Danyael Lutgens

The relative contribution of cognition and symptomatic remission to functional outcome following treatment of a first episode of psychosis.

OBJECTIVE Functional recovery remains the primary goal following treatment of a psychotic disorder, especially after a first episode. Evidence regarding relative contributions of predictors of functional outcome, including symptoms and cognition, remains equivocal. The objective of the study was to determine the relative contribution of cognition, in particular verbal memory, and symptomatic remission to social and occupational functioning while controlling for established predictors of functioning in a large sample of patients presenting with a first episode of a schizophrenia spectrum or affective psychosis. METHOD Patients (aged 14-35 years) met DSM-IV criteria for a first episode of a schizophrenia spectrum or affective psychosis and had been admitted to the Prevention and Early Intervention Program for Psychoses, Montreal, Quebec, Canada, between 2003 and 2009 for treatment and follow-up for 2 years. Established predictors (duration of untreated psychosis, medication adherence, age at onset, substance use, premorbid adjustment), verbal memory, and length of positive and negative symptom remission were regressed on functioning (using the Strauss Carpenter Scale) at 1 (n = 208) and 2 (n = 159) years. Regressions were conducted with established predictors in the first step, followed by verbal memory and consecutive months of combined positive and negative symptom remission in the third step. Regressions were then repeated with length of positive and negative symptom remission, respectively. RESULTS Length of combined positive and negative symptom remission explained the most variance in functioning at 1 (R² adjusted = 0.35, F₉,₁₂₉ = 9.33, P < .001) and 2 (R² adjusted = 0.38, F₉,₉₇ = 8.21, P < .001) years, and verbal memory contributed only slightly to such outcome. While length of remission of negative symptoms was a stronger predictor of functioning than remission of positive symptoms at 1 year, length of positive symptom remission also made a large contribution at 2 years. CONCLUSIONS These results highlight the importance of achieving and maintaining remission of both negative and positive symptoms for longer periods in patients with a first episode of a psychotic disorder and the need for effective interventions to do so.

Long-acting injectable antipsychotics: evidence of effectiveness and use.

Objective To review the evidence for the role of long-acting injectable (LAI) antipsychotics (APs), especially the second-generation AP (SGA) LAIs, in the treatment of schizophrenia and to discuss the use rates of LAIs in Canada. Method A search of online medical databases was conducted of the published literature (1995–2012) of the effects of LAIs on the domains of remission, adherence, relapse, and hospitalization. Results obtained from randomized controlled trials (RCTs), systematic reviews, meta-analyses, and large-scale observational studies were included. Expert consensus data were also solicited on LAI use within a Canadian context. Results While the efficacy of LAIs, compared with placebo, is well established, the evidence from RCTs is equivocal for any specific advantage for SGA LAIs, compared with oral medications, probably owing to challenges in conducting such RCTs. Evidence from methodologically less rigorous studies and from clinical practice suggests some advantages in achieving and maintaining remission, risk of relapse, and hospitalization. The rate of LAI (first-generation AP and SGA) use from published outpatient studies is low at 6.3% in Canada, compared with 15% to 80% worldwide. However, there is a relatively high rate of use in specific early psychosis programs and in conjunction with community treatment orders in Canada. Conclusions LAIs are at least as effective as oral APs in the treatment of psychotic disorders. The former may have specific advantages for patients who demonstrate covert nonadherence. The underuse of LAIs in Canada needs to be better understood and addressed.

A five-year randomized parallel and blinded clinical trial of an extended specialized early intervention vs. regular care in the early phase of psychotic disorders: study protocol

BackgroundSpecialized Early Intervention services (SEI) for first episode psychosis are shown to be effective for the treatment of positive and negative symptoms, medication adherence, rates of relapse, substance abuse disorders, functional outcome and quality of life at two-year treatment follow up. However, it is also reported that these benefits are not maintained when SEI is not sustained. The objective of this trial is to test the efficacy of a 3-year extension of a SEI service (following 2 years of SEI prior to randomization) for the maintenance and consolidation of therapeutic gains as compared to regular care in the community.MethodsFollowing an initial 2 years of SEI, patients are randomized to receive either 3-years of continued SEI or regular care. SEI provided at three sites within the McGill network of SEI services, using a model of treatment comprised of: modified assertive case management; psycho education for families; multiple family intervention; cognitive behavioural therapy; and substance abuse treatment and monitoring. Blinded research assistants conduct ongoing evaluation of the outcome variables every three months. The primary outcome measure is remission status measured both as the proportion of patients in complete remission and the mean length of remission achieved following randomization during the additional three years of follow up. Based on preliminary data, it is determined that a total of 212 patients are needed to achieve adequate statistical power. Intent to treat with the last observation carried forward will be the primary method of statistical analysis.DiscussionThe “critical period” hypothesis posits that there is a five year window during which the effects of the nascent psychotic illness can be countered and the impact of the disorder on symptomatic and functional outcomes can be offset through active and sustained treatment. Providing SEI throughout this critical period may solidify the benefits of treatment such that gains may be more sustainable over time as compared to intervention delivered for a shorter period. Findings from this study will have implications for service provision in first episode psychosis.Trial registrationISRCTN11889976

Psychological and psychosocial interventions for negative symptoms in psychosis: Systematic review and meta-analysis

BackgroundNegative symptoms observed in patients with psychotic disorders undermine quality of life and functioning. Antipsychotic medications have a limited impact. Psychological and psychosocial interventions, with medication, are recommended. However, evidence for the effectiveness of specific non-biological interventions warrants detailed examination.AimsTo conduct a meta-analytic and systematic review of the literature on the effectiveness of non-biological treatments for negative symptoms in psychotic disorders.MethodWe searched for randomised controlled studies of psychological and psychosocial interventions in psychotic disorders that reported outcome on negative symptoms. Standardised mean differences (SMDs) in values of negative symptoms at the end of treatment were calculated across study domains as the main outcome measure.ResultsA total of 95 studies met our criteria and 72 had complete quantitative data. Compared with treatment as usual cognitive-behavioural therapy (pooled SMD -0.34, 95% CI -0.55 to -0.12), skills-based training (pooled SMD -0.44, 95% CI -0.77 to -0.10), exercise (pooled SMD -0.36, 95% CI -0.71 to -0.01), and music treatments (pooled SMD -0.58, 95% CI -0.82 to -0.33) provide significant benefit. Integrated treatment models are effective for early psychosis (SMD -0.38, 95% CI -0.53 to -0.22) as long as the patients remain in treatment. Overall quality of evidence was moderate with a high level of heterogeneity.ConclusionsSpecific psychological and psychosocial interventions have utility in ameliorating negative symptoms in psychosis and should be included in the treatment of negative symptoms. However, more effective treatments for negative symptoms need to be developed.

Factors Associated with Delays of Days to Decades to Criminal Prosecutions of Child Sexual Abuse

Until the latter part of the 20th century, legal doctrines made it almost impossible to successfully prosecute in criminal court a case involving child sexual abuse (CSA), whether the complaint was timely or delayed. Many English-speaking countries have abrogated most formal legal barriers to prosecuting CSA cases, and courts are faced with the singular challenge of adjudicating sexual offenses against children that are reported to have happened years or decades earlier. We conducted analyses of 4,237 criminal complaints of CSA heard in Canadian criminal courts. There were several differences between timely and delayed prosecutions that led us to conclude that delayed prosecutions of CSA are common and due, in part, to the nature of the offense. Offense duration was associated with longer delays to prosecution. When the accused had access to the child through his position in the community, length of delay to prosecution was very long, particularly for male complainants. More research is needed on delayed CSA prosecutions, particularly given an apparent trend for jurisdictions to abolish barriers to criminal prosecutions of CSA that occurred years or decades earlier.

Comparing three‐year extension of early intervention service to regular care following two years of early intervention service in first‐episode psychosis: a randomized single blind clinical trial

This study aimed to determine if, following two years of early intervention service for first‐episode psychosis, three‐year extension of that service was superior to three years of regular care. We conducted a randomized single blind clinical trial using an urn randomization balanced for gender and substance abuse. Participants were recruited from early intervention service clinics in Montreal. Patients (N=220), 18‐35 years old, were randomized to an extension of early intervention service (EEIS; N=110) or to regular care (N=110). EEIS included case management, family intervention, cognitive behaviour therapy and crisis intervention, while regular care involved transfer to primary (community health and social services and family physicians) or secondary care (psychiatric outpatient clinics). Cumulative length of positive and negative symptom remission was the primary outcome measure. EEIS patients had a significantly longer mean length of remission of positive symptoms (92.5 vs. 63.6 weeks, t=4.47, p<0.001), negative symptoms (73.4 vs. 59.6 weeks, t=2.84, p=0.005) and both positive and negative symptoms (66.5 vs. 56.7 weeks, t=2.25, p=0.03) compared to regular care patients. EEIS patients stayed in treatment longer than regular care patients (mean 131.7 vs. 105.3 weeks, t=3.98, p<0.001 through contact with physicians; 134.8 ± 37.7 vs. 89.8 ± 55.2, t=6.45, p<0.0001 through contact with other health care providers) and received more units of treatment (mean 74.9 vs. 39.9, t=4.21, p<0.001 from physicians, and 57.3 vs. 28.2, t=4.08, p<0.001 from other health care professionals). Length of treatment had an independent effect on the length of remission of positive symptoms (t=2.62, p=0.009), while number of units of treatment by any health care provider had an effect on length of remission of negative symptoms (t=−2.70, p=0.008) as well as total symptoms (t=−2.40, p=0.02). Post‐hoc analysis showed that patients randomized to primary care, based on their better clinical profile at randomization, maintained their better outcome, especially as to remission of negative symptoms, at the end of the study. These data suggest that extending early intervention service for three additional years has a positive impact on length of remission of positive and negative symptoms compared to regular care. This may have policy implications for extending early intervention services beyond the current two years.

Predictors of cognition in first episode psychosis

PURPOSE Cognitive deficits are common in the first episode of psychosis (FEP) and may begin much earlier. While some evidence suggests that the decline in cognition occurs over the untreated symptomatic period, including the prodromal phase, others point to these deficits being present even earlier. We aimed to investigate the differential effect of untreated symptomatic and pre-morbid phases on cognition in a large sample of FEP. METHODS Two hundred and sixty eight FEP patients, admitted into a specialized early intervention service, were administered neuro-cognitive tests. The Circumstances of Onset and Relapse Schedule (CORS) was administered for measurement of duration of untreated psychosis (DUP), the duration of untreated illness (DUI) and demographic factors. The Pre-morbid Adjustment Scale (PAS) was used to measure different domains of pre-morbid adjustment. Seventy three healthy controls were also recruited for neuro-cognitive comparison. RESULTS We observed no effect of DUP and a minimal effect of DUI on cognitive functioning in FEP. Instead, the early educational pre-morbid adjustment domain was most strongly associated with cognition and predicted both global cognitive and verbal memory outcome in FEP. CONCLUSION Our results suggest that symptoms associated with the symptomatic phase of a FEP do not influence cognitive functioning in FEP. Instead, cognitive deficits in FEP may predate illness onset and may indicate susceptibility to such illness.

The impact of caregiver familiarity with mental disorders on timing of intervention in first-episode psychosis

Based on prior research, we hypothesized that personal or family familiarity with psychosis would have a different effect on pathways to care as compared to personal or family familiarity with mental disorders.