Sherezad Abadi

Determinants of help-seeking and system related components of delay in the treatment of first-episode psychosis

INTRODUCTION Knowledge about factors that influence different components of duration of untreated psychosis (DUP) is important for designing interventions to reduce DUP. METHOD We tested associations between help-seeking and referral components of DUP (DUP-H and DUP-R, respectively) and the following predictor variables: age, gender, ethnicity, living arrangement, pre-morbid adjustment, age at onset of psychosis, diagnosis, level of symptoms, type of first and total number of mental health contacts prior to and after the onset of psychosis in a sample of 98 first-episode psychosis patients (FEP). RESULTS Longer DUP-HS was significantly associated with earlier age at onset, diagnosis of schizophrenia spectrum psychosis and poor pre-morbid adjustment during adolescence. Longer DUP-R was associated with earlier age at onset and first help-seeking contact having been made with a non-medical professional. CONCLUSIONS Relatively non-malleable patient characteristics are likely to influence delay in help-seeking while more malleable systemic characteristics influence delay associated with referral for specialized treatment.

Sex differences in the cortisol response to awakening in recent onset psychosis

A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been suggested as a factor in the etiology and exacerbation of psychosis, but has not been reported consistently. Sex differences are apparent in many aspects of psychotic disorders and may explain some of the equivocation associated with the regulation of the HPA axis in the illness. The present study compared the cortisol response to awakening (CRA) in 27 patients (16 men and 11 women) with recent onset of psychosis (within the past 2 years) and 40 age and gender matched controls. Within the patient group, we also assessed the relationship between the CRA and positive and negative symptoms of psychosis, anxiety and depression. The CRA in patients was not significantly different from controls. However, within the patient group, we observed a significant sex difference, with a blunted cortisol response to awakening in men but not in women (F=7.26; p<0.002). This difference could not be explained by differences between male and female patients in awakening time, medication, or diagnosis of schizophrenia vs. affective psychosis. Cortisol levels were not related to symptom measures. Our findings demonstrate a dysregulation of the HPA axis in male patients with recent onset of psychosis. This sex specificity might be related to and explain in part the unfavorable course of the illness observed in men.

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

Medication-Adherent First-Episode Psychosis Patients Also Relapse: Why?

Objective: Poor adherence to medication is a major determinant of relapse following treatment of first-episode psychosis (FEP). However, medication-adherent patients also relapse. We examined what factors influence the risk of relapse after controlling for adherence. Method: We selected a sample of fully adherent patients (n = 65) who had achieved remission at one point. We then compared patients who relapsed, using 2 different definitions of relapse, to those who did not relapse by 12 months on age, sex, premorbid adjustment, duration of untreated psychosis, length of prodrome, and substance abuse. Results: Among the 65 medication-adherent patients in remission, 9 (14%) relapsed according to criteria for relapse requiring a change in medication. These patients differed from those who remained in remission only in the pattern of premorbid adjustment (greater proportion with deteriorating pattern), although this was not independent of other variables. No differences were found on any other variable. Using a more commonly used metric for relapse, based on symptom ratings alone, an additional 14 (21.5%) patients relapsed. Substance abuse significantly predicted relapse, with substance abusers having more than 25 times the odds of relapsing by 12 months (OR 25.6; 95% CI 2.4 to 278.1, P = 0.008). Conclusion: Using a more conservative definition of relapse in this adherent-to-medication population, we find a very low rate of relapse associated, at least partially, with poor premorbid adjustment. As substance abuse was a significant predictor of symptomatic relapse, this would suggest that there should be a greater emphasis on interventions focused on reducing substance abuse in FEP.

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.

The Clinic for Assessment of Youth at Risk (CAYR): 10 years of service delivery and research targeting the prevention of psychosis in Montreal, Canada

In the context of an increasing focus on indicated prevention of psychotic disorders, we describe the operation of the Clinic for Assessment of Youth at Risk (CAYR) over 10 years, a specialized service for identification, monitoring and treatment of young individuals who meet ultra‐high risk (UHR) criteria for psychosis, and its integration within the Prevention and Early Intervention Program for Psychosis (PEPP) in Montreal, Canada.

Therapeutic effectiveness and tolerability of aripiprazole as initial choice of treatment in first episode psychosis in an early intervention service: A one-year outcome study

INTRODUCTION Aripiprazole has been associated with a low prevalence of metabolic side effects as compared to other second generation antipsychotic (SGA) medications mostly in patients with long standing illness. The purpose of the present study was to assess specifically the effectiveness and safety of aripiprazole as a first choice for antipsychotic therapy for young patients presenting with a previously untreated first episode of a psychotic disorder (FEP). METHODS Seventy-three patients presenting with a FEP and with minimal prior exposure to antipsychotic medications were recruited to be part of an open label naturalistic outcome study using aripiprazole as the first choice of antipsychotic medication. Data on positive, negative and total symptom severity including general psychopathological symptoms, level of functioning and metabolic indices were collected prospectively over a one-year period. RESULTS As compared to baseline, patients treated with aripiprazole (mean dose 9.6mg) improved significantly on measures of positive (p<0.001), negative (p<0.001) and total severity-general psychopathology symptoms (p<0.001) and level of functioning (p<0.001). Seventy two percent of the participants achieved positive symptom remission and 50% achieved total remission (positive and negative) at one year of follow up. Unlike reports on patients with longer standing illness, significant weight gain (p<0.001) was observed, with 44% of participants experiencing >7% increase in body weight. CONCLUSION FEP patients starting treatment with aripiprazole improved on symptoms and social and occupational functioning. Aripiprazole was well tolerated except for a significant weight gain.

Description, evaluation and scale-up potential of a model for rapid access to early intervention for psychosis

This paper aims to describe the entry protocol of the Prevention and Early Intervention for Psychosis Program (PEPP)‐Montreal, an early intervention program for psychosis. The protocol is designed to fulfil a key objective of the early intervention movement—reducing delays to accessing high‐quality care. The paper also aims to describe how this rapid entry protocol can be deployed in other services interested in reducing delays in initiating treatment.

Gender differences in childhood trauma in first episode psychosis: Association with symptom severity over two years

Early life adversity is associated with increased risk for psychosis onset and poor clinical outcome. Male compared to female patients often show a more severe course of psychotic illness. The aim of the present study was to investigate gender differences in childhood trauma (CT) and their impact on symptomatic and functional outcome following psychosis onset. The study included 210 patients (144 men, 66 women) diagnosed with a first-episode of psychosis (FEP). Early adversity was assessed with the Childhood Trauma Questionnaire. Psychotic symptoms and general functioning were rated with the Brief Psychiatric Rating Scale and Global Assessment of Functioning scale at baseline, 12 and 24 months of follow-up in an established early intervention service. Male patients reported higher rates of physical or emotional neglect, whereas female patients indicated significantly higher rates of emotional abuse. More severe CT was related to higher levels of depression in women and to negative symptoms in men. Distinct CT effects were observed on positive and negative symptom severity and global functioning in male patients at 24 months. Emotional abuse was the strongest predictor of depression in both genders. In male patients only, emotional abuse predicted positive symptom severity and impaired global functioning, whereas emotional neglect predicted more severe negative symptoms. Our results suggest differences in CT experiences in male and female FEP patients, with a more pronounced impact on longer-term outcome in male patients. The findings support the notion that sex differences in stress vulnerability account for the relatively poor illness course in male psychosis patients.