Linda Kader

Can a targeted psychological intervention be effective for young people following a first manic episode? Results from an 18-month pilot study.

Aim: There is a scarce literature describing psychological interventions for a young, first‐episode cohort who have experienced psychotic mania. This study aimed to assess whether a manualized psychological intervention could be effective in reducing symptomatology and relapse, and improve functional outcome in this population.

Are we missing opportunities for early intervention in bipolar disorder

Clinical staging informs the assessment, prognosis and choice of therapies in a diverse range of medical specialities, such as cardiac disorders and oncology. However, it is only relatively recently that psychiatry has begun to explore staging as a conceptual framework to understand the progression of psychiatric disorders, and how this may inform prognosis and man-agement choices. However, a substantial body of new data is available to inform this topic. Therefore, it appears timely to examine some of the evidence regarding early intervention and the staging of clini-cal approaches, specifically as they relate to bipolar disorder.Considerable evidence has emerged in recent years for a staging model in medi-cine, particularly for disorders such as cancer, HIV and liver disease. According to this model, disorders progress in identi-fiable phases, which have specific features and require specifically adapted interven-tions. There is recognition that while pro-gression through various phases may not be applicable to all patients with a particu-lar disorder, this concept can nevertheless reflect an aggregate picture. The staging model has also attracted interest in psychiatry as it provides the opportunity for specialized and stage-appropriate interventions that may mini-mize the risk for further illness progression, and facilitate recovery early in the course. Specifically, recent models developed for psychotic disorders and later adapted to bipolar disorders, have described categories ranging from stage 0 (describing and iden-tifying risk factors for a disorder in the absence of any clear symptoms), through to stages 1a and 1b (comprising mild, non-specific identifiable prodromal symptoms, respectively), stage 2 (comprising the first episode), stages 3a, 3b and 3c (compris-ing subthreshold, threshold and persistent relapse, respectively), to stage 4 (referring to persisting unremitting symptoms that may have been nonresponsive to treatment)

Quetiapine v. lithium in the maintenance phase following a first episode of mania: randomised controlled trial

BackgroundLithium and quetiapine are considered standard maintenance agents for bipolar disorder yet it is unclear how their efficacy compares with each other.AimsTo investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania.MethodMaintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry - ACTRN12607000639426.)ResultsIn total, 61 individuals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment × visit interactions were observed for measures of overall psychopathology, psychotic symptoms and functioning. Planned and post hoc comparisons further demonstrated the superiority of lithium treatment over quetiapine.ConclusionsIn people with first-episode mania treated with a combination of lithium and quetiapine, continuation treatment with lithium rather than quetiapine is superior in terms of mean levels of symptoms during a 1-year evolution.

Olanzapine or chlorpromazine plus lithium in first episode psychotic mania: An 8-week randomised controlled trial

BACKGROUND Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments. METHODS Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures. RESULTS Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons. CONCLUSIONS Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.

The impact of past direct-personal traumatic events on 12-month outcome in first episode psychotic mania: Trauma and early psychotic mania

Objective: Past traumatic events have been associated with poorer clinical outcomes in people with bipolar disorder. However, the impact of these events in the early stages of the illness remains unclear. The aim of this study was to investigate whether prior traumatic events were related to poorer outcomes 12 months following a first episode of psychotic mania. Methods: Traumatic events were retrospectively evaluated from patient files in a sample of 65 participants who had experienced first episode psychotic mania. Participants were aged between 15 and 28 years and were treated at a specialised early psychosis service. Clinical outcomes were measured by a variety of symptomatic and functioning scales at the 12-month time-point. Results: Direct-personal traumatic experiences prior to the onset of psychotic mania were reported by 48% of the sample. Participants with past direct-personal trauma had significantly higher symptoms of mania (p=0.02), depression (p=0.03) and psychopathology (p=0.01) 12 months following their first episode compared to participants without past direct-personal trauma, with medium to large effects observed. After adjusting for baseline scores, differences in global functioning (as measured by the Global Assessment of Functioning scale) were non-significant (p=0.05); however, participants with past direct-personal trauma had significantly poorer social and occupational functioning (p=0.04) at the 12-month assessment with medium effect. Conclusions: Past direct-personal trauma may predict poorer symptomatic and functional outcomes after first episode psychotic mania. Limitations include that the findings represent individuals treated at a specialist early intervention centre for youth and the retrospective assessment of traumatic events may have been underestimated.

Atypical Antipsychotics Cause an Acute Increase in Cutaneous Hand Blood Flow in Patients with Schizophrenia and Schizoaffective Disorder

Objective: Clinical studies suggest resting thermoregulatory cutaneous vasomotor tone could be increased in schizophrenia, resulting in reduced hand blood flow. In animal models, atypical antipsychotics including clozapine potently inhibit sympathetic neural outflow to the thermoregulatory cutaneous vascular beds. We have now determined whether antipsychotic medication administration is associated with an acute increase in hand blood flow in patients with schizophrenia and schizoaffective disorder, and whether this increase correlates with clinical status. Method: Hand temperature was measured with an infrared camera in 12 patients with chronic schizophrenia or schizoaffective disorder 30 min prior to, then 30 and 60 min following medication. Clinical status was assessed via the Brief Psychiatric Rating Scale (BPRS). Results were compared using regression and repeated measures analysis of variance. Results: A robust and significant increase in hand temperature (p < 0.001) was observed following antipsychotic administration. The mean increase after 60 min was 4.1 ± 2.4°C. This increase was significantly associated with colder hand temperature prior to medication (p < 0.05; suggestive of increased resting vasoconstriction) and with more severe psychiatric symptoms (p < 0.05). Conclusions: Atypical antipsychotics were associated with increased hand blood flow, consistent with inhibition of thermoregulatory sympathetic outflow to the cutaneous vascular bed in patients with schizophrenia and schizoaffective disorder. This increase correlated with symptom severity. Hand temperature increase following antipsychotic medication may therefore be a simple and informative physiological marker of disease activity and potential response in patients with schizophreniform disorders. Given that antipsychotics also inhibit sympathetic outflow to brown adipose tissue, which normally converts energy to heat, future studies should examine whether antipsychotic-induced hand temperature increase is associated with antipsychotic-induced weight gain.

Seasonal influences on first-episode admission in affective and non-affective psychosis

Background: Since bipolar affective disorder has been recorded, clinicians treating patients with this disorder have noted the cyclic nature of episodes, particularly an increase in mania in the spring and summer months and depression during winter. Objective: The aim of this study was to investigate seasonality in symptom onset and service admissions over a period of 10 years in a group of patients (n= 359) with first-episode (FE) mania (n= 133), FE schizoaffective disorder (n= 49) and FE schizophrenia (n= 177). Method: Patients were recruited if they were between 15 and 28 years of age and if they resided in the geographical mental health service catchment area. The number of patients experiencing symptom onset and service admission over each month and season was recorded. Results: In terms of seasonality of time of service admission, the results indicate a high overall seasonality (particularly in men), which was observed in both the schizoaffective and the bipolar groups. In terms of seasonality of symptom onset, the results indicate that seasonality remains in the male bipolar group, but other groups have no seasonal trend. Conclusions: This provides further evidence that systems mediating the entrainment of biological rhythms to the environment may be more pronounced in BPAD than in schizoaffective disorder and schizophrenia. These results may help facilitate the preparedness of mental heath services for patients at different times of the year.

Health-related quality of life and functioning in bipolar disorder: the impact of pharmacotherapy.

Bipolar disorder has a major deleterious impact on many aspects of a patient’s functioning and health-related quality of life. Although the formal measurement of these deficits has been neglected until recently, many well-designed trials now include an assessment of functioning and health-related quality of life using one or more rating scales. This review describes recent developments in the measurement of functioning and health-related quality of life in bipolar disorder, and discusses the evidence that medications that improve symptoms in bipolar disorder also offer clinically relevant benefits in functioning and health-related quality of life. Direct comparisons of the benefits of medications including atypical antipsychotics are problematic due to differences in trial populations, study durations and rating scales. Data from quetiapine trials indicate that this medication offers prompt and sustained improvement of functioning in patients with mania and enhancement of health-related quality of life in patients with bipolar depression, to accompany the significant improvements in mood episodes.

Speaker 3: Michael Berk, Australia

Introduction: First-episode mania (FEM) is the first feasible diagnostic and therapeutic opportunity. Lithium is established as a first-line treatment for bipolar disorder. More recently antipsychotic drugs including quetiapine have been found to be effective in the treatment of mania, depression and in maintenance. However, the comparative benefits of these agents in the maintenance phase after a first episode of mania are unclear. This study compared the differential clinical effect of Lithium and Quetiapine after a first episode of mania. Method: The study was a single-blind, randomised controlled trial of 61 participants in remission from a first episode of severe mania. Participants were stabilised on the combination of lithium or quetiapine and were then randomised to either agent as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive clinical battery including mood, functioning, psychotic and quality of life measures conducted at baseline, month 3 and month 12 follow-up time-points. Results: At endpoint, there was an advantage for lithium over quetiapine on measures of depression, psychosis and global impression. Conclusion: This study suggests that in a group of young individuals with a first episode of mania, lithium may have clinical advantages over quetiapine over the maintenance phase. This data is in contrast to some published reports suggesting broad equivalence, and raises questions about stage specific patterns of response as well as differential efficacy in classic severe mania.

Poster #124 DECREASED HAND BLOOD FLOW CORRELATES WITH SYMPTOM SEVERITY AND IS ACUTELY INCREASED BY ATYPICAL ANTIPSYCHOTIC MEDICATION IN PATIENTS WITH SCHIZOPHRENIA AND SCHIZOAFFECTIVE DISORDER

associated with altered brain structure, in particular regions rich in CB1 receptors.Antipsychotics induce down-regulation of CB1 in the brain. A lower density of CB1 induced by antipsychotics could represent an adaptative mechanism that reduces the ECS-mediated suppression of GABA release, contributing to the normalization of cognitive functions. Clinical remission of schizophrenia has been reported to be accompanied by significant decreases in CB2 mRNA levels in peripheral blood mononuclear cells. It also has been revealed a close relation between diminished CB2 function and increased susceptibility to schizophrenia. Moreover, deletion of CB2 has a relation with schizophrenia-like behaviors in knock-out mice. Methods: 65 patients with a first episode of psychosis of less than one year since the onset and 75 healthy controls were recruited. We collected demographic, clinical, functional, therapeutical and cannabis use data of the subjects. CB1 and CB2 levels were determinated by Western-Blott method in PBMC. Results: There were no statistical significant differences between patients and controls in age or sex distribution. The mean age of onset of the psychotic episode was 21.45. The mean duration of untreated psychosis (DUP) was 80.64 days. 82% of the patients were diagnosed of non-affective psychosis episodes, while 18% were affective psychosis. On the PANSS scale, the mean total score was 54.03, the mean positive subscale score 11.05, the mean negative subscale score 15.17, and the mean general subscale score 27.82. On the YOUNG scale for mania, the mean total score was 1.02. Theglobal assessment of functioning scale (GAF) mean score was 66.48. Around the 20% of the patients were not taking any antipsychotic drug, 30% risperidone, 13% olanzapine, 9% clozapine, 9% paliperidone and the rest with other antipsychotics. 10% was taking lithium. 25% of the patients and 15% of the controls were active cannabis users. CB1 and CB2 levels were still being determined by the abstract deadline. Discussion: Our main hypothesis is that activation of key mediators in immune and inflammatory responses is a process involved in the primary neuronal stress phenomenon that occurs from the onset of psychotic illness. This dysregulation may be regulated by the ECS. Exogenous cannabis use may alter this regulatory system. CB1 and CB2 upregulation may be involved in anti-inflammatory own brain regulation to stress, and its determination in PBMCmay mirror cerebral activity.