Discontinuation of psychotropic medication: a synthesis of evidence across medication classes.

Pharmacotherapy is an effective treatment modality across psychiatric disorders. Nevertheless, many patients discontinue their medication at some point. Evidence-based guidance for patients, clinicians, and policymakers on rational discontinuation strategies is vital to enable the best, personalized treatment for any given patient. Nonetheless, there is a scarcity of guidelines on discontinuation strategies. In this perspective, we therefore summarize and critically appraise the evidence on discontinuation of six major psychotropic medication classes: antidepressants, antipsychotics, benzodiazepines, mood stabilizers, opioids, and stimulants. For each medication class, a wide range of topics pertaining to each of the following questions are discussed: (1) Who can discontinue (e.g., what are risk factors for relapse?); (2) When to discontinue (e.g., after 1 year or several years of antidepressant use?); and (3) How to discontinue (e.g., what's the efficacy of dose reduction compared to full cessation and interventions to mitigate relapse risk?). We thus highlight how comparing the evidence across medication classes can identify knowledge gaps, which may pave the way for more integrated research on discontinuation.

Accelerated brain aging as a biomarker for staging in bipolar disorder: an exploratory study.

BACKGROUND: Two established staging models outline the longitudinal progression in bipolar disorder (BD) based on episode recurrence or inter-episodic functioning. However, underlying neurobiological mechanisms and corresponding biomarkers remain unexplored. This study aimed to investigate if global and (sub)cortical brain structures, along with brain-predicted age difference (brain-PAD) reflect illness progression as conceptualized in these staging models, potentially identifying brain-PAD as a biomarker for BD staging. METHODS: In total, 199 subjects with bipolar-I-disorder and 226 control subjects from the Dutch Bipolar Cohort with a high-quality T1-weighted magnetic resonance imaging scan were analyzed. Global and (sub)cortical brain measures and brain-PAD (the difference between biological and chronological age) were estimated. Associations between individual brain measures and the stages of both staging models were explored. RESULTS: A higher brain-PAD (higher biological age than chronological age) correlated with an increased likelihood of being in a higher stage of the inter-episodic functioning model, but not in the model based on number of mood episodes. However, after correcting for the confounding factors lithium-use and comorbid anxiety, the association lost significance. Global and (sub)cortical brain measures showed no significant association with the stages. CONCLUSIONS: These results suggest that brain-PAD may be associated with illness progression as defined by impaired inter-episodic functioning. Nevertheless, the significance of this association changed after considering lithium-use and comorbid anxiety disorders. Further research is required to disentangle the intricate relationship between brain-PAD, illness stages, and lithium intake or anxiety disorders. This study provides a foundation for potentially using brain-PAD as a biomarker for illness progression.

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.

Feasibility and Acceptability of Group Interpersonal and Social Rhythm Therapy for Recurrent Mood Disorders: A Pilot Study.

OBJECTIVE: Interpersonal and social rhythm therapy (IPSRT) was developed to empower patients with mood disorders by stabilizing underlying disturbances in circadian rhythms and by using strategies from interpersonal psychotherapy. Group IPSRT has not been studied with a transdiagnostic sample of patients across the life span with either major depressive disorder or bipolar disorder. METHODS: Thirty-eight outpatients, ages 26-80, with major depressive disorder or bipolar disorder in any mood state were recruited from clinics in the Netherlands and were treated with 20 sessions (two per week) of group IPSRT. Recruitment results, dropout rates, and session adherence were used to assess feasibility. The modified Client Satisfaction Questionnaire (CSQ) and a feedback session were used to measure treatment acceptability. Changes in mood symptoms, quality of life, and mastery were also measured. RESULTS: Participants' mean±SD age was 65.4±10.0 years. Participants were diagnosed as having major depressive disorder (N=14, 37%) or bipolar disorder (N=24, 63%). The dropout rate was relatively low (N=9, 24%). High CSQ scores (32.3±5.2 of 44.0 points) and low dropout rates indicated the acceptability and feasibility of group IPSRT for major depressive disorder and bipolar disorder. Quality of life 3 months after completion of treatment was significantly higher than at baseline (p<0.01, Cohen's d=-0.69). No significant differences were found between pre- and postintervention depressive symptom scores. CONCLUSIONS: Twice-weekly group IPSRT for older outpatients with major depressive disorder or bipolar disorder was feasible and acceptable. Future research should evaluate the short- and long-term efficacy of group IPSRT for major depressive disorder and bipolar disorder among patients of all ages.

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.

A multicomponent positive psychology intervention for euthymic patients with bipolar disorder to improve mental well-being and personal recovery: A pragmatic randomized controlled trial.

OBJECTIVE: Mental well-being and personal recovery are important treatment targets for patients with bipolar disorder (BD). The goal of this study was to evaluate the effectiveness of an 8-week group multicomponent positive psychology intervention (PPI) for euthymic patients with BD as an adjunct to treatment as usual (TAU) compared to TAU alone. METHODS: Patients with BD were randomized to receive TAU (n = 43) or the PPI in addition to TAU (n = 54). The primary outcome was well being measured with the Mental Health Continuum-Short Form. Personal recovery was measured with the Questionnaire about the Process of Recovery. Data were collected at baseline, mid-treatment, post-treatment and 6- and 12-month follow-up. Life chart interviews were conducted at 12 months to retrospectively assess recurrence of depression and mania. RESULTS: Significant group-by-time interaction effects for well-being and personal recovery were found favouring the PPI. At post-treatment, between-group differences were significant for well-being (d = 0.77) and personal recovery (d = 0.76). Between-group effects for well-being were still significant at 6-month follow-up (d = 0.72). Effects on well-being and personal recovery within the intervention group were sustained until 12-month follow-up. Survival analyses showed no significant differences in time to recurrence. CONCLUSIONS: The multicomponent PPI evaluated in this study is effective in improving mental well-being and personal recovery in euthymic patients with BD and would therefore be a valuable addition to the current treatment of euthymic BD patients. The fact that the study was carried out in a pragmatic RCT demonstrates that this intervention can be applied in a real-world clinical setting.

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.

Bipolar I and bipolar II subtypes in older age: Results from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) project.

OBJECTIVES: The distinction between bipolar I disorder (BD-I) and bipolar II disorder (BD-II) has been a topic of long-lasting debate. This study examined differences between BD-I and BD-II in a large, global sample of OABD, focusing on general functioning, cognition and somatic burden as these domains are often affected in OABD. METHODS: Cross-sectional analyses were conducted with data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) database. The sample included 963 participants aged ≥50 years (714 BD-I, 249 BD-II). Sociodemographic and clinical factors were compared between BD subtypes including adjustment for study cohort. Multivariable analyses were conducted with generalized linear mixed models (GLMMs) and estimated associations between BD subtype and (1) general functioning (GAF), (2) cognitive performance (g-score) and (3) somatic burden, with study cohort as random intercept. RESULTS: After adjustment for study cohort, BD-II patients more often had a late onset ≥50 years (p = 0.008) and more current severe depression (p = 0.041). BD-I patients were more likely to have a history of psychiatric hospitalization (p < 0.001) and current use of anti-psychotics (p = 0.003). Multivariable analyses showed that BD subtype was not related to GAF, cognitive g-score or somatic burden. CONCLUSION: BD-I and BD-II patients did not differ in terms of general functioning, cognitive impairment or somatic burden. Some clinical differences were observed between the groups, which could be the consequence of diagnostic definitions. The distinction between BD-I and BD-II is not the best way to subtype OABD patients. Future research should investigate other disease specifiers in this population.

Clinical profiles of subsequent stages in bipolar disorder: Results from the Dutch Bipolar Cohort.

INTRODUCTION: The manifestation of bipolar disorder (BD) is hypothesized to be determined by clinical characteristics such as familial loading, childhood abuse, age at onset, illness duration, comorbid psychiatric disorders, addiction, treatment resistance, and premorbid cognitive functioning. Which of these are associated with a more severe course and worse outcome is currently unknown. Our objective is to find a combination of clinical characteristics associated with advancement to subsequent stages in two clinical staging models for BD. METHODS: Using cross-sectional data from the Dutch Bipolar Cohort, staging was applied to determine the progression of bipolar-I-disorder (BD-I; N = 1396). Model A is primarily defined by recurrence of mood episodes, ranging from prodromal to chronicity. Model B is defined by level of inter-episodic functioning, ranging from prodromal to inability to function autonomously. For both models, ordinal logistic regression was conducted to test which clinical characteristics are associated with subsequent stages. RESULTS: For model A, familial loading, childhood abuse, earlier onset, longer illness duration, psychiatric comorbidity, and treatment resistance were all predictors for a higher stage in contrast to addiction and cognitive functioning. For model B, childhood abuse, psychiatric comorbidity, cognitive functioning, and treatment resistance were predictors for a more severe stage, whereas age at onset, illness duration, and addiction were not. DISCUSSION/CONCLUSIONS: Differences in clinical characteristics across stages support the construct validity of both staging models. Characteristics associated with a higher stage largely overlapped across both models. This study is a first step toward determining different clinical profiles, with a corresponding course and outcome.

Is social functioning in older age patients with bipolar disorder associated with affective and/or non-affective cognition?

OBJECTIVES: Previous research showed impairments in non-affective cognition, affective cognition, and social functioning in adult patients with bipolar disorder (BD). Only 37% of adult BD patients recovers in social functioning, and both aspects of cognition are important constructs of influence. The role of affective cognition in older age bipolar disorder (OABD) patients is still unclear. Therefore, the aim of our study was to examine the separate and combined effects of affective cognition and non-affective cognition on social functioning. METHODS: The current study included 60 euthymic patients (aged >60) of the Dutch Older Bipolar Study. Affective cognition was measured by Theory of Mind and Emotion Recognition. Non-affective cognition was assessed through the measurements of attention, learning and memory, and executive functioning. Social functioning was examined through global social functioning, social participation, and meaningful contacts. The research questions were tested with linear and ordinal regression analyses. RESULTS: Results showed a positive association of all non-affective cognitive domains with global social functioning. Associations between affective cognition and social functioning were non-significant. Results did show an interaction between non-affective and affective cognition. CONCLUSIONS: Associations between non-affective cognition and social functioning were confirmed, associations between affective cognition and social function were not found. For generalizability, studies with a greater sample size are needed. Conducting additional research about OABD patients and affective cognition is important. It may lead to more insight in impairment and guide tailored treatment that focusses more on all aspects of recovery and the needs of OABD patients.

Illness progression in older-age bipolar disorder: Exploring the applicability, dispersion, concordance, and associated clinical markers of two staging models for bipolar disorder in an older population.

OBJECTIVES: The validity and applicability of two existing staging models reflecting illness progression have been studied in bipolar disorder (BD) in adults, but not in older adult populations. Staging model A is primarily defined by the number and recurrence of mood episodes, model B is defined by the level of inter-episodic functioning. This study aimed to explore the applicability, dispersion, and concordance of, and associations with clinical markers in these two staging models in older-age bipolar disorder (OABD). METHODS: Using cross-sectional data from the Dutch Older Bipolars study, OABD outpatients (N = 126, ≥50 years) were staged using models A and B. Dispersion over the stages and concordance between the models were assessed. Associations were explored between model stages and clinical markers (familial loading, childhood abuse, illness duration, episode density, treatment resistance, Mini-Mental State Examination, and composite cognitive score). RESULTS: Ninety subjects could be assigned to model A, 111 to model B, 80 cases to both. The majority (61%) had multiple relapses (model A, stage 3C) but were living independently (model B, stage I-III). Concordance between models was low. For model A, the markers childhood abuse, illness duration, and episode density significantly increased over subsequent stages. Model B was not associated with a significant change in any marker. CONCLUSIONS: Assigning stages to OABD subjects was possible for both models, with age-related adjustments for model B. Model B as currently operationalized may be less suitable for OABD or may measure different aspects of illness progression, reflected by its low correspondence with model A and lack of associated clinical markers.

Consensus on nomenclature for clinical staging models in bipolar disorder: A narrative review from the International Society for Bipolar Disorders (ISBD) Staging Task Force.

OBJECTIVES: Clinical staging is widely used in medicine to map disease progression, inform prognosis, and guide treatment decisions; in psychiatry, however, staging remains a hypothetical construct. To facilitate future research in bipolar disorders (BD), a well-defined nomenclature is needed, especially since diagnosis is often imprecise with blurred boundaries, and a full understanding of pathophysiology is lacking. METHODS: Under the auspices of the International Society of Bipolar Disorders, a Task Force of international experts was convened to review, discuss, and integrate findings from the scientific literature relevant to the development of a consensus staging model and standardize a terminology that could be used to advance future research including staging of BD and related disorders. RESULTS: Consensus opinion and areas of uncertainty or difference were identified in regard to terms referring to staging as it may apply to BD, to at-risk status and subthreshold stages, and to various clinical stages of BD as it is currently diagnosed. CONCLUSION: The use of a standardized nomenclature about the clinical stages of BD will facilitate communication about research on clinical and pathological components of this heterogeneous group of disorders. The concepts presented are based on current evidence, but the template provided allows for further refinements as etiological advances come to light.

Cognitive performance in older-age bipolar disorder: Investigating psychiatric characteristics, cardiovascular burden and psychotropic medication.

OBJECTIVE: This study aimed to explore a large range of candidate determinants of cognitive performance in older-age bipolar disorder (OABD). METHODS: A cross-sectional study was performed in 172 BD patients aged ≥50 years. Demographics, psychiatric characteristics and psychotropic medication use were collected using self-report questionnaires and structured interviews. The presence of cardiovascular risk factors was determined by combining information from structured interviews, physical examination and laboratory assessments. Cognitive performance was investigated by an extensive neuropsychological assessment of 13 tests, covering the domains of attention, learning/ memory, verbal fluency and executive functioning. The average of 13 neuropsychological test Z-scores resulted in a composite cognitive score. A linear multiple regression model was created using forward selection with the composite cognitive score as outcome variable. Domain cognitive scores were used as secondary outcome variables. RESULTS: The final multivariable model (N = 125), which controlled for age and education level, included number of depressive episodes, number of (hypo)manic episodes, late onset, five or more psychiatric admissions, lifetime smoking, metabolic syndrome and current use of benzodiazepines. Together, these determinants explained 43.0% of the variance in composite cognitive score. Late onset and number of depressive episodes were significantly related to better cognitive performance whereas five or more psychiatric admissions and benzodiazepine use were significantly related to worse cognitive performance. CONCLUSION: Psychiatric characteristics, cardiovascular risk and benzodiazepine use are related to cognitive performance in OABD. Cognitive variability in OABD thus seems multifactorial. Strategies aimed at improving cognition in BD should include cardiovascular risk management and minimizing benzodiazepine use.

Psychiatric symptoms during the COVID-19 outbreak in older adults with bipolar disorder.

OBJECTIVES: Older adults with bipolar disorder (OABD) are vulnerable for a COVID-19 infection via multiple pathways. It is essential for OABD to adhere to the COVID-19 measures, with potential consequences for the psychiatric symptoms. This situation offers the unique opportunity to investigate factors of vulnerability and resilience that are associated with psychiatric symptoms in OABD. METHODS: This study included 81 OABD patients aged over 50 years. Factors measured at baseline in patients that participated in 2017/2018 were compared with factors measured during the COVID-19 outbreak. RESULTS: Participants experienced less psychiatric symptoms during COVID-19 than (67.9% euthymic) than at baseline (40.7% euthymic). There was no difference in loneliness between COVID-19 and baseline. Not having children, more feelings of loneliness, lower mastery, passive coping style and neuroticism were associated with more psychiatric symptoms during COVID-19 measures. CONCLUSIONS: Participants experienced less psychiatric symptoms during COVID-19 measures when compared to baseline. Our results indicate promising targets for psychological interventions aimed at curing and preventing recurrence in OABD and improving quality of life in this growing vulnerable group.

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.

Exploring the clinical utility of two staging models for bipolar disorder.

OBJECTIVE: To assess the clinical utility of two staging models for bipolar disorder by examining distribution, correlation, and the relationship to external criteria. These are primarily defined by the recurrence of mood episodes (model A), or by intra-episodic functioning (model B). METHODS: In the Dutch Bipolar Cohort, stages according to models A and B were assigned to all patients with bipolar-I-disorder (BD-I; N = 1396). The dispersion of subjects over the stages was assessed and the association between the two models calculated. For both models, change in several clinical markers were concordant with the stage was investigated. RESULTS: Staging was possible in 87% of subjects for model A and 75% for model B. For model A, 1079 participants (93%) were assigned to stage 3c (recurrent episodes). Subdividing stage 3c with cut-offs at 5 and 10 episodes resulted in subgroups containing 242, 510, and 327 subjects. For model B, most participants were assigned to stage II (intra-episodic symptoms, N = 431 (41%)) or stage III (inability to work, N = 451 (43%)). A low association between models was found. For both models, the clinical markers "age at onset," "treatment resistance," and "episode acceleration" changed concordant with the stages. CONCLUSION: The majority of patients with BD-I clustered in recurrent stage 3 of Model A. Model B showed a larger dispersion. The stepwise change in several clinical markers supports the construct validity of both models. Combining the two staging models and sub-differentiating the recurrent stage into categories with cut-offs at 5 and 10 lifetime episodes improves the clinical utility of staging for individual patients.

More assortative mating in US compared to European parents and spouses of patients with bipolar disorder: implications for psychiatric illness in the offspring.

The effect of assortative mating on offspring is often not considered. Here, we present data on illness in the spouse and the parents of patients with bipolar disorder as they affect illness in the offspring. A history of psychiatric illness (depression, bipolar disorder, suicide attempt, alcohol abuse, drug abuse, and "other" illness) was elicited for the parents, spouse, and the offspring of 968 patients with bipolar disorder (540 of whom had children) who gave informed consent for participation in a treatment outcome network. Assortative mating for a mood disorder in the spouse and parents in those from the United States (US) was compared to those from the Netherlands and Germany and related to illnesses in the offspring. There was more illness and assortative mating for a mood disorder in both the spouse and patient's parents from the US compared to Europe. In the parents of the US patients, assortative mating for a mood disorder was associated with more depression, bipolar disorder, alcohol, and "other" illness in the offspring. Compared to the Europeans, there was more assortative mating for mood and other disorders in two generations of those from the US. This bilineal positivity for a parental mood disorder was related to more depression a second generation later in the patients' offspring. In clinical assessment of risk of illness in the offspring, the history of psychiatric illness in the spouse and patient's parents might provide additional information.

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.

What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium.

AIMS: To systematically review the existing trials on optimal serum levels for lithium for maintenance treatment of bipolar disorder and to develop clinical recommendations. METHODS: Systematic literature search. Discussion of major characteristics, limitations, methodological quality, and results of selected trials. Delphi survey consisting of clinical questions and corresponding statements. For statements endorsed by at least 80% of the members, consensus was considered as having been achieved. RESULTS: With strict inclusion criteria no studies could be selected, making it difficult to formulate evidence-based recommendations. After loosening the inclusion criteria 7 trials were selected addressing our aims at least to some extent. Four of these studies suggest better efficacy being associated with lithium serum levels in a range above a lower threshold around 0.45/0.60 and up to 0.80/1.00 mmol/L. These findings support the outcome of the Delphi survey. CONCLUSIONS: For adults with bipolar disorder there was consensus that the standard lithium serum level should be 0.60-0.80 mmol/L with the option to reduce it to 0.40-0.60 mmol/L in case of good response but poor tolerance or to increase it to 0.80-1.00 mmol/L in case of insufficient response and good tolerance. For children and adolescents there was no consensus, but the majority of the members endorsed the same recommendation. For the elderly there was also no consensus, but the majority of the members endorsed a more conservative approach: usually 0.40-0.60 mmol/L, with the option to go to maximally 0.70 or 0.80 mmol/L at ages 65-79 years, and to maximally 0.70 mmol/L over age 80 years.