Shifting Perspectives on the Challenges of Shared Decision Making in Mental Health Care.

Although shared decision making (SDM) has become the most preferable way in doctor-patient communication, it is not fully implemented in mental health care likely due to the complex nature of psychiatric syndromes and treatments. In this review we provide a systematic overview of all perceived and reported barriers to SDM in the literature, acknowledging field-specific challenges, and offering perspectives to promote its wider use. We conducted a systematic search of the wider literature in different databases and included all publications mentioning specified barriers to SDM in psychiatric care. Relevant data and opinions were categorised into micro-, meso- and macro-level themes and put into clinical perspective. We derived 20 barriers to SDM from 100 studies and reports. Eight were on micro-level care delivery, seven involved meso-level issues, five concerned macro-level themes. The multitude of perceived and actual barriers to SDM underline the challenges its implementation poses in mental health care, some of which can be resolved while others are inherent to the nature of the care, with its long-term relationships, complex dynamics, and social consequences, all requiring a flexible approach. We present four perspectives to help change views on the potential of SDM in mental health care.

Longitudinal clinical and functional outcome in distinct cognitive subgroups of first-episode psychosis: a cluster analysis.

BACKGROUND: Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes. METHODS: 204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up. RESULTS: Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present. CONCLUSIONS: Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

Concurrent lithium and haemodialysis treatment: Clinical recommendations based on the literature and a multicentre survey.

INTRODUCTION: Lithium has an irreplaceable role in the treatment of severe mood disorders, but declining renal function associated with its use leads to clinical dilemmas. Although not often applied, and requiring close monitoring and multidisciplinary actions, concurrent lithium and haemodialysis treatment (CLHT) is a feasible option. To our knowledge, however, there are no detailed consensus- or evidence-based treatment guidelines or directives on its delivery. METHODS: To fill this gap, we reviewed the literature and surveyed psychiatrists and nephrologists with experience in CLHT using a self-designed questionnaire. Our goal was to form an integrated picture of the current knowledge and clinical practices of CLHT and formulate practical recommendations for colleagues being confronted with patients with renal dysfunction requiring lithium to help manage their mood disorder. RESULTS: We identified 14 case reports and case series describing CLHT and one systematic review concluding CLHT to be effective. Ten nephrologists and six psychiatrists practising in the Netherlands completed our questionnaire, providing details on collaboration, lithium dosing regimens, serum level evaluations and additional amenities and services they deemed necessary during CLHT delivery. DISCUSSION: We found that CLHT appears to be safe and effective and argue that delivery is a shared responsibility and needs continuous multidisciplinary finetuning. To facilitate delivery, we provide a flowchart for the initiation or reinstatement of lithium therapy in haemodialysis patients and a practical guide for CLHT, including an easy-to-use rule of thumb for calculating the lithium target dose.

Body weight gain in clozapine-treated patients: Is norclozapine the culprit?

The antipsychotic drug clozapine is associated with weight gain. The proposed mechanisms include blocking of serotonin (5-HT2a/2c ), dopamine (D2 ) and histamine (H1 ) receptors. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2) to norclozapine, a metabolite with more 5-HT2c -receptor and less H1 blocking capacity. We hypothesized that norclozapine serum levels correlate with body mass index (BMI), waist circumference and other parameters of the metabolic syndrome. We performed a retrospective cross-sectional study in 39 patients (female n = 8 (20.5%), smokers n = 18 (46.2%), average age 45.8 ± 9.9 years) of a clozapine outpatient clinic in the Netherlands between 1 January 2017 and 1 July 2020. Norclozapine concentrations correlated with waist circumference (r = 0.354, P = .03) and hemoglobin A1c (HbA1c) (r = 0.34, P = .03). In smokers (smoking induces CYP1A2), norclozapine concentrations correlated with waist circumference (r = 0.723, P = .001), HbA1c (r = 0.49, P = .04) and BMI (r = 0.63, P = .004). Elucidating the relationship between norclozapine and adverse effects of clozapine use offers perspectives for interventions and treatment options.

On the use of positive test strategies when diagnosing mental disorders.

BACKGROUND: Despite the adverse impact diagnostic errors can have, clinical interviewing and decision-making in psychiatric practice have received relatively little empirical attention. When diagnosing patients, clinicians tend to fall back on a specific (heuristic) rule of thumb, the positive test strategy, a confirmatory approach that increases the risk of confirmation bias. METHOD AND RESULTS: A group of 83 clinical psychologists and psychiatrists was asked to give their diagnostic hypotheses about two vignettes. We found them to self-generate significantly (i.e., p < .01; d = 1.57) more confirming than disconfirming questions to test their initial diagnostic impressions, with supervisors considering significantly more differential diagnoses than the less experienced post-grads/residents. When offered a list of 100 potentially relevant diagnostic queries, the supervisors selected fewer confirming and proportionally more disconfirming themes. CONCLUSIONS: Our results demonstrate that irrespective of clinical experience mental-health clinicians indeed tend to use a confirmatory thinking style that contrasts with the stricter principle of falsification. More field-based research on this topic is needed, as well as studies probing whether a systematized diagnostic approach is feasible in psychiatric practice and increases diagnostic accuracy and patient satisfaction.

Inhibition of CYP2D6 with low dose (5 mg) paroxetine in patients with high 10-hydroxynortriptyline serum levels-A prospective pharmacokinetic study.

The antidepressant nortriptyline is metabolized by cytochrome P450 2D6 (CYP2D6) to the less active and more cardiotoxic drug metabolite, 10-hydroxynortriptyline. High serum levels of this metabolite (>200 µg/L) may lead to withdrawal of nortriptyline therapy. Adding CYP2D6 inhibitors reduce the metabolic activity of CYP2D6 (phenoconversion) and so decrease the forming of hydroxynortriptyline. In this study, 5 mg paroxetine is administered to patients with high hydroxynortriptyline concentrations (>200 µg/L). The shift in number of patients to therapeutic nortriptyline (50-150 µg/L) and safe hydroxynortriptyline (<200 µg/L) concentrations, and the degree of phenoconversion, expressed as the change in ratio nortriptyline/hydroxynortriptyline concentrations before and after paroxetine addition, are prospectively observed and described. After paroxetine addition, 12 patients (80%) had therapeutic nortriptyline and safe hydroxynortriptyline concentrations. Hydroxynortriptyline concentrations decreased in all patients. The average nortriptyline/hydroxynortriptyline concentrations ratio increased from 0.32 to 0.59. This study shows that 5 mg paroxetine addition is able to lower high hydroxynortriptyline serum levels to safe ranges.

The Incidence of Post-Electroconvulsive Therapy Headache: A Systematic Review.

Headache is a common side effect of electroconvulsive therapy (ECT), but reports on its incidence vary widely. A broad array of treatment regimens have been proposed in the literature. The pathophysiology of post-ECT headache is unclear but a vascular origin has been suggested. A systematic literature search was executed in PubMed and Embase to identify relevant articles. Articles were screened on title, abstract, and full text according to predefined inclusion and exclusion criteria. Study characteristics and results concerning the incidence of post-ECT headache were extracted, and a weighted mean incidence was calculated. Forty-seven relevant articles were found, of which 36 reported on the incidence of post-ECT headache in patients and 9 on the incidence in sessions. The incidence of post-ECT headache varied greatly in the literature. The weighted mean incidence in patients was 32.8%, as 786 of a total population of 2399 patients experienced headache. The weighted mean incidence in sessions was between 9.4% (246 of 2604 sessions) and 12.1% (236/1958 sessions). The variation in incidences of post-ECT headache found might be due to different methods of measuring headache, different study designs, and different drugs used for anesthesia. The mean-weighted incidence of post-ECT headache in patients was 32.8% and in sessions between 9.4% and 12.1%.

Weight changes associated with antiepileptic mood stabilizers in the treatment of bipolar disorder.

OBJECTIVE: To present up-to-date information and recommendations on the management of body weight changes during the use of antiepileptic mood stabilizers in bipolar disorder to help clinicians and patients make well-informed, practical decisions. DATA SOURCES: Umbrella review. Systematic reviews and meta-analyses on the prevention, treatment, and monitoring of body weight changes as a side effect of the mood stabilizers valproate, lamotrigine, topiramate, and carbamazepine were identified in Embase (2010-2015, no language restrictions). STUDY SELECTION: The search yielded 18 relevant publications on antiepileptic mood stabilizers and weight changes in bipolar disorder. DATA EXTRACTION: Relevant scientific evidence was abstracted and put into a clinical perspective by a multidisciplinary expert panel of clinicians with expertise in the treatment of bipolar disorders across all age groups and a patient representative. RESULTS: Valproate has been proven to be associated with weight gain in up to 50% of its users, and can be detected 2-3 months after initiation. Carbamazepine has been proven to have a low risk of weight gain. Lamotrigine and topiramate are associated with weight loss. Other option for this sentence = Weigth gain has been proven to be associated with valproate use in up to 50% of its users, and can be detected within 2-3 months after initiation. CONCLUSION: Each antiepileptic mood stabilizer has specific effects on body weight and accordingly requires a discrete education, prevention, monitoring, and treatment strategy. Clinicians are recommended to adopt an active, anticipatory approach, educating patients about weight change as an important side effect in order to come to informed shared decisions about the most suitable mood stabilizer.

Correction to: Weight changes associated with antiepileptic mood stabilizers in the treatment of bipolar disorder.

In the original version of this article unfortunately two tables have been missing. By mistake they have been published as Supplementary Material. We apologize for any inconvenience caused. The original article has been corrected.

The Direct and Long-Term Effects of Raloxifene as Adjunctive Treatment for Schizophrenia-Spectrum Disorders: A Double-Blind, Randomized Clinical Trial.

BACKGROUND AND HYPOTHESIS: Several studies suggest that raloxifene, a selective estrogen receptor modulator, improves symptoms and cognition in post-menopausal women with Schizophrenia-Spectrum Disorders (SSD). We aimed to assess the effects of adjunctive raloxifene in women and men with SSD. STUDY DESIGN: This parallel, randomized, double-blind, placebo-controlled trial included adult SSD patients across the Netherlands and Belgium. Participants were stratified by age, sex, and global functioning and randomly assigned 1:1 to 12-week add-on raloxifene or placebo. Primary outcomes were symptom severity at 6, 12, and 38 weeks and cognition at 12 and 38 weeks, as measured with the Positive and Negative Syndrome Scale and the Brief Assessment of Cognition in Schizophrenia, respectively. Intention-to-treat analyses were performed using linear mixed-effect models. STUDY RESULTS: We assessed 261 patients for eligibility, of which 102 (28% female) were assigned to raloxifene (n = 52) or placebo (n = 48). Although we found no main effect of raloxifene, secondary sex-specific analysis showed that in women, raloxifene had beneficial effects on negative symptoms at week 6 (LSM -2.92; adjusted P = 0.020) and week 12 (LSM -3.12; adjusted P = 0.030), and on working memory at week 38 (LSM 0.73; adjusted P = 0.040), while having negative effects on working memory at week 38 in men (LSM -0.53; adjusted P = 0.026). The number of adverse events was similar between groups. CONCLUSIONS: Our results do not support the use of raloxifene in patients with SSD in general, but suggest female-specific beneficial effects of raloxifene on negative symptoms and working memory. Our findings encourage further research on sex-specific pharmacotherapeutic treatment.

Evaluation of a Collaborative Care Program for Patients With Treatment-Resistant Schizophrenia: Protocol for a Multiple Case Study.

BACKGROUND: Approximately one-third of all patients with schizophrenia are treatment resistant. Worldwide, undertreatment with clozapine and other effective treatment options exist for people with treatment-resistant schizophrenia (TRS). In this respect, it appears that regular health care models do not optimally fit this patient group. The Collaborative Care (CC) model has proven to be effective for patients with severe mental illness, both in primary care and in specialized mental health care facilities. The key principles of the CC model are that both patients and informal caregivers are part of the treatment team, that a structured treatment plan is put in place with planned evaluations by the team, and that the treatment approach is multidisciplinary in nature and uses evidence-based interventions. We developed a tailored CC program for patients with TRS. OBJECTIVE: In this paper, we provide an overview of the research design for a potential study that seeks to gain insight into both the process of implementation and the preliminary effects of the CC program for patients with TRS. Moreover, we aim to gain insight into the experiences of professionals, patients, and informal caregivers with the program. METHODS: This study will be underpinned by a multiple case study design (N=20) that uses a mixed methods approach. These case studies will focus on an Early Psychosis Intervention Team and 2 Flexible Assertive Community treatment teams in the Netherlands. Data will be collected from patient records as well as through questionnaires, individual interviews, and focus groups. Patient recruitment commenced from October 2020. RESULTS: Recruitment of participants commenced from October 2020, with the aim of enrolling 20 patients over 2 years. Data collection will be completed by the end of 2023, and the results will be published once all data are available for reporting. CONCLUSIONS: The research design, framed within the process of developing and testing innovative interventions, is discussed in line with the aims of the study. The limitations in clinical practice and specific consequences of this study are explained. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35336.

Barriers and facilitators for systematically registering adverse drug reactions in electronic health records: a qualitative study with Dutch healthcare professionals.

BACKGROUND: Systematically registering ADRs in electronic health records (EHRs) likely contribute to patient safety as it enables the exchange of drug safety data. Currently, ADRs registrations by healthcare professionals (HCPs) is suboptimal. This study aimed to identify barriers and facilitators perceived by HCPs to register ADRs systematically in EHRs. RESEARCH DESIGN AND METHODS: A qualitative study with individual interviews was conducted among specialist physicians and hospital pharmacists from 10 different Dutch hospitals. A semi-structured interview guide was used to identify experienced barriers and facilitators for systematically registering ADRs. Data was analyzed following thematic analysis. Themes within barriers and facilitators were aligned with the Capability-Opportunity-Motivation-Behavior (COM-B) framework. RESULTS: In total, 16 HCPs were interviewed. Identified barriers were: lack of knowledge to recognize ADRs, time constraints, inadequate IT system, lack of support, stuck in routine, and not recognizing the importance of registering ADRs. Identified facilitators were: enhanced knowledge and awareness of ADRs, functional IT systems, expanding accountability for registration, and motivation toward registering. CONCLUSIONS: Barriers and facilitators for registering spanned all aspects of the COM-B model and occurred in individual, social and environmental domains. Addressing these aspects could improve the registration of ADRs and may contribute to patient safety.

Simvastatin Augmentation for Patients With Early-Phase Schizophrenia-Spectrum Disorders: A Double-Blind, Randomized Placebo-Controlled Trial.

Schizophrenia-spectrum disorders (SSD) are associated with increased inflammatory markers, both in brain and periphery. Augmentation with drugs that lower this pro-inflammatory status may improve clinical presentation. Simvastatin crosses the blood-brain barrier, has anti- inflammatory and neuroprotective effects and reduces metabolic syndrome. In this study, we investigated if 12 months of simvastatin augmentation can improve symptoms and cognition in patients with early SSD. This double-blind placebo-controlled trial included 127 SSD patients across the Netherlands, <3 years after their diagnosis. From these, 119 were randomly assigned 1:1 to simvastatin 40 mg (n = 61) or placebo (n = 58), stratified for sex and study site. Primary outcomes were symptom severity and cognition after 12 months of treatment. Depression, symptom subscores, general functioning, metabolic syndrome, movement disorders, and safety were secondary outcomes. Intention to treat analyses were performed using linear mixed models and ANCOVA. No main effect of simvastatin treatment was found on total symptom severity after 12 months of treatment as compared to placebo (X2(1) = 0.01, P = .90). Group differences varied over time (treatment*time X2(4) = 11.2; P = .025), with significantly lower symptom severity in the simvastatin group after 6 months (mean difference = -4.8; P = .021; 95% CI: -8.8 to -0.7) and at 24 months follow-up (mean difference = -4.7; P = .040; 95% CI: -9.3 to -0.2). No main treatment effect was found for cognition (F(1,0.1) = 0.37, P = .55) or secondary outcomes. SAEs occurred more frequently with placebo (19%) than with simvastatin (6.6%). This negative finding corroborates other large scale studies on aspirin, minocycline, and celecoxib that could not replicate positive findings of smaller studies, and suggests that anti-inflammatory augmentation does not improve the clinical presentation of SSD.

Systematic review and practical guideline for the prevention and management of the renal side effects of lithium therapy.

Lithium is the first line therapy of bipolar mood disorder. Lithium-induced nephrogenic diabetes insipidus (Li-NDI) and lithium nephropathy (Li-NP, i.e., renal insufficiency) are prevalent side effects of lithium therapy, with significant morbidity. The objective of this systematic review is to provide an overview of preventive and management strategies for Li-NDI and Li-NP. For this, the PRISMA guideline for systematic reviews was used. Papers on the prevention and/or treatment of Li-NDI or Li-NP, and (influenceable) risk factors for development of Li-NDI or Li-NP were included. We found that the amount of evidence on prevention and treatment of Li-NDI and Li-NP is scarce. To prevent Li-NDI and Li-NP we advise to use a once-daily dosing schedule, target the lowest serum lithium level that is effective and prevent lithium intoxication. We emphasize the importance of monitoring for Li-NDI and Li-NP, as early diagnosis and treatment can prevent further progression and permanent damage. Collaboration between psychiatrist, nephrologist and patients themselves is essential. In patients with Li-NDI and/or Li-NP cessation of lithium therapy and/or switch to another mood stabilizer should be considered. In patients with Li-NDI, off label therapy with amiloride can be useful.

Raloxifene augmentation in men and women with a schizophrenia spectrum disorder: A study protocol.

Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered.

To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial.

BACKGROUND: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition-a finding that was not replicated in another recently published long-term study. METHODS/DESIGN: The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3-6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years. DISCUSSION: The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse. TRIAL STATUS: Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026. TRIAL REGISTRATION: European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 June 2017.

Psychomotor planning is deficient in recent-onset schizophrenia.

BACKGROUND: Psychomotor slowing is regarded as an important clinical phenomenon in schizophrenia and simple graphic tasks consistently revealed deficits in the (implicit) planning and execution of motor actions in patients with chronic schizophrenia. The aim of the present study is to test the hypothesis that such deficits are already present in patients with recent-onset schizophrenia. METHODS: Psychomotor performance and several aspects of movement planning were analyzed in 36 patients with recent-onset schizophrenia and a group of 33 matched healthy controls. Participants were required to draw patterns varying in complexity in three different figure-copying tasks, match and draw simple symbols in the Digit Symbol Substitution Test (DSST) and connect target circles with varying orientations in a newly developed Line Sequencing Task. RESULTS: Relative to the controls, the patients showed significantly longer initiation times when the patterns in the copying tasks became more complex, suggesting increased difficulty in movement planning. Overall, they were not slowed in the execution stages. In the cognitively more demanding DSST, the patients were significantly slowed in both the initiation and movement phases. Moreover, they selected less optimal movement directions in the Line Sequencing Task. CONCLUSIONS: Psychomotor planning deficits are already present in the early stages of schizophrenia and involve deficient planning but intact motor action. Planning difficulties can be detected in motor sequences as well. The results indicate that the cognitive deficit in schizophrenia also affects the implicit planning of very simple movements.