Lithium-discontinuation-induced treatment refractoriness revisited.

BACKGROUND: Lithium is effective in the long-term treatment of bipolar disorder. Concerns have been raised about non-responsiveness after discontinuation and resuming previously effective lithium prophylaxis. We reviewed the available literature on this so-called lithium-discontinuation-induced treatment refractoriness (LDITR). RESULTS: We found 11 case reports and six cohort studies including 403 patients addressing LDITR, and one nation-wide register study providing some additional data on LDITR. Pooling all cohort studies, the percentages of non-responders during re-treatment with lithium ranged from 3.6 to 27.7%, with an average of 17.3%. Non-responsiveness was associated with longer duration of lithium treatment before discontinuation, longer duration of bipolar disorder before start of lithium, faster tapering off lithium, and longer duration of discontinuation. CONCLUSIONS: There may be a subgroup in whom lithium discontinuation-induced treatment refractoriness exists. However, the vast majority of people respond when lithium is restarted. Moreover, it may be necessary to continue lithium beyond the first relapses to restore long-term prophylactic efficacy.

Predicting which intervention works better for whom: Moderators of treatment effect of Mindfulness-Based Cognitive Therapy and Positive Psychology Intervention in patients with bipolar disorder.

BACKGROUND: This study aimed to identify moderators of treatment effect (i.e. depressive symptoms and well-being) of Mindfulness-Based Cognitive Therapy (MBCT) and Positive Psychology Intervention (PPI) in patients with bipolar disorder. METHODS: Data were drawn from two multicenter randomized controlled trials investigating effectiveness of MBCT vs treatment as usual (TAU; n = 144) and PPI vs TAU (n = 97) in bipolar disorder. Outcomes were assessed at baseline, posttreatment, and 12 months after baseline. Data were analyzed using separate linear regression models, comparing the pooled MBCT or PPI outcomes to TAU, and comparing MBCT to PPI. RESULTS: The exploratory analyses not corrected for multiple comparisons showed a number of variables that were associated with stronger response to the interventions, including higher baseline anxiety, lower well-being, and lower levels of self-focused positive rumination, well-being, and self-compassion, and variables associated with a stronger response to either MBCT (higher levels of depression and anxiety and being married) or PPI (being male). After correcting for multiple testing, depressive symptoms appeared to be the most robust variable associated with better response to MBCT than PPI. LIMITATIONS: The RCTs handled slightly different enrollment criteria and outcome measures. CONCLUSIONS: The most robust finding is that patients with more severe symptomatology seem to benefit more from MBCT than PPI. CLINICAL IMPLICATIONS: This is a first step to improve personalized assignment of third-wave CBT interventions for patients with bipolar disorder. However, before definite treatment assignment criteria can be formulated and implemented in clinical practice, these findings should be replicated.

Do you feel up when you go up? A pilot study of a virtual reality manic-like mood induction paradigm.

OBJECTIVES: In order to understand the working mechanisms of mania, it is necessary to perform studies during the onset of manic (-like) mood states. However, clinical mania is difficult to examine experimentally. A viable method to study manic mood like states is mood induction, but mood induction tasks thus far show variable effectiveness. METHODS: In this pilot study, a new paradigm to induce mood through virtual reality (VR) is examined. Both state characteristics, namely changes in emotion, and trait characteristics, such as high and low scores on the hypomanic personality scale (HPS), were measured in 65 students. These students participated in either a neutral VR mood induction or an activating VR mood induction in which excitement, goal directedness, and tension (being aspects of mania) were induced. All participants performed a risk-taking behavioural task, Balloon Analogue Risk Task (BART). RESULTS: The experimental VR task induced excitement and tension. In participants with higher sensitivity to hypomanic personality (HPS), irritation increased in response to activation whereas it decreased in the low HPS group, and excitement increased more steeply in the low HPS group. There were no effects on the behavioural task. CONCLUSIONS: The VR task is effective in inducing relevant state aspects of hypomania and is suitable as a paradigm for future experimental studies. Activation of dual affective states (excitement and tension) is an essential aspect in manic-like mood induction paradigms.

Bipolarity in Older individuals Living without Drugs (BOLD): Protocol and preliminary findings.

INTRODUCTION: Although clinical guidelines regard prophylactic medication as the cornerstone of treatment, it is estimated almost half of patients with bipolar disorder (BD) live without medication. This group is underrepresented in research but can provide indispensable knowledge on natural course, resilience and self-management strategies. We aim to describe the clinical phenotype of patients diagnosed with BD who have discontinued maintenance treatment. METHODS: The mixed-methods BOLD study included 58 individuals aged 50 years and over with BD that did not use maintenance medication in the past 5 years. A preliminary, quantitative comparison of clinical characteristics between BOLD and our pre-existing cohort of >220 older BD outpatients with medication (Dutch Older Bipolars, DOBi) was performed. RESULTS: BD-I, psychiatric comorbidities, number of mood episodes and lifetime psychotic features were more prevalent in BOLD compared to DOBi. BOLD participants had a younger age at onset and reported more childhood trauma. BOLD participants reported fewer current mood symptoms and higher cognitive, social, and global functioning. LIMITATIONS: Our findings may not be generalizable to all individuals diagnosed with BD living without maintenance medication due to selection-bias. CONCLUSION: A group of individuals exists that meets diagnostic criteria of BD and is living without maintenance medication. They appear to be relatively successful in terms of psychosocial functioning, although they do not have a milder clinical course than those on maintenance medication. The high prevalence of childhood trauma warrants further investigation. Future analyses will examine differences between BOLD and DOBi per domain (e.g. cognition, physical health, psychosocial functioning, coping).

Development and validation of a Manic Thought Inventory.

OBJECTIVE: This article describes the development and psychometric evaluation of the Manic Thought Inventory (MTI), a patient-driven self-report inventory to assess the presence of typical (hypo)manic cognitions. METHODS: The initial item pool was generated by patients with bipolar disorder (BD) type I and assessed for suitability by five psychiatrists specialized in treating BD. Study 1 describes the item analysis and exploratory factor structure of the MTI in a sample of 251 patients with BD type I. In study 2, the factor structure was validated with confirmatory factor analysis, and convergent and divergent validity were assessed in an independent sample of 201 patients with BD type I. RESULTS: Study 1 resulted in a 50-item version of the MTI measuring one underlying factor. Study 2 confirmed the essentially unidimensional underlying construct in a 47-item version of the MTI. Internal consistency of the 47-item version of the MTI was excellent (α = 0.97). The MTI showed moderate to large positive correlations with other measures related to mania. It was not correlated with measures of depression. CONCLUSION: The MTI showed good psychometric properties and can be useful in research and clinical practice. Patients could use the MTI to select items that they recognize as being characteristic of their (hypo)manic episodes. By monitoring and challenging these items, the MTI could augment current psychological interventions for BD.

Course of subthreshold manic symptoms and related risk factors in the general population: A three-year follow-up study.

OBJECTIVES: Subthreshold manic symptoms (subM) are a risk factor for the onset and recurrence of bipolar disorder (BD). Individuals with subM may benefit from preventive interventions, however, their development is hampered by a lack of knowledge on subM prevalence and subsequent course. This study examines subM characteristics, course, and risk factors for an unfavourable course. METHODS: In a Dutch representative, population-based sample aged 18-64 (N = 4618), we assessed subM, defined as the occurrence of manic core symptoms (elation/irritability), without meeting full DSM-IV criteria for BD I or II in the past 3 years. Comparison groups had either no manic symptoms (noM) or hypomania/mania in the context of BD (mBD) in the past 3 years. Furthermore, we differentiated a mild and moderate type of subM, based on the number of manic symptoms. A subsequent three-year course was assessed prospectively. RESULTS: SubM had a three-year prevalence of 4.9%. Its prevalence, characteristics, and course were in between noM and mBD, and there were few differences between mild and moderate subM. Over the 3-year follow-up, 25.0% of individuals with subM had persistent subM and another 6.1% transitioned to mBD. Eleven significant risk factors for this unfavourable course were found. The most important were a history of depression/dysthymia (OR 3.75, p ≤ 0.001), living alone (OR 2.61, p ≤ 0.01) and elevated neuroticism score (OR 1.21, p ≤ 0.001). CONCLUSIONS: This study supports the validity and clinical relevance of subM as a BD prodrome. It demonstrates that subM symptoms often persist or increase during follow-up and identifies 11 risk factors that are associated with an unfavourable course.

Designing and testing of a health-economic Markov model to assess the cost-effectiveness of treatments for Bipolar disorder: TiBipoMod.

Background: Bipolar disorder is an often recurrent mood disorder that is associated with a significant economic and health-related burden. Increasing the availability of health-economic evidence may aid in reducing this burden. The aim of this study is to describe the design of an open-source health-economic Markov model for assessing the cost-effectiveness of interventions in the treatment of Bipolar Disorders type I and II, TiBipoMod. Methods: TiBipoMod is a decision-analytic Markov model that allows for user-defined incorporation of both pharmacological and non-pharmacological interventions for the treatment of BD. TiBipoMod includes the health states remission, depression, (hypo)mania and death. Costs and effects are modeled over a lifetime horizon from a societal and healthcare perspective, and results are presented as the total costs, Quality-Adjusted Life Years (QALY), Life Years (LY), and incremental costs per QALYs and LYs gained. Results: Functionalities of TiBipoMod are demonstrated by performing a cost-utility analysis of mindfulness-based cognitive therapy (MBCT) compared to the standard of care. Treatment with MBCT resulted in an increase of 0.18 QALYs per patient, and a dominant incremental cost-effectiveness ratio per QALY gained for MBCT at a probability of being cost-effective of 71% when assuming a €50,000 willingness-to-pay threshold. Conclusion: TiBipoMod can easily be adapted and used to determine the cost-effectiveness of interventions in the treatment in Bipolar Disorder type I and II, and is freely available for academic purposes upon request at the authors.

A Feasibility Study of the Addition of STEPPS in Outpatients With Bipolar Disorder and Comorbid Borderline Personality Features: Promises and Pitfalls.

Background: Pharmacotherapy is a cornerstone in bipolar disorder (BD) treatment whereas borderline personality disorder (BPD) is treated primarily with psychotherapy. Given the overlap in symptomatology, patients with BD may benefit from psychotherapy designed for BPD. Aims: This paper reports the findings of a non-controlled open feasibility study of STEPPS training in patients with BD and borderline personality features (BPF). Methods: Outpatients with BD were screened for BPD, and if positive interviewed with SCID-II. Patients with at least three BPF, always including impulsivity and anger burst, were included in the intervention study. Severity of BD and BPD and quality of life were assessed. Descriptive statistics were performed. Results: Of 111 patients with BD 49.5% also screened positive on BPD according to PDQ-4+, and 52.3% of these had BPD according to SCID-II. Very few participants entered the intervention study, and only nine patients completed STEPPS. Descriptive statistics showed improvement on all outcome variables post treatment, but no longer at 6-month follow up. We reflect on the potential reasons for the failed inclusion. Conclusion: Features of BPD were highly prevalent in patients with BD. Still, recruiting patients for a psychological treatment originally designed for BPD proved to be difficult. Feedback of participants suggests that the association of STEPPS with "borderline" had an aversive effect, which may have caused limited inclusion for screening and subsequent drop-out for the treatment. Therefore, STEPPS should be adapted for BD to be an acceptable treatment option. Clinical Trial Registration: www.ClinicalTrials.gov/3856, identifier: NTR4016.

Adverse or therapeutic? A mixed-methods study investigating adverse effects of Mindfulness-Based Cognitive Therapy in bipolar disorder.

BACKGROUND: Mindfulness-Based Interventions (MBIs) are widely used in clinical and non-clinical populations, but little attention has been given to potential adverse effects (AEs). AIMS: This study aimed to gain insight in the prevalence and course of AEs during Mindfulness-Based Cognitive Therapy (MBCT) for patients with bipolar disorder (BD). METHOD: The current mixed-methods study was conducted as part of a RCT on (cost-) effectiveness of MBCT in 144 patients with BD (Trial registered on 25th of April 2018, ClinicalTrials.gov, NCT03507647). During MBCT, occurrence of AEs was monitored prospectively, systematically, and actively (n = 72). Patients who reported AEs were invited for semi-structured interviews after completing MBCT (n = 29). Interviews were analysed with directed content analysis, using an existing framework by Lindahl et al. RESULTS: AEs were reported by 29 patients, in seven of whom the experiences could not be attributed to MBCT during the interview. AEs were reported most frequently up to week 3 and declined afterwards. Baseline anxiety appeared to be a risk factor for developing AEs. Seven existing domains of AEs were observed: cognitive, perceptual, affective, somatic, conative, sense of self, and social. Influencing factors were subdivided into predisposing, precipitating, perpetuating, and mitigating factors. With hindsight, more than half of patients considered the reported AEs as therapeutic rather than harmful. CONCLUSIONS: Although the occurrence of AEs in MBCT for patients with BD is not rare, even in this population with severe mental illness they were not serious or had lasting bad effects. In fact, most of them were seen by the patients as being part of a therapeutic process, although some patients only experienced AEs as negative.

Guideline concordance and outcome in long-term naturalistic treatment of bipolar disorder - a one-year longitudinal study using latent change models.

BACKGROUND: Only few studies investigated the relation between concordance with treatment guidelines and treatment outcome in everyday treatment of bipolar disorder (BD). Prospective studies are scarce. METHODS: A nationwide, naturalistic, prospective study on the relation between guideline concordance and treatment outcome in the long-term outpatient treatment of patients with BD. Participants completed a survey on treatments received and various outcome measures at baseline and after one year. RESULTS: Of 839 patients who completed the baseline survey, 615 (73.3%) also completed the follow-up survey. Consistent with our a priori hypothesis, cross-sectional analyses at baseline showed correlations between guideline concordance with quality of life (r = .17, p < .001), treatment satisfaction (r = .17, p <.001), and impaired functioning (r = -.10, p = .04). At follow-up, guideline concordance was correlated with severity of illness (r = -.10, p = .05), quality of life (r = .18, p < .001), and treatment satisfaction (r = .15, p < .001). Concerning three additional hypotheses on longitudinal relations between concordance and outcome measures, only a positive relation was found between change in guideline concordance and change in quality of life. LIMITATIONS: Selection bias may have occurred by inclusion of patients with neither a very severe nor a very mild course of illness. CONCLUSIONS: Although guideline concordance was high throughout the study, change in guideline concordance was positively associated with change in quality of life, suggesting that especially in long-term treatment, continuous efforts to optimize ongoing treatment is essential.

The influence of social, psychological, and cognitive factors on the clinical course in older patients with bipolar disorder.

OBJECTIVES: Research on factors that contribute to recurrence in older adults with bipolar disorder (OABD) is sparse. Previous research showed that clinical factors (e.g., age of onset, lifetime psychotic features, and suicide risk) were not associated with the recurrence in OABD. In younger adults, worse social functioning, coping style, and worse cognitive functioning are found to be associated with an unfavorable course of bipolar disorder. Therefore, this study is focusing on social, psychological, and cognitive factors in OABD. More insight in these factors is essential in order to develop and further specify preventive and treatment interventions. METHODS: Data were used from the Dutch Older Bipolars (DOBi) cohort study. We included 64 patients for 3-year follow-up measurements, who were divided in a recurrent group and a nonrecurrent group. Logistic regression analyses were conducted to assess associations between social, psychological, and cognitive factors, and nonrecurrence. RESULTS: 39.1% reported at least one recurrence during the 3-year follow-up period. No significant associations were found between the social, psychological, and cognitive factors and having a recurrence during the follow-up period. DISCUSSION: Participants in the recurrent group were younger, more often female and less likely to have children. Our results suggest that results from the adult bipolar disorder population cannot be extrapolated to OABD patients, underlining the need for longitudinal studies in OABD.

The feasibility of mindfulness-based cognitive therapy for people with bipolar disorder: a qualitative study.

BACKGROUND: Mindfulness- Based Cognitive Therapy (MBCT) could be a promising psychosocial intervention for people with bipolar disorder (BD). However, little is known about the feasibility of MBCT for people with BD. In this study we explore the facilitators and barriers people with BD experience of an adapted MBCT program. METHOD: This qualitative study is part of a large, multicenter randomized controlled trial on MBCT for BD (trial registration number: NCT03507647). The present study included 16 participants with BD who participated in an 8-week adapted MBCT program. Semi- structured interviews exploring the feasibility, with a particular focus on the bipolar symptoms, were recorded verbatim, transcribed and analyzed. For reasons of triangulation, teachers were interviewed as well. RESULTS: Participants reported different barriers and facilitators of MBCT, both generally as well as with regard to their bipolar disorder. Four key themes arose: the training itself, psychosocial factors, personal characteristics and the bipolar disorder. Themes were further divided in subthemes. CONCLUSION: The adapted MBCT program seemed to be feasible for people with BD. Depressive symptoms often acted as a barrier for participating in MBCT, suggesting that participants might need additional support when depressed. Manic symptoms could act both as a barrier and facilitator, suggesting that the occurrence of (hypo)mania does not necessarily have to be an exclusion criterion for participation. Further clinical and research implications are suggested. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03507647. Registered 25th of April 2018, https://clinicaltrials.gov/ct2/show/NCT03507647 .

A multi-center naturalistic study of a newly designed 12-sessions group psychoeducation program for patients with bipolar disorder and their caregivers.

BACKGROUND: Psychoeducation (PE) for bipolar disorder (BD) has a first-line recommendation for the maintenance treatment phase of BD. Formats vary greatly in the number of sessions, whether offered individually or in a group, and with or without caregivers attending. Due to a large variation in formats in the Netherlands, a new program was developed and implemented in 17 outpatient clinics throughout the country. The current study investigated the feasibility of a newly developed 12-sessions PE group program for patients with BD and their caregivers in routine outpatient practice and additionally explored its effectiveness. METHODS: Participants in the study were 108 patients diagnosed with BD, 88 caregivers and 35 course leaders. Feasibility and acceptance of the program were investigated by measures of attendance, and evaluative questionnaires after session 12. Preliminary treatment effects were investigated by pre- and post-measures on mood symptoms, attitudes towards BD and its treatment, levels of self-management, and levels of expressed emotion. RESULTS: There was a high degree of satisfaction with the current program as reported by patients, caregivers, and course leaders. The average attendance was high and 83% of the patients and 75% of the caregivers completed the program. Analyses of treatment effects suggest positive effects on depressive symptoms and self-management in patients, and lower EE as experienced by caregivers. CONCLUSIONS: This compact 12-sessions psychoeducation group program showed good feasibility and was well accepted by patients, caregivers, and course leaders. Preliminary effects on measures of self-management, expressed emotions, and depressive symptoms were promising. After its introduction it has been widely implemented in mental health institutions throughout the Netherlands.

Supported Housing as a recovery option for long-stay patients with severe mental illness in a psychiatric hospital in South India: Learning from an innovative de-hospitalization process.

Individuals with severe mental illness have long been segregated from living in communities and participating in socio- cultural life. In recent years, owing to progressive legislations and declarations (in India and globally), there has been a growing movement towards promoting social inclusion and community participation, with emphasis on the need to develop alternative and inclusive care paradigms for persons with severe mental illness. However, transitions from inpatient care to community settings is a complex process involving implications at multiple levels involving diverse stakeholders such as mental health service users, care providers, local communities and policy makers. This article studies how the transition from a hospital setting to a community-based recovery model for personals with severe mental illness can be facilitated. It reflects on the innovative process of creating a Supported Housing model in South India, where 11 MH Service users transitioned from a psychiatric ECRC to independent living facilities. Experiences in various phases of the project development, including care provider- and community level responses and feedback were scrutinised to understand the strategies that were employed in enabling the transition. Qualitative methods (including in-depth interviews and naturalistic observations) were used with residents and staff members to explore the challenges they encountered in stabilizing the model, as well as the psychosocial benefits experienced by residents in the last phase. These were complemented with a Brief Psychiatric Rating Scale (BPRS) and WHO Quality of Life scale to compare baseline and post-assessment results and an increase of quality of life. Results display a significant reduction of psychiatric symptoms in patients (p< 0.5). It also describes the challenges encountered in the current context, and strategies that were used to respond and adapt the model to address these concerns effectively. Positive behavioural and psycho-emotional changes were observed amongst the residents, significant amongst those being enhanced in their mobility and participation. The article concludes by discussing the implications of this study for the development of innovative community-based models in wider contexts.

The characteristics of psychotic features in bipolar disorder.

BACKGROUND: In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors. METHODS: In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models. RESULTS: A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (ß = -0.09, t = -3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (ß = 0.09, t = 3.04, p = 0.002). CONCLUSIONS: In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.

The challenges of living with bipolar disorder: a qualitative study of the implications for health care and research.

BACKGROUND: In mental health care, clinical practice is often based on the best available research evidence. However, research findings are difficult to apply to clinical practice, resulting in an implementation gap. To bridge the gap between research and clinical practice, patients' perspectives should be used in health care and research. This study aimed to understand the challenges people with bipolar disorder (BD) experience and examine what these challenges imply for health care and research needs. METHODS: Two qualitative studies were used, one to formulate research needs and another to formulate healthcare needs. In both studies focus group discussions were conducted with patients to explore their challenges in living with BD and associated needs, focusing on the themes diagnosis, treatment and recovery. RESULTS: Patients' needs are clustered in 'disorder-specific' and 'generic' needs. Specific needs concern preventing late or incorrect diagnosis, support in search for individualized treatment and supporting clinical, functional, social and personal recovery. Generic needs concern health professionals, communication and the healthcare system. CONCLUSION: Patients with BD address disorder-specific and generic healthcare and research needs. This indicates that disorder-specific treatment guidelines address only in part the needs of patients in everyday clinical practice.

A nationwide study on concordance with multimodal treatment guidelines in bipolar disorder.

BACKGROUND: Most previous studies on concordance with treatment guidelines for bipolar disorder focused on pharmacotherapy. Few studies have included other treatment modalities. AIMS: To study concordance with the Dutch guideline of various treatment modalities in outpatient treatment settings for patients with bipolar disorder and to identity factors associated with concordance. METHODS: A nationwide non-interventional study using psychiatrists' and patients' surveys. RESULTS: 839 patients with bipolar or schizoaffective disorder bipolar type were included. Concordance with the guideline was highest for participation of a psychiatrist in the treatment (98%) and for maintenance pharmacotherapy (96%), but lower for supportive treatment (73.5%), use of an emergency plan (70.6%), psychotherapy (52.2%), group psychoeducation (47.2%), and mood monitoring (47%). Presence of a written treatment plan, a more specialized treatment setting, more years of education, and diagnosis of bipolar I disorder versus bipolar II, bipolar NOS, or schizoaffective disorder were significantly associated with better concordance. CONCLUSION: In contrast to pharmacotherapy, psychosocial treatments are only implemented to a limited extend in everyday clinical practice in bipolar disorder. More effort is needed to implement non-pharmacological guideline recommendations for bipolar disorder.