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Pharmacological and Psychosocial Interventions for FEP

The management of FEP requires great sensitivity and clinical skill and is optimally delivered in specialized services that stream such patients and families separately from older people at later stages of illness. Low-dose antipsychotic medications and a range of intensive psychological and social interventions are essential to maximize recovery and minimize secondary morbidity. These clinical interventions have been heavily researched in recent years and incorporated into detailed clinical practice guidelines.49-51 Given the focus on recovery in this chapter, a detailed exposition of the management of FEP will not be provided here, although it is vital that this phase of illness is optimally managed in order that speedy and sustained recovery is more likely.

Recovery and the Critical Period

Most young people who experience their first episode of psychosis achieve symptomatic remission.52 However, they remain at high risk for relapse, with a recent meta-analysis of 29 longitudinal follow-up studies showing a pooled relapse rate of 54% (40-63%) by 3 years.53 Furthermore, discontinuation of treatment is associated with relapse rates of at least 80% within 5 years with treatment in mainstream services.54-56

Current expert consensus treatment guidelines for early psychosis recommend that, following remission, maintenance antipsychotic medication should be prescribed for at least 12 months before discontinuation is attempted.57 This has become accepted practice due to the risks of disease progression, further disruption to psychosocial functioning, and the development of treatment resistance.58,59 However, there is a growing debate about the balance between the risks and benefits of maintenance medication and its optimum duration to maximize recovery and prevent relapse. The argument for long-term maintenance antipsychotic medication has been challenged by two key recent findings: first, a recent 7-year follow-up study of first-episode patients who had achieved remission in their first year of treatment has shown that recovery was not jeopardized, but rather improved, when their total exposure to antipsychotic medication was controlled via a dose reduction/discontinuation strategy.60 This study involved randomizing 128 patients who had achieved remission to either a dose reduction/discontinuation strategy or maintenance treatment for 18 months. At 18 months, the relapse rate in the dose reduction/discontinu- ation group was more than double that in the maintenance treatment group (43% vs. 21%), with functional outcomes similar in both groups.61 However, at 7-year follow-up, the outcomes had changed dramatically: the relapse rates in both groups were not significantly different, with the excess in the dose reduc- tion/discontinuation group being confined to the first 3 years, whereas those in the dose reduction/discontinuation group had achieved twice the level of functional recovery of those in the maintenance therapy group (40.4% vs. 17.6%).

Second, there is new correlational evidence for an association between level of exposure to antipsychotic medication over time and reductions in brain volume in early psychosis,62,63 thus adding to the established list of physical health, tolerability, and acceptability problems.

Relapse prevention has long been the main goal of treatment. This is not surprising, given that relapses are risky, distressing, and can set back recovery in all domains. The high rate of medication nonadherence/discontinuation in young people with early psychosis is one of the strongest risk factors for relapses in young people with early psychosis.53 However, modest exacerbations of symptoms, which are more common in the first 3-5 years after diagnosis, may be a price worth paying in early remitters, at least for better longer term functional recovery,64 particularly because young people tend to give more weight to the recovery of their social functioning as opposed to symptom recovery alone.65 66 Furthermore, there is good evidence to suggest that a significant percentage of young people who experience a first psychotic episode can achieve full functional recovery even in the presence of residual positive symptoms.23

The emphasis on relapse prevention should therefore be balanced with a focus on functional recovery and the cost of long-term continuous antipsychotic treatment, which evidence suggests contributes to the longer term suppression of functioning. A promising balanced strategy includes a dose minimization strategy combined with intensive and recovery-focused psychosocial treatments, with vigilant monitoring for early signs of relapse.56 However, whether some FEP patients can be safely treated with minimal medication intervention, especially when a more intensive psychosocial safety net is provided, remains an open question that needs to be addressed in further large-scale studies.

Successful relapse prevention67,68 and vocational69 programs have been developed that focus on functional recovery rather than symptomatic recovery alone. Such programs could be offered in the context of medication discontinuation, with careful monitoring for signs of relapse. Our EPISODE II study was the first randomized controlled trial (RCT) comparing CBT for relapse prevention plus recommended FEP treatment with recommended treatment alone.68 A significant treatment effect on relapse rates was shown at 7-month follow-up in young people who had reached remission on positive symptoms. We also showed that this effect was sustained at 12 months, and, beyond this, relapse rates were kept to historically very low levels.68 Importantly, and in accordance with the dose reduction/withdrawal trial discussed earlier, adherence to maintenance antipsychotic medication in our RCT appears to have suppressed psychosocial functioning, suggesting that a strong focus on medication maintenance may interfere with long-term recovery.67

Despite wanting to work, more than 40% of young people with early psychosis are unemployed. Employment is an important pathway to other areas of functioning, and it increases the opportunities for social and economic participation. Supported employment, and in particular individual placement and support, is currently the most effective model for promoting vocational recovery. The key elements of this model are that it focuses on the competitive job market; it is open to anyone with a mental illness who wants to look for work, irrespective of their mental state; job searching begins immediately, with potential jobs being chosen on the basis of the young person’s preferences; the program is integrated within the mental health service’s treatment team; and support is available for as long as it is needed and continues after employment is obtained, depending on the individual’s needs.70 We have successfully implemented this program for young people with early psychosis and found that those who received 6 months of individual placement and support for vocational recovery plus their recommended usual treatment had significantly better outcomes on employment (85% vs. 28% in the control group), hours worked per week, jobs acquired, and longevity of employment compared to those who received their usual treatment alone.69 This model can also be applied to educational settings, as a study from the United Kingdom has shown.71

Intensive psychosocial interventions to promote, support, and maintain a meaningful recovery are particularly important for young people with early psychosis because this age group is uniquely vulnerable to ongoing secondary disability. Ideally, these interventions should be maintained at an appropriate level of intensity for each individual for the critical period of the first

5 years after diagnosis,39 when the risk of ongoing and entrenched secondary disability is highest. Strategies targeted at maximizing functional recovery, such as the relapse prevention and vocational interventions outlined here, may complement and enhance each other and, when combined with an appropriate approach to medication, can significantly improve the outcome for many young people. Our group is now studying the translation of many of these psychosocial interventions to online formats that may allow more effective maintenance of recovery after discharge from specialized early psychosis settings.72,73

Despite the availability of a wide range of medications and psychosocial care as described earlier, a percentage of patients (up to 20%) will fail to achieve remission and recovery from their first episode of psychosis.74 They need to be proactively screened for and identified, and intensive CBT and clozapine should be offered around the 6-month point following entry to care.75 We previously described how this safety net strategy operates within a first-episode program.50,74

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