Martin Lambert

The impact of substance use disorders on clinical outcome in 643 patients with first-episode psychosis.

Objective:  Studies investigating the impact of comorbid substance use disorders (SUD) in psychosis have tended to focus on cross‐sectional data, with few studies examining the effects of substance use course on clinical outcome. The main aim of the present study was to assess the impact of baseline SUD and course of SUD on remission of positive symptoms.

Current Issues in Schizophrenia: Overview of Patient Acceptability, Functioning Capacity and Quality of Life

The increasing interest in the subjective wellbeing and quality of life (QoL) of patients with schizophrenia represents a conceptual extension of therapeutic outcome criteria. For a long time, the reduction of positive symptoms alone was the most important outcome parameter, but the development of atypical antipsychotic drugs in the early 1990s resulted in the adoption of more wide-reaching measures of therapeutic outcome. Patient satisfaction appears to be strongly related to their willingness to be or stay engaged in psychosocial and pharmacological treatment, and therefore to the symptomatic and functional outcome. Existing studies that deal with QoL and subjective wellbeing differ in their methodology and are difficult to compare because of varying underlying concepts of QoL or subjective wellbeing, different assessment scales or small sample sizes. Although QoL is a heterogeneous concept, it is clearly correlated with a number of factors, including illness, medication and stress process-related variables. Various protective factors have been identified; among these are personality traits, the degree of social support and treatment interventions. In clinical studies, atypical antipsychotic agents are associated with greater improvements in QoL and subjective wellbeing than are conventional agents. The reason for this is probably the ability of atypical agents to have a positive impact on factors most associated with QoL, such as negative and affective symptoms and drug tolerability. The most appropriate clinical approach to maximize QoL and subjective wellbeing for patients with schizophrenia is to use atypical antipsychotic drugs as a first-line treatment approach. Ideally, an atypical drug which is known not to have a negative effect on attention, affect or motivation should be chosen.

Impact of duration of untreated psychosis on pre-treatment, baseline, and outcome characteristics in an epidemiological first-episode psychosis cohort

INTRODUCTION To assess the impact of duration of untreated psychosis (DUP) on baseline and 18-month follow-up characteristics controlling for relevant confounders in an epidemiological first-episode psychosis (FEP) cohort. METHOD The Early Psychosis Prevention and Intervention Centre (EPPIC) in Australia admitted 786 FEP patients from January 1998 to December 2000. Data were collected from medical files using a standardized questionnaire. Data from 636 patients were analyzed. RESULTS Median DUP was 8.7 weeks. Longer DUP was associated with worse premorbid functioning (p<0.001), higher rate of schizophrenia-spectrum disorders (p<0.001), and younger age at onset of psychosis (p=0.004). Longer DUP was not associated with baseline variables but with a lower rate of remission of positive symptoms (p<0.001) and employment/occupation (p<0.001), a higher rate of persistent substance use (p=0.015), worse illness severity (p<0.001) and global functioning (p<0.001) at follow-up after controlling for relevant confounders, explaining approximately 5% of variance of remission of positive symptoms (p<0.001) in the total sample and 3% in schizophrenia-spectrum disorders excluding bipolar I disorder (p=0.002). Outcome was significantly worse when DUP exceeded 1-3 months. CONCLUSION Avoiding pitfalls of non-epidemiological studies, DUP appears to be a modest independent predictor of prognosis in the medium-term. Results support the need for assertive early detection strategies.

Rates and predictors of remission and recovery during 3 years in 392 never-treated patients with schizophrenia

Objective:  Few studies have prospectively examined remission and recovery as well as their predictors in schizophrenia simultaneously. Aims of the study were to identify remission and recovery rates as well as their predictors in schizophrenia.

The CATIE and CUtLASS Studies in Schizophrenia: Results and Implications for Clinicians

Numerous double-blind studies have compared second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs), with most finding better efficacy and tolerability for SGAs. However, these ‘efficacy trials’ were generally short term and included only highly selected patients. Mostly because of weight gain and other metabolic effects of the SGAs, as well as their high acquisition price, the debate on the (cost) effectiveness of the SGAs led to two pragmatic clinical trials with no sponsorship by industry. Both trials had broad inclusion criteria and long follow-up, and tried to mimic clinical routine: CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) and CUtLASS (Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study).1493 patients participated in CATIE, an 18-month, double-blind trial comparing the SGAs olanzapine, quetiapine, risperidone and ziprasidone with the FGA perphenazine. If efficacy or tolerability was insufficient, patients were re-randomized to a medication other than the one they previously received. Improvement of psychopathology and of quality of life was only moderate. Overall, 74% of patients discontinued study medication before 18 months, and the median time to discontinuation was 4.6 months. Aside from olanzapine (time to discontinuation 9.2 months), the other SGAs did not differ from each other or from perphenazine. Except for adverse effects as a reason for discontinuation, differences between the SGAs and the FGA were minimal. In CUtLASS, a 12-month open-label trial, 277 patients were randomized to receive an FGA or a SGA. Again, efficacy was rather similar between the two groups, with only limited improvement of psychopathology and quality of life. The authors of both trials concluded that SGAs do not markedly differ from FGAs regarding compliance, quality of life and effectiveness.The methodological problems of both trials have been discussed extensively. Patients had psychotic symptoms that were moderate in severity and were at least partially treatment resistant. The marginal improvement observed indicated that this population might not be appropriate to detect differences between FGAs and SGAs. Specific issues of CATIE include the exclusion of patients with tardive dyskinesia in the perphenazine arm and the high discontinuation rate. In CUtLASS, the concept of including 13 different FGAs and four SGAs in the respective classes was problematic. It is of interest that the most widely prescribed drug was sulpiride — of the FGAs, this is probably the ‘most atypical’ drug. Aside from the finding that the advantages of the SGAs are not as strong as early trials and marketing suggested or promised, the trials do not provide much helpful information regarding everyday practice. For tardive dyskinesia, no conclusions at all can be drawn. Similarly, methodological problems inhibited the detection of the other major advantage of the SGAs, i.e. the improved subjective well-being/ quality of life while receiving these agents. It is well known that patients’ and doctors’ perspectives differ markedly, and the Quality of Life Scale (QLS), an expert-rated scale used in both trials, might not be sensitive enough to detect the subjective advantages reported by the majority of patients in other trials.CATIE and CUtLASS suggest that SGAs do not live up to all the previous expectations. However, even if most of these advantages are debatable, the lower risk of tardive dyskinesia and the better subjective effects should be strong enough reasons to favour these drugs. There is no single antipsychotic that is best for every schizophrenia patient, as individual responses differ markedly. For successfully individualized treatment, a multitude of anti-psychotic options are needed.

PANSS Syndromes and Quality of Life in Schizophrenia

Background: Results from factor analysis studies have suggested that a five-dimensional structure appears to be a better representation of the psychopathological data of the PANSS. The purpose of this study was the detailed investigation of the association of schizophrenia syndromes and single symptoms with quality of life (QOL) in acute and remitted patients. The leading hypotheses were: (1) affective symptoms, especially depression and anxiety, are mostly associated with QOL longitudinally and (2) in the acute phase, QOL is also associated with positive schizophrenia symptoms. Methods: For the present study, schizophrenia and schizophreniform patients were studied on admission, at the end of the acute phase and 6 months after hospitalization. Psychopathology was measured using the PANSS syndromes, QOL was assessed using disease-specific (SWN) and generic (MLDL, EDLQ) scales. Results: Eighty-four patients entered the study and were assessed during the acute phase taking into account their history and actual treatment. Results revealed anxiety as the most important symptom and depression as the most important syndrome associated with different areas of QOL during and after hospitalization. Also cognitive and negative symptoms were associated with different QOL domains, but both positive symptom clusters showed no substantial association with QOL. Conclusions: Results of this longitudinal study investigating psychopathology and QOL in schizophrenia provide further support for the need to consider the psychopathological state and treatment setting when measuring QOL in schizophrenia and the need for a differential analysis of schizophrenia symptoms and QOL in the acute, mid-term and long-term phase. Anxiety reduction should be a critical goal of treatment in order to prevent further QOL impairment.

Randomized double blind comparison of olanzapine vs. clozapine on subjective well-being and clinical outcome in patients with schizophrenia

Objective:  This randomized double‐blind multicenter trial evaluated the effects of olanzapine vs. clozapine on subjective well‐being, quality of life (QOL) and clinical outcome.

Subjective well-being under neuroleptic treatment and its relevance for compliance

Objective:  To review the concept of ‘subjective well‐being under neuroleptic treatment’, its development and clinical relevance, particularly regarding compliance.

Treated incidence of first-episode psychosis in the catchment area of EPPIC between 1997 and 2000.

Objective:  To identify the treated incidence of psychosis in catchment of the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia.

Prevalence and predictors of suicide attempt in an incidence cohort of 661 young people with first-episode psychosis

Objectives: Studies investigating suicidal behaviour in psychosis rarely focus on incidence cohorts of first-episode patients. This is important, because patients who refuse study participation have higher rates of comorbid substance use disorders and longer duration of untreated psychosis as well as worse course illness, variables potentially linked to higher prevalence of suicidal behaviour. The aims of the present study were therefore to examine the prevalence and predictors of suicide and suicide attempt before and during the first 18–24months of treatment. Method: A retrospective file audit of 661 patients was carried out. Results: Six patients (0.9%) died by suicide, 93 (14.3%) attempted suicide prior to entry, and 57 (8.7%) did so during treatment. Predictors of suicide attempt were: previous attempt (odds ratio (OR)=45.54, 95% confidence interval (CI)=9.46–219.15), sexual abuse (OR=8.46, 95%CI=1.88–38.03), comorbid polysubstance (OR=13.63, 95%CI=2.58–71.99), greater insight (OR=0.17, 95%CI=0.06–0.49), lower baseline Global Assessment of Functioning Scale and Scale of Occupational and Functional Assessment score (OR=0.96, 95%CI=0.62–0.91; OR=0.98, 95%CI=0.95–0.99), and longer time in treatment (OR=1.05, 95%CI=1.03–1.08). Conclusions: The prevalence of suicidal behaviour was high, indicating that suicidal behaviour in incidence populations is higher than in non-epidemiological cohorts of first-episode patients. The rate of repetition of suicide attempt among the sample, however, was lower than expected, suggesting that specialist services can play a role in reducing suicide risk.