Kingsley Crisp

Who needs antipsychotic medication in the earliest stages of psychosis? A reconsideration of benefits, risks, neurobiology and ethics in the era of early intervention

In recent years, early intervention services have attempted to identify people with a first episode of psychosis as early as possible, reducing the duration of untreated psychosis and changing the timing of delivery of interventions. The logic of early intervention is based partly on accessing people in a more treatment responsive stage of illness in which psychosocial damage is less extensive, and partly on remediating a putatively active process of neuroprogression that leads to pathophysiological, symptomatic and structural changes, hence improving symptomatic and functional outcomes. However, as in other areas of health care, earlier identification of new patients may mean that different treatment approaches are indicated. The corollary of early detection is that the sequence and complexion of treatment strategies for first episode psychosis has been revaluated. Examples include the minimal effective dosage of antipsychotic medication and the content of psychosocial interventions. With the substantial reductions of DUP now seen in many early psychosis services, based on clinical staging and stepped care principles, it is even possible that the immediate introduction of antipsychotic medication may not be necessary for all first episode psychosis cases, but that potentially safer interventions, which may be more acceptable to many patients, such as comprehensive psychosocial intervention, may constitute effective treatment at least for a subgroup of patients. In this paper, we review this theoretical background and describe a randomised controlled trial currently underway at the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne designed to test outcomes for first episode psychosis patients in response to two different treatments: intensive psychosocial intervention plus antipsychotic medication versus intensive psychosocial intervention plus placebo. This is a theoretically and pragmatically novel study in that it will provide evidence as to whether intensive psychosocial intervention alone is sufficient for a subgroup of first episode psychosis patients in a specialised early intervention service, and provide a test of the heuristic clinical staging model. By experimentally manipulating duration of untreated psychosis, the study will also provide a methodologically strong test of the effect of delaying the introduction of antipsychotic medication, as well as helping to disentangle the effects of antipsychotic medications and the putative neurobiological processes associated with brain changes and symptom profiles in the early phase of psychotic disorders. The study has been carefully crafted to satisfy critical ethical demands in this challenging research domain.

Family Outcomes From a Randomized Control Trial of Relapse Prevention Therapy in First-Episode Psychosis

OBJECTIVE We have previously reported that our combined individual and family cognitive-behavioral therapy (CBT) relapse prevention therapy (RPT) was effective in reducing relapse rates compared to treatment as usual (TAU) within a specialist program for young, first-episode psychosis patients who had reached remission on positive symptoms. Here, we report the outcomes for family participants of DSM-IV-diagnosed first-episode psychosis patients recruited between November 2003 and May 2005 over a 2.5-year follow-up period. The primary hypothesis was that, compared to family members receiving TAU, family participants who received RPT would have significantly improved appraisals of stressors related to caregiving. Secondary hypotheses were that RPT would be associated with reduced expressed emotion and improved psychological distress. METHOD Family members were assessed at baseline and at 7-month, 12-month, 18-month, 24-month, and 30-month follow-up on appraisal of caregiving, expressed emotion, and psychological distress using the Experience of Caregiving Inventory, The Family Questionnaire, and the General Health Questionnaire of 28 Items, respectively. The family component of RPT was based on family behavioral therapy for schizophrenia with a specific focus on psychoeducation and CBT for relapse prevention. RESULTS Thirty-two families received RPT, and 31 families received TAU. There were significant group effects for aspects of the appraisal of caregiving, including negative symptoms, positive personal experiences, and total positive score on the Experience of Caregiving Inventory. Time effects were evident for emotional overinvolvement and for aspects of the appraisal of caregiving. There were no significant effects for psychological distress. CONCLUSIONS The relatives of patients who received RPT perceived less stress related to their relatives negative symptoms and an increase in perceived opportunities to make a positive contribution to the care of their relative compared to carers in the TAU condition. Cognitive-behavioral therapy for relapse prevention showed promise in improving the experience of caregiving for family members of first-episode psychosis patients over a 2.5-year follow-up period. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12605000514606.

Predictors of Adherence to Cognitive-Behavioural Therapy in First-Episode Psychosis:

Objective: To investigate predictors of adherence with a cognitive-behavioural intervention in first-episode psychosis (FEP) patients. Method: Predictors of adherence to cognitive-behavioural therapy (CBT) were longitudinally investigated in the experimental arm of a randomized controlled trial designed to evaluate the effectiveness of a CBT intervention for relapse prevention early in the course of psychosis when compared with treatment as usual within 2 high quality, youth oriented, specialist FEP programs (the EPISODE II trial). Results: Longer duration of untreated psychosis (DUP) and poorer level of insight predicted poor adherence to CBT. This association remained significant after controlling for potential confounders. Conclusions: Treatment delay may decrease adherence with CBT in FEP patients. Reducing DUP and promoting insight early in the course of psychosis are likely to enhance adherence with CBT.

A Randomized Controlled Trial of Relapse Prevention Therapy for First-Episode Psychosis Patients: Outcome at 30-Month Follow-Up

The effectiveness of a novel 7-month psychosocial treatment designed to prevent the second episode of psychosis was evaluated in a randomized controlled trial at 2 specialist first-episode psychosis (FEP) programs. An individual and family cognitive behavior therapy for relapse prevention was compared with specialist FEP care. Forty-one FEP patients were randomized to the relapse prevention therapy (RPT) and 40 to specialist FEP care. Participants were assessed on an array of measures at baseline, 7- (end of therapy), 12-, 18-, 24-, and 30-month follow-up. At 12-month follow-up, the relapse rate was significantly lower in the therapy condition compared with specialized treatment alone (P = .039), and time to relapse was significantly delayed for those in the relapse therapy condition (P = .038); however, such differences were not maintained. Unexpectedly, psychosocial functioning deteriorated over time in the experimental but not in the control group; these differences were no longer statistically significant when between-group differences in medication adherence were included in the model. Further research is required to ascertain if the initial treatment effect of the RPT can be sustained. Further research is needed to investigate if medication adherence contributes to negative outcomes in functioning in FEP patients who have reached remission, or, alternatively, if a component of RPT is detrimental.

A randomized controlled trial of bibliotherapy for carers of young people with first-episode psychosis

Caring for young people with first-episode psychosis (FEP) is challenging and can adversely affect carer well-being, with limited evidence-based support materials available. We aimed to examine whether completion of a self-directed problem-solving bibliotherapy among carers of young people with FEP led to a better experience of caring, less distress and expressed emotion, and better general health than carers who only received treatment as usual (TAU). A randomized controlled trial was conducted across two early-intervention psychosis services in Melbourne, Australia. A total of 124 carers were randomized to problem-solving bibliotherapy intervention (PSBI) or TAU and assessed at baseline, 6-week and 16-week follow-up. Intent-to-treat analyses were carried out and indicated that recipients of PSBI had a more favorable experience of caring than those receiving TAU, and these effects were sustained at both follow-up time points. Across the other measures, both groups demonstrated improvements by week 16, although the PBSI group tended to improve earlier. The PSBI group experienced a greater reduction in negative emotional evaluations of the need to provide additional support to young people with FEP than the TAU group by week 6, while the level of psychological distress decreased at a greater rate from baseline to 6 weeks in the PSBI compared with the TAU group. These findings support the use of problem-solving bibliotherapy for first-time carers, particularly as a cost-effective adjunct to TAU.

The EPISODE II trial of cognitive and family therapy for relapse prevention in early psychosis: Rationale and sample characteristics

Background: High rates of remission are associated with effective treatments for first-episode psychosis (FEP). However, the goal of relapse prevention remains elusive for many remitted FEP patients. Aims: This paper describes the clinical and functional status of remitted FEP patients at a specialist service, and outlines the rationale and methodology of a randomized controlled trial of a multimodal relapse prevention therapy for these patients. Method: Eighty one remitted FEP patients and 63 of their family members attending the Early Psychosis Prevention and Intervention Centre (EPPIC) were randomized to treatment as usual (TAU) or to a relapse prevention therapy (RPT). Baseline data included demographics, Axis I and II diagnoses, psychiatric symptoms, functional status, and family distress, burden, and communication styles. Results: The findings indicated high rates of depressive and negative symptoms and substance abuse problems. Less than half of the patients had returned to employment. A high rate of depressive and anxiety symptoms was evident amongst family members, and burden was comparable to results from other FEP studies. Conclusions: FEP patients who reach remission have wide-ranging clinical and psychosocial needs. Relapse risk remains high, and relapse prevention is a critical priority. Family members also need specific interventions. Declaration of interest: This study described in this paper has been funded by an independent research grant from Eli Lilly via the Lilly Melbourne Academic Psychiatry Consortium.

Enhancing Treatment Fidelity in Psychotherapy Research: Novel Approach to Measure the Components of Cognitive Behavioural Therapy for Relapse Prevention in First-Episode Psychosis

Objectives: Establishing treatment fidelity is one of the most important aspects of psychotherapy research. Treatment fidelity refers to the methodological strategies used to examine and enhance the reliability and validity of psychotherapy. This study sought to develop and evaluate a measure specifically designed to assess fidelity to the different therapeutic components (i.e. therapy phases) of the individual intervention of a psychotherapy clinical trial (the EPISODE II trial). Method: A representative sample of sessions stratified by therapy phase was assessed using a specifically developed fidelity measure (Relapse Prevention Therapy–Fidelity Scale, RPT-FS). Each RPT-FS subscale was designed to include a different component/phase of therapy and its major therapeutic ingredients. Results: The measure was found to be reliable and had good internal consistency. The RPT-FS discriminated, almost perfectly, between therapy phases. The analysis of the therapeutic strategies implemented during the intervention indicated that treatment fidelity was good throughout therapy phases. While therapists primarily engaged in interventions from the appropriate therapeutic phase, flexibility in therapy was evident. Conclusions: This study described the development of a brief, reliable and internally consistent measure to determine both treatment fidelity and the therapy components implemented throughout the intervention. This methodology can be potentially useful to determine those components related to therapeutic change.

Moderated Online Social Therapy: A Model for Reducing Stress in Carers of Young People Diagnosed with Mental Health Disorders

Family members caring for a young person diagnosed with the onset of mental health problems face heightened stress, depression, and social isolation. Despite evidence for the effectiveness of family based interventions, sustaining access to specialist family interventions is a major challenge. The availability of the Internet provides possibilities to expand and sustain access to evidence-based psychoeducation and personal support for family members. In this paper we describe the therapeutic model and the components of our purpose-built moderated online social therapy (MOST) program for families. We outline the background to its development, beginning with our face-to-face EPISODE II family intervention, which informed our selection of therapeutic content, and the integration of recent developments in positive psychology. Our online interventions for carers integrate online therapy, online social networking, peer and expert support, and online social problem solving which has been designed to reduce stress in carers. The initial version of our application entitled Meridian was shown to be safe, acceptable, and feasible in a feasibility study of carers of youth diagnosed with depression and anxiety. There was a significant reduction in self-reported levels of stress in caregivers and change in stress was significantly correlated with use of the system. We have subsequently launched a cluster RCT for caregivers with a relative diagnosed with first-episode psychosis. Our intervention has the potential to improve access to effective specialist support for families facing the onset of serious mental health problems in their young relative.