Julie A. Carbray

Child- and Family-Focused Cognitive-Behavioral Therapy for Pediatric Bipolar Disorder: Development and Preliminary Results

OBJECTIVE To describe child- and family-focused cognitive-behavioral therapy (CFF-CBT), a new developmentally sensitive psychosocial intervention for pediatric bipolar disorder (PBD) that is intended for use along with medication. CFF-CBT integrates principles of family-focused therapy with those of CBT. The theoretical framework is based on (1). the specific problems of children and families coping with bipolar disorder, (2). a biological theory of excessive reactivity, and (3). the role of environmental stressors in outcome. CFF-CBT actively engages parents and children over 12 hour-long sessions. METHOD An exploratory investigation was conducted to determine the feasibility of CFF-CBT. Participants included 34 patients with PBD (mean age 11.33 years, SD = 3.06) who were treated with CFF-CBT plus medication in a specialty clinic. Treatment integrity, adherence, and parent satisfaction were assessed. Symptom severity and functioning were evaluated before and after treatment using the severity scales of the Clinical Global Impression Scales for Bipolar Disorder (CGI-BP) and the Childrens Global Assessment Scale (CGAS) respectively. RESULTS On completion of therapy, patients with PBD showed significant reductions in severity scores on all CGI-BP scales and significantly higher CGAS scores compared to pretreatment results. High levels of treatment integrity, adherence, and satisfaction were achieved. CONCLUSIONS CFF-CBT has a strong theoretical and conceptual foundation and represents a promising approach to the treatment of PBD. Preliminary results support the potential feasibility of the intervention.

Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder.

OBJECTIVE To determine the relative effects of risperidone and divalproex in pediatric mania. METHODS This is a double-blind, randomized, outpatient clinical trial with 66 children and adolescents (mean age= 10.9 ± 3.3 years; age range= 8-18 years) with mania who were randomly assigned to either risperidone (0.5-2 mg/day, n= 33) or divalproex (60-120 μg/mL, n= 33) for a six-week period. Measures included the Young Mania Rating Scale (YMRS) and Child Depression Rating Scale-Revised (CDRS-R). RESULTS Mixed-effects regression models, with interaction between time and the active drug as predictors, found that the risperidone group had more rapid improvement than the divalproex group (p < 0.05), although final scores did not differ significantly between groups. Mixed models using only those subjects who completed the six-week study found similar results. The response rate on YMRS was 78.1% for risperidone and 45.5% for divalproex (p < 0.01). The remission rate for risperidone was 62.5%, compared with 33.3% for divalproex (p < 0.05). Improvement on the CDRS-R was significantly higher for the risperidone group relative to the divalproex group (p < 0.05). There were no significant differences between groups in safety, but subject retention was significantly higher at study endpoint in the risperidone group (p < 0.01). Dropout rate was 24% in the risperidone group and 48% in the divalproex group, with increased irritability being the most common reason for dropout in the latter. There was no significant weight gain in either group. CONCLUSION Results suggest that risperidone was associated with more rapid improvement and greater reduction in manic symptoms compared to divalproex. Although the results suggest that both drugs are safe, risperidones lower attrition rate and lower rate of adverse events may suggest better toleration. Clinical trials with larger samples are required to confirm these preliminary findings.

Effectiveness of lamotrigine in maintaining symptom control in pediatric bipolar disorder

OBJECTIVE The aim of this study was to test the effectiveness and safety of lamotrigine in maintenance of manic and depressive symptom control in pediatric bipolar disorder (PBD). METHODS A 14-week open trial was conducted with 46 subjects presenting with mania or hypomania. Lamotrigine was slowly titrated to a therapeutic dose over an 8-week period, during which acute symptoms were stabilized using second-generation antipsychotics (SGA), followed by a 6-week lamotrigine monotherapy phase. RESULTS The response rate on manic symptoms (Young Mania Rating Score [YMRS] <12) was 72%, on depressive symptoms was 82% (Childrens Depression Rating Scale-Revised [CDRS-R] <40), and the remission rate was 56% at the 14-week end point, on an average end-point lamotrigine dose of 1.8 mg/lb. There was further reduction in depressive symptoms during the lamotrigine maintenance phase. Benign rash was noted in 6.4% of patients. Out of half of the subjects who were in remission at 8 week, 3 subjects (23%) relapsed by week 14. CONCLUSION Lamotrigine monotherapy appears to be effective in maintaining symptom control of manic and depressive symptoms in PBD and shows minimal adverse effects, although a future double-blind controlled trial is needed to confirm this finding. Portal of entry for lamotrigine treatment can be during acute illness and can sustain symptom control after establishing mood stabilization.

Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder: fMRI outcomes

The aim of this research was to determine the relative effects of risperidone and divalproex on brain function in pediatric mania. This is a double-blind 6-week functional magnetic resonance imaging trial with 24 unmedicated manic patients randomized to risperidone or divalproex, and 14 healthy controls (HCs) matched for IQ and demographic factors (mean age: 13.1±3.3years). A pediatric affective color matching task, in which subjects matched the color of a positive, negative or neutral word with one of two colored circles, was administered. The primary clinical measure was the Young Mania Rating Scale (YMRS). The risperidone group, relative to HC, showed an increase in activation from pre- to post-treatment in right pregenual and subgenual anterior cingulate cortex and decreased activation in bilateral middle frontal gyrus during the negative condition; and decreased activation in left inferior and medial, and right middle frontal gyri, left inferior parietal lobe, and right striatum with positive condition. In the divalproex group, relative to HC, there was an increased activation in right superior temporal gyrus in the negative condition; and in left medial frontal gyrus and right precuneus with the positive condition. Greater pre-treatment right amygdala activity with negative and positive condition in the risperidone group, and left amygdala activity with positive condition in divalproex group, predicted poor response on YMRS. Risperidone and divalproex yield differential patterns of prefrontal activity during an emotion processing task in pediatric mania. Increased amygdala activity at baseline is a potential biomarker predicting poor treatment response to both the risperidone and divalproex.

Targeting Ruminative Thinking in Adolescents at Risk for Depressive Relapse: Rumination-Focused Cognitive Behavior Therapy in a Pilot Randomized Controlled Trial with Resting State fMRI.

This pilot randomized control trial was designed to examine whether Rumination-Focused Cognitive Behavior Therapy (RFCBT) reduces rumination and residual depressive symptoms among adolescents with a history of Major Depressive Disorder (MDD) who are at risk for relapse. We also examined whether these changes in symptoms were associated with changes in functional connectivity of the posterior cingulate cortex (PCC), a key node in the default mode network (DMN). Thirty-three adolescents (ages 12–18) were randomized to eight weeks of RFCBT or an assessment only (AO) control. Twenty two adolescents successfully completed fMRI scans pre- and post-intervention. Adolescents were recruited from the clinic and community and met criteria for at least one previous episode of MDD and were currently in full or partial remission. An Independent Evaluator interviewed parent and child before and after the eight-week intervention. The left PCC (-5, -50, 36) seed was used to probe resting state functional connectivity of the DMN. Adolescents who received RFCBT demonstrated reduced rumination (F = -2.76, df = 112, p < .01, 95% CI [-4.72,-0.80]) and self-report depression across eight weeks (F = -2.58, df = 113, p < .01, 95% CI [-4.21, -0.94]). Youth who received RFCBT also demonstrated significant decreases in connectivity between the left PCC and the right inferior frontal gyrus (IFG) and bilateral inferior temporal gyri (ITG). Degree of change in connectivity was correlated with changes in self-report depression and rumination. These data suggest that rumination can be reduced over eight weeks and that this reduction is associated with parallel decreases in residual depressive symptoms and decreased functional connectivity of the left PCC with cognitive control nodes. These changes may enhance the ability of vulnerable youth to stay well during the transition to adulthood. Trial Registration: ClinicalTrials.gov NCT01905267

Advanced Practice Psychiatric Nurses Legislative Update: State of the States, 2010

This article provides an update regarding individual state legislation for advanced practice psychiatric nursing, building on previous briefings. Specific attention is given to independent versus collaborative practice regulations, titling, and prescriptive authority. There is review of contemporary issues and focus on scope and standards of practice, workforce data, certification, and advanced practice regulatory models.