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).

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.

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.

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.

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.

[Renal complications of lithium use: to cease or to continue?] / Nierschade bij lithiumgebruik: stoppen of doorgaan?

Lithium is the most effective maintenance therapy for patients with bipolar disorder. Important renal adverse effects of chronic lithium use include nephrogenic diabetes insipidus (prevalence circa 20%) and chronic kidney disease (prevalence circa 10-20% after 5-9 years of lithium use). Chronic lithium use is linked with slowly progressive chronic kidney disease, though it rarely leads to end-stage renal failure (prevalence of 0.5-1.5%). It is currently not possible to predict which patients are susceptible to renal complications of lithium use. The most important risk factors for these renal adverse effects are age, duration of lithium use and chronic exposure to high lithium serum levels. It is unclear if discontinuation of lithium therapy is beneficial in patients with existing chronic kidney disease. As a result of a shared decision making process, in some patients continuation of lithium therapy may be an option despite existing lithium-induced renal complications. Future studies could investigate determinants of a good lithium response, possible predictors of lithium-induced renal adverse effects, and the effect of pharmacological interventions on lithium-induced renal complications.

A research agenda for bipolar disorder developed from a patients' perspective.

BACKGROUND: Diagnosis and treatment of bipolar disorder is complex. Health care is supported by clinical guidelines, which are highly based on scientific evidence. However, such care does not necessarily correspond to preferred care according to patients. In order to narrow the gap between scientifically based guidelines and the patient's perceptions of the best clinical practice, additional research is needed. The aim of this study was to create a patient based research agenda for bipolar disorder to enhance the alignment between patients' needs and care system. METHODS: A mixed method study design was employed consisting of two phases: consultation and prioritization. In the consultation phase, six focus group discussions with patients (n = 35) were conducted to explore research needs according to patients, resulting in 23 research topics. Subsequently, these topics were prioritized by means of a questionnaire with patients (n = 219). RESULTS: Patients with bipolar disorder mentioned a variety of research topics covered by the following five themes: causes of disorder; pharmacotherapy; non-pharmacological treatment; diagnosis; and recovery & recovery oriented care. 'Etiology' was the topic with highest priority. DISCUSSION: The theme 'causes of disorder' is prioritized highest. We argue that this can be explained by the added value of an explanatory framework for appropriate treatment and recovery. The theme 'recovery & recovery oriented care' is currently underrepresented in actual research. It is argued that in order to bridge the knowledge and implementation gap, social science and health system research is needed in addition to biomedical research.

The user experiences and clinical outcomes of an online personal health record to support self-management of bipolar disorder: A pretest-posttest pilot study.

BACKGROUND: Self-management comprises knowledge, behavior, activities and resources providing people with bipolar disorder (BD) control over fluctuating mood and activity-patterns. The 'Self-management and Dialogue in Bipolar Disorder' project entailed the tailoring of an online personal health record (PHR) originally designed for the chronically ill to monitor condition and share information with their clinician to people with BD (PHR-BD). The aim of this study was to evaluate the feasibility, utility and user-experiences of participants with BD, relatives, and healthcare professionals who worked with the PHR-BD. METHODS: Post-test online closed- and open ended questionnaires were used to collect information on utility, and user-experiences with PHR-BD. A pre-posttest design to evaluate clinical effects on quality of life, empowerment, symptom reduction, changes in mood and activity, and illness burden and severity at baseline and at 12-months follow-up. RESULTS: Sixty-six participants with BD logged in at baseline. At study endpoint thirty-nine participants with BD, eleven professionals and one family caregiver filled out the evaluations. No significant differences in the clinical outcomes from baseline were found. Qualitative evaluations showed a frequent utility of the mood chart modules, improved communication between clinician and participant with BD and, increased insight in influencing factors of mood fluctuations. LIMITATIONS: Small convenience sample, no controls. CONCLUSIONS: The option to alternate the interface from a prospective to a retrospective mood chart , and integration with the personal crisis plan was considered to be of added value in self-managing BD. The findings of this study will guide the future implementation of the PHR-BD.

Low self-recognition and awareness of past hypomanic and manic episodes in the general population.

BACKGROUND: Bipolar disorder is often underdiagnosed and undertreated. Its detection and correct diagnosis highly relies on the report of past hypomanic or manic episodes. We investigated the recognition and awareness of past hypomanic and manic episodes in a sample of respondents with bipolar disorder selected from a general population study. METHODS: In a reappraisal study from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), we further investigated 40 respondents with lifetime bipolar disorder confirmed by the structured clinical interview for DSM-IV (SCID). Respondents were asked about awareness of past depressive, manic and hypomanic episodes, illness characteristics and treatment history. RESULTS: Most respondents (82.5 %) recognized that they had experienced a depressive episode while 75 % had consulted a health professional for a depressive episode. Only a minority (22.5 %) recognized that they had experienced a (hypo)manic episode and only 17.5 % had consulted a health professional for a (hypo)manic episode. Only 12.5 % of the respondents reported having received a diagnosis of bipolar disorder. Recognition of previous (hypo)manic episodes was not related to severity of bipolar disorder. CONCLUSIONS: In routine clinical practice history-taking on a syndromal level, i.e., only inquiring whether a patient presenting with depression ever experienced a hypomanic or manic episode or received treatment for such an episode, is not sufficient to confirm or exclude a diagnosis of bipolar disorder. Other efforts, such as an interview with a significant other and the use of self report questionnaires or (semi-)structured interviews may be needed to recognize previous manic symptoms in patients with depression.

Treatment of bipolar disorder in the Netherlands and concordance with treatment guidelines: study protocol of an observational, longitudinal study on naturalistic treatment of bipolar disorder in everyday clinical practice.

BACKGROUND: While various guidelines on the treatment of bipolar disorder have been published over the last decades, adherence to guidelines has been reported to be low. In this article we describe the protocol of a nationwide, multicenter, longitudinal, non-intervention study on the treatment of bipolar disorder in the Netherlands. Study aims are to provide information on the nature and content of outpatient treatment of bipolar disorder, to determine to what extent treatment is in concordance with the Dutch guideline for the treatment of bipolar disorder (2008), and to investigate the relationship of guideline concordance with symptomatic and functional outcome. METHODS/DESIGN: Between December 2009 and February 2010, all psychiatrists registered as member of the Dutch Psychiatric Association received a questionnaire with questions about their treatment setting, and whether they would be willing to participate in further research. Psychiatrists treating adult outpatients with bipolar disorder were invited to participate. Consenting psychiatrist subsequently approached all their patients with bipolar disorder. The study is performed with written patient and caregiver surveys at baseline and after 12 months, including data on demographics, illness characteristics, organization of care, treatments received, symptomatic and functional outcome, quality of life, and burden of care for informal caregivers. DISCUSSION: This study will provide information on the naturalistic treatment of bipolar disorder in the Netherlands, as well as degree of concordance of this treatment with the Dutch guideline, and its relationship with symptomatic and functional outcome. Limitations of a survey-based study are discussed.

The effectiveness of restarted lithium treatment after discontinuation: reviewing the evidence for discontinuation-induced refractoriness.

OBJECTIVES: We sought to determine whether the risk of relapse in patients with bipolar disorder is higher after discontinuation and restart of lithium treatment as compared to continuous lithium treatment in these same patients. METHODS: We conducted literature searches in the Pubmed, Embase, Cochrane, and PsycINFO databases with cross-reference checks. Relevant data were extracted and pooled for meta-analysis. RESULTS: Five relevant studies were included for review, of which three studies qualified for the meta-analysis and included a total of 212 analyzed cases. Two studies found lithium to be less effective after discontinuation and reintroduction and three studies found no decreased effectiveness. The pooled odds ratio for the occurrence of one or more relapses after interruption of lithium treatment compared to continuous treatment was 1.40 (95% confidence interval: 0.85-2.31; p = 0.19). CONCLUSIONS: Although studies are scarce, review and meta-analysis of the available literature does not provide convincing evidence that lithium is less effective when treatment is discontinued and restarted, compared to uninterrupted treatment.

Hypercalcemia in patients with bipolar disorder treated with lithium: a cross-sectional study.

BACKGROUND: Lithium-induced hyperparathyroidism (LIH) is a relative underrecognized complication of long-term lithium treatment. Hypercalcemia may be the first, but often overlooked, sign of LIH. Symptoms of LIH can be similar to the underlying psychiatric illness, which may cause a significant doctor's delay in diagnosing LIH. The aim of this study was to determine the prevalence of hypercalcemia in a cohort of psychiatric patients. METHODS: In this cross-sectional study, we collected data from 314 patients treated with lithium in an outpatient clinic for bipolar disorder. Patients with bipolar disorder from the same clinics, who had never been treated with lithium and of whom serum calcium levels were available, were included as controls (n = 15). Patient characteristics and laboratory results were collected during the period of June 2010 till June 2011. RESULTS: The mean serum calcium level was 2.49 (SD 0.11) mmol/l. The point prevalence of hypercalcemia (>2.60 mmol/l) was 15.6%. In a comparable group of psychiatric patients not using lithium, the mean serum calcium level was 2.37 mmol/l, and none of these patients had hypercalcemia (p = 0.001). The duration of lithium treatment was the only significant predictor for the development of hypercalcemia (p = 0.002). DISCUSSION: The prevalence of hypercalcemia in lithium-treated patients was significantly higher than that in non-lithium treated controls and correlated to the cumulative time lithium was used in this cross-sectional study. We recommend that serum calcium levels should be routinely tested in patients using lithium for timely detection of LIH or hypercalcemia due to other causes.

[Lithium-induced hyperparathyroidism]. / Lithium-geïnduceerde hyperparathyreoïdie.

Lithium is a medication successfully being used for the treatment of bipolar disorder. Lithium-induced hyperparathyroidism (LIH) is a little known complication that may arise due to the use of lithium. Symptoms of LIH are often similar to the underlying psychiatric illness for which lithium was indicated. It is thus difficult to differentiate between these, resulting in significant 'doctors' delay' in the diagnosis of LIH. The authors present three cases in this article. In the first case concerning a 51-year-old woman, they illustrate that LIH and subsequent hypercalcaemia are often diagnosed by coincidence. In the second case concerning a 47-year-old woman, they show that it can be quite complicated to locate the underlying aberration of the parathyroid and that medication may be an eligible alternative to surgery. In the third case, a 56-year-old woman, they show the need for cogency regarding appropriate surgical strategy as recurrences are quite common.