Disorders - Bipolar Disorders
Singh, M. K., Nimarko, A. F., Garrett, A.
S., Gorelik, A. J., Roybal, D. J., Walshaw, P. D., Chang, K. D., Miklowitz, D. J.
OBJECTIVE: We compared intrinsic network connectivity in symptomatic youths at high risk
(HR) for bipolar disorder (BD) and healthy comparison (HC) youths. In HR youths, we also investigated treatment-related changes in intrinsic
connectivity after family-focused therapy for high-risk youths (FFT-HR) vs standardized family psychoeducation.\rMETHOD: HR youths (N = 34; age 9-17
years; mean 14 years, 56% girls and 44% boys) with depressive and/or hypomanic symptoms and at least 1 first- or second-degree relative with BD I or
II were randomly assigned to 4 months of FFT-HR (12 sessions of psychoeducation, communication, and problem-solving skills training) or enhanced care
(EC; 3 family and 3 individual psychoeducation sessions). Before and after 4 months of treatment, participants underwent resting state functional
magnetic resonance imaging (rs-fMRI). A whole-brain independent component analysis compared rs-fMRI networks in HR youths and 30 age-matched HC
youths at a pretreatment baseline. Then we identified pretreatment to posttreatment (4-month) changes in network connectivity in HR youths receiving
FFT-HR (n = 16) or EC (n = 18) and correlated these changes with depression improvement.\rRESULTS: At baseline, HR youths had greater connectivity
between the ventrolateral prefrontal cortex (VLPFC) and the anterior default mode network (aDMN) than did HCs (p = .004). Over 4 months of treatment,
FFT-HR-assigned HR youths had increased VLPFC-aDMN connectivity from pre- to posttreatment (p = .003), whereas HR youths in EC showed no significant
change over time (p = .11) (treatment by time interaction, t31 = 3.33, 95% CI = 0.27-1.14, p = .002]. Reduction in depression severity
over 4 months inversely correlated with enhanced anterior DMN (r = -0.71) connectivity in the FFT-HR but not in the EC (r = -0.07) group (z = -2.17,
p = .015).\rCONCLUSION: Compared to standard psychoeducation, FFT-HR is associated with stronger connectivity between the VLPFC and aDMN, suggesting
possible enhancements of self-awareness, illness awareness, and emotion regulation.\rCLINICAL TRIAL REGISTRATION INFORMATION: Early Intervention for
Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.
Journal of the American Academy of
Child & Adolescent Psychiatry, 60(4) : 458-469
- Year: 2021
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions
(any), Family therapy
Saraf, G., Moazen-Zadeh, E., Pinto, J. V., Ziafat, K., Torres, I. J., Kesavan, M., Yatham, L.
N.
Early intervention approaches are
built on the premise of preventing disability, burden, and cognitive sequelae caused by bipolar disorder. The objective of this systematic review was
to characterise the effectiveness of all the available psychological and pharmacological treatments for early intervention in people at high risk of
developing bipolar disorder. The study was registered with PROSPERO (CRD42019133420). We did a systematic search to identify studies published in ten
databases up to March 27, 2020. Randomised controlled trials and cohort studies that assessed the effect of pharmacological or psychological
interventions in people at high risk of developing bipolar disorder were included. Studies of first episodes of mania were excluded. Eligible papers
were assessed for quality and data were extracted. The primary outcomes were change in manic and depressive symptoms from baseline to endpoint. Of
the 2856 citations retrieved by our search, 16 studies were included; five evaluated pharmacotherapeutic strategies (three randomised controlled
trials and two open-label studies), ten assessed psychotherapeutic strategies (four randomised controlled trials and six open-label studies), and one
randomised controlled trial assessed combination therapy; these 16 trials included a total of 755 participants at high risk of developing bipolar
disorder. Quality assessment indicated fair to good quality for open-label studies, and a high risk of bias in four randomised controlled trials.
Among the pharmacotherapeutic interventions, there is preliminary support for the efficacy of aripiprazole in reducing mood symptoms in people at
high risk of developing bipolar disorder. Psychological interventions were effective for various outcomes. There was substantial methodological
heterogeneity across studies. This systematic review underscores the need for multicentre, prospective, methodologically homogeneous studies
evaluating conversion to bipolar disorder as an outcome measure.
The Lancet. Psychiatry, 8(1) : 64-
75
- Year: 2021
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention), Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Psychological Interventions
(any)
Patino, L. R., Klein, C. C., Strawn, J. R., Blom, T. J., Tallman, M. J., Adler, C. M., Welge, J. A., DelBello, M. P.
Objective: To compare the efficacy and tolerability of lithium versus quetiapine for the treatment of manic or
mixed episodes in youths with early course bipolar I disorder. Methods: Six-week, randomized, double-blind clinical trial of lithium versus
quetiapine for the treatment of adolescents with acute manic/mixed episode. Target dose of quetiapine dose was adjusted to a target dose of 400-600
mg and target serum level for lithium was 1.0-1.2 mEq/L. Primary outcome measure was baseline-to-endpoint change in the Young Mania Rating Scale
(YMRS). Secondary outcomes were treatment response (50% or more decrease from baseline in YMRS score) and remission (YMRS score <= 12, Children's
Depression Rating Scale-Revised [CDRS-R] total score <= 28 and Clinical Global Impression Bipolar Severity Scale [CGI-BP-S] overall score of <= 3,
respectively). Results: A total of 109 patients were randomized (quetiapine = 58 and lithium = 51). Participants in the quetiapine treatment group
showed a significantly greater reduction in YMRS score than those in the lithium group (-11.0 vs. -13.2; p < 0.001; effect size 0.39). Response rate
was 72% in the quetiapine group and 49% in the lithium group (p = 0.012); no differences in remission rates between groups were observed. Most
frequent side effects for lithium were headaches (60.8%), nausea (39.2%), somnolence (27.5%), and tremor (27.5%); for quetiapine somnolence (63.8%),
headaches (55.2%), tremor (36.2%), and dizziness (36.2%) were evidenced. Participants receiving quetiapine experienced more somnolence (p < 0.001),
dizziness (p < 0.05), and weight gain (p < 0.05). Conclusions: Treatment with both lithium and quetiapine led to clinical improvement. Most study
participants in this study experienced a clinical response; however, less than half of the participants in this study achieved symptomatic remission.
The head-to-head comparison of both treatment groups showed quetiapine was associated with a statistically significant greater rate of response and
overall symptom reduction compared with lithium. Trial registration: (PsycInfo Database Record (c) 2022 APA, all rights reserved)
Journal of Child and Adolescent
Psychopharmacology, 31(7) : 485-493
- Year: 2021
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Lithium
Patel, R. S., Veluri, N., Patel, J., Patel, R., Machado, T., Diler, R.
Objectives: To evaluate the efficacy in reduction of depressive symptoms, and safety and tolerability
of second-generation antipsychotics (SGAs) to manage pediatric bipolar depression (PBD). Methods: We conducted a systematic review for randomized
clinical trials (RCTs) for PBD in MEDLINE, Scopus, and EMBASE. Four (quetiapine: 2, lurasidone: 1, olanzapine-fluoxetine combination [OFC]: 1) out of
569 studies met the criteria for inclusion in meta-analysis. RevMan was used for statistical analysis, and the mean difference (MD) between mean
children's depression rating scale-revised (CDRS-R) score was used to measure treatment difference between SGA and placebo. Results: Lurasidone
displayed a significant reduction in depressive symptoms (MD -5.70, 95% confidence interval [CI] -8.67 to -2.73) in PBD, followed by OFC (MD -5.00,
95% CI -8.64 to -1.36) and quetiapine (MD -2.30, 95% CI -6.80 to 2.20; MD 1.00, 95% CI -9.88 to 11.88). The response was significantly higher for
lurasidone (59.5% vs. 36.5%; p < 0.001) and OFC (78.2% vs. 59.2%, p = 0.003) compared with placebo. There was no statistically significant MD in
treatment and response rates between quetiapine and placebo in all RCTs. The weighted mean CDRS-R total score difference was -4.58 (95% CI -6.59 to
-2.56) and overall effect was significant (p < 0.00001). Importantly, the p value for heterogeneity was 0.46, which indicated that there was no
heterogeneity between outcomes of the studies. The number needed to treat (NNT) for lurasidone was 4.3, followed by OFC (NNT = 5.3) and quetiapine
(NNT = 12.5; NNT = 25). Conclusion: Our findings showed lurasidone and OFC were more efficacious than placebo for acute depressive episodes in PBD.
RCTs of treatments for PBD remain scarce pressing the need for more research. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Journal of Child and Adolescent Psychopharmacology, 31(8) : 521-
530
- Year: 2021
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Onishi, Y., Mikami, K., Kimoto, K., Watanabe, N., Takahashi, Y., Akama, F., Yamamoto, K., Matsumoto, H.
The effectiveness and safety of
antipsychotics have not been fully established in children and adolescents. Many antipsychotics approved for use in adults are prescribed off-label
to children and adolescents. We investigated the effectiveness and tolerability of antipsychotics for children and adolescents with schizophrenia and
bipolar disorder. A literature review of the empirical evidence regarding the use of antipsychotics, particularly second-generation antipsychotics,
in children and adolescents showed that these drugs were safe and effective for this population. Antipsychotics were similarly effective for
treatment of schizophrenia and bipolar disorder in children and adolescents. When prescribing antipsychotics to this population, clinicians should
consider adverse events and the discontinuation rate in treated patients. However, the current evidence shows a lack of consensus regarding the use
of antipsychotics in children and adolescents.
Journal of Nippon Medical School = Nihon Ika Daigaku Zasshi, 88(1) : 10-
16
- Year: 2021
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Musselman, M., Faden, J., Citrome, L.
Asenapine is a second-generation (atypical) antipsychotic medication not available in a pill that can be swallowed; rather, it
is commercialized in sublingual and transdermal formulations. This is a consequence of extensive first-pass metabolism if ingested. The sublingual
formulation is approved in many jurisdictions for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder and
is available generically. The efficacy profile is well characterized in a number of clinical trials, including an off-label use for the management of
agitation. Obstacles to its use include food and drink restrictions, twice-daily dosing and adverse effects such as dysgeusia (distorted, altered, or
unpleasant taste) and oral hypoesthesia (numbness). Transdermal asenapine was approved by the US Food and Drug Administration in 2019 for the
treatment of schizophrenia in adults. Efficacy was established in a registrational study examining acutely ill inpatients with schizophrenia. The
patch needs to changed once daily. Obstacles to its use include the potential for skin reactions such as erythema and pruritis, and being a branded
product, it is more costly than other options. This is a narrative review of the chemistry and pharmacokinetics/pharmacodynamics of asenapine, as
well as summarizing the efficacy and tolerability of both sublingual and transdermal asenapine, and its possible place in treatment.Copyright © The
Author(s), 2021.
Therapeutic Advances in Psychopharmacology, 11 :
- Year: 2021
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Miklowitz, D. J., Weintraub, M. J., Posta, F., Denenny, D. M., Chung, B.
The implementation of evidence-based psychotherapies often requires significant
commitments of time and expense from mental health providers. Psychotherapy protocols with rapid and efficient training and supervision requirements
may have higher levels of uptake in publicly funded clinics. Family-focused therapy (FFT) is a 4-month, 12-session treatment for bipolar and
psychosis patients consisting of psychoeducation, communication training, and problem-solving skills training. In a pilot randomized trial, we
compared two methods of training community clinicians in FFT: (a) high intensity (n = 24), consisting of a 6-hour in-person didactic workshop
followed by telephone supervision for every session with training cases; or (b) low-intensity training (n = 23), consisting of a 4-hour online
workshop covering the same material as the in-person workshop followed by telephone supervision after every third session with training cases. Of 47
clinician participants, 18 (11 randomly assigned to high intensity, 7 to low) enrolled 34 patients with mood or psychotic disorders (mean age 16.5
+/- 2.0 years; 44.1% female) in an FFT implementation phase. Expert supervisors rated clinicians' fidelity to the FFT manual based on taped family
sessions. We detected no differences in fidelity scores between clinicians in the two training conditions, nor did patients treated by clinicians in
high- versus low-intensity training differ in end-of-treatment depression or mania symptoms. Levels of parent/offspring conflict improved in both
conditions. Although based on a pilot study, the results suggest that low-intensity training of community clinicians in FFT is feasible and can
result in rapid achievement of fidelity benchmarks without apparent loss of treatment efficacy. Copyright © 2021 Family Process Institute.
Family process., 29 :
- Year: 2021
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Family therapy, Other service delivery and improvement
interventions
Miklowitz, D. J., Schneck, C., Chang, K.
Objectives: There are recognizable risk factors for the onset of
bipolar disorder (BD) in children and adolescents with a family history of BD: depression, hypomania, mood instability, and anxiety. In high-risk
youth defined by these criteria, we examined whether family-focused treatment (FFT) was more effective than standard psychoeducation in reducing the
rate of mood disorder episodes and suicidal thinking/behavior over a follow-up of 1 to 4 years. Method(s): We randomly allocated 127 symptomatic
youth (mean age = 13.2 years) with either MDD or unspecified (subthreshold) bipolar disorder to: a) 12 sessions of FFT; or b) 6 sessions of standard
psychoeducation, both of which are given in 4 months. Youth in both conditions received medications for mood disorder and comorbid conditions when
clinically indicated. An independent evaluator interviewed the youth and parent(s) every 4 months for up to 48 months to measure mood disorder
symptoms, recovery/recurrence, and individual and family functioning. Result(s): Youth in FFT did not differ from those in standard psychoeducation
on time to recovery from their index symptoms. However, youth in FFT had longer periods between recovery and emergence of the next mood disorder
episode (chi2 = 5.44; p = 0.02; hazard ratio, 0.55; 95% CI, 0.48-0.92), and between randomization and next mood episode (chi2 =
4.44; p = 0.03; hazard ratio, 0.59; 95% CI, 0.35-0.97) compared to youth in standard psychoeducation. Youth in both conditions showed improvements in
symptom severity over time, although distinct course patterns were observed over 1 to 4 years of follow-up. Youth in FFT had lower levels of suicidal
thinking and behavior than youth in the comparison condition. Conclusion(s): FFT appears to be an effective early intervention for youth at high risk
for BD, especially for preventing new-onset depressive episodes. Treatment appears to be most effective when levels of family conflict are reduced.
There is considerable heterogeneity in the course of mood symptoms in high-risk youth, and treatment may need to be revisited in booster sessions to
have long-term effects. BRD, FT, P Copyright © 2021
Journal of the American Academy of Child and Adolescent Psychiatry, 60(10
Supplement) : S262
- Year: 2021
- Problem: Bipolar Disorders, Depressive Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions
(any), Family therapy, Psychoeducation
Li, W., Lei, D., Tallman, M. J., Patino, L. R., Gong, Q., Strawn, J. R., DelBello, M. P., McNamara, R. K.
Introduction: Mood disorders are associated with fronto-limbic structural and functional abnormalities and deficits in omega-3
polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Emerging evidence also suggests that n-3 PUFA,
which are enriched in fish oil, promote cortical plasticity and connectivity. The present study performed a graph-based connectome analysis to
investigate the role of n-3 PUFA in emotion-related network organization in medication-free depressed adolescent bipolar offspring. Method(s): At
baseline patients (n = 53) were compared with healthy controls (n = 53), and patients were then randomized to 12-week double-blind treatment with
placebo or fish oil. At baseline and endpoint, erythrocyte EPA+DHA levels were measured and fMRI scans (4 Tesla) were obtained while performing a
continuous performance task with emotional and neutral distractors (CPT-END). Graph-based analysis was used to characterize topological properties of
large-scale brain network organization. Result(s): Compared with healthy controls, patients exhibited lower erythrocyte EPA+DHA levels (p = 0.0001),
lower network clustering coefficients (p = 0.029), global efficiency (p = 0.042), and lower node centrality and connectivity strengths in frontal-
limbic regions (p<0.05). Compared with placebo, 12-week fish oil supplementation increased erythrocyte EPA+DHA levels (p<0.001), network clustering
coefficient (p = 0.005), global (p = 0.047) and local (p = 0.023) efficiency, and node centralities mainly in temporal regions (p<0.05). Limitation
(s): The duration of fish oil supplementation was relatively short and the sample size was relatively small. Conclusion(s): These findings provide
preliminary evidence that abnormalities in emotion-related network organization observed in depressed high-risk youth may be amenable to modification
through fish oil supplementation. Copyright © 2021
, 292 : 319-
327
- Year: 2021
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Complementary & Alternative
Interventions (CAM), Fish oil (Omega-3 fatty acids), Omega 3 fatty
acids (e.g. fish oil, flax oil)
Lei, D., Li, W., Tallman, M. J., Patino, L., McNamara, R. K., Strawn, J. R., Klein, C. C., Nery, F. G., Fleck, D. E., Qin,
K., Ai, Y., Yang, J., Zhang, W., Lui, S., Gong, Q., Adler, C. M., Sweeney, J. A., DelBello, M. P.
The goals of the current study were to determine whether topological organization of brain structural networks is altered in
youth with bipolar disorder, whether such alterations predict treatment outcomes, and whether they are normalized by treatment. Youth with bipolar
disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. High-resolution MRI images were collected from
children and adolescents with bipolar disorder who were experiencing a mixed or manic episode (n = 100) and healthy youth (n = 63). Brain networks
were constructed based on the similarity of morphological features across regions and analyzed using graph theory approaches. We tested for
pretreatment anatomical differences between bipolar and healthy youth and for changes in neuroanatomic network metrics following treatment in the
youth with bipolar disorder. Youth with bipolar disorder showed significantly increased clustering coefficient (Cp) (p = 0.009) and characteristic
path length (Lp) (p = 0.04) at baseline, and altered nodal centralities in insula, inferior frontal gyrus, and supplementary motor area. Cp, Lp, and
nodal centrality of the insula exhibited normalization in patients following treatment. Changes in these neuroanatomic parameters were correlated
with improvement in manic symptoms but did not differ between the two drug therapies. Baseline structural network matrices significantly
differentiated medication responders and non-responders with 80% accuracy. These findings demonstrate that both global and nodal structural network
features are altered in early course bipolar disorder, and that pretreatment alterations in neuroanatomic features predicted treatment outcome and
were reduced by treatment. Similar connectome normalization with lithium and quetiapine suggests that the connectome changes are a downstream effect
of both therapies that is related to their clinical efficacy. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Neuropsychopharmacology, 46(7) : 1315-1323
- Year: 2021
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Lithium
Keramatian, K., Chakrabarty, T., Saraf, G., Yatham, L. N.
PURPOSE OF REVIEW: Atypical antipsychotics are increasingly used in the treatment of
bipolar disorder (BD). This systematic review provides an overview of recently published randomized controlled trials (RCTs) on the efficacy and
safety of atypical antipsychotics in BD.\rRECENT FINDINGS: Several studies supported efficacy of quetiapine monotherapy in acute bipolar I (BDI) and
bipolar II (BDII) depression. Moreover, quetiapine adjunctive therapy showed superior efficacy to placebo in treatment-resistant bipolar depression.
Cariprazine 1.5 mg was effective in treating bipolar I depression. Aripiprazole 400 mg IM once monthly was effective in preventing manic episodes
with minimal metabolic effects. In youth with BD, lurasidone was effective and well-tolerated for acute depression while asenapine showed efficacy in
treating acute manic and mixed episodes. Recently published RCTs generally support the efficacy of atypical antipsychotics in different phases of BD.
Future studies should focus on understudied populations including pediatric BD and geriatric BD and BDII, as well as a focus on cognitive functioning
and quality of life measures.
Current Psychiatry Reports, 23(7) : 39
- Year: 2021
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Psychological Interventions
(any)
Grunze, A., Amann, B. L., Grunze, H.
Background
and
Medicina, 57(5) : 30
- Year: 2021
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Anticonvulsants/mood stabilisers (excl. lithium)