Autism in adult psychiatric out-patients: self-reported suicidal ideation, suicide attempts and non-suicidal self-injury.

BACKGROUND: The prevalence of self-reported suicidal ideation, suicide attempts and non-suicidal self-injury (NSSI) remains unclear among adults with autism unrecognised in childhood who attend psychiatric services. AIMS: We aimed to estimate the prevalence of suicidal ideation, suicide attempts and NSSI; identify factors associated with suicide attempts and NSSI; and describe NSSI in this group. METHOD: Sixty-three new patients at an adult psychiatric out-patient clinic (57% women, mean age 32 years) who met full (n = 52) or subthreshold (two A criteria and minimum of two B criteria; n = 11) DSM-5 criteria for autism spectrum disorder were included in the study. Clinical assessments included overall diagnostic review, Paykel's questions on passive and active suicidality, evaluation of NSSI with the Functional Assessment of Self-Mutilation, and results of cognitive tests. One follow-up of medical records was made. RESULTS: In this sample of psychiatric out-patients identified as first having autism in adulthood, almost a third (31%) of patients reported suicidal ideation during the past month, 86% had lifetime suicidal ideation and 25% reported at least one suicide attempt. Factors associated with suicide attempts included hazardous or harmful alcohol use and/or drug-related problems, and severity of depression. A total of 44% reported NSSI. Factors associated with NSSI were female sex, history of suicidal plans and antisocial personality disorder. Substance or alcohol use were often overlooked, especially in women. CONCLUSIONS: Suicidal ideation, suicide attempts and NSSI were very common in adults with autism who were recently referred to an out-patient psychiatric service. Suicidal ideation and NSSI were more common than suicide attempts. Clinicians should always consider suicidal ideation and NSSI in adult psychiatric patients with autism.

Sex-specific differences and similarities of olanzapine and risperidone on avoidance suppression in rats in the conditioned avoidance response test.

It is well known that antipsychotic drugs (APDs) are more effective in reducing symptoms in women than in men, and that women are more sensitive to the side effects of APDs. Therefore, it is of great importance that sex differences in drug responses are considered already in the early stages of drug development. In this study, we investigated whether sex-specific differences could be observed in response to the commonly prescribed APDs olanzapine and risperidone using the conditioned avoidance response (CAR) test. To this end we tested the effect of 1.25 and 2.5 mg/kg olanzapine and 0.25 and 0.4 mg/kg risperidone using female and male Wistar rats in the CAR test. Whereas there were no significant differences between the female and male rats in response to either dose of olanzapine administration, an injection of 0.4 mg/kg risperidone significantly suppressed avoidance more in female rats than in male rats. In addition, we found that the estrous cycle of the female rats did not have a significant effect on the avoidance response. In conclusion, we show that there are sex-specific differences as well as similarities between female and male rats in the CAR test and novel APDs should be tested on female and male rats in the future.

Economic impact of reducing treatment gaps in depression.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent across Europe. While evidence-based treatments exist, many people with MDD have their condition undetected and/or untreated. This study aimed to assess the cost-effectiveness of reducing treatment gaps using a modeling approach. METHODS: A decision-tree model covering a 27-month time horizon was used. This followed a care pathway where MDD could be detected or not, and where different forms of treatment could be provided. Expected costs pertaining to Germany, Hungary, Italy, Portugal, Sweden, and the UK were calculated and quality-adjusted life years (QALYs) were estimated. The incremental costs per QALY of reducing detection and treatment gaps were estimated. RESULTS: The expected costs with a detection gap of 69% and treatment gap of 50% were €1236 in Germany, €476 in Hungary, €1413 in Italy, €938 in Portugal, €2093 in Sweden, and €1496 in the UK. The incremental costs per QALY of reducing the detection gap to 50% ranged from €2429 in Hungary to €10,686 in Sweden. The figures for reducing the treatment gap to 25% ranged from €3146 in Hungary to €13,843 in Sweden. CONCLUSIONS: Reducing detection and treatment gaps, and maintaining current patterns of care, is likely to increase healthcare costs in the short term. However, outcomes are improved, and reducing these gaps to 50 and 25%, respectively, appears to be a cost-effective use of resources.

The 'lost generation' in adult psychiatry: psychiatric, neurodevelopmental and sociodemographic characteristics of psychiatric patients with autism unrecognised in childhood.

BACKGROUND: Patients with 'underlying' autism spectrum disorder (ASD) constitute a significant minority in adult out-patient psychiatry. Diagnoses of previously unrecognised ASD are increasing in adults. Characteristics of patients with autism within adult out-patient psychiatry have not been sufficiently explored, and there have not been any systematic comparisons of characteristics between patients with and those without autism within adult out-patient psychiatric populations. AIMS: To examine psychiatrically relevant characteristics in autistic adult psychiatric out-patients, and to compare the characteristics with non-autistic adult psychiatric out-patients. METHOD: We assessed 90 patients who were referred to a Swedish psychiatric out-patient clinic and screened for ASD during 2019-2020. Sixty-three patients met the DSM-5 criteria for ASD or 'subthreshold' ASD. The 27 who did not meet the criteria for ASD were used as a comparison group. Assessments were made with structured and well-validated instruments, including parent ratings of developmental history. RESULTS: No differences were found between the groups regarding self-reported sociodemographic variables. The ASD group showed a higher number of co-occurring psychiatric disorders than the non-ASD group (t(88) = 5.17, 95% CI 1.29-2.91, d = 1.19). Functional level was lower in the ASD group (t(88) = -2.66, 95% CI -9.46 to -1.27, d = -0.73), and was predicted by the number of co-occurring psychiatric disorders. CONCLUSIONS: The results underscore the need for thorough assessment of psychiatric disorders in autistic patients in adult psychiatric services. ASD should be considered as a possible 'underlying' condition in adult psychiatry, and there is no easy way of ruling out ASD in this population.

Resource utilization in mental illness - evaluation of an instrument for measuring direct costs of treatment for patients with severe mental illness (SMI).

PURPOSE: Serious mental illnesses (SMIs) exert a considerable financial burden on health-care systems. In this study, the resource utilization in mental illness (RUMI) tool was developed and employed to evaluate resource utilization in patients with SMI. MATERIALS AND METHODS: Data from 107 patients with SMI treated in four psychiatric outpatient clinics in Sweden were collected. The relationships between costs for physical and psychiatric care, social services, and the justice system, to self-reported health and quality of life, educational level, Global Assessment of Functioning (GAF), the Clinical Global Impressions scale score (CGI), and body mass index (BMI) were studied. RESULTS: Sixteen out of 107 patients accounted for 74% of the total costs. The mean and median cost for 6 months included in the survey for social services, family and social welfare and healthcare, psychiatric and physical treatment interventions, mean 8349 EUR, median 2599 EUR per patient (currency value for 2021). Education and psychosocial function (GAF) were both negatively correlated with costs for the social services (education, r=-0.207, p < 0.014; GAF, r=-0.258, p < 0.001). CGI was correlated with costs for physical and psychiatric healthcare (r = 0.161, p < 0.027), social services support (r = 0.245, p = 0.002) and total cost (r = 0.198, p = 0.007). BMI correlated with costs for psychiatric and physical health settings interventions (r = 0.155, p < 0.019) and for somatic and psychiatric medicines (r = 0.154, p < 0.019). CONCLUSION: The RUMI scale was acceptable and enabled estimation of resource utilization in a comparable manner across different care settings. Such comparable data have potential to provide a basis for budgeting and resource allocation.

Distal radius fractures and risk of incident neurocognitive disorders in older adults: a retrospective cohort study.

INTRODUCTION: Distal radius fractures (DRF) are associated with increased risk of subsequent fractures and physical decline in older adults. This study aims to evaluate the risk cognitive decline following DRF and potential for timely screening and intervention. METHODS: A cohort of 1046 individuals 50-75 years of age with DRF were identified between 1995 and 2015 (81.5% female; mean age 62.5 [± 7.1] years). A control group (N = 1044) without history of DRF was matched by age, sex, and fracture date (i.e., index). The incidence of neurocognitive disorders (NCD) in relation to DRF/index was determined. Group comparisons were adjusted by age and comorbidity measured by the Elixhauser index. RESULTS: The DRF group had a greater incidence of NCD compared to the control group (11.3% vs. 8.2%) with a 56% greater relative risk (HR = 1.56, 95% Cl: 1.18, 2.07; p = 0.002) after adjusting for age and comorbidity. For every 10-year age increase, the DRF group was over three times more likely to develop a NCD (HR = 3.23, 95% Cl: 2.57, 4.04; p < 0.001). CONCLUSION: DRF in adults ages 50 to 75 are associated with increased risk of developing neurocognitive disorders. DRF may represent a sentinel opportunity for cognitive screening and early intervention. Distal radius fractures (DRF) have been associated with greater risk of future fractures and physical decline. This study reports that DRF are also associated with greater risk of developing neurocognitive disorders in older adults. Timely intervention may improve early recognition and long-term outcomes for older adults at risk of cognitive decline.

Prevalence of Autism Spectrum Disorders in Adult Outpatient Psychiatry.

Relatively little has been published about the prevalence of autism in adults with psychiatric disorders. In this study, all new patients referred to an adult psychiatric outpatient clinic in Sweden between November 2019 and October 2020 (n = 562) were screened for autism spectrum disorders using the Ritvo Autism and Asperger Diagnostic Scale Screen (RAADS-14). Out of the 304 (58%) responders, 197 who scored above the cut off (14) were invited to participate in an in-depth assessment. Twenty-six of the 48 that participated in the assessment met criteria for ASD and an additional eight had subthreshold ASD symptoms. We estimated the prevalence of ASD in this population to at least 18.9%, with another 5-10% having subthreshold symptoms.

Community-Based Support and Social Services and Their Association with Frailty Factors in Older People with Intellectual Disability and Affective and Anxiety Disorders: A Swedish National Population-Based Register Study.

Affective and anxiety diagnoses are common in older people with intellectual disability (ID). The aim was to describe support and social services for older people with ID and affective and/or anxiety diagnoses, also to investigate in this study group the association between support and social services and frailty factors in terms of specialist healthcare utilisation, multimorbidity, polypharmacy, level of ID and behavioural impairment. Data was selected from four population-based Swedish national registries, on 871 identified persons with affective and/or anxiety diagnoses and ID. Multivariate regression analysis was used to investigate associations between frailty factors during 2002-2012 and social services in 2012. People with multimorbidity who frequently utilised specialist healthcare were less likely to utilise residential arrangements. Those with polypharmacy were more likely utilise residential arrangements, and receive personal contact. People with moderate, severe/profound levels of ID were more likely to utilise residential arrangements and to pursue daily activities.

Healthcare utilisation patterns among older people with intellectual disability and with affective and anxiety diagnoses in comparison with the general population.

OBJECTIVES: This study investigates specialist healthcare visits of older people with intellectual disability ID having affective and anxiety diagnoses in comparison with the general population, as well as across different levels of ID, behavioural impairment, and living in special housing in Sweden. METHOD: The study is a retrospective national-register-based study from 2002-2012 of people with ID 55 years and older (n = 7936) and a control group the same size matched by birth year and sex from the general population at the end of study. The study groups comprised those with affective (n = 918) and anxiety (n = 825) diagnoses who visited specialist healthcare, including data about living in special housing at the end of study in 2012. RESULTS: Older people with ID and with affective and anxiety diagnoses have a higher risk of inpatient and unplanned visits to psychiatric and somatic healthcare than the general population. The average length of stay in inpatient psychiatric healthcare was higher in older people with ID and anxiety diagnoses than in the general population. Within the ID group, more inpatient and unplanned visits were made by those with moderate and severe levels of ID, behavioural impairment, and living in special housing. CONCLUSION: Older people with ID and affective and anxiety diagnoses are more likely to have inpatient and unplanned visits for specialist healthcare than the general population. Future research should explore the quality of healthcare services delivered by healthcare providers to older people with ID and with affective and anxiety diagnoses.

Sex-Specific Associations Between Bipolar Disorder Pharmacological Maintenance Therapies and Inpatient Rehospitalizations: A 9-Year Swedish National Registry Study.

Background: Long-term pharmacological maintenance therapy is often essential among people with bipolar disorder to reduce the need for inpatient care. Sex-specific responses to maintenance therapies are expected but remain largely unknown. Here, we examined for sex-specific associations between common maintenance therapies for bipolar disorder with inpatient rehospitalizations following patients' index discharges during 2006-2014. Methods: Population-based data on maintenance therapies and rehospitalizations were extracted from Swedish national registries. We adopted the within-individual design to compare the time on- vs. off- maintenance therapy for males and females, respectively. Extended stratified Cox proportional hazards regression models were employed to quantify the rate of rehospitalization as a function of common maintenance drugs and other important time-varying control variables. Results: Our primary analysis included 22,681 bipolar disorder rehospitalizations by 6,400 males and 9,588 (60.0%) females over an observation time of 62,813 person-years. The time spent on- vs. off- maintenance lithium, lamotrigine, quetiapine, or olanzapine was statistically significant upon adjustment among either sex for reducing the rate of bipolar rehospitalizations. Adjusted sex-specific statistically significant associations were also observed. Among females, the time on- (vs. off-) long-acting injectable risperidone reduced the rate of bipolar rehospitalizations by 73% (56-84%), carbamazepine by 44% (18-62%), aripiprazole by 29% (13-42%), and valproate by 23% (11-33%); whereas among males, ziprasidone by 65% (41-79%). Conclusion: The effectiveness of most maintenance therapies is generally comparable and uniform among both males and females. Despite some statistically significant sex-specific associations, estimates for each drug were fairly consistent between sexes.

Suicide mortality after discharge from inpatient care for bipolar disorder: A 14-year Swedish national registry study.

Bipolar disorder has long been associated with increased risks for suicidality; though factors associated with dying by suicide remain obscure. Here, we retrospectively examine the associations between the different phases of bipolar illness and other common comorbidities with death by suicide in the 120 days following each discharge for Swedes first admitted as inpatients for bipolar disorder during the years 2000-2014. Data on admissions and suicide deaths were extracted from the Swedish National Patient Register and the Cause of Death Register, respectively. ICD-10 diagnostic codes were used to define the phases: depressive, manic, mixed, and other; and the comorbidities: specific substance use disorders, attention deficit hyperactivity disorder, and personality disorders. Extended Cox regressions were employed to model the time to death by suicide as a function of the bipolar phases, comorbidities, and other important control variables. Our analysis included 60,643 admissions by 22,402 patients over an observation time of 15,187 person-years. Overall, 213 (35.7%) of all suicides occurred within 120 days of discharge. Upon adjustment and compared to the depressive phases, manic phases were significantly associated with a far lower hazard of dying by suicide (HR 0.34, 95% CI: 0.21-0.56, p < 0.001), though mixed phases were not (HR 0.92, 95% CI: 0.48-1.73, p = 0.957). With regard to comorbidity, only sedative use disorder remained significantly associated with dying by suicide upon adjustment (HR 2.08, 95% CI: 1.41-3.06, p = 0.001). Vigilant monitoring of patients post discharge and of prescription practices are recommended.

Pharmacotherapy for mood and anxiety disorders in older people with intellectual disability in comparison with the general population.

BACKGROUND: People with intellectual disability (ID) have high prevalence of psychiatric disorders, but even higher rates of prescription of psychotropic drugs. METHODS: Using Swedish national registers, we identified a group of older people with ID and diagnosis of mood disorders (ICD-10 codes F32-F39) and/or anxiety (ICD-10 code F4) during 2006-2012 (n = 587) and a referent group of people from the general population with the same diagnoses during the same time period (n = 434). For both groups, we collected information on prescription of anxiolytics, hypnotics and sedatives, antidepressants, and GABA-agonists. RESULTS: Among those with a diagnosis of anxiety, people with ID were more likely than those in the general population to be prescribed anxiolytics (Relative Risk 1.32 [95% Confidence Interval 1.19-1.46]) and GABA-agonists (1.10 [1.08-1.31]). Moreover, among those with anxiety but without mood disorders, ID was associated with increased prescription of antidepressants (1.20 [1.03-1.39]). Within the ID cohort, behaviour impairment and MSP (i.e. moderate, severe, or profound) ID was associated with increased prescription of anxiolytics, both among those with anxiety (1.15 [1.03-1.30] for behaviour impairment and 1.23 [1.10-1.38] for MSP ID) and among those with mood disorders (1.14 [0.97-1.35] for behaviour impairment and 1.26 [1.04-1.52] for MSP ID). Moreover, MSP ID was associated with increased prescription of GABA-agonists among those with anxiety (1.23 [1.10-1.38]). CONCLUSIONS: The excess prescription of anxiolytics but not antidepressants may suggest shortages in the psychiatric health care of older people with intellectual disability and mood and anxiety disorders.

Gender influence on the bipolar disorder inpatient length of stay in Sweden, 2005-2014: A register-based study.

BACKGROUND: The influence of gender on bipolar disorder is controversial and it is unclear if inpatient care differs between men and women. Here, we investigate for gender differences in the inpatient length of stay for Swedes admitted for bipolar disorder and explore other factors that could explain any observed association. METHODS: Admission data were extracted from the Swedish National Patient Register and included all patients first admitted to a psychiatric inpatient unit with a bipolar disorder diagnosis, circa 2005-2014. Patients were then retrospectively followed for subsequent hospitalizations. Diagnostic subtypes were categorized by ICD-10 clusters: depressive, depressive with psychotic features, manic, manic with psychotic features, mixed, and other. Psychotropic therapies preceding the corresponding admissions were attained from the Prescribed Drug Register. Mixed-effects zero-truncated negative binomial regressions were employed to model the length of stay per admission. RESULTS: Analysis included 39,653 admissions by 16,271 inpatients (60.0% women). Overall, when compared to men, women spent 7.5% (95% CI: 4.2-11.0%, p < 0.001) extra days hospitalized per admission. However, upon adjusting for candidate confounders, including the bipolar subtype, and selected comorbidities and psychotropics, the association weakened wherein women then spent 3.7% (95% CI: 0.1-6.9%, p = 0.028) extra days hospitalized per admission. LIMITATIONS: The integrity of register data can be variable and the adherence to outpatient dispensed psychotropics could not be validated. CONCLUSION: Although the influence of gender on the bipolar disorder inpatient length of stay is evident, other factors attenuate and better explain this crude observation.

The occurrence of comorbidities with affective and anxiety disorders among older people with intellectual disability compared with the general population: a register study.

BACKGROUND: Little is known regarding the burden of comorbidities among older people with intellectual disability (ID) who have affective and anxiety disorders. Therefore, we aimed to investigate the occurrence and risk of psychiatric and somatic comorbidities with affective and/or anxiety disorders in older people with ID compared to the general population. METHODS: This population study was based on three Swedish national registers over 11 years (2002-2012). The ID group was identified in the LSS register, which comprises of data on measures in accordance with the Act Concerning Support and Service for Persons with Certain Functional Impairments (n = 7936), and a same-sized reference cohort from the Total Population Register was matched by sex and year of birth. The study groups consisted of those with affective (n = 918) and anxiety (n = 825) disorder diagnoses. The information about diagnoses were collected from the National Patient Register based on ICD-10 codes. RESULTS: The rate of psychiatric comorbidities with affective and anxiety disorders was approximately 11 times higher for people with ID compared to the general reference group. The two most common psychiatric comorbidities occurred with affective and anxiety disorders were Unspecified non-organic psychosis and Other mental disorders due to brain damage and dysfunction and to physical disease (8% for each with affective disorders and 7 and 6% with anxiety disorders, respectively). In contrast, somatic comorbidity comparisons showed that the general reference group was 20% less likely than the ID cohort to have comorbid somatic diagnoses. The most commonly occurring somatic comorbidities were Injury, poisoning and certain other consequences of external causes (49 and 47% with affective and anxiety disorders, respectively) and Signs and symptoms and abnormal clinical and laboratory findings not elsewhere classified (44 and 50% with affective and anxiety disorders, respectively). CONCLUSION: Older people with ID and with affective and anxiety diagnoses are more likely to be diagnosed with psychiatric comorbidities that are unspecified, which reflects the difficulty of diagnosis, and there is a need for further research to understand this vulnerable group. The low occurrence rate of somatic diagnoses may be a result of those conditions being overshadowed by the high degree of psychiatric comorbidities.

Outcome of a psychosocial health promotion intervention aimed at improving physical health and reducing alcohol use in patients with schizophrenia and psychotic disorders (MINT).

BACKGROUND: Life expectancy is reduced by 19 years in men and 17 in women with psychosis in Sweden, largely due to cardiovascular disease. AIM: Assess whether a psychosocial health promotion intervention improves cardiometabolic risk factors, quality of life, and severity of illness in patients with psychotic disorders more than treatment as usual. METHODS: A pragmatic intervention trial testing a manual-based multi-component health promotion intervention targeting patients with psychosis. The Swedish intervention was adapted from IMPaCT therapy, a health-promotion program based on motivational interviewing and cognitive behavioral therapy, designed to be incorporated into routine care. The intervention group consisted of 119 patients and the control group of 570 patients from specialized psychosis departments. Outcome variables were assessed 6 months before intervention during the run-in period, again at the start of intervention, and 12 months after the intervention began. The control group received treatment as usual. RESULTS: The intervention had no significant effect on any of the outcome variables. However, BMI, waist circumference, systolic BP, heart rate, HbA1c, general health, and Clinical Global Impressions Scale score improved significantly during the run-in period before the start of the active intervention (observer effect). The multi-component design meant that treatment effects could only be calculated for the intervention as a whole. CONCLUSION: The results of the intervention are similar to those of the U.K. IMPaCT study, in which the modular health-promotion intervention had little effect on cardiovascular risk indicators. However, in the current study, the run-in period had a positive effect on cardiometabolic risk factors.

Demographic and diagnostic profiles of older people with intellectual disability and prescription of antipsychotics.

PURPOSE: To describe demographic and diagnostic profiles in a national cohort of older people with intellectual disability (ID) who were prescribed antipsychotics. METHODS: Using national registers, we identified people with ID who were 55 + years in 2012 (n = 7936), as well as a subcohort with complete information on demographic factors (sex, year of birth, severity of ID, presence of behavior impairment, and residence in special housing; n = 1151). Data regarding diagnoses and prescription of antipsychotics were added for the time period 2006-2012. The potential effects of demographic factors and diagnoses on the prescription of sedating and less-sedating antipsychotics, respectively, were assessed in separate models by estimating the relative risks (RRs) of prescription. RESULTS: Of the demographic factors, severe/profound ID (RR 1.17), behavior impairment (RR 1.34), and living in special housing (RR 1.25) were associated with prescription of sedating antipsychotics, whereas only behavior impairment (RR 1.42) was associated with prescription of less-sedating antipsychotics. For both sedating and less-sedating antipsychotics, the diagnoses with the largest association (i.e., highest relative risk) were schizophrenia (RR 2.17 for sedating and RR 1.81 for less-sedating) and ID (RR 1.84 and RR 1.68, respectively), followed by disorders of psychological development (for sedating antipsychotics, RR 1.57) and organic mental disorders (for less-sedating antipsychotics, RR 1.55). CONCLUSIONS: The associations between prescription of antipsychotics and demographic factors and non-psychotic diagnoses, respectively, suggest that older people with ID may be prescribed antipsychotic medication without thorough psychiatric diagnosing. If so, there is a need for improving the abilities of health care professionals to properly diagnose and manage psychiatric illness in this population.

Randomised control trial of the effectiveness of an integrated psychosocial health promotion intervention aimed at improving health and reducing substance use in established psychosis (IMPaCT).

BACKGROUND: People with psychosis have a reduced life expectancy of 10-20 years, largely due to cardiovascular disease. This trial aimed to determine the effectiveness of a modular health promotion intervention (IMPaCT Therapy) in improving health and reducing cardiovascular risk in psychosis. METHODS: A multicentre, two arm, parallel cluster RCT was conducted across five UK mental health NHS trusts. Community care coordinators (CC) were randomly assigned to training and supervision in delivering IMPaCT Therapy or treatment as usual (TAU) to current patients with psychosis (cluster). The primary outcome was the physical and mental health subscales of the Short form-36 (SF-36) questionnaire. RESULTS: Of 104 care coordinators recruited, 52 (with 213 patients) were randomised to deliver IMPaCT therapy and 52 (with 193 patients) randomised to TAU. Of 406 patients, 318 (78%) and 301 (74%) attended 12- and 15-month follow-up respectively. IMPaCT therapy showed no significant effect on the physical or mental health component SF-36 scores versus TAU at 12 or 15 months. No effect was observed for cardiovascular risk indicators, except for HDL cholesterol, which improved more with IMPACT therapy than TAU (Treatment effect (95% CI); 0.085 (0.007 to 0.16); p = 0.034). The 22% of patients who received >180 min of IMPACT Therapy in addition to usual care achieved a greater reduction in waist circumference than did controls, which was clinically significant. CONCLUSION: Training and supervising community care coordinators to use IMPaCT therapy in patients with psychosis is insufficient to significantly improve physical or mental health quality of life. The search for effective, pragmatic interventions deliverable in health care services continues. TRIAL REGISTRATION: The trial was retrospectively registered with ISRCTN registry on 23/4/2010 at ISRCTN58667926 ; recruitment started on 01/03/2010 with first randomization on 09.08.2010 ISRCTN58667926 .

Anxiety, irritability, and agitation as indicators of bipolar mania with depressive symptoms: a post hoc analysis of two clinical trials.

BACKGROUND: Symptoms of anxiety, irritability, and agitation (AIA) are prevalent among patients with bipolar I disorder (BD-I) mania with depressive symptoms, and could potentially be used to aid physicians in the identification of this more severe form of BD-I. Using data from two clinical trials, the aims of this post hoc analysis were to describe the phenomenology of bipolar mania in terms of AIA and depressive symptoms, and to evaluate the influence of these symptoms on the likelihood of remission during treatment. METHODS: Patients with a BD-I manic or mixed episode (Diagnostic and Statistical Manual of Mental Disorders IV criteria) were randomised to 3 weeks of double-blind treatment with asenapine, placebo, or olanzapine (active comparator). Anxiety was defined as a score of ≥3 on the Positive and Negative Syndrome Scale 'anxiety' item, irritability as a score of ≥4 on the Young Mania Rating Scale (YMRS) 'irritability' item, and agitation as a score of ≥3 on the YMRS 'increased motor activity-energy' item. Depressive symptoms were defined as a score of ≥1 on three or more individual Montgomery-Åsberg Depression Rating Scale (MADRS) items, or a MADRS Total score of ≥20. RESULTS: A total of 960 patients with BD-I were analysed, 665 with a manic episode and 295 with a mixed episode. At baseline, 61.4% had anxiety, 62.4% had irritability, 76.4% had agitation, and 34.0% had all three AIA symptoms ('severe AIA'); 47.3% had three or more depressive symptoms, and 13.5% had a MADRS total score of ≥20. Anxiety, irritability, and severe AIA (but not agitation) were statistically significantly more common in patients with depressive symptoms. Patients with anxiety or severe AIA at baseline were statistically significantly less likely to achieve remission (YMRS total <12). In general, remission rates were higher with asenapine and olanzapine than with placebo, irrespective of baseline AIA or depressive symptoms. CONCLUSIONS: Assessment of AIA symptoms in bipolar mania could enable physicians to identify patients with more severe depressive symptoms, allowing for appropriate intervention. Assessment and monitoring of AIA may help physicians to predict which patients may be harder to treat and at risk for self-harm. Trial registration ClinicalTrials.gov NCT00159744, NCT00159796. Registered 8 September 2005 (retrospectively registered).