Characteristics of responders and non-responders to risperidone monotherapy or placebo in co-occurring bipolar disorder and anxiety disorder

Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences, VA Palo Alto Health Care System, 3801, Miranda Avenue (151T), Palo Alto, CA 94304, USA
European Psychiatry (Impact Factor: 3.44). 11/2011; 28(3). DOI: 10.1016/j.eurpsy.2011.08.001
Source: PubMed


Clinical characteristics predicting response and remission to psychopharmacological treatment of bipolar disorder (BD) and co-occurring anxiety disorders have been understudied. We hypothesized that non-response to risperidone or placebo in individuals with co-occurring BD and anxiety symptoms would be associated with a more severe clinical course of BD, and certain demographic variables. This study was a secondary analysis of a randomized, double-blind, parallel, 8-week study comparing risperidone monotherapy and placebo in individuals with BD plus current panic disorder, current generalized anxiety disorder (GAD), or lifetime panic disorder (n=111) [31]. We compared clinical characteristics of responders (50% improvement on the Hamilton Anxiety Scale [HAM-A]) and non-responders as well as remitters (HAM-A<7) and non-remitters in risperidone treatment (n=54) and placebo (n=57) groups. For non-responders in the risperidone group, co-occurring lifetime panic disorder was significantly more common than for non-responders in the placebo group. Apart from this, no significant differences in course of illness or demographics were found either between or across groups for patients with BD and co-occurring anxiety symptoms receiving risperidone or placebo in this acute phase study.

1 Follower
7 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bipolar disorder often co-occurs with anxiety disorders. Evidence suggests that second-generation antipsychotics (SGAs) may be useful in treating both conditions. This study examined the efficacy of ziprasidone in the treatment of these disorders. This 3-site, randomized, double-blind, placebo-controlled, parallel group, 8-week trial of ziprasidone monotherapy examined 49 subjects with bipolar disorder and lifetime panic disorder (with or without agoraphobia) or generalized anxiety disorder (GAD) experiencing moderately severe anxiety symptoms at entrance into the study. Both bipolar disorder and anxiety diagnoses were based on DSM-IV-TR criteria. Patients were screened and randomized from June 25, 2010, through August 23, 2011. Primary outcome measures were the Clinical Global Impressions-21 Anxiety Scale (CGI-21 Anxiety) and the Sheehan Disability Scale (SDS), with secondary measures monitoring anxiety and mood symptoms. Last-observation-carried-forward analyses demonstrated that patients in the ziprasidone group did not improve significantly more than those in the placebo group on the CGI-21 Anxiety (F1 = 0.34; P = .564) or SDS (F1 = 0.26; P = .611). Secondary analysis using hierarchical linear modeling found similar results (CGI-21 Anxiety: F1 = 1.82; P = .178; and SDS: F1 = 0.70; P = .408). Regardless of group, time in the study was associated with significant decrease in anxiety (F1 = 11.08; P = .001) and total disability (F1 = 26.16; P < .001). Patients in the ziprasidone group showed a greater increase in abnormal involuntary movement, and 81.8% (n = 9) of the subjects who withdrew from the study due to adverse events, serious adverse events, or side effects were in the ziprasidone group. Results suggest that ziprasidone monotherapy was not associated with a clinically significant improvement in anxiety symptoms or improved function for patients with bipolar disorder, lifetime panic disorder or GAD, and concurrent moderately severe anxiety symptoms, and it was associated with a more negative side-effect profile relative to placebo. identifier: NCT01172652.
    The Journal of Clinical Psychiatry 11/2013; 75(1). DOI:10.4088/JCP.12m08297 · 5.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: As research expands our understanding of underlying placebo mechanisms, interest turns to the clinical application of placebos. Whether placebos are appropriate and effective in the management of chronic pain in older people deserves considerable attention. The evidence suggests that adults of any age are responsive to placebos, and that placebo treatments can be effective for many conditions prevalent in older people. Though placebos in general already seem to be used with some regularity in medical practice, the use of placebos alone for chronic pain is probably unjustified unless other treatments are inadvisable or have been exhausted. However maximising the mechanisms that underpin placebo analgesia such as expectancy or the psychosocial context should be encouraged and would be considered a feature of good clinical practice. It would also be anticipated that older people may see an additional benefit with placebo treatments when such treatments reduce existing or planned medication regimes, as older people typically experience more comorbidities, increased susceptibility to adverse drug reactions, and altered pharmacological responses to drugs. Further research is still needed in placebo related treatment paradigms for the management of chronic pain in older people.
    Maturitas 12/2014; 79(4). DOI:10.1016/j.maturitas.2014.09.006 · 2.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the four-site Treatment of Severe Childhood Aggression (TOSCA) study, addition of risperidone to stimulant and parent training moderately improved parent-rated disruptive behavior disorder (DBD) symptoms. This secondary study explores outcomes other than DBD and attention-deficit/hyperactivity disorder (ADHD) as measured by the Child and Adolescent Symptom Inventory-4R (CASI-4R). A total of 168 children ages 6-12 with severe aggression (physical harm), DBD, and ADHD were randomized to parent training plus stimulant plus placebo (basic treatment) or parent training plus stimulant plus risperidone (augmented treatment) for 9 weeks. All received only parent training plus stimulant for the first 3 weeks, then those with room for improvement received a second drug (placebo or risperidone) for 6 weeks. CASI-4R category item means at baseline and week 9 were entered into linear mixed-effects models for repeated measures to evaluate group differences in changes. Mediation of the primary DBD outcome was explored. Parent ratings were nonsignificant with small/negligible effects, but teacher ratings (n=46 with complete data) showed significant augmented treatment advantage for symptoms of anxiety (p=0.013, d=0.71), schizophrenia spectrum (p=0.017, d=0.45), and impairment in these domains (p=0.02, d=0.26), all remaining significant after false discovery rate correction for multiple tests. Improvement in teacher-rated anxiety significantly (p=0.001) mediated the effect of risperidone augmentation on the primary outcome, the Disruptive-total of the parent-rated Nisonger Child Behavior Rating Form. Addition of risperidone to parent training plus stimulant improves not only parent-rated DBD as previously reported, but also teacher-rated anxiety-social avoidance. Improvement in anxiety mediates improvement in DBD, suggesting anxiety-driven fight-or-flight disruptive behavior with aggression, with implications for potential treatment strategies. Clinicians should attend to possible anxiety in children presenting with aggression and DBD. Clinical Trial Registry: Treatment of Severe Childhood Aggression (The TOSCA Study). NCT00796302.
    Journal of child and adolescent psychopharmacology 04/2015; 25(3):203-212. DOI:10.1089/cap.2014.0104 · 2.93 Impact Factor