Disorders - Bipolar Disorders
Wiener, C. David., Molina, M. L., Moreira, F. P., dos-Passos, M. B., Jansen, K., da-Silva, R. A., de-Mattos, S., Luciano, D., Oses, J. P.
The aim of this study was to evaluate the impact of psychoeducation in serum
levels of BDNF, NGF and GDNF in young adults presenting bipolar disorder (BD). This is a randomized clinical trial including 39 young adults (18-29
years) diagnosed with BD through the Structured Clinical Interview for DSM-IV (SCID-CV). Participants were randomized in two treatment groups: usual
treatment (medication) and combined intervention (medication plus psychoeducation). Depressive symptoms were assessed using the Hamilton Depression
Rating Scale (HDRS) and severity of manic and hypomanic symptoms was evaluated through the Young Mania Rating Scale (YMRS). The serum levels of
trophic factors were measured with an ELISA kit. In both intervention groups, there was an improvement in depressive symptoms significantly between
baseline and post-intervention. In the combined intervention, GDNF serum levels increased significantly from baseline to post-intervention. However,
there were no differences in BDNF and NGF serum levels. In the usual treatment group, no changes were observed in serum levels of GDNF, BDNF, and NGF
the post-intervention in individuals. Our data suggests that only combined intervention was effective in improving depressive symptoms and increasing
GDNF levels in a sample of young adults with bipolar disorder. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
Psychiatry Research, 257 : 367-
371
- Year: 2017
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions
(any), Psychoeducation
Reinares, M., Bonnin, C. M., Hidalgo-Mazzei, D., Sanchez-Moreno, J., Colom, F., Vieta, E.
The reciprocal relationship between bipolar disorder
(BD) and the family system highlights the importance of adjunctive family intervention. However, its implementation in clinical practice is not
widespread. To update the knowledge in this field and identify areas of uncertainty this manuscript present a comprehensive overview of the
bidirectional relationship between BD and family variables, and a systematic review of the evidence-based studies published up to March 2015 on the
efficacy of adjunctive family intervention in BD. Findings show that not only specific family's attitudes/interactions affect the course of BD but
that equally the illness itself has a strong impact on family functioning, caregivers' burden and health. Regarding family intervention, there are
methodological differences between studies and variability in the sample characteristics and the intervention used. Most evidence-based studies
support the efficacy of adjunctive family treatment in the illness outcomes, both in youth and adult population, as well as benefits for caregivers.
The results emphasize the need to involve caregivers in the therapeutic management of BD through tailored interventions based on patients'
characteristics and family needs.
Clinical Psychology Review, 43 : 47-
57
- Year: 2016
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder), At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions
(any), Other Psychological Interventions
Strakowski, S. M., Fleck, D. E., Welge, J., Eliassen, J. C., Norris, M., Durling, M., Komoroski, R. A., Chu, W. J., Weber, W., Dudley, J. A., Blom, T. J., Stover, A., Klein, C., Strawn, J. R., DelBello, M. P., Lee, J. H., Adler, C. M.
OBJECTIVES:
We tested the hypothesis that, with treatment, functional magnetic resonance imaging (fMRI) regional brain activation in first-episode mania would
normalize - i.e., that differences from healthy subjects would diminish over time, and would be associated with clinical remission status,
potentially identifying neuroanatomic treatment response markers.\rMETHODS: Forty-two participants with bipolar I disorder were recruited during
their first manic episode, pseudo-randomized to open-label lithium or quetiapine, and followed for 8 weeks. fMRI scans were obtained at baseline and
then after 1 and 8 weeks of treatment, while participants performed a continuous performance task with emotional distracters. Healthy participants
received fMRI scans at these same intervals. Specific region-of-interest (ROI) activations within prefrontal emotional networks were assessed as
potential measures of treatment response.\rRESULTS: ROI data were reduced using exploratory factor analysis, which identified five factors that were
organizationally consistent with functional anatomic models of human emotion modulation. Half of the participants with bipolar disorder achieved
remission by Week 8 and were contrasted with the other half that did not. Analyses demonstrated that, in the bipolar disorder group in general,
treatment led to decreases in activation across brain regions toward healthy subject values. However, differences in activation changes were observed
between subjects with bipolar disorder who did or did not achieve remission in subcortical and amygdala factors.\rCONCLUSIONS: These findings provide
evidence for potential neuroanatomic treatment response markers in first-episode bipolar disorder.
Bipolar Disorders, 18(6) : 490-501
- Year: 2016
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Lithium
MacPherson, H. A., West, A. E., Weinstein, S.
Objectives: Mediation analyses are important for discerning mechanisms of change and essential therapeutic components
in CBT. Few studies have identified mediators of CBT for youth-internalizing disorders; only one trial evaluated treatment mechanisms for youth with
mixed mood diagnoses. The current study evaluated mediators in the randomized trial of child- and family-focused CBT (CFF-CBT), with adjunctive to
pharmacotherapy versus enhanced treatment as usual (TAU) for pediatric BD. Methods: Sixty-nine children (ages 7-13 years; mean age= 9.19 years; SD=
1.61; 58 percent male; 52 percent Caucasian) with pediatric BD were randomly assigned to CFF-CBT or TAU. Both treatments consisted of 12 short-term
and six maintenance sessions. CFF-CBT included an intensive focus on parent and family-level interventions, including psychoeducation, parenting
skills, selfcare, and family problem-solving skills. Primary outcomes (child mania, depression, global functioning) and candidate mediators (family
functioning and environment, parenting skills and coping, child coping) were assessed at baseline and at 4, 8, 12 (post-treatment), and 39 weeks
(follow-up). Results: Children receiving CFF-CBT exhibited significant improvement in mania and depression by posttreatment and global functioning
over a 6-month follow-up. Candidate child, family, and parent mediators were evaluated via a series of mixed-effects regression models following the
test of joint significance approach. Mediators were assessed at each wave via parent/child self-report. Parenting skills/coping, family flexibility,
and family-coping skills significantly improved across treatment in CFF-CBT versus TAU (P < 0.05, d= 0.50-0.59). Moreover, parenting skills/coping
mediated improvements in child mania (d= 0.62) and global functioning (d= 0.55), family flexibility mediated enhanced global functioning (d= 0.48),
and family coping mediated reduced depression (d= 0.81). Child coping was not a significant mediator. Conclusions: CFF-CBT may affect children's
mood and functioning by improving parenting skills and coping, family flexibility, and family-positive reframing. Limitations include concurrent
change of mediators and outcomes and attrition. Clinical implications include a focus on parent and family functioning as key treatment mechanisms of
child symptom response to CFF-CBT.
Journal of the American
Academy of Child and Adolescent Psychiatry, 55 (10 Supplement 1) : S14
- Year: 2016
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions
(any), Cognitive & behavioural therapies (CBT)
Fallah, E., Arman, S., Najafi, M., Shayegh, B.
Objective Many studies have supported the role of protein kinase C (PKC)
inhibitors in the physiopathology and treatment of bipolar disorder in adults. Tamoxifen is one of the drugs with the effect of PKC inhibition. This
study aimed to determine the effect of tamoxifen on the rate of improvement mania symptoms in the sample of children and adolescents with acute
mania. Materials & Methods In this randomized, placebo-controlled clinical trial study, registered in www.irct.ir with the code of
IRCT201410126418N3, overall 44 patients with bipolar disorder with acute manic episode were randomly assigned into treatment and control groups. The
serum levels of lithium and tamoxifen among the participants in the treatment groups were 0.8 -1.1 mg and 20-40 mg per day respectively. Serum level
of lithium among participants in the control group was similar. The main comparisons were made based on the Young Mania Rating Scale (YMRS) and
Children Depression Inventory (CDI) scores of the participants at baseline and at the end of each study week. The pharmacological side effects of
serum level of lithium were examined weekly. Analysis of Covariance(ANCOVA) test was used for the statistical analysis. Results There was no
difference in the baseline score of YMRS and CDI in the treatment and control groups while a statistical significant difference (P < 0.05) in these
scores was found between and within the groups. Conclusion The addition of tamoxifen to lithium causes a significant difference in reducing the
symptoms of mania and depression in the treatment group compared to the control group. Copyright © 2016 Iranian Child Neurology Society. All Rights
Reserved.
Iranian Journal of Child Neurology, 10(2) : 16-
25
- Year: 2016
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Lithium, Other biological interventions
Daglas, R., Cotton, S. M., Allott, K., Yucel, M., Macneil, C. A., Hasty, M. K., Murphy, B., Pantelis, C., Hallam, K. T., Henry, L. P., Conus,
P., Ratheesh, A., Kader,
L., Wong, M.
T., McGorry, P. D., Berk, M.
BACKGROUND: Cognitive deficits have been
reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to
compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania.\rMETHODS: The design was
a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or
quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive
cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points.\rRESULTS: There was a significant interaction between
group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated
participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions
between group and time for other measures of cognition.\rCONCLUSION: Although the effects of lithium and quetiapine treatment were similar for most
cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency
in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general
functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.
European Psychiatry: the Journal of the Association of European Psychiatrists, 31 : 20-
8
- Year: 2016
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Lithium
Detke, H. C., DelBello, M. P., Landry,
J,, Hoffmann, V. P., Heinloth, A., Dittmann, R. W.
Objectives: To evaluate the 52-week safety/tolerability of oral olanzapine for adolescents with schizophrenia or bipolar mania and
compare effectiveness of a standard versus intense behavioral weight intervention in mitigating risk of weight gain. Methods: Patients 13-17 years
old with schizophrenia (Brief Psychiatric Rating Scale for Children [BPRS-C] total score > 30; item score >= 3 for hallucinations, delusions, or
peculiar fantasies) or bipolar I disorder (manic or mixed episode; Young Mania Rating Scale [YMRS] total score >= 15) received open-label olanzapine
(2.5-20 mg/day) and were randomized to standard (n = 102; a single weight counseling session) or intense (n = 101; weight counseling at each study
visit) weight intervention. The primary outcome measure was mean change in body mass index (BMI) from baseline to 52 weeks using mixed-model repeated
measures. Symptomatology was also assessed. Results: No statistically significant differences between groups were observed in mean baseline-to-52-
week change in BMI (standard: +3.6 kg/m2; intense: +2.8 kg/m2; p = 0.150) or weight (standard: +12.1 kg; intense: +9.6 kg; p = 0.148). Percentage of
patients at endpoint who had gained >= 15% of their baseline weight was 40% for the standard group and 31% for the intense group (p = 0.187).
Safety/tolerability results were generally consistent with those of previous olanzapine studies in adolescents, with the most notable exception being
the finding of a mean decrease in prolactin. On symptomatology measures, patients with schizophrenia had a mean baseline-to-52-week change in BPRS-C
of -32.5 (standard deviation [SD] = 10.8), and patients with bipolar disorder had a mean change inYMRSof -16.7 (SD = 8.9), with clinically and
statistically significant improvement starting at 3-4 days for each. Conclusions: Long-term weight gain was high in both groups, with no
statistically significant differences between the standard or intense behavioral weight interventions in BMI or weight. Safety, tolerability, and
effectiveness findings were generally consistent with the known profile of olanzapine in adolescents. (PsycINFO Database Record (c) 2017 APA, all
rights reserved)
Journal of Child and Adolescent Psychopharmacology, 26(10) : 922-
934
- Year: 2016
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Other Psychological Interventions
Cardoso, T. de A., Campos-Mondin, T., Reyes, A. N., Zeni, C. P., Souza, L. D. de M., da-Silva, R.
A., Jansen, K.
The objective was to evaluate the effect of psychoeducation on
biological rhythm and in the reduction of depressive, anxious, and manic symptoms at 12 months' follow-up. This was a randomized clinical trial with
young adults aged 18 to 29 years, diagnosed with bipolar disorder. Biological rhythm was assessed with the Biological Rhythm Interview Assessment in
Neuropsychiatry (BRIAN). Participants were randomized for combined intervention (psychoeducation plus medication) or treatment-as-usual (medication
alone). The sample consisted of 61 patients (29 TAU; 32 combined intervention). Although it failed to separate by a marginal difference, the combined
intervention seems to be more effective than TAU in relation to improvement of depressive symptoms at post-intervention (p = 0.074) and regulation of
sleep/social domain at 6 months' follow-up (p = 0.057). Improvement of depressive symptoms as well as regulation of sleep and social activities are
known to prevent episode onset and thus improve long-term outcomes.;
The Journal Of Nervous And
Mental Disease, 203(10) : 792-797
- Year: 2015
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Psychological Interventions
(any), Psychoeducation
Conus, P., Berk, M., Cotton, S. M., Kader, L., Macneil, C., Hasty, M. K., Hallam, K., Lambert, M., Murphy, B. P., McGorry, P. D.
Background: Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide
treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as
add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar
efficacy for both treatments.; Methods: Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side
effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated
survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine
treatment group differences over time on safety and efficacy measures.; Results: Ethics committee approval to delay informed consent procedure until
recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our
hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was
observed in the olanzapine group which did not survive correction for multiple comparisons.; Conclusions: Olanzapine and chlorpromazine have a
similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of
olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.; Copyright © 2015 Elsevier Masson SAS.
All rights reserved.
European Psychiatry, 30(8) : 975-
982
- Year: 2015
- Problem: Bipolar Disorders, Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder), First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Typical Antipsychotics (first generation), Atypical Antipsychotics (second
generation), Lithium
Findling, R. L., Chang, K., Robb, A., Foster, V. J., Horrigan,
J., Krishen, A., Wamil, A., Kraus, J. E., Delbello, M.
Objective This study aimed to compare the efficacy of lamotrigine versus placebo in 10- to 17-year-olds with
bipolar I disorder (BP-I) who were receiving conventional bipolar disorder treatment. Method In this randomized withdrawal trial, patients with BP-I
of at least moderate severity received lamotrigine during an =18-week open-label phase. Patients who maintained a stable lamotrigine dose for =2
weeks and Clinical Global Impression-Bipolar Severity of Illness (CGI-BP[S]) score of =3 for =6 consecutive weeks were randomized to double-blind
lamotrigine or placebo for =36 weeks. Results Of 301 patients enrolled, 298 comprised the open-label intention-to-treat population, with 173 (58%)
randomized. Of these patients, 41 (24%) completed the study. In the open-label phase, the mean (SD) baseline CGI-BP(S) rating was 4.4 (0.57), and the
mean (standard error [SE]) time to stabilization was 101 (1.6) days. During the randomized phase, mean (SE) time to occurrence of a bipolar event
(TOBE) for lamotrigine versus placebo (primary endpoint) was 155 (14.7) versus 50 (3.8), 163 (12.2) versus 120 (12.2), and 136 (15.4) versus 107
(13.8) days for the 3 index mood states (depressed, manic/hypomanic, mixed). The primary stratified log-rank analysis of TOBE was not statistically
significant (hazard ratio [HR] = 0.63; p =.072); however, the prespecified Cox regression analysis favored lamotrigine (p =.047). In 13- to 17-year-
olds, log-rank analysis of TOBE significantly favored lamotrigine (HR = 0.46; p =.015), but not in 10- to 12-year-olds (HR = 0.93; p =.877).
Dermatologic events were reported in 4% (open-label phase) and 2% (randomized phase) of patients receiving lamotrigine. Suicidality-related adverse
events were reported in 7% (open-label phase) and 7% (randomized phase) of patients receiving lamotrigine. Conclusion Although the primary analysis
failed to detect a benefit of add-on lamotrigine for BP-I in 10- to 17-year-olds, lamotrigine may be effective in a subset of older adolescents.
Journal of the American Academy of Child & Adolescent
Psychiatry, 54(12) : 1020-1031.e3
- Year: 2015
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Anticonvulsants/mood stabilisers (excl. lithium), Medication dose
reduction/discontinuation
Findling, R. L., Landbloom, R. L., Szegedi, A., Koppenhaver, J., Braat, S., Zhu, Q., Mackle, M., Chang, K., Mathews, M.
Objective To evaluate
asenapine versus placebo in 403 patients aged 10 to 17 years with bipolar I disorder currently in manic or mixed episodes. Method In this double-
blind, placebo-controlled, international trial, patients were randomized 1:1:1:1 to placebo, asenapine 2.5, 5, or 10 mg b.i.d. (twice daily). Primary
efficacy measure was change from baseline in Young-Mania Rating Scale (YMRS) total score at day 21. Analyses of patients with/without attention-
deficit/hyperactivity disorder (ADHD) and with/without stimulant use were performed. Results The mean difference in asenapine versus placebo in YMRS
was -3.2 (p =.0008), -5.3 (p <.001), and -6.2 (p <.001) for asenapine 2.5, 5, and 10 mg b.i.d., respectively. Treatment-emergent adverse events with
an incidence =5% and at least twice placebo were somnolence, sedation, hypoesthesia oral, paresthesia oral, and increased appetite. The asenapine
groups had a higher incidence of =7% weight gain (range, 8.0%-12.0%) versus placebo (1.1%; p <.05). The mean change from baseline in fasting insulin
was larger for patients treated with asenapine than those with placebo (asenapine 2.5 mg b.i.d.: 73.375 pmol/L; asenapine 5 mg b.i.d.: 114.042
pmol/L; asenapine 10 mg b.i.d.: 59.846 pmol/L; placebo: 3.690 pmol/L). The mean changes from baseline for lipid parameters and glucose were also
larger in asenapine groups than in the placebo group. No safety differences were observed with respect to ADHD and stimulant use. Conclusion All
asenapine doses versus placebo were superior based on change in YMRS at day 21. Asenapine was generally well tolerated in patients aged 10 to 17
years with bipolar I disorder in manic or mixed states. Increases in weight and fasting insulin were associated with asenapine.
Journal of the American Academy of Child & Adolescent Psychiatry, 54(12) : 1032-
1041
- Year: 2015
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Findling, R. L., Robb,
A., McNamara, N. K., Pavuluri, M. N., Kafantaris,
V., Scheffer, R., Frazier, J. A., Rynn, M., DelBello, M., Kowatch, R. A., Rowles, B. M., Lingler, J., Martz, K., Anand, R., Clemons, T. E., Taylor-Zapata, P.
BACKGROUND:
Lithium is a benchmark treatment for bipolar disorder in adults. Definitive studies of lithium in pediatric bipolar I disorder (BP-I) are lacking.
METHODS: This multicenter, randomized, double-blind, placebo-controlled study of pediatric participants (ages 7-17 years) with BP-I/manic or mixed
episodes compared lithium (n = 53) versus placebo (n = 28) for up to 8 weeks. The a priori primary efficacy measure was change from baseline to the
end of study (week 8/ET) in the Young Mania Rating Scale (YMRS) score, based on last-observation-carried-forward analysis. RESULTS: The change in
YMRS score was significantly larger in lithium-treated participants (5.51 [95% confidence interval: 0.51 to 10.50]) after adjustment for baseline
YMRS score, age group, weight group, gender, and study site (P =.03). Overall Clinical Global Impression-Improvement scores favored lithium (n = 25;
47% very much/much improved) compared with placebo (n = 6; 21% very much/much improved) at week 8/ET (P =.03). A statistically significant increase
in thyrotropin concentration was seen with lithium (3.0 ± 3.1 mIU/L) compared with placebo (-0.1 ± 0.9 mIU/L; P =.001). There was no statistically
significant between-group difference with respect to weight gain. CONCLUSIONS: Lithium was superior to placebo in reducing manic symptoms in
pediatric patients treated for BP-I in this clinical trial. Lithium was generally well tolerated in this patient population and was not associated
with weight gain, distinguishing it from other agents commonly used to treat youth with bipolar disorder.
Pediatrics, 136(5) : 885-
894
- Year: 2015
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Lithium