Disorders - Psychosis Disorders
Eack, S., Wojtalik, J., Keshavan, M.
Background: The purpose of this investigation was to examine the long-term trajectories of cognitive, functional, and clinical outcomes following Cognitive Enhancement Therapy (CET) in early course schizophrenia. Method(s): Schizophrenia outpatients from a 2-year randomized clinical trial of CET applied in the early course of the illness are completing a 10-year post-treatment follow-up study. Participants from the original trial have completed a comprehensive battery of cognitive, functional, and clinical assessments identical to those in the original trial. Composite indexes were calculated for processing speed, neurocognition, social cognition, functioning, and symptomatology. Linear growth curve models were used to examine longitudinal durability differences in these five domains 10-years following treatment with either CET or an Enriched Supportive Therapy (EST) comparison treatment. Result(s): Social-cognitive ability favoring CET was stable across the 10-year follow-up period, with continued evidence of group separation and little evidence of erosion of efficacy. Some reduction in functioning was observed in both groups after completing treatment (all p < .001), but after 10 years patients in CET retained a higher level of functioning over the follow-up period. Finally, group separation favoring CET in symptomatology continued to persist relative to EST over the course of 10-year follow-up. Conclusion(s): Although these data are considered preliminary, the results suggest that CET is an effective treatment that contributes to long-term and stable improvements in cognition and functional outcome in people with schizophrenia treated in the early course of the illness.
Early Intervention in Psychiatry, 12 (Supplement 1) : 33
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
, First episode (psychosis only)
-
Treatment and intervention: Psychological Interventions (any)
, Cognitive remediation therapy, Supportive therapy
Bhattacharyya, S., Wilson, R., Allen, P., Bossong, M., Appiah-Kusi, E., McGuire, P.
Background: There has been growing interest in the therapeutic potential of Cannabidiol (CBD) stemming from independent evidence that CBD has antipsychotic and anxiolytic properties in patients with mental health disorders. CBD has been found to be non-inferior to antipsychotic medication in a 4-week clinical trial in acute schizophrenia (Leweke et al 2012) and also has been found to reduce anxiety symptoms in social phobia and following public speaking. Human data also suggest that it attenuates the cognitive impairments associated with use of the main psychoactive ingredient in cannabis. However, whether CBD may be useful in relieving symptoms and distress in patients at clinical high-risk of psychosis (CHR) has never been tested. Furthermore, how the beneficial effect of CBD on psychotic and anxiety symptoms may be mediated in the brain remains unclear. The aim of the present study was to investigate whether short-term treatment with CBD was associated with preliminary evidence of therapeutic benefit and understand the neurocognitive mechanisms. Methods: We investigated the effects of short-term (21 days) treatment with CBD on psychotic and anxiety symptoms in 33 CHR patients, using a placebocontrolled, double-blind, parallel-arm design (CBD arm- 16; placebo arm- 17). In the subjects who received 21 days of treatment, we used fMRI in conjunction with a verbal memory task to assess the effect of CBD relative to placebo treatment on medial temporal and striatal function. Results: Of the 33 CHR patients recruited into the trial, 31 completed treatment for 21 days. Following 21-day treatment (intention-to-treat, last observation carried forward analysis), CBD-treated (n=16) CHR patients showed a significantly greater reduction in anxiety (p=0.02) and in distress associated with psychotic symptoms (p=0.03) and a trend (p=0.14) toward greater reduction in the severity of psychotic symptoms compared to those treated with placebo (n=17) CHR patients (Figure 4). In addition, CBD was tolerated as well as placebo. Consistent with our predictions, treatment with CBD (n=15) attenuated the engagement during verbal encoding of the parahippocampal cortex, but increased activation in the putamen in CHR patients. A similar pattern of activation was evident during verbal recall, with CBD treatment associated with increased engagement in the putamen. Discussion: Results from our proof-of-concept study suggest that 3-week treatment with CBD has beneficial effects on anxiety, attenuated psychotic symptoms and the distress associated with psychotic symptoms. They also suggest that short-term treatment with CBD modulates both medial temporal and striatal function in CHR patients, regions that are critically implicated in the CHR state. Coupled with the absence of significant adverse effects associated with CBD, a particularly important issue in relation to the treatment of CHR individuals, not all of whom develop a full-blown psychotic disorder, these data indicate that long-term treatment with CBD is likely to be efficacious in CHR patients.
Schizophrenia Bulletin, 44 (Supplement 1) : S28
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions (any)
, Other biological interventions
Breier, A., Liffick, E., Hummer, T. A., Vohs, J. L., Yang, Z., Mehdiyoun, N. F., Visco, A. C., Metzler, E., Zhang, Y., Francis, M. M.
BACKGROUND: Currently approved medications for schizophrenia are relatively ineffective for negative symptoms and cognitive impairment. N-Acetyl Cysteine (NAC) is a neuroprotective agent that improved general symptoms, cognitive impairment and negative symptoms in some but not all studies, but failed to improve positive symptoms in patients with schizophrenia. Progressive brain mass loss (PBML) has been consistently observed in early phase schizophrenia. NAC mitigates the deleterious effects oxidative stress, inflammation and glutamatergic excitotoxicity and these three pathological processes are hypothesized to contribute to PBML.
METHODS: In this study, we assessed the effects NAC (3600mg/day) in a 52-week, double-blind, placebo controlled trial on symptoms, and cognition in early phase schizophrenia spectrum disorders (N=60). In the context of the clinical trial, we explored the effects of NAC on brain morphology.
RESULTS: NAC significantly improved (timexgroup) PANSS total (F=14.7, p<0.001), negative (F=5.1, p=0.024) and disorganized thought (F=13.7, p<0.001) symptom scores. NAC failed to improve PANSS positive symptoms and BACS cognitive scores. In preliminary analyses, baseline right (r=-0.48, p=0.041) and left (r=-0.45, p=0.018) total cortical thickness, and thickness in other cortical regions, were associated with NAC related improvement in PANSS total scores, but NAC, as compared to placebo, did not significantly impact brain morphology over the study treatment period.
CONCLUSIONS: These results replicate some but not all previous findings of NAC efficacy. Preliminary results suggest that NAC's symptom effects may be related to structural integrity, but NAC failed to demonstrate treatment effects on longitudinal measures of brain morphology. ClinicalTrials.gov Identifier: NCT01339858.
Schizophrenia Research, 199 : 395-402
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Other biological interventions
Bucci, S., Barrowclough, C., Ainsworth, J., Machin, M., Morris, R., Berry, K., Emsley, R., Lewis, S., Edge, D., Buchan, I., Haddock, G.
Background: Timely access to intervention for psychosis is crucial yet problematic. As such, health care providers are forming digital strategies for addressing mental health challenges. A theory-driven digital intervention that monitors distressing experiences and provides real-time active management strategies could improve the speed and quality of recovery in psychosis, over and above conventional treatments. This study assesses the feasibility and acceptability of Actissist, a digital health intervention grounded in the cognitive model of psychosis that targets key early psychosis domains.
Methods: A proof-of-concept, single, blind, randomized controlled trial of Actissist, compared to a symptom-monitoring control. Thirty-six early psychosis patients were randomized on a 2:1 ratio to each arm of the trial. Actissist was delivered via a smartphone app over 12-weeks; clinical and functional assessment time-points were baseline, post-treatment and 22-weeks. Assessors' blind to treatment condition conducted the assessments. Acceptability was examined using qualitative methods.
Results: Actissist was feasible (75% participants used Actissist at least once/day; uptake was high, 97% participants remained in the trial; high follow-up rates), acceptable (90% participants recommend Actissist), and safe (0 serious adverse events), with high levels of user satisfaction. Treatment effects were large on negative symptoms, general psychotic symptoms and mood. The addition of Actissist conferred benefit at post-treatment assessment over routine symptom-monitoring and treatment as usual.
Conclusions: This is the first controlled proof-of-concept trial of a theory-driven digital health intervention for early psychosis. Actissist is feasible and acceptable to early psychosis patients, with a strong signal for treatment efficacy. Trial Registration: ISRCTN: 34966555.
Schizophrenia Bulletin, 44(5) : 1070-1080
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Complementary & Alternative Interventions (CAM)
, Service Delivery & Improvement, Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
, Mindfulness based therapy, Relaxation
, Technology, interventions delivered using technology (e.g. online, SMS)
Burke, E., Wojcik, J., Seidman, L. J., Green, A., Woo, T. U. W.
Background: The overt symptoms and deficits of schizophrenia (SZ) typically emerge during late adolescence and early adulthood, followed by a period of post-onset functional deterioration. This peri-onset period temporally coincides with the final maturation of the prefrontal cortex (PFC), which is characterized by a process of extensive pruning of synaptic connectivities. Developmental maturation of inhibitory neurotransmission may play a key role in regulating the onset and duration of peri-adolescent synaptic pruning. We hypothesize that a deficit in the developmental increase in inhibitory neurotransmission may disturb the PFC synaptic pruning process and hence contribute to the onset and the functional deterioration that is characteristic of the early course of SZ. Enhancement of inhibitory neurotransmission may therefore restore the integrity of PFC neural circuitry, which may then lead to lasting improvements in cognitive deficits and clinical symptoms. Methods: Here, we report preliminary data on the possible efficacy of tiagabine (Gabitril), which is a selective uptake inhibitor of the GABA (gamma-aminobutyric acid) transporter GAT-1, in the treatment of recentonset schizophrenia. Subjects were randomized to receive either tiagabine or placebo added on to their antipsychotic regimen. Results: Our data suggest that treatment with tiagabine during the early course of the illness can modulate PFC activation, as demonstrated by functional magnetic resonance imaging during working memory, and improve negative symptoms. Discussion: Taken together, the proposed treatment strategy represents an effort to actively translate preclinical findings in SZ research into clinically testable hypotheses. This kind of translational approach, we believe, will ultimately lead to breakthrough in the treatment and possible prevention of SZ.
Schizophrenia Bulletin, 44 (Supplement 1) : S235-S236
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Anticonvulsants/mood stabilisers (excl. lithium)
Chang, W. C., Kwong, V. W. Y., Or-Chi-Fai, P., Lau, E. S. K., Chan, G. H. K., Jim, O. T. T., Hui, C. L. M., Chan, S. K. W., Lee, E. H. M., Chen, E. Y. H.
OBJECTIVE: Functional remission represents an intermediate functional milestone toward recovery. Differential relationships of negative symptom sub-domains with functional remission in first-episode psychosis are understudied. We aimed to examine rate and predictors of functional remission in people with first-episode psychosis in the context of a 3-year follow-up of a randomized controlled trial comparing 1-year extension of early intervention (i.e. 3-year early intervention) with step-down psychiatric care (i.e. 2-year early intervention).
METHOD: A total of 160 participants were recruited upon completion of a 2-year specialized early intervention program for first-episode psychosis in Hong Kong and underwent a 1-year randomized controlled trial comparing 1-year extended early intervention with step-down care. Participants were followed up and reassessed 3 years after inclusion to the trial (i.e. 3-year follow-up). Functional remission was operationalized as simultaneous fulfillment of attaining adequate functioning (measured by Social and Occupational Functioning Scale and Role Functioning Scale) at 3-year follow-up and sustained employment in the last 6 months of 3-year study period. Negative symptom measure was delineated into amotivation (i.e. motivational impairment) and diminished expression (i.e. reduced affect and speech output). Data analysis was based on 143 participants who completed follow-up functional assessments.
RESULTS: A total of 31 (21.7%) participants achieved functional remission status at 3-year follow-up. Multivariate regression analysis showed that lower levels of amotivation ( p = 0.010) and better functioning at study intake ( p = 0.004) independently predicted functional remission (Final model: Nagelkerke R2 = 0.40, chi2 = 42.9, p < 0.001). Extended early intervention, duration of untreated psychosis and diminished expression did not predict functional remission.
CONCLUSION: Only approximately one-fifths of early psychosis patients were found to achieve functional remission. Functional impairment remains an unmet treatment need in the early stage of psychotic illness. Our results further suggest that amotivation may represent a critical therapeutic target for functional remission attainment in early psychosis.
Australian & New Zealand Journal of Psychiatry, : 4867418758918
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Case management
, Other service delivery and improvement interventions
Chen, E., Hui, C., Chang, W. C., Chan, S., Lee, E., Honer, W.
Background: Clinical decision to dis/continue antipsychotics in patients remitted from first-episode psychosis is important. Existing short-term evidence suggests that patients who discontinued antipsychotics had more relapses. Data on long-term outcomes are lacking; with only one open-label study suggesting better long-term recovery outcome in patients who had early medication discontinuation. We examined the long-term effect of early medication discontinuation in year 2 following first-episode remission for patients with no residual psychotic symptoms. Methods: We followed-up 178 first-episode psychosis patients who participated in a 1-year randomized controlled trial (RCT) on medication discontinuation. Patients were randomized into receiving either a medication maintenance group or a placebo discontinuation group. After the RCT, all patients received usual psychiatric care. Poor long-term clinical outcome was defined as a composite of persistent psychotic symptoms, a requirement for clozapine, or suicide. Results: There were no differences between patients who were included (n=142) and excluded (n=36) from the study with regard to their baseline demographics, clinical and functioning. At 10 years, more patients in the early discontinuation group (35/89, 39%) had poor clinical outcome than patients in the maintenance group (19/89, 21%) (P<0.01). Relapse during the RCT has partly mediated the significant relationship between early medication discontinuation and poor outcome at 10-year. Discussion: Whether to discontinue medication following successful treatment of first episode psychosis is a difficult clinical decision. In first episode psychosis with a full initial response to antipsychotic treatment, continued need for medication is important for the first three years after starting treatment, to prevent relapse, and decrease the risk for a poor long-term outcome.
Schizophrenia Bulletin, 44 (Supplement 1) : S97
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Medication dose reduction/discontinuation
Conus, P., Seidman, L. J., Fournier, M., Xin, L., Cleusix, M., Baumann, P. S., Ferrari, C., Cousins, A., Alameda, L., Gholam-Rezaee, M., Golay, P., Jenni, R., Woo, T. U. W., Keshavan, M. S., Eap, C. B., Wojcik, J., Cuenod, M., Buclin, T., Gruetter, R., Do, K. Q.
Biomarker-guided treatments are needed in psychiatry, and previous data suggest oxidative stress may be a target in schizophrenia. A previous add-on trial with the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in chronic patients. We aim to study NAC's impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox markers (brain GSH [GSHmPFC], blood cells GSH levels [GSHBC], GSH peroxidase activity [GPxBC]). No changes in negative or positive symptoms or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on neurocognition (processing speed). NAC also led to increases of GSHmPFC by 23% (P = .005) and GSHBC by 19% (P = .05). In patients with high-baseline GPxBC compared to low-baseline GPxBC, subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC. In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest baseline levels. However, NAC led to some neurocognitive improvements and an increase in brain GSH levels, indicating good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help identify a subgroup of patients who improve their positive symptoms with NAC. Thus, future trials with antioxidants in EP should consider biomarker-guided treatment. Copyright © The Author(s) 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.
Schizophrenia Bulletin, 44(2) : 317-327
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Other biological interventions
Drake, R., Nordentoft, M., Haddock, G., Ainsworth, J., Lewis, S.
Background: We hypothesised that a multi-modal psychosocial intervention (PSI) after first episodes of non-affective psychosis would increase antipsychotic adherence, improve functioning and prevent readmission in a multicentre, blind-rated, randomised controlled trial. Methods: Following treatment of first episode non-affective psychosis with amisulpride, olanzapine or clozapine (those remitting after phases 1-3 of the OPTIMISE program or dropping-out but willing to enter the adherence trial) patients with DSM-IV schizophreniform disorder, schizophrenia, or schizoaffective disorder were eligible for allocation to PSI or treatment as usual (TAU). PSI involved: i) e-learning via a psychoeducational website; ii) mHealth intervention with 3 months SMS medication reminders configured by participants; iii) motivational interviewing targeting adherence over 6 weeks. Primary outcome measures at 3 and 12 month follow-up were Compliance Rating Scale (score 1-7 worst to best), and Social and Occupational Function Assessment Scale (SOFAS; 0-100). Secondary outcomes included remission, Drug Attitudes Inventory (DAI), and EuroQoL quality of life scale. We present interim analyses of 3 month data with general linear and logistic regression models, clustered by centre and adjusted for baseline scores and demographics. Results: Recruitment time, now finished, was extended to reach target sample size, so 12 month data are incomplete. 258 were allocated to PSI or TAU. 18 dropped-out before baseline assessment: 240 entered the modified intention to treat analysis (PSI 121, TAU 119). After PSI, 71% were followed-up at 3 months; after TAU, 80%. No baseline variable significantly predicted this attrition. Webpages covering illness and treatment had 244-290 hits each. Only 24% of the PSI group set up SMS text reminders. At least 70% attended motivational interviewing, 77% of these for all sessions. Mean California Patient Alliance Scale item score was 5.2 (95% Confidence Interval, CI, 5.0, 5.3; score 1-7 poor-good). Mean baseline SOFAS (SD) for the PSI group was 62 (14); for TAU 62 (15). General linear modelling of 12 week data included baseline CRS and drug attitudes: marginal mean SOFAS after PSI was 65.3 (CI 62.6, 68.0) and after TAU 61.4 (CI 59.3, 63.4; p0.025; standardised effect size Glass' DELTA=0.41). Median (IQR) compliance score was 6 (5,7) at baseline for PSI and 6 (6,7) for TAU; and 6 (5,7) at 3 months in both groups (ordinal logistic regression, p0.36). In secondary analyses 3 month DAI did not differ significantly between PSI and TAU (marginal means 13.5 v 11.5, bootstrapped p0.164). EuroQoL wellbeing score was significantly better after PSI (marginal means 76.0 v 69.1, bootstrapped p0.003) and remission was significantly commoner (72 v 54%, binary logistic regression p0.007). No analysis result was sensitive to probability weighted adjustment for drop out. Discussion: Interim analyses indicate that immediately after PSI social function and wellbeing improved significantly and remission was commoner. Adherence and DAI did not differ significantly. Either PSI's immediate benefits were non-specific or adherence measures failed to capture its effect. Longer term effects are unclear until definitive analyses planned before 2018.
Schizophrenia Bulletin, 44 (Supplement 1) : S50
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions (any)
, Motivational interviewing, includes Motivational Enhancing Therapy, Technology, interventions delivered using technology (e.g. online, SMS)
Francis, M. M., Hummer, T. A., Vohs, J. L., Yung, M. G., Visco, A. C., Mehdiyoun, N. F., Kulig, T. C., Um, M., Yang, Z., Motamed, M., Liffick, E., Zhang, Y., Breier, A.
Cognitive dysfunction is a core facet of schizophrenia that is present early in the course of the illness and contributes to diminished functioning and outcomes. Repetitive transcranial magnetic stimulation (rTMS) is a relatively new neuropsychiatric intervention. Initially used in treatment resistant depression, investigators are now studying rTMS for other psychiatric diseases such as schizophrenia. In this study we examined the effect of high frequency rTMS on cognitive function in a group of individuals with early phase psychosis. Twenty subjects were randomized (1:1) in double-blind fashion to rTMS or sham condition. Over two weeks subjects underwent ten sessions of high frequency, bilateral, sequential rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Prior to beginning and following completion of study treatment, subjects completed a cognitive assessment and magnetic resonance imaging. Subjects receiving rTMS, compared to sham treatment, displayed improvement on a standardized cognitive battery both immediately following the course of study treatment and at follow-up two weeks later. Imaging results revealed that left frontal cortical thickness at baseline was correlated with treatment response. The study treatment was found to be safe and well tolerated. These results suggest that rTMS may hold promise for the treatment of cognitive dysfunction in the early phase of psychosis, and that MRI may provide biomarkers predicting response to the treatment.
Brain Imaging & Behavior, : 31
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Transcranial magnetic stimulation (TMS)
Huang, M., Yu, L., Pan, F., Lu, S., Hu, S., Hu, J., Chen, J., Jin, P., Qi, H., Xu, Y.
BACKGROUND: This study was conducted to evaluate the efficacy and metabolic effects of paliperidone palmitate (PP) injections against oral olanzapine in first-episode schizophrenia (FES) patients.
METHODS: Eligible patients were randomized to receive PP or olanzapine. Efficacy assessments and weight-related parameters were assessed at baseline, weeks 1, 5, 9, and endpoint or at early withdrawal. Lipid, glucose, insulin and prolactin were evaluated at baseline and endpoint or at early withdrawal.
RESULTS: The Positive And Negative Syndrome Scale (PANSS) scores declined significantly after treatment in both groups. Significant increases in weight-related parameters from baseline to endpoint were shown in both groups. Although there was no significant difference in PANSS scores and weight-related parameters between the two groups through the whole 13-week study. The increased level of triglyceride and HOMA-IR at endpoint from baseline in the olanzapine group was higher than the PP group. There was a stronger elevation of prolactin level in the PP group.
CONCLUSIONS: In summary, PP and olanzapine showed similar improvement in the treatment of FES patients. This study also reinforced the necessity for regular monitoring of metabolic parameters in schizophrenia patients prescribed atypical antipsychotics. Clinical trial registration numbers: ChiCTR-IOR-14005304. Date of registration: 2014-10-11.
Progress in Neuro-Psychopharmacology & Biological Psychiatry, 81 : 122-130
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Hui, C. L., Honer, W. G., Lee, E. H., Chang, W. C., Chan, S. K., Chen, E. S., Pang, E. P., Lui, S. S., Chung, D. W., Yeung, W. S., Ng, R. M., Lo, W. T., Jones, P. B., Sham, P., Chen, E. Y.
Background: The long-term consequences of discontinuing antipsychotic medication after successful treatment of first-episode psychosis are not well studied. We assess the relation between early maintenance therapy decisions in first-episode psychosis and the subsequent clinical outcome at 10 years. Methods: This is a 10 year follow-up study, spanning Sept 5, 2003, to Dec 30, 2014, of a randomised, double-blind trial in seven centres in Hong Kong in which 178 patients with first-episode psychosis with full positive symptom resolution after at least 1 year of antipsychotic treatment were given maintenance treatment (n = 89; oral quetiapine 400 mg daily) or early treatment discontinuation (n = 89; placebo) for 12 months. After the trial, patients received naturalistic treatment. Overall this cohort of patients will have received about 3 years of treatment before entering the follow-up phase of the study: about 2 years of maintenance treatment before study entry and 1 year of treatment in the trial. The primary outcome of this follow-up was the proportion of patients in each group (including those for whom direct follow-up was not available) with good or poor long-term clinical outcomes at 10 years, with poor outcome defined as a composite of persistent psychotic symptoms, a requirement for clozapine treatment, or death by suicide. The randomised trial was registered with ClinicalTrials.gov, number NCT00334035, and the follow-up study was registered with ClinicalTrials.gov, number NCT01926340. Findings: Poor 10 year clinical outcome occurred in 35 (39%) of 89 patients in the discontinuation group and 19 (21%) of 89 patients in the maintenance treatment group (risk ratio 1.84, 95% CI 1.15-2.96; p = 0.012). Suicide was the only serious adverse event that occurred in the follow-up phase (four [4%] patients in the early discontinuation group vs two [2%] in the maintenance group). Interpretation: In patients with first-episode psychosis with a full initial response to treatment, medication continuation for at least the first 3 years after starting treatment decreases the risk of relapse and poor long-term clinical outcome. (PsycINFO Database Record (c) 2018 APA, all rights reserved)
The Lancet Psychiatry, 5(5) : 432-442
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Medication dose reduction/discontinuation