[Tapering maintenance treatment for bipolar disorders]. / Hoogste tijd voor onderzoek naar het afbouwen van onderhoudsbehandeling voor bipolaire stoornissen.

BACKGROUND: In bipolar disorder (BD) preventive maintenance treatment is the rule, yet the scientific evidence supporting this is limited. AIM: To argue the need for research into the gradual discontinuation of maintenance treatment for (BD). METHOD: A narrative review of evidence regarding the effectiveness of maintenance treatment for (BD), supplemented by exploration of potential reasons behind the predominant reliance on pharmacological interventions. RESULTS: Evidence for maintenance treatment primarily focuses on clinical effectiveness, while individuals with bipolar disorder may prioritize other outcome measures. Much research on (BD) centers on neurobiological or genetic aspects. CONCLUSION: A non-pharmacologic approach for longterm treatment in BD has been understudied. The desire of many individuals with bipolar disorder to managing their vulnerability with minimal (or no) medication necessitates thorough research on who, when, and how maintenance medication can be successfully tapered.

How to study psychological mechanisms of mania? A systematic review on the methodology of experimental studies on manic mood dysregulation of leading theories on bipolar disorder.

INTRODUCTION: Although there are several psychological theories on bipolar disorders (BD), the empirical evidence on these theories through experimental studies is still limited. The current study systematically reviews experimental methods used in studies on the main theories of BD: Reward Hypersensitivity Theory (RST) or Behavioral Activation System (BAS), Integrative Cognitive Model (ICM), Positive Emotion Persistence (PEP), Manic Defense theory (MD), and Mental Imagery (MI). The primary aim is to provide an overview of the used methods and to identify limitations and suggest areas of improvement. METHODS: A systematic search of six databases until October 2023 was conducted. Study selection involved two independent reviewers extracting data on experimental study design and methodology. RESULTS: A total of 84 experimental studies were reviewed. BAS and RST were the most frequently studied theories. The majority of these experimental studies focus on mechanisms of reward sensitivity. Other important elements of the reviewed theories, such as goal setting and-attainment, situation selection (avoidance or approach), activation, affective/emotional reactivity, and regulatory strategies, are understudied. Self-report and neuropsychological tasks are most often used, while mood induction and physiological measures are rarely used. CONCLUSION: There is a need for more consensus on the operationalization of psychological theories of mania. Standardization of test batteries could improve comparability among studies and foster a more systematic approach to experimental research. Research on affective (activated) states is still underrepresented in comparison with studies on trait vulnerabilities.

How to make online mood-monitoring in bipolar patients a success? A qualitative exploration of requirements.

BACKGROUND: The Life-Chart Method (LCM) is an effective self-management treatment option in bipolar disorder (BD). There is insufficient knowledge about the consumers' needs and desires for an e-monitoring solution. The first step towards a new mood monitoring application is an extended inventory among consumers and professionals. METHODS: The aim of the current study was: to identify opinions about online mood monitoring of patients with BD and professionals and to identify preferences on design, technical features and options facilitating optimal use and implementation of online mood monitoring. This study used a qualitative design with focus-groups. Participants were recruited among patients and care providers. Three focus-groups were held with eight consumers and five professionals. RESULTS: The focus-group meetings reveal a shared consciousness of the importance of using the Life-Chart Method for online mood monitoring. There is a need for personalization, adjustability, a strict privacy concept, an adjustable graphic report, and a link to early intervention strategies in the design. Due to the fact that this is a qualitative study with a relative small number of participants, so it remains unclear whether the results are fully generalizable. We can't rule out a selection bias. CONCLUSIONS: This study demonstrates the importance of involving stakeholders in identifying a smartphone-based mood charting applications' requirements. Personalization, adjustability, privacy, an adjustable graphic report, and a direct link to early intervention strategies are necessary requirements for a successful design. The results of this value specification are included in the follow-up of this project.

The course of bipolar disorder in pregnant versus non-pregnant women.

BACKGROUND AND RATIONALE: Although it has been suggested that pregnancy may influence the course of bipolar disorder (BD), studies show contradictory results. Until now, no studies included a finegrained validated method to report mood symptoms on a daily basis, such as the lifechart method (LCM). The aim of the present study is to investigate the course of BD during pregnancy by comparing LCM scores of pregnant and non-pregnant women. METHODS: Study design: Comparison of LCM scores of two prospective observational BD cohort studies, a cohort of pregnant women (n = 34) and a cohort of non-pregnant women of childbearing age (n = 52). Main study parameters are: (1) proportions of symptomatic and non-symptomatic days; (2) symptom severity, frequency, and duration of episodes; (3) state sequences, longitudinal variation of symptom severity scores. RESULTS: No differences in clinical course variables (symptomatic days, average severity scores, frequency, and duration of episodes in BD were found between pregnant and non-pregnant women. With a combination of State Sequence Analysis (SSA) and cluster analysis on the sequences of daily mood scores three comparable clusters were found in both samples: euthymic, moderately ill and severely ill. The distribution differences between pregnant and non-pregnant women were significant, with a majority of the pregnant women (68%) belonging to the moderately ill cluster and a majority of the non-pregnant women (46%) to the euthymic cluster. In pregnant women the average daily variation in mood symptoms as assessed with Shannon's entropy was less than in non-pregnant women (respectively 0.43 versus 0.56). CONCLUSIONS: Although the use of daily mood scores revealed no difference in overall course of BD in pregnant versus non-pregnant women, more pregnant than non-pregnant women belonged to the moderately ill cluster, and during pregnancy the variation in mood state was less than in non-pregnant women. Further research is necessary to clarify these findings.

[Mental disorders in a dental practice. Psychomood disorders]. / Serie: Psychische stoornissen in de mondzorgpraktijk. Stemmings­stoornissen.

Individuals with a depressive or bipolar mood disorder have a higher prevalence of somatic comorbidities, including dental problems. This is partly due to impaired self-care, smoking, alcohol use, and an unhealthy diet, and partly due to the often long-term use of medication. Depression has a negative impact on concentration and motivation and increases anxiety and avoidant behavior. In addition, there are indications for an interaction between stress, psychopathology, neuro-inflammatory processes and somatic health. These (temporary) factors must be taken into consideration in dental care for persons suffering from depression. Also, one must be alert for interactions between psychiatric medications and medications used in dental care. Especially in chronic psychiatric disorders, a coordinated care between dentist, general practitioner, and psychiatrist is of importance.

[Carbamazepine and quetiapine: a neglected, but highly relevant interaction]. / Carbamazepine en quetiapine: een onderbelichte, maar zeer relevante interactie.

We describe a case of concomitant use of carbamazepine and quetiapine, with a highly relevant interaction that requires attention. The combination of these drugs can be prescribed in psychiatry, for example in bipolar disorder, but also in other disciplines. Pharmacotherapy is one of the cornerstones in the treatment of bipolar disorders, and a combination of drugs is frequently used. Carbamazepine, an anti-epileptic drug that is effective as a mood stabilizer, and quetiapine, a second-generation antipsychotic, are both recommended in the Dutch guideline. Besides monotherapy is a combination of both drugs possible. It is striking that carbamazepine and quetiapine have a strong pharmacokinetic interaction via the metabolizing liver enzyme, CYP3A4. This interaction results in a factor 10 reduction of quetiapine blood levels. This may result in a possible loss of clinical efficacy of quetiapine.

A cognitive behavioural group therapy for bipolar disorder using daily mood monitoring.

BACKGROUND AND AIM: This study investigated the effects of group cognitive behavioural therapy (CBT) for patients with bipolar disorder. The development of CBT for this disorder is relatively under-explored. METHOD: Participants with bipolar I or II disorder were treated with group CBT in addition to treatment as usual. The effectiveness of the protocol was explored through sequence analysis of daily mood monitoring prior to, during and after the intervention. Also, a repeated measures design was used assessing symptomatology, dysfunctional attitudes, sense of mastery, psychosocial functioning, and quality of life at start and end of intervention, and at follow-up 2 and 12 months later. RESULTS: The results indicate that variation in mood states diminished over the course of the intervention. Also, there was a change from depressive states to more euthymic states. Greater number of reported lifetime depressive episodes was associated with greater diversity of mood states. There was an increase in overall psychosocial functioning and self-reported psychological health following the intervention. Improvement continued after treatment ended until follow-up at 2 months, and measured 1 year later, for outcomes representing depression, general psychosocial functioning and self-reported psychological health. Due to small sample size and the lack of a control group the results are preliminary. CONCLUSIONS: The results of this pilot study suggest that both offering CBT in group interventions and sequence analysis of time series data are helpful routes to further explore when improving standard CBT interventions for patients suffering from bipolar disorder.

Renal concentrating ability and glomerular filtration rate in lithium-treated patients.

BACKGROUND: Lithium is the most effective drug for mood stabilization in bipolar disorder. However, lithium exposure has been associated with an impaired renal concentrating ability (RCA) and glomerular filtration rate (GFR). We examined RCA and estimated GFR in a cohort of patients treated with lithium. METHODS: 134 patients (≥ 18 years of age) with a mood disorder treated with lithium were screened; 100 patients were included. Demographic and clinical characteristics and blood and urine samples were collected. Additionally, a dDAVP-test was performed to determine maximal RCA. RESULTS: A dDAVP-test was performed in 98 patients (37 males, 61 females). Mean age was 51 years (SD: 12), median duration of lithium therapy 7 years (IQR: 4-15), mean maximal urine osmolality (Uosmol) 725 mOsmol/kg (SD: 153), and median eGFR 84 ml/min/1.73 m2 (IQR: 68-95). Fifty patients (51%) had an impaired RCA and 17 patients (17%) had nephrogenic diabetes insipidus (Uosmol 600-800 and < 600 mOsmol/kg, respectively). Notably, clinical symptoms did not predict an impaired RCA. Nineteen patients (19%) had an eGFR ≤ 60 ml/min/ 1.73 m2. Multivariable regression analysis showed a significant association between the duration of lithium treatment and maximal Uosmol (B = -6.1, 95%-CI: -9.4, -2.9, p < 0.001) and eGFR (B = -0.6, 95%-CI: 0.2, -3.3; p < 0.01). CONCLUSIONS: RCA is impaired in the majority of lithium-treated patients. Both RCA and eGFR are inversely associated with the duration of lithium therapy. Prospective follow-up will enable us to evaluate if abnormalities in RCA can be used to predict the development of lithium-induced chronic kidney disease.

[Earlier recognition of bipolar disorder - necessity and advice for clinical practice]. / Tijdige herkenning van bipolaire stoornissen; noodzaak en praktijkadviezen.

BACKGROUND: There is an average 10-year delay in diagnosing bipolar disorder, hampering the application of effective therapeutic interventions.
AIM: To investigate factors contributing to early recognition.
METHOD: We give a stage-oriented overview of the opportunities for early recognition.
RESULTS: Recognition in stage 0 (at-risk) and stage 1 (prodromal) is yet impossible. In stage 2 (syndromal) there are opportunities for better recognition in patients presenting with depression by conducting a thorough (collateral) psychiatric assessment, family history and by applying additional screening tools. CONCLUSIONS There are opportunities for better recognition of bipolar disorder in the syndromal stage.

Study protocol of a multicenter randomized controlled trial of mindfulness-based cognitive therapy and treatment as usual in bipolar disorder.

BACKGROUND: Despite multiple pharmacological interventions, many people with bipolar disorder (BD) experience substantial residual mood symptoms, even in the absence of severe mood episodes, which have a negative impact on the course of illness and quality of life. Limited data are available on how to optimize treatment for BD, especially for those who suffer from persistent and residual depressive symptoms. Preliminary evidence suggests Mindfulness-Based Cognitive Therapy (MBCT) as a psychological treatment option for BD. This study aims to investigate whether adding MBCT to treatment as usual (TAU) will result in symptomatic and functional improvements in adults with BD compared to TAU alone. METHODS/DESIGN: This study is a prospective, evaluator blinded, multicenter, randomized controlled trial of MBCT + TAU and TAU alone in 160 adults with bipolar type I and type II. Assessments will be conducted at baseline (T0), mid-treatment (Tmid), and at 3 (T1), 6 (T2), 9 (T3), 12 (T4), and 15 (T5) months follow-up. Primary outcome is post-treatment severity of depressive symptoms (Inventory of Depressive Symptomatology- Clinician administered). Secondary outcomes are severity of (hypo) manic symptoms, anxiety, relapse rates, overall functioning, positive mental health, and cost-effectiveness. As possible mediators will be assessed rumination of negative affect, dampening and rumination of positive affect, mindfulness skills, and self-compassion. DISCUSSION: This study will provide valuable insight into the (cost-)effectiveness of MBCT on clinician- and self-rated symptoms of BD, relapse rates, positive mental health, and overall functioning. TRIAL REGISTRATION: NCT03507647 . Registered 25th of April 2018.

Evaluation of clarity of presentation and applicability of monitoring instructions for patients using lithium in clinical practice guidelines for treatment of bipolar disorder.

OBJECTIVES: Clinical practice guidelines (CPGs) for treatment of bipolar disorder (BD) aim to provide guidance to health care professionals on monitoring of patients using lithium. The aim was to assess the clarity of presentation and applicability of monitoring instructions for patients using lithium in CPGs for treatment of BD. METHODS: CPGs for treatment of BD were selected from acknowledged professional organizations from multiple continents. CPGs were rated on the clarity of presentation and applicability of lithium monitoring instructions using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The applicability of monitoring instructions was assessed according to the Systematic Information for Monitoring (SIM) score. Monitoring instructions were considered applicable when a SIM score of ≥3 was found. RESULTS: The clarity of presentation for six out of the nine CPGs was good (>70%) using the AGREE II tool. Only one CPG scored >70% on applicability. Descriptions of the resource implications and facilitators of and barriers to monitoring were most often missing. All CPGs contained instructions for monitoring of lithium serum levels and renal and thyroid function. Information provided in monitoring instructions (n = 247) was in general applicable to clinical practice (77%) based on the SIM score. Overall, a median SIM score of 3 (interquartile range 3-4) was found. CONCLUSIONS: Improvement of the applicability of CPGs is recommended, and can be achieved by describing the resource implications and facilitators of and barriers to monitoring. In addition, information on critical values and instructions on how to respond to aberrant monitoring parameters are needed. With such improvements, CPGs may better aid health care professionals to monitor patients using lithium.

[The effects of pharmacological and psychotherapeutic treatment of comorbid anxiety disorders in patients with bipolar disorder]. / De effectiviteit van medicamenteuze en psychotherapeutische behandeling van comorbide angststoornissen bij patiënten met bipolaire stoornis.

BACKGROUND: The co-occurrence of bipolar disorder and anxiety disorder is associated with a worse prognosis. Clinical guidelines do not give clear therapeutic recommendations on this subject.
AIM: To review the evidence on the effectiveness of both psychotherapy and pharmacotherapy for anxiety disorders in patients with a bipolar disorder.
METHOD: A systematic search in PubMed, Embase, Cochrane en Psycinfo and subsequent screening of potential studies resulted in 11 included studies.
RESULTS: Five studies examined the effect of pharmacotherapy on treatment of comorbid anxiety disorders. One of these studies showed that both olanzapine and lamotrigine provided positive results in treating the anxiety disorders, with olanzapine being the more effective of the two. Conflicting results were found for quetiapine and valproic acid. The conclusion of one study was that risperidone was not effective. No studies were found researching the effect of psychotherapy on treatment of comorbid anxiety disorders. However, two case studies and four studies that included patients with mixed diagnoses, including bipolar disorder, proposed evidence that behavioral and cognitive behavioral therapy (cbt) had a positive effect on treatment of the comorbid anxiety disorder.
CONCLUSION: There is little evidence on the treatment of comorbid anxiety disorders in people with bipolar disorder. Psychotherapy is preferred due to the uncertainty of the effects of pharmacotherapy and the associated risk of causing side effects. Pharmacotherapy can be considered in cases where this is insufficiently effective.

Monitoring of patients treated with lithium for bipolar disorder: an international survey.

BACKGROUND: Adequate monitoring of patients using lithium is needed for optimal dosing and for early identification of patients with (potential) ADEs. The objective was to internationally assess how health care professionals monitor patients treated with lithium for bipolar disorder. METHODS: Using networks of various professional organizations, an anonymous online survey was conducted among health care professionals prescribing lithium. Target lithium serum levels and frequency of monitoring was assessed together with monitoring of physical and laboratory parameters. Reasons to and not to monitor and use of guidelines and institutional protocols, and local monitoring systems were investigated. RESULTS: The survey was completed by 117 health care professionals incorporating responses from twenty-four countries. All prescribers reported to monitor lithium serum levels on a regular basis, with varying target ranges. Almost all (> 97%) monitored thyroid and renal function before start and during maintenance treatment. Reported monitoring of other laboratory and physical parameters was variable. The majority of respondents (74%) used guidelines or institutional protocols for monitoring. In general, the prescriber was responsible for monitoring, had to request every monitoring parameter separately and only a minority of patients was automatically invited. CONCLUSIONS: Lithium serum levels, renal and thyroid function were monitored by (almost) all physicians. However, there was considerable variation in other monitoring parameters. Our results help to understand why prescribers of lithium monitor patients and what their main reasons are not to monitor patients using lithium.

[Bipolar disorder and alcohol use disorder: practical recommendations for treatment, based on a literature review]. / Bipolaire stoornissen en alcoholafhankelijkheid; praktische aanbevelingen voor behandeling op basis van een systematische literatuurstudie.

BACKGROUND: A fairly large proportion (25-50%) of patients with bipolar disorder (bd) also suffer from comorbid alcohol use disorder (aud). However, little is known how this type of morbidity should be treated. It is also unclear whether the current guidelines on bd have been influenced by aud.
AIM: To provide an overview of recent literature concerning the diagnosis and treatment of comorbid bd and aud.
METHOD: We systematically reviewed studies that have addressed three treatment options for this group of patients: pharmaco-therapy, psychological interventions and self-management techniques.
RESULTS: If health professionals decide to treat bd using a pharmaco-therapeutic intervention, they must proceed with caution because the patient may also be suffering from aud. From the very limited number of published articles on this subject, we conclude that the best solution to the problem is to add valproate to the lithium-based treatment. There is also limited evidence that other effective treatments may include the use of integrated psychological interventions, cognitive behavioural therapy and self-management techniques, but these possibilities need further investigation.
CONCLUSION: Treatment of patients suffering from both bd and aud should always focus on both disorders, either simultaneously or separately. If this approach is successful it is vitally important that care is better organised and that there is cooperation between institutions involved in treating addiction disorders and departments that specialise in the care of bd. These improvements are likely to lead to further developments and to more research into new forms of integrated treatment.

[The general practitioner in charge of treatment of patients with bipolar disorder: an exploratory study]. / De huisarts als primaire behandelaar van patiënten met een bipolaire stoornis: een exploratief onderzoek.

BACKGROUND: The role of the general practitioner (gp) in the treatment of severe psychiatric disorders, including bipolar disorder (bd), is under discussion. AIM: To investigate how many patients with a recognised bd are being treated for their illness exclusively in the setting of primary care and to find out how many patients are registrated as having bd on their gp's file. METHOD: We made an exploratory study in a gp's database containing data for 14,254 Dutch adult patients in the Amsterdam over a period of 3.5 years (2010-2013). RESULTS: We found that the gp was in charge of the treatment of bd in less than one patient per practice. The percentage of patients officially recognised as having bd in the database we studied was 0.15%, a percentage that is much lower than the percentage of bd in the Dutch population as a whole. There are several possible explanations for this discrepancy. CONCLUSION: Given these low numbers, it is unlikely that the gps can have adequate experience of giving their bd patients the latest type of treatment. In view of the increasing role played by gps in the treatment of bd, it is important that there is strong collaboration with specialised mental health care, and that a low threshold prevails for consultation and referral.

[Fatal aortarupture following electroconvulsive therapy]. / Aortaruptuur als fatale complicatie bij elektroconvulsietherapie.

Electroconvulsive therapy (ect) is a highly effective and safe form of treatment in psychiatry. However, fatal cardiovascular complications are rarely discussed in the literature. We describe the case of a 49-year old man who died from a ruptured aorta following treatment with ect.

High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls.

BACKGROUND: Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their relatives have similar lower intellectual and educational performance as that observed in schizophrenia. METHOD: This cross-sectional study investigated intelligence and educational performance in two outpatient samples [494 BD-I patients, 952 schizophrenia spectrum (SCZ) patients], 2231 relatives of BD-I and SCZ patients, 1104 healthy controls and 100 control siblings. Mixed-effects and regression models were used to compare groups on intelligence and educational performance. RESULTS: BD-I patients were more likely to have completed the highest level of education (odds ratio 1.88, 95% confidence interval 1.66-2.70) despite having a lower IQ compared to controls (ß = -9.09, S.E. = 1.27, p < 0.001). In contrast, SCZ patients showed both a lower IQ (ß = -15.31, S.E. = 0.86, p < 0.001) and lower educational levels compared to controls. Siblings of both patient groups had significantly lower IQ than control siblings, but did not differ on educational performance. IQ scores did not differ between BD-I parents and SCZ parents, but BD-I parents had completed higher educational levels. CONCLUSIONS: Although BD-I patients had a lower IQ than controls, they were more likely to have completed the highest level of education. This contrasts with SCZ patients, who showed both intellectual and educational deficits compared to healthy controls. Since relatives of BD-I patients did not demonstrate superior educational performance, our data suggest that high educational performance may be a distinctive feature of bipolar disorder patients.

Childhood abuse, family history and stressors in older patients with bipolar disorder in relation to age at onset.

OBJECTIVES: The aim of this study is to explore the family history of psychiatric disorders, childhood abuse, and stressors in older patients with Bipolar Disorder (BD) and the association of these variables with the age at onset of BD. METHODS: The Questionnaire for Bipolar Disorder (QBP) and the Mini International Neuropsychiatric Interview (MINI-Plus) were obtained from 78 patients aged 60 and over to determine diagnosis, age at onset of the first affective episode, childhood abuse, family history of psychiatric disorders and past and recent stressful life events. RESULTS: Increased family history of psychiatric disorders was the only factor associated with an earlier age at onset of BD. Less family history of psychiatric disorders and more negative stressors were significantly associated with a later age at onset of the first (hypo)manic episode. LIMITATIONS: Age at onset, history of childhood abuse, and past stressful life events were assessed retrospectively. Family members of BD patients were not interviewed. CONCLUSIONS: Our findings suggest that age at onset can define distinct BD phenotypes. More specifically there was a stronger heredity of BD and other psychiatric disorders in patients with an early age of onset of BD. Negative stressors may play a specific role in patients with a late age at onset of a first (hypo)manic episode.

[Forcing patients with bipolar disorder to make a financial contribution to secondary psychiatric care may make them forsake care completely]. / Vraaguitval bij poliklinische patiënten met een bipolaire stoornis als gevolg van de eigen bijdrage in de tweedelijns-ggz.

BACKGROUND: In 2012 patients were required to make a personal financial contribution for secondary mental health care over and above their standard insurance fee. According to current guidelines, the majority of patients with bipolar disorder must be treated as outpatients at psychiatric clinics. It was to be expected that some patients would decide to discontinue their outpatient treatment on account of the newly imposed personal financial contribution. AIM: To obtain insight into the size and characteristics of the group of patients with bipolar disorder who were thinking about giving up treatment or had already decided to give it up because of the imposition of the personal financial contribution; also to find out which factors influenced patients' decisions and to discover how patients perceived the role of the GP as the provider of subsequent psychiatric care. METHOD: We conducted an exploratory study by sending a survey to all outpatients receiving treatment at three clinics specialising in the treatment of bipolar disorder. RESULTS: 640 patients responded to the survey (55% response); 15% of these patients were thinking about giving up treatment or had already decided to stop their treatment. They were influenced primarily by financial considerations. Two-thirds of the respondents did not consider that the GP was as a suitable alternative to outpatient care at a clinic. Even patients with moderate to serious symptoms were considering leaving secondary care. CONCLUSION: The obligatory financial contribution for secondary mental health care could have considerable consequences for a small number of patients with severe mood disorder who are currently treated as outpatients in secondary facilities. The increase in the compulsory & squo;own risk' insurance fee as from 2013 could have similar consequences.