ABSTRACTAimsWhile suboptimal medication adherence is a widely recognized problem for people with bipolar disorder (BD), it is less clear how individual characteristics are associated with varying levels of adherence and how specific adherence barriers impact behaviors. This interim analysis from an ongoing randomized controlled trial (RCT) examined associations between patient‐reported adherence, adherence barriers, and mood symptoms among poorly adherent individuals with BD.MethodsRCT participants were adults age ≥ 18 years old with BD Type 1 or 2, difficulties with medication adherence, and actively symptomatic as measured by Brief Psychiatric Rating Scale (BPRS) score ≥ 36, Young Mania Rating Scale (YMRS) > 8, or Montgomery Asberg Depression Rating Scale (MADRS) > 8. Adherence was assessed using the self‐reported Tablets Routine Questionnaire (TRQ) and grouped into 3 clinically relevant groups: those with TRQs < 20% (good adherence), ≥ 20% and < 50% (fair adherence), and ≥ 50% (poor adherence). Adherence barriers were assessed with the Oxford Bipolar Knowledge Questionnaire (OBQ), Self‐Report Habit Index (SRHI), Communication Styles Scale (CSS), and Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES 8A).ResultsAnalysis was derived from screening and baseline data on the first 129 randomized participants. Mean age was 42.18 (SD = 13.04) years, with 76.74% (n = 99) female and 41.09% (n = 53) non‐White. The mean past 7‐day percentage of days with missed BD medications using TRQ was 34.34% (SD = 30.32) at screening and 24.82% (SD = 27.70) at baseline. The average time between screening visit and baseline was 18.90 (SD = 12.46) days. Comparing adherence groups, MADRS and BPRS were significantly higher in those with worse adherence both at screening and baseline (p < 0.05 for all). With respect to BD adherence barriers, only SRHI was significantly inversely correlated with TRQ at screening (p < 0.001) and both SRHI and SOCRATES 8A (Taking steps sub‐scale) were significantly inversely correlated with TRQ at baseline (p = 0.001 and p = 0.022, respectively).ConclusionsPoorly adherent individuals with BD have significantly more severe global psychopathology and worse depressive severity. Significant adherence barriers include lifestyle routines that do not promote regular medication‐taking and engagement in reducing the use of substances. Given the extensive burden of poor adherence in BD, adherence promotion efforts should target specific and actionable barriers.Trial RegistrationClinicalTrials.gov identifier: NCT04622150

ABSTRACTAimThis study aimed to evaluate associations in bipolar disorder (BD) across multimodal measures of white matter microstructure (using diffusion tensor imaging; DTI), cognitive, behavioral, and brain electrophysiological measures (using electroencephalography; EEG).MethodsSubjects were recruited through the Psychosis and Affective Research Domains and Intermediate Phenotypes Consortium (n = 45 bipolar with psychosis, n = 40 bipolar without psychosis, n = 66 healthy subjects). DTI data were used to quantify the white matter variables, fractional anisotropy (FA) and radial diffusivity (RD). The Brief Assessment of Cognition in Schizophrenia (BACS), Stop Signal Task (SST), pro‐ and anti‐saccades, auditory event‐related potentials (ERPs), and intrinsic brain activity were used as estimates of brain function.ResultsThe combined BD group differed from healthy controls, but no differences between BD with and without psychosis were observed. BD‐related white matter abnormalities were seen across multiple tracts: right cingulum–cingulate gyrus, bilateral anterior thalamic radiation, bilateral superior longitudinal fasciculus, right inferior longitudinal fasciculus, and forceps major. Results also showed modestly compromised cognitive performance and elevated intrinsic EEG activity associated with BD.ConclusionsFurther analysis indicated worse white matter integrity related to higher intrinsic EEG and modestly higher ERPs. These multimodal analyses are likely to aid in creating future informative diagnostic, etiological, and treatment targets for BD.

Inpatient depression is associated with high morbidity and significant cognitive impairment. Inpatient treatment often focuses on short-term stabilization with medication. Readmission rates are high. We examined the impact of a novel psychological intervention, activation therapy (AT, Behavioural Activation combined with Cognitive Activation), versus treatment as usual (TAU) on readmission rates, and cognitive, functional, and depression outcomes, in inpatient depression. A randomised controlled trial in adults hospitalised with a major depressive episode. Inpatients were randomised to AT (8 individual sessions over 2 weeks) or not (TAU). Key time points were baseline (on admission) and 14 weeks after baseline. The primary outcome was psychiatric hospital readmission rates within 12 weeks of discharge. Secondary outcomes were cognition, general functioning, depression, and 'deactivation' symptoms (change from baseline to 14 weeks). Ninety-seven individuals were randomised to AT (n = 47) or TAU (n = 50). Readmission rates did not differ between treatment arms (34% vs. 40%; OR = 0.76, CI = 0.30-1.90). Significant improvements for verbal learning and memory (d = 0.42) and general functioning (d = 0.58) were in favour of the AT versus TAU arms. Per protocol analysis showed additional significant effects of AT on psychomotor speed (d = 0.64) and clinician-rated depression symptoms (d = 0.56). No significant effects were observed for other secondary outcomes (subjective cognition, self-reported depression symptoms, and deactivation symptoms). The AT intervention showed durable, pro-cognitive effects. Further adaptations of AT, such as the addition of maintenance sessions as patients transition to community-based care, need exploring.

Dr. Benjamin I. Goldstein acknowledges his position as RBC Investments Chair in Children's Mental Health and Developmental Psychopathology at CAMH, a joint Hospital-University Chair between the University of Toronto, CAMH, and the CAMH Foundation. Dr. Mikaela K. Dimick is the recipient of a Postdoctoral Award from the Canadian Institutes of Health Research. All other authors report no actual or potential conflicts of interest. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Few studies have addressed medication adherence in adolescents and young adults (AYAs) with bipolar disorder (BD). This 6-month prospective randomized-controlled trial (RCT) tested customized adherence enhancement for adolescents and young adults (CAE-AYA), a behavioral intervention for AYAs versus enhanced treatment as usual (ETAU). Inclusion criteria were AYAs age 13-21 with BD type I or II with suboptimal adherence defined as missing ≥20% of medications. Assessments were conducted at Screening, Baseline, and weeks 8, 12 and 24. Primary outcome was past 7 day self-reported Tablets Routine Questionnaire (TRQ) validated by electronic pillbox monitoring (SimpleMed). Symptom measures included the Hamilton Depression Rating Scale (HAM-D) and Young Mania Rating Scale (YMRS). The mean sample age (N = 36) was 19.1 years (SD = 2.0); 66.7% (N = 24) female, BD Type I (81%). The mean missed medication on TRQ for the total sample was 35.4% (SD = 28.8) at screening and 30.4% (SD = 30.5) at baseline. Both CAE-AYA and ETAU improved on TRQ from screening to baseline. Baseline mean missed medication using SimpleMed was 51.6% (SD = 38.5). Baseline HAM-D and YMRS means were 7.1 (SD = 4.7) and 6.0 (SD = 7.3), respectively. Attrition rate at week 24 was 36%. Baseline to 24-week change on TRQ, adjusting for age, gender, educational level, living situation, family history, race, and ethnicity, showed improvement favoring CAE-AYA versus ETAU of 15%. SimpleMed interpretation was limited due to substantial missing data. There was a significant reduction in depression favoring CAE-AYA. CAE-AYA may improve adherence in AYAs with BD, although conclusions need to be made cautiously given study limitations. ClinicalTrials.gov identifier: NCT04348604.