Is there high-quality evidence indicating that interventions for people at risk of developing psychosis are effective?
Psychoses are serious mental conditions characterised by a loss of contact with reality. The first clear episode of psychosis can be preceded by a 'prodromal' period of at least six months, where a person experiences gradual non-specific changes in thoughts, perceptions, behaviours and functioning. Although an individual is experiencing changes, they have not yet started to experience the more obvious psychotic symptoms such as delusions (fixed false beliefs) or hallucinations (perceptions without a cause). A number of services with treatment approaches that combine pharmacotherapy, psychotherapy and psychosocial treatments, developed worldwide, are now focusing on prevention of psychosis in people at risk by giving treatments during this prodromal period. This review assesses the evidence available concerning the effects of different treatment approaches for people not yet diagnosed with a non affective psychosis but who are in the prodromal stage of psychosis.
Searching for evidence
On 8 June 2016 and 4 August 2017 we ran electronic searches of the Cochrane Schizophrenia's specialised register of studies in order to find clinical studies that randomly allocated individuals at risk of developing psychosis to receive various treatments for preventing development of psychosis.
We were able to include 20 studies with 2151 participants. These studies analysed a wide range of treatments. All the review findings are of, at very best, low quality. There is some suggestion from one small study that people at risk of psychosis may benefit from taking omega-3 fatty acids in terms of reduced transition to psychosis. Other studies found adding antipsychotic drugs to supportive-care packages did not seem to make much difference in terms of transition to full illness. When cognitive behavioural therapy (CBT) + supportive therapy was compared with supportive therapy alone around 8% of participants treated allocated to the combination of CBT and supportive therapy transitioned to psychosis during follow-up by 18 months, compared with double that percentage in people who just received supportive therapy. This could be important but these data are of very low quality. All other testing of CBT and other packages of care found no clear difference between treatments for transition to psychosis.
There has been considerable effort and expense invested testing treatment approaches for prevention of the first episode of schizophrenia. Currently, there is some low-quality evidence suggesting that omega-3 fatty acids may be effective, but there is no high-quality evidence to suggest that any type of treatment is effective, and no firm conclusions can be made.
There has been considerable research effort in this area and several interventions have been trialled. The evidence available suggests that omega-3 fatty acids may prevent transition to psychosis but this evidence is low quality and more research is needed to confirm this finding. Other comparisons did not show any clear differences in effect for preventing transition to psychosis but again, the quality of this evidence is very low or low and not strong enough to make firm conclusions.
Psychosis is a serious mental condition characterised by a loss of contact with reality. There may be a prodromal period or stage of psychosis, where early signs of symptoms indicating onset of first episode psychosis (FEP) occur. A number of services, incorporating multimodal treatment approaches (pharmacotherapy, psychotherapy and psychosocial interventions), developed worldwide, now focus on this prodromal period with the aim of preventing psychosis in people at risk of developing FEP.
The primary objective is to assess the safety and efficacy of early interventions for people in the prodromal stage of psychosis.
The secondary objective is, if possible, to compare the effectiveness of the various different interventions.
We searched Cochrane Schizophrenia's study‐based Register of studies (including trials registers) on 8 June 2016 and 4 August 2017.
All randomised controlled trials (RCTs) evaluating interventions for participants older than 12 years, who had developed a prodromal stage of psychosis.
Review authors independently inspected citations, selected studies, extracted data, and assessed study quality.
We included 20 studies with 2151 participants. The studies analysed 13 different comparisons. Group A comparisons explored the absolute effects of the experimental intervention. Group B were comparisons within which we could not be clear whether differential interactive effects were also ongoing. Group C comparisons explored differential effects between clearly distinct treatments.
A key outcome for this review was ‘transition to psychosis’. For details of other main outcomes please see 'Summary of findings' tables.
In Group A (comparisons of absolute effects) we found no clear difference between amino acids and placebo (risk ratio (RR) 0.48 95% confidence interval (CI) 0.08 to 2.98; 2 RCTs, 52 participants; very low-quality evidence). When omega-3 fatty acids were compared to placebo, fewer participants given the omega-3 (10%) transitioned to psychosis compared to the placebo group (33%) during long-term follow-up of seven years (RR 0.24 95% CI 0.09 to 0.67; 1 RCT, 81 participants; low-quality evidence).
In Group B (comparisons where complex interactions are probable) and in the subgroup focusing on antipsychotic drugs added to specific care packages, the amisulpiride + needs-focused intervention (NFI) compared to NFI comparison (no reporting of transition to psychosis; 1 RCT, 102 participants; very low-quality evidence) and the olanzapine + supportive intervention compared to supportive intervention alone comparison (RR 0.58 95% CI 0.28 to 1.18; 1 RCT, 60 participants; very low-quality evidence) showed no clear differences between groups.
In the second Group B subgroup (cognitive behavioural therapies (CBT)), when CBT + supportive therapy was compared with supportive therapy alone around 8% of participants allocated to the combination of CBT and supportive therapy group transitioned to psychosis during follow-up by 18 months, compared with double that percentage in the supportive therapy alone group (RR 0.45 95% CI 0.23 to 0.89; 2 RCTs, 252 participants; very low-quality evidence). The CBT + risperidone versus CBT + placebo comparison identified no clear difference between treatments (RR 1.02 95% CI 0.39 to 2.67; 1 RCT, 87 participants; very low-quality evidence) and this also applies to the CBT + needs-based intervention (NBI) + risperidone versus NBI comparison (RR 0.75 95% CI 0.39 to 1.46; 1 RCT, 59 participants; very low-quality evidence).
Group C (differential effects) also involved six comparisons. The first compared CBT with supportive therapy. No clear difference was found for the ‘transition to psychosis’ outcome (RR 0.74 95% CI 0.28 to 1.98; 1 RCT, 72 participants; very low-quality evidence). The second subgroup compared CBT + supportive intervention was compared with a NBI + supportive intervention, again, data were equivocal, few and of very low quality (RR 6.32 95% CI 0.34 to 117.09; 1 RCT, 57 participants). In the CBT + risperidone versus supportive therapy comparison, again there was no clear difference between groups (RR 0.76 95% CI 0.28 to 2.03; 1 RCT, 71 participants; very low-quality evidence).
The three other comparisons in Group C demonstrated no clear differences between treatment groups. When cognitive training was compared to active control (tablet games) (no reporting of transition to psychosis; 1 RCT, 62 participants; very low quality data), family treatment compared with enhanced care comparison (RR 0.54 95% CI 0.18 to 1.59; 2 RCTs, 229 participants; very low-quality evidence) and integrated treatment compared to standard treatment comparison (RR 0.57 95% CI 0.28 to 1.15; 1 RCT, 79 participants; very low-quality evidence) no effects of any of these approaches was evident.