Clinical insight among persons with schizophrenia spectrum disorders treated with amisulpride, aripiprazole or olanzapine: a semi-randomised trial.

BACKGROUND: Antipsychotic treatment may improve clinical insight. However, previous studies have reported inconclusive findings on whether antipsychotics improve insight over and above the reduction in symptoms of psychosis. These studies assessed homogeneous samples in terms of stage of illness. Randomised studies investigating a mixed population of first- and multiepisode schizophrenia spectrum disorders might clarify this disagreement. METHODS: Our data were derived from a pragmatic, rater-blinded, semi-randomised trial that compared the effectiveness of amisulpride, aripiprazole and olanzapine. A sample of 144 patients with first- or multiepisode schizophrenia spectrum disorders underwent eight assessments during a 1-year follow-up. Clinical insight was assessed by item General 12 from the Positive and Negative Syndrome Scale (PANSS). We analysed latent growth curve models to test if the medications had a direct effect on insight that was over and above the reduction in total psychosis symptoms. Furthermore, we investigated whether there were differences between the study drugs in terms of insight. RESULTS: Based on allocation analysis, all three drugs were associated with a reduction in total psychosis symptoms in the initial phase (weeks 0-6). Amisulpride and olanzapine were associated with improved insight over and above what was related to the reduction in total psychosis symptoms in the long-term phase (weeks 6-52). However, these differential effects were lost when only including the participants that chose the first drug in the randomisation sequence. We found no differential effect on insight among those who were antipsychotic-naïve and those who were previously medicated with antipsychotics. CONCLUSIONS: Our results suggest that antipsychotic treatment improves insight, but whether the effect on insight surpasses the effect of reduced total psychosis symptoms is more uncertain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01446328, 05.10.2011.

Impact of childhood trauma on antipsychotic effectiveness in schizophrenia spectrum disorders: A prospective, pragmatic, semi-randomized trial.

Antipsychotic medications are generally effective in ameliorating psychotic symptoms in schizophrenia spectrum disorders (SSDs). Identifying predictors associated with poor treatment response is important for a personalized treatment approach. Childhood trauma (CT) may have a general and differential effect on the effectiveness of different types of antipsychotics in SSDs. The Bergen-Stavanger-Trondheim-Innsbruck (BeSt InTro) study is a pragmatic, researcher-initiated, semi-randomized trial. The present study aimed to investigate symptom change (the Positive and Negative Syndrome Scale) from baseline to 1, 3, 6, 12, 26, 39 and 52 weeks of antipsychotic treatment (amisulpride, aripiprazole and olanzapine) by group (CT/no CT). Participants (n = 98) with diagnoses within the schizophrenia spectrum (F20-29 in the International Classification of Diseases - 10th Revision) were randomized to receive amisulpride, aripiprazole or olanzapine, and for this study categorized into groups of none and low CT, and moderate to severe CT according to thresholds defined by the Childhood Trauma Questionnaire Short-Form manual. CT in SSDs predicted an overall slower treatment response and less antipsychotic effectiveness after 26 weeks of treatment, which was statistically nonsignificant at 52 weeks. Secondary analyses showed a differential effect of CT related to type of antipsychotic medication: patients with SSDs and CT who received olanzapine showed less antipsychotic effectiveness throughout 52 weeks of treatment. The intention-to-treat and per-protocol analyses were convergent. Our findings indicate that in patients with SSD and CT, delayed response to antipsychotics could be expected, and a longer evaluation period before considering change of medication may be recommended.

Does childhood trauma influence cognitive functioning in schizophrenia? The association of childhood trauma and cognition in schizophrenia spectrum disorders.

Childhood trauma (CT) is a risk factor for schizophrenia spectrum disorders (SSDs), and cognitive impairment is a core feature and a vulnerability marker of SSDs. Studies of the relationship between CT and cognitive impairment in SSDs are inconclusive. In addition, few studies have examined differential effects of CT subtypes, e.g. physical, sexual or emotional abuse/neglect, on cognitive functioning. The present study therefore aimed to examine the effects of CT and CT subtypes on cognitive impairment in SSD. Participants (n = 78) with SSDs completed a comprehensive neuropsychological test battery and the Childhood Trauma Questionnaire Short-Form (CTQ-SF). We compared global cognitive performance as well as scores in seven subdomains (verbal abilities, visuospatial abilities, learning, memory, attention/working memory, executive abilities and processing speed) between participants reporting no CT and those reporting CT experiences using independent samples t-tests as well as linear regression analyses to control for possible confounders. CT subtype physical neglect was associated with attention and working memory after controlling for positive and negative psychosis symptoms, years of education, antipsychotics, gender and age, and adjustment of multiple testing. Our results indicate that the observed heterogeneity in cognitive impairment in SSDs, especially attention/working memory abilities, may in part be associated with childhood physical neglect.

Trajectories of depressive symptoms in the acute phase of psychosis: Implications for treatment.

Depression is common in schizophrenia and associated with negative outcomes. Previous studies have identified heterogeneity in treatment response in schizophrenia. We aimed to investigate different trajectories of depression in patients suffering from psychosis and predictors of change in depressive symptoms during antipsychotic treatment. Two hundred and twenty-six patients >18 years acutely admitted due to psychosis were consecutively included and the follow-up was 27 weeks. The Calgary Depression Scale for Schizophrenia (CDSS) sum score was the primary outcome. Latent growth curve (LGCM) and Growth Mixture Models (GMM) were conducted. Predictors were the Positive sum score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), Schizophrenia spectrum/non-spectrum psychoses, gender and being antipsychotic naive at inclusion. We found support for three depression-trajectories, including a high- (14.7%), a low depression-level (69.6%) class and a third depressed class quickly decreasing to a low level (15.7%). Change in CDSS was associated with change in PANSS positive score in all time intervals (4 weeks: b = 0.18, p < 0.001, 3 months: 0.21, p < 0.023, 6 months: 0.43, p < 0.001) and with a diagnosis within schizophrenia spectrum but not with antipsychotic naivety or gender. The schizophrenia-spectrum patients had less depressive symptoms at inclusion (-2.63, p < 0.001). In conclusion, an early responding and a treatment refractory group were identified. The treatment-refractory patients are candidates for enhanced anti-depressive treatment, for which current evidence is limited. The post-psychotic depression group was characterized by depressive symptoms in the acute phase as well. We could not identify differentiating characteristics of the depression trajectories.

Suicidality in schizophrenia spectrum disorders: the relationship to hallucinations and persecutory delusions.

BACKGROUND: Assessment of suicide risk is crucial in schizophrenia and results concerning risk contributed by hallucinations and persecutory delusions are inconsistent. We aimed to determine factors associated with suicidal ideation and plans at the time of acute admission in patients suffering from schizophrenia spectrum disorders. METHODS: One hundred and twenty-four patients older than 18 years admitted to an acute psychiatric ward due to psychosis were consecutively included. Predictors of suicidal ideation and suicide plans at the time of admission were examined with multinominal logistic regression and structural equation modelling (SEM). The study design was pragmatic, thus entailing a clinically relevant representation. RESULTS: Depression Odds Ratio (OR) 12.9, Drug use OR 4.07, Hallucinations OR 2.55 and Negative symptoms OR 0.88 significantly predicted Suicidal ideation. Suspiciousness/ Persecution did not. Only Depression and Hallucinations significantly predicted Suicide plans. In the SEM-model Anxiety, Depression and Hopelessness connected Suspiciousness/Persecution, Hallucinations and Lack of insight with Suicidal ideation and Suicide plans. CONCLUSIONS: The study contributes to an increasing evidence base supporting an association between hallucinations and suicide risk. We want to emphasise the importance of treating depression and hallucinations in psychotic disorders, reducing hopelessness while working with insight and reducing drug abuse in order to lower suicide risk. TRIAL REGISTRATION: ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/NCT00932529.

Self-harm induced somatic admission after discharge from psychiatric hospital - a prospective cohort study.

BACKGROUND: Few studies have examined rate and predictors of self-harm in discharged psychiatric patients. AIMS: To investigate the rate, coding, timing, predictors and characteristics of self-harm induced somatic admission after discharge from psychiatric acute admission. METHOD: Cohort study of 2827 unselected patients consecutively admitted to a psychiatric acute ward during three years. Mean observation period was 2.3 years. Combined register linkage and manual data examination. Cox regression was used to investigate covariates for time to somatic admission due to self-harm, with covariates changing during follow-up entered time dependently. RESULTS: During the observation period, 10.5% of the patients had 792 somatic self-harm admissions. Strongest risk factors were psychiatric admission due to non-suicidal self-harm, suicide attempt and suicide ideation. The risk was increased throughout the first year of follow-up, during readmission, with increasing outpatient consultations and in patients diagnosed with recurrent depression, personality disorders, substance use disorders and anxiety/stress-related disorders. Only 49% of the somatic self-harm admissions were given hospital self-harm diagnosis. CONCLUSIONS: Self-harm induced somatic admissions were highly prevalent during the first year after discharge from acute psychiatric admission. Underdiagnosing of self-harm in relation to somatic self-harm admissions may cause incorrect follow-up treatments and unreliable register data.

Neurocognitive effectiveness of quetiapine, olanzapine, risperidone, and ziprasidone: a pragmatic, randomized trial.

PURPOSE: Cognitive effects of second generation antipsychotics (SGAs) are indicated in efficacy studies but the generalizability of the results may be limited by rigid designs and selected samples. The aim of this naturalistic, industry-independent study is to investigate whether differential neurocognitive effectiveness can be found among olanzapine, quetiapine, risperidone, and ziprasidone in a clinically relevant sample with psychosis. SUBJECTS AND METHODS: Adult patients acutely admitted to an emergency ward for psychosis were randomized to risperidone, olanzapine, quetiapine or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale and a repeatable neurocognitive test battery. RESULTS: A total of 226 patients were included and 171 patients underwent neurocognitive assessments. The sample had a global cognitive performance score at baseline about one standard deviation below that of the general population. The ziprasidone group had the fastest increase in global functioning which was significantly superior to that of the olanzapine group for the entire follow-up period. Before 90 days, the quetiapine group had the fastest increase which was statistically superior to the olanzapine group. DISCUSSION: Ziprasidone and quetiapine demonstrated superiority to olanzapine in increasing global neurocognitive performance in this naturalistic sample.

Time-dependent effect analysis of antipsychotic treatment in a naturalistic cohort study of patients with schizophrenia.

OBJECTIVE: Evidence based treatment of schizophrenia as well as antipsychotic drug utility patterns have changed considerably in recent years and the present study aims to investigate the current level of unplanned hospital readmissions in a cohort of patients with schizophrenia, and to determine the risk-reducing effects of current antipsychotic drug treatment. METHOD: An open cohort study included all consecutively discharged patients with schizophrenia in a 3-year period (n=277). The treatment-dependent variables were entered in a multivariate Cox survival analyses with time to unplanned readmission as the dependent variable. RESULTS: 11.2% of patients were readmitted within 30 days of discharge, and 44.8% were readmitted within 12 months. Antipsychotic monotherapy reduced the risk of readmission by 74.9%. Treatment in CMHC also had a risk-reducing effect. The prescription rate of clozapine in this sample was 10.1%. DISCUSSION: The over-all level of unplanned readmissions was in correspondence with the findings of others. Current antipsychotic drug treatment independently offers strong protection against unplanned readmissions. There may be a potential for further optimalizing antipsychotic drug treatment according to treatment guidelines. CONCLUSIONS: Unplanned readmissions are very common for patients with schizophrenia but antipsychotic drug treatment is associated with a strong risk-reducing effect in this regard.