benefits of actual treatment with medication in class 1.

Delinquent behavior and emerging substance use in the MTA at 36 months: prevalence, course, and treatment effects.

OBJECTIVE: To compare delinquent behavior and early substance use between the children in the Multimodal Treatment Study of Children With ADHD (MTA; N = 487) and those in a local normative comparison group (n = 272) at 24 and 36 months postrandomization and to test whether these outcomes were predicted by the randomly assigned treatments and subsequent self-selected prescribed medications. METHOD: Most MTA children were 11 to 13 years old by 36 months. Delinquency seriousness was coded ordinally from multiple measures/reporters; child-reported substance use was binary. RESULTS: Relative to local normative comparison group, MTA children had significantly higher rates of delinquency (e.g., 27.1% vs. 7.4% at 36 months; p = .000) and substance use (e.g., 17.4% vs. 7.8% at 36 months; p = .001). Children randomized to intensive behavior therapy reported less 24-month substance use than other MTA children (p = .02). Random effects ordinal growth models revealed no other effects of initial treatment assignment on delinquency seriousness or substance use. By 24 and 36 months, more days of prescribed medication were associated with more serious delinquency but not substance use. CONCLUSIONS: Cause-and-effect relationships between medication treatment and delinquency are unclear; the absence of associations between medication treatment and substance use needs to be re-evaluated at older ages. Findings underscore the need for continuous monitoring of these outcomes as children with attention-deficit/hyperactivity disorder enter adolescence.

Treatment-related changes in objectively measured parenting behaviors in the multimodal treatment study of children with attention-deficit/hyperactivity disorder.

The present study examined treatment outcomes for objectively measured parenting behavior in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD). Five hundred seventy-nine ethnically and socioeconomically diverse children with ADHD-combined type (ages 7.0-9.9 years) and their parent(s) were recruited at 6 sites in the United States and Canada and randomly assigned to 1 of 4 treatment groups for 14 months of active intervention: medication management (MedMgt), intensive behavior therapy, combination of the 2 (Comb), or a community-treated comparison (CC). Baseline and posttreatment laboratory observations of parent-child interactions were coded by observers blind to treatment condition. Comb produced significantly greater improvements in constructive parenting than did MedMgt or CC, with effect sizes approaching medium for these contrasts. Treatment effects on child behaviors were not significant. The authors discuss the importance of changes in parenting behavior for families of children with ADHD and the need for reliable and objective measures in evaluating treatment outcome.

Assessing medication effects in the MTA study using neuropsychological outcomes.

BACKGROUND: While studies have increasingly investigated deficits in reaction time (RT) and RT variability in children with attention deficit/hyperactivity disorder (ADHD), few studies have examined the effects of stimulant medication on these important neuropsychological outcome measures. METHODS: 316 children who participated in the Multimodal Treatment Study of Children with ADHD (MTA) completed the Conners' Continuous Performance Test (CPT) at the 24-month assessment point. Outcome measures included standard CPT outcomes (e.g., errors of commission, mean hit reaction time (RT)) and RT indicators derived from an Ex-Gaussian distributional model (i.e., mu, sigma, and tau). RESULTS: Analyses revealed significant effects of medication across all neuropsychological outcome measures. Results on the Ex-Gaussian outcome measures revealed that stimulant medication slows RT and reduces RT variability. CONCLUSIONS: This demonstrates the importance of including analytic strategies that can accurately model the actual distributional pattern, including the positive skew. Further, the results of the study relate to several theoretical models of ADHD.

Peer-assessed outcomes in the multimodal treatment study of children with attention deficit hyperactivity disorder.

Peer-assessed outcomes were examined at the end of treatment (14 months after study entry) for 285 children (226 boys, 59 girls) with attention deficit hyperactivity disorder (ADHD) who were rated by their classmates (2,232 classmates total) using peer sociometric procedures. All children with ADHD were participants in the Multimodal Treatment Study of Children with ADHD (MTA). Treatment groups were compared using the orthogonal treatment contrasts that accounted for the largest amount of variance in prior MTA outcome analyses: Medication Management + Combined Treatment versus Behavior Therapy + Community Care; Medication Management versus Combined Treatment; Behavior Therapy versus Community Care. There was little evidence of superiority of any of the treatments for the peer-assessed outcomes studied, although the limited evidence that emerged favored treatments involving medication management. Post hoc analyses were used to examine whether any of the four treatment groups yielded normalized peer relationships relative to randomly selected-classmates. Results indicated that children from all groups remained significantly impaired in their peer relationships.

Nine months of multicomponent behavioral treatment for ADHD and effectiveness of MTA fading procedures.

We examined 9-month data from the 14-month NIMH Multimodal Treatment Study of Children with ADHD (the MTA) as a further check on the relative effect of medication (MedMgt) and behavioral treatment (Beh) for attention-deficit/hyperactivity disorder (ADHD) while Beh was still being delivered at greater intensity than at 14-month endpoint, and conversely as a check on the efficacy of the MTA behavioral generalization/maintenance procedures. Intention-to-treat analysis at 9 months showed essentially the same results as at 14 months, after Beh had been completely faded; MedMgt and the combination (Comb) of medication and Beh were significantly superior to Beh and community care (CC) for ADHD and oppositional-defiant (ODD) symptoms, with mixed results for social skills and internalizing symptoms. All treatment-group differences examined as changes in slopes from 9 to 14 months were nonsignificant (we found general improvement for all groups). Slopes from baseline to 9 months correlated highly (r > .74, p < .0001) with slopes from baseline to 14 months for all groups. The time function from baseline to 14 months showed a significant linear, but not quadratic, trend for the main outcome measure (a composite of parent- and teacher-rated ADHD and ODD symptoms) for all groups. Findings suggest that in contrast to the hypothesized deterioration in the relative benefit of Beh between 9 and 14 months (after completion of fading), the MTA Beh generalization and maintenance procedures implemented through 9 months apparently yielded continuing improvement through 14 months, with preservation of the relative position of Beh compared to other treatment strategies.

Effects of ethnicity on treatment attendance, stimulant response/dose, and 14-month outcome in ADHD.

From the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder--a randomized clinical trial of 579 children ages 7-9 years receiving 14 months of medication management, behavioral treatment, combination, or community care--the authors matched each African American and Latino participant with randomly selected Caucasian participants of same sex, treatment group, and site. Although Caucasian children were significantly less symptomatic than African American and Latino children on some ratings, response to treatment did not differ significantly by ethnicity after controlling for public assistance. Ethnic minority families cooperated with and benefited significantly from combination (multimodal) treatment (d = 0.36, compared with medication). This incremental gain withstood statistical control for mother's education, single-parent status, and public assistance. Treatment for lower socioeconomic status minority children, especially if comorbid, should combine medication and behavioral treatment.

Which treatment for whom for ADHD? Moderators of treatment response in the MTA.

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.