Interpersonal psychotherapy for mood and behavior dysregulation: Pilot randomized trial.

BACKGROUND: Youth with chronic irritability and excessive reactivity, diagnosed as disruptive mood dysregulation disorder (DMDD), have social impairment in multiple settings (i.e., peers, school, and home). This paper presents a pilot randomized trial assessing the feasibility, acceptability, and preliminary efficacy of interpersonal psychotherapy (IPT) for mood and behavior dysregulation (IPT-MBD), an adapted version of IPT for depressed adolescents. IPT-MBD focuses on decreasing outbursts and irritability and improving interpersonal interactions. METHODS: Nineteen adolescents (aged 12-17) with DMDD or its research precursor, severe mood dysregulation, were randomly assigned to IPT-MBD (n = 10) or treatment-as-usual (TAU, n = 9) in a 24-week psychosocial intervention study. Assessments of mood symptoms and overall functioning were conducted by an independent evaluator, blinded to treatment, every 4 weeks. Parent and self-report irritability measures were collected every 4 weeks. RESULTS: Eighty percent of participants randomized to the IPT-MBD arm completed the study. Also, participants enrolled in the IPT-MBD arm attended >80% of therapy sessions. Parents and teens agreed that the frequency and duration of therapy were appropriate and were satisfied with IPT-MBD treatment. Clinical global impression scales for severity and improvement showed statistically greater improvement in the IPT-MBD group compared to TAU. CONCLUSIONS: In this small pilot randomized trial, IPT-MBD was feasible and acceptable to parents and teens. There was significantly more improvement in the IPT-MBD group compared to TAU. IPT-MBD holds promise as a potentially effective psychosocial intervention for clinically impaired youth with DMDD and warrants further investigation in a larger randomized trial.

Interpersonal Psychotherapy for Adolescents With Mood and Behavior Dysregulation: Evidence-Based Case Study.

Interpersonal psychotherapy for depressed adolescents, an evidence-based psychotherapy, has been adapted for youth with chronic irritability and excessive reactivity (i.e., temper outbursts), to create Interpersonal Psychotherapy for Mood and Behavior Dysregulation (IPT-MBD). Youth with chronic irritability and excessive reactivity were originally conceptualized as severe mood dysregulation (SMD) and in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) as disruptive mood dysregulation disorder. Because outbursts are the most prominent symptom, behavioral management strategies are typically a common focus of treatment. These outbursts, along with other mood symptoms, result in significant impairment in multiple domains, with a particularly adverse impact on interpersonal functioning. For this reason improving relationships is an important target for treatment. We present an evidence-based case study of an adolescent who met research criteria for SMD and who received the IPT-MBD intervention as part of a research study. Monthly ratings assessing severity and improvement of SMD symptoms were conducted by an independent evaluator. This adolescent had an overall improvement in SMD symptoms, attended all scheduled therapy sessions, and parent and teen reported satisfaction with the treatment. We discuss factors that may influence the effectiveness of this treatment.

An evidence map of psychosocial interventions for the earliest stages of bipolar disorder.

Depression, schizophrenia, and bipolar disorder are three of the four most burdensome problems in people aged under 25 years. In psychosis and depression, psychological interventions are effective, low-risk, and high-benefit approaches for patients at high risk of first-episode or early-onset disorders. We review the use of psychological interventions for early-stage bipolar disorder in patients aged 15-25 years. Because previous systematic reviews had struggled to identify information about this emerging sphere of research, we used evidence mapping to help us identify the extent, distribution, and methodological quality of evidence because the gold standard approaches were only slightly informative or appropriate. This strategy identified 29 studies in three target groups: ten studies in populations at high risk for bipolar disorder, five studies in patients with a first episode, and 14 studies in patients with early-onset bipolar disorder. Of the 20 completed studies, eight studies were randomised trials, but only two had sample sizes of more than 100 individuals. The main interventions used were family, cognitive behavioural, and interpersonal therapies. Only behavioural family therapies were tested across all of our three target groups. Although the available interventions were well adapted to the level of maturity and social environment of young people, few interventions target specific developmental psychological or physiological processes (eg, ruminative response style or delayed sleep phase), or offer detailed strategies for the management of substance use or physical health.

Early intervention for adolescents at high risk for the development of bipolar disorder: pilot study of Interpersonal and Social Rhythm Therapy (IPSRT).

Interpersonal and Social Rhythm Therapy (IPSRT) delays bipolar disorder (BP) recurrence in adults by stabilizing daily routines and sleep/wake cycles. Because adolescence is a key developmental stage for illness onset and altered social and sleep patterns, this period may prove optimal for intervention with adolescents at-risk for BP. We describe a treatment development trial of IPSRT for adolescents at-risk for BP by virtue of a positive family history. Adolescents with a first-degree relative with BP were evaluated for Axis I psychopathology via semistructured interview, and relatives' BP diagnoses were confirmed via record review. IPSRT consisted of 12 sessions delivered over 6 months. Outcome variables including sleep, mood symptoms, and functioning were assessed via clinician interview and self-/parent-report at pretreatment, 3 months, and posttreatment (6 months). Thirteen adolescents attended at least one IPSRT session. Half of the sample denied Axis I psychopathology at intake; the remainder met criteria for a range of internalizing and externalizing disorders. Families reported high satisfaction with IPSRT, yet, on average, participants attended about half of scheduled sessions. Missed sessions were primarily associated with parental BP illness severity. Data indicate significant change in select sleep/circadian patterns (i.e., less weekend sleeping in and oversleeping) with treatment. Preliminary data suggest the IPSRT focus on stabilizing daily rhythms and interpersonal relationships may be beneficial for adolescents at-risk for BP. Controlled trials with longitudinal follow-up are needed to examine whether early intervention for at-risk youth helps prevent or delay disorder.

Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study.

OBJECTIVE: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. METHOD: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. RESULTS: Of the 116 youths randomized in the acute trial, 54 entered maintenance treatment (molindone, n = 20; olanzapine, n = 13; risperidone, n = 21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (n = 15), inadequate efficacy (n = 14), or study nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. CONCLUSIONS: Only 12% of youths with early-onset schizophrenia spectrum disorders continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for early-onset schizophrenia spectrum disorders. Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703.

Interpersonal and social rhythm therapy for adolescents with bipolar disorder: treatment development and results from an open trial.

BACKGROUND: In adolescents and adults, bipolar disorder (BD) is associated with significant morbidity, mortality, and impairment in psychosocial and occupational functioning. IPSRT is an empirically supported adjunctive psychotherapy for adults with bipolar disorder, which has been shown to help delay relapse, speed recovery from a bipolar depressive episode, and increase occupational and psychosocial functioning in adults with BD. This study is designed to describe the adolescent-specific developmental adaptations made to IPSRT (i.e., IPSRT-A) and to report the results from an open trial of IPSRT-A with 12 adolescents with a bipolar spectrum disorder. METHOD: Interpersonal and Social Rhythm Therapy was adapted to be developmentally relevant to adolescents with bipolar disorder. Twelve adolescents (mean age 16.5+/-1.3 years) diagnosed with a bipolar spectrum disorder participated in 16-18 sessions of adjunctive IPSRT-A over 20 weeks. Manic, depressive, and general symptoms and global functioning were measured at baseline, monthly during treatment, and at post-treatment. Adolescent satisfaction with treatment was also measured. RESULTS: Feasibility and acceptability of IPSRT-A were high; 11/12 participants completed treatment, 97% of sessions were attended, and adolescent-rated satisfaction scores were high. IPSRT-A participants experienced significant decreases in manic, depressive, and general psychiatric symptoms over the 20 weeks of treatment. Participants' global functioning increased significantly as well. Effect sizes ranged from medium-large to large. CONCLUSIONS: IPSRT-A appears to be a promising adjunctive treatment for adolescents with bipolar disorder. A current randomized controlled trial is underway to examine effects of adjunctive IPSRT-A on psychiatric symptoms and psychosocial functioning.

Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study.

OBJECTIVE: Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. METHOD: This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment. RESULTS: In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. CONCLUSIONS: Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia and schizoaffective disorder. The safety findings related to weight gain and metabolic problems raise important public health concerns, given the widespread use of second-generation antipsychotics in youth for nonpsychotic disorders.

The Collaborative Lithium Trials (CoLT): specific aims, methods, and implementation.

BACKGROUND: Lithium is a benchmark treatment for bipolar illness in adults. However, there has been relatively little methodologically stringent research regarding the use of lithium in youth suffering from bipolarity. METHODS: Under the auspices of the Best Pharmaceuticals for Children Act (BPCA), a Written Request (WR) pertaining to the study of lithium in pediatric mania was issued by the United States Food and Drug Administration (FDA) to the National Institute of Child Health and Human Development (NICHD) in 2004. Accordingly, the NICHD issued a Request for Proposals (RFP) soliciting submissions to pursue this research. Subsequently, the NICHD awarded a contract to a group of investigators in order to conduct these studies. RESULTS: The Collaborative Lithium Trials (CoLT) investigators, the BPCA-Coordinating Center, and the NICHD developed protocols to provide data that will: (1) establish evidence-based dosing strategies for lithium; (2) characterize the pharmacokinetics and biodisposition of lithium; (3) examine the acute efficacy of lithium in pediatric bipolarity; (4) investigate the long-term effectiveness of lithium treatment; and (5) characterize the short- and long-term safety of lithium. By undertaking two multi-phase trials rather than multiple single-phase studies (as was described in the WR), the feasibility of the research to be undertaken was enhanced while ensuring all the data outlined in the WR would be obtained. The first study consists of: (1) an 8-week open-label, randomized, escalating dose Pharmacokinetic Phase; (2) a 16-week Long-Term Effectiveness Phase; (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. The second study consists of: (1) an 8-week, double-blind, parallel-group, placebo-controlled Efficacy Phase; (2) an open-label Long-Term Effectiveness lasting either 16 or 24 weeks (depending upon blinded treatment assignment during the Efficacy Phase); (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. In December of 2006, enrollment into the first of these studies began across seven sites. CONCLUSION: These innovative studies will not only provide data to inform the labeling of lithium in children and adolescents with bipolar disorder, but will also enhance clinical decision-making regarding the use of lithium treatment in pediatric bipolar illness. TRIAL REGISTRATION: NCT00442039.

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

OBJECTIVE: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. METHOD: Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. RESULTS: From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. CONCLUSIONS: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): demographic and clinical characteristics.

OBJECTIVE: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. METHOD: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites. Diagnosis was made via structured and clinical interviews. Assessments of psychiatric symptoms and social and global functioning were included. RESULTS: A total of 119 youths were enrolled. The mean age at illness onset was 11.1 +/- 3.5 years. Patients with SZ and schizoaffective disorder had similar ratings on the Positive and Negative Symptom Scale, Brief Psychiatric Rating Scale for Children, and Clinical Global Impression-Severity Scale. The overall level of functioning was similar in the two groups. A comparison to published reports of adults with SZ indicates that these youths may have more severe symptoms based on results of the Positive and Negative Symptom Scale. CONCLUSIONS: This is one of the largest samples of youths with SZ spectrum disorders studied to date and the largest assessment of youths with schizoaffective disorder. High rates of symptoms and general psychopathology were noted. There was a substantial degree of social and functional impairment. The symptom profiles are consistent with, but more severe than, those reported in the adult literature.

Adapting interpersonal and social rhythm therapy to the developmental needs of adolescents with bipolar disorder.

Interpersonal and social rhythm therapy (IPSRT) is a manual-based adjunctive psychotherapy specific to the treatment of bipolar disorder. This paper reviews the theoretical rationale and empirical evidence for the efficacy of IPSRT in combination with pharmacotherapy for adults with bipolar I disorder. We then provide an overview of the developmental modifications being made to IPSRT to increase its relevance to adolescents with bipolar disorder.

Phenomenology and diagnostic stability of youths with atypical psychotic symptoms.

OBJECTIVE: This study aimed to better characterize the phenomenology and diagnostic stability of youths that report atypical psychotic symptoms. METHOD: In a 2-year longitudinal follow-up study, youths reporting atypical psychotic symptoms (n = 20) were compared with youths with schizophrenia (n = 27) and youths with bipolar disorder with psychotic features (n = 22) on psychotic, dissociative, and general symptomatology, comorbid diagnoses, previous abuse, and overall functioning. Diagnoses were obtained using structured diagnostic interviews (i.e., the Structured Clinical Interview for DSM-IV and the Diagnostic Interview for Children and Adolescents). RESULTS: None of the subjects reporting atypical psychotic symptoms went on to develop a classic psychotic illness by the year 2 follow-up. These subjects had significantly higher rates of abuse and dissociative symptoms, and were significantly more likely to receive a diagnosis of posttraumatic stress disorder (PTSD) or a depressive disorder than youths with schizophrenia or bipolar disorder. CONCLUSION: Our findings suggest that youths with atypical, fleeting, or situationally specific hallucinations are more likely to have a mood or anxiety disorder (such as PTSD) than a current or prodromal psychotic illness.

Stress, social rhythms, and behavioral activation: psychosocial factors and the bipolar illness course.

Current, more sophisticated models of bipolar disorder emphasize the interaction of psychosocial factors with biology as determinants of the long-term illness course. Recent research has documented the effects of psychosocial stress on the onset of new episodes, exacerbation of symptoms, and response to pharmacologic treatment in bipolar individuals. In this article, relevant theories and empiric findings regarding these relationships will be reviewed. In particular, two specific pathways relating psychosocial stressors to the onset of mania (eg, social rhythm disruption and behavioral activation) will be explicated.

Recovery of ovarian activity in women with functional hypothalamic amenorrhea who were treated with cognitive behavior therapy.

OBJECTIVE: To determine whether cognitive behavior therapy (CBT) targeted to problematic attitudes common among women with functional hypothalamic amenorrhea would restore ovarian function. DESIGN: Randomized, prospective, controlled intervention. SETTING: Clinical research center in an academic medical institution. PATIENT(S): Sixteen women participated who had functional hypothalamic amenorrhea; were of normal body weight; and did not report psychiatric conditions, eating disorders, or excessive exercise. INTERVENTION(S): Subjects were randomized to CBT or observation for 20 weeks. MAIN OUTCOME MEASURE(S): Serum levels of E(2) and P and vaginal bleeding were monitored. RESULT(S): Of eight women treated with CBT, six resumed ovulating, one had partial recovery of ovarian function without evidence of ovulation, and one did not display return of ovarian function. Of those randomized to observation, one resumed ovulating, one had partial return of ovarian function, and six did not recover. Thus, CBT resulted in a higher rate of ovarian activity (87.5%) than did observation (25.0%), chi(2) = 7.14. CONCLUSION(S): A cognitive behavioral intervention designed to minimize problematic attitudes linked to hypothalamic allostasis was more likely to result in resumption of ovarian activity than observation. The prompt ovarian response to CBT suggests that a tailored behavioral intervention offers an efficacious treatment option that also avoids the pitfalls of pharmacological modalities.

Premorbid functioning in early-onset psychotic disorders.

OBJECTIVE: To examine the premorbid characteristics of youths with early-onset psychotic disorders. METHOD: Subjects with early-onset psychotic disorders received an extensive diagnostic evaluation upon entry into the study, including a historic review of premorbid functioning using the Premorbid Adjustment Scale. RESULTS: Youths with schizophrenia (n = 27), bipolar disorder (n = 22), and psychosis not otherwise specified (NOS) (n = 20) were included. High rates of premorbid behavioral problems and academic difficulties were noted across all subjects. Youths with schizophrenia had higher rates of premorbid social withdrawal and global impairment. They also tended to have fewer friends. The psychosis NOS group had significantly higher rates of abuse histories and posttraumatic stress disorder. CONCLUSIONS: Premorbid abnormalities are common features of early-onset psychotic disorders. The social withdrawal and peer problems specific to youths with schizophrenia likely represent early manifestations of negative symptoms. The abuse histories in the psychosis NOS group may explain the atypical nature of their reported psychotic symptoms, which in many cases are likely posttraumatic phenomena.