Disorders - Psychosis Disorders
Deakin, B., Suckling, J., Barnes, T. R. E., Byrne,
K., Chaudhry, I. B., Dazzan, P., et al.
BACKGROUND: The antibiotic minocycline has neuroprotective and anti-
inflammatory properties that could prevent or reverse progressive neuropathic changes implicated in recent-onset schizophrenia. In the BeneMin study,
we aimed to replicate the benefit of minocycline on negative symptoms reported in previous pilot studies, and to understand the mechanisms involved.
\rMETHODS: In this randomised, double-blind, placebo-controlled trial, we recruited people with a schizophrenia-spectrum disorder that had begun
within the past 5 years with continuing positive symptoms from 12 National Health Service (NHS) trusts. Participants were randomly assigned according
to an automated permuted blocks algorithm, stratified by pharmacy, to receive minocycline (200 mg per day for 2 weeks, then 300 mg per day for the
remainder of the 12-month study period) or matching placebo, which were added to their continuing treatment. The primary clinical outcome was the
negative symptom subscale score of the Positive and Negative Syndrome Scales (PANSS) across follow-ups at months 2, 6, 9, and 12. The primary
biomarker outcomes were medial prefrontal grey-matter volume, dorsolateral prefrontal cortex activation during a working memory task, and plasma
concentration of interleukin 6. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN49141214, and the EU
Clinical Trials register (EudraCT) number is 2010-022463-35I.\rFINDINGS: Between April 16, 2013, and April 30, 2015, we recruited 207 people and
randomly assigned them to receive minocycline (n=104) or placebo (n=103). Compared with placebo, the addition of minocycline had no effect on ratings
of negative symptoms (treatment effect difference -0.19, 95% CI -1.23 to 0.85; p=0.73). The primary biomarker outcomes did not change over time and
were not affected by minocycline. The groups did not differ in the rate of serious adverse events (n=11 in placebo group and n=18 in the minocycline
group), which were mostly due to admissions for worsening psychiatric state (n=10 in the placebo group and n=15 in the minocycline group). The most
common adverse events were gastrointestinal (n=12 in the placebo group, n=19 in the minocycline group), psychiatric (n=16 in placebo group, n=8 in
minocycline group), nervous system (n=8 in the placebo group, n=12 in the minocycline group), and dermatological (n=10 in the placebo group, n=8 in
the minocycline group).\rINTERPRETATION: Minocycline does not benefit negative or other symptoms of schizophrenia over and above adherence to routine
clinical care in first-episode psychosis. There was no evidence of a persistent progressive neuropathic or inflammatory process underpinning negative
symptoms. Further trials of minocycline in early psychosis are not warranted until there is clear evidence of an inflammatory process, such as
microgliosis, against which minocycline has known efficacy.\rFUNDING: National Institute for Health Research Efficacy and Mechanism Evaluation (EME)
programme, an MRC and NIHR partnership.
The Lancet. Psychiatry, 5(11) : 885-
894
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Other biological interventions
Puig, O.
Early-onset schizophrenia (EOS), defined as the manifestation of psychotic symptoms prior to
18 years of age, is a less common and phenotypically more severe form of the disorder, and implies generalized neurocognitive impairment. Cognitive
remediation therapy (CRT) is a strategy-learning approach targeting cognitive deficits with the ultimate goal of improving functional outcome. The
height neural plasticity during childhood and adolescence suggests that they may be \"sensitive periods\" to treatment effects but it is also
possible that having EOS may confer damage that reduces the ability of the brain to benefit from CRT. Objective(s): To examine the efficacy of CRT in
improving cognition and functional outcomes in a sample of symptomatically stable but cognitively disabled adolescents with EOS. Method(s):
Randomized, controlled trial of individually delivered CRT plus treatment-as-usual (n = 25) compared with treatment-as-usual (TAU, n = 25). Clinical
symptoms and cognitive and functional performance were assessed before and after treatment in both groups and after 3 months in the CRT group.
Result(s): After CRT, significant improvements were found in verbal memory and executive functions. The derived cognitive composite score showed an
improvement after the treatment and this change was reliable in more than two-thirds of the treated patients. Improvements were also found after CRT
in daily living and adaptive functioning, and in family burden. Cognitive but not functional changes were maintained after 3 months. Conclusion(s):
Cognitive and functional improvements can be achieved through CRT in adolescents with EOS but additional strategies may be needed to enhance the
durability of functional gains.
Early Intervention in Psychiatry, 12
(Supplement 1) : 41
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions
(any), Cognitive remediation
therapy
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
Francey, S., Nelson, B., Jessica, G., Lara, B., Yuen, H. P., O'Donoghue, B., Fornito, A., Alvarez-Jimenez, M., Harrigan,
S., McGorry, P.
There are risks associated with the use of
antipsychotic medication (AP). These include adverse neurological and metabolic effects and measurable changes in brain structure. APs may even be
associated with poorer functional recovery. The STAGES Study is a noninferiority design randomised double blind placebo controlled study that
examines whether a subgroup of people with FEP can recover without AP, and considers the effects on functioning, physical health, cognition, and
brain structure of AP versus withholding AP. Young people with FEP were screened for study eligibility and recruited if they met stringent inclusion
criteria indicating low-risk of harm to self or others, and adequate social support. Participants were randomly assigned to receive either low dose
AP (MIPT group) or placebo (PIPT group) for six months, and all participants received intensive psychosocial treatment. Ninety young people (mean age
18.5 years) were randomised and 81 commenced trial medication. Thirty-four percent of participants completed the six month medication phase and there
were more completers in the placebo group than the medication group. On the primary outcome measure of SOFAS there was significant evidence that the
placebo group was not inferior to the medication group (SOFAS: MIPT mean = 61.5, SD = 13.4; PIPT mean = 61.7, SD = 16.8). The two groups were found
to be very similar on all psychopathology assessments and measures of functioning at both baseline and following treatment, suggesting that the
outcomes of the two treatment regimes were not different with respect to symptoms and functioning.
Early Intervention in Psychiatry, 12 (Supplement
1) : 70
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Typical Antipsychotics (first generation), Atypical Antipsychotics (second
generation), Medication dose
reduction/discontinuation, Psychological Interventions
(any)
Kahn, R. S., Winter-van-Rossum, I., Leucht, S., McGuire, P., Lewis,
S. W., Leboyer, M., et al.
BACKGROUND: No established treatment algorithm exists for patients with
schizophrenia. Whether switching antipsychotics or early use of clozapine improves outcome in (first-episode) schizophrenia is unknown.\rMETHODS:
This three-phase study was done in 27 centres, consisting of general hospitals and psychiatric specialty clinics, in 14 European countries and
Israel. Patients aged 18-40 years who met criteria of the DSM-IV for schizophrenia, schizophreniform disorder, or schizoaffective disorder were
treated for 4 weeks with up to 800 mg/day amisulpride orally in an open-label design (phase 1). Patients who did not meet symptomatic remission
criteria at 4 weeks were randomly assigned to continue amisulpride or switch to olanzapine (<=20 mg/day) during a 6-week double-blind phase, with
patients and staff masked to treatment allocation (phase 2). Randomisation was done online by a randomisation website; the application implemented
stratification by site and sex, and applied the minimisation method for randomisation. Patients who were not in remission at 10 weeks were given
clozapine (<=900 mg/day) for an additional 12 weeks in an open-label design (phase 3). The primary outcome was the number of patients who achieved
symptomatic remission at the final visits of phases 1, 2, and 3, measured by intention-to-treat analysis. Data were analysed with a generalised
linear mixed model, with a logistic link and binomial error distribution. This trial is registered with ClinicalTrials.gov, number NCT01248195, and
closed to accrual.\rFINDINGS: Between May 26, 2011, and May 15, 2016, we recruited 481 participants who signed informed consent. Of the 446 patients
in the intention-to-treat sample, 371 (83%) completed open-label amisulpride treatment, and 250 (56%) achieved remission after phase 1. 93 patients
who were not in remission continued to the 6-week double-blind switching trial, with 72 (77%) patients completing the trial (39 on olanzapine and 33
on amisulpride); 15 (45%) patients on amisulpride versus 17 (44%) on olanzapine achieved remission (p=0.87). Of the 40 patients who were not in
remission after 10 weeks of treatment, 28 (70%) started on clozapine; 18 (64%) patients completed the 12-week treatment, and five (28%) achieved
remission. The number of serious adverse events did not differ between the treatment arms in phase 2: one patient on olanzapine was admitted to
hospital because of an epileptic seizure, and one patient on amisulpride was admitted to hospital twice because of exacerbations of psychotic
symptoms. Over the course of the trial, two serious suicide attempts were reported.\rINTERPRETATION: For most patients in the early stages of
schizophrenia, symptomatic remission can be achieved using a simple treatment algorithm comprising the sequential administration of amisulpride and
clozapine. Since switching to olanzapine did not improve outcome, clozapine should be used after patients fail a single antipsychotic trial-not until
two antipsychotics have been tried, as is the current recommendation.\rFUNDING: European Commission Seventh Framework Program.
The Lancet. Psychiatry, 5(10) : 797-
807
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only), Treatment resistant/treatment refractory
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Firth, J., Rosenbaum, S., Ward, P. B., Curtis, J., Teasdale, S. B., Yung, A. R., Sarris, J.
AIM: The effects of nutrient-based treatments, including adjunctive vitamin or antioxidant supplementation, have been
explored extensively in long-term schizophrenia. However, no systematic evaluation of trials in \"first-episode psychosis\" (FEP) has been conducted,
despite the potential benefits of using these treatments during the early stages of illness. Therefore, we aimed to review all studies examining
efficacy, tolerability and the biological mechanisms of action, of nutrient supplementation in FEP.\rMETHODS: A systematic review of electronic
databases was conducted from inception to July 2017. All information on feasibility, clinical outcomes and mechanistic findings from nutrient
supplementation clinical trials was extracted and systematically synthesized.\rRESULTS: Eleven studies with a total of 451 patients with FEP (from 8
independent randomized controlled trials) were eligible for inclusion. Six studies examined omega-3 fatty acids, with inconsistent effects on
psychiatric symptoms. However, mechanistic studies found significant improvements in hippocampal neuronal health and brain glutathione. Antioxidants
\"n-acetyl cysteine\" (n = 1) and vitamin C (n = 2) also improved oxidative status in FEP, which was associated with reduced psychiatric symptoms. No
benefits were found for vitamin E (n = 1). Finally, one study trialling the amino acid taurine, showed significant improvements in positive symptoms
and psychosocial functioning.\rCONCLUSION: There is preliminary evidence that taurine improves outcomes in FEP, whereas effects of omega-3 and
antioxidant vitamins/amino-acids are inconsistent; perhaps mainly benefitting patients with high levels of oxidative stress. Future studies should
evaluate multifaceted dietary and supplementation interventions in FEP; targeting-specific nutritional deficits and the range of aberrant biological
processes implicated in the disorder.
Early Intervention in Psychiatry, 12(5) : 774-
783
- Year: 2018
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Complementary & Alternative
Interventions (CAM), Fish oil (Omega-3 fatty acids), Omega 3 fatty
acids (e.g. fish oil, flax oil), Vitamins and supplements
Hui, C., Honer, W., Lee, E., Chan, S., Chang, W. C., Chen, E.
Whether to discontinue or continue antipsychotics medication in remitted first-
episode psychosis is a difficult clinical decision. Consistent short-term evidence suggests that maintenance medication is effective in relapse
prevention. However, long-term outcome data are lacking; with only one open-label study suggesting better recovery outcome in patients who had early
dose reduction/discontinuation. We examined the long-term effect of early medication discontinuation in a remitted first-episode psychosis cohort in
Hong Kong. We followed-up 178 first-episode psychosis patients who had previously participated in a 12-month randomized controlled trial on
medication discontinuation (placebo) or continuation (quetiapine). Following the trial, all patients received usual psychiatric care. Poor clinical
outcome was defined as a composite of persistent psychotic symptoms, a requirement for clozapine, or suicide at 10 years. We found no significant
differences between patients who were successfully traced after 10 years (n = 142) and those who were not (n = 36) in terms of their basic
demographics, symptoms and functioning at baseline. At 10 years, more patients in the early discontinuation group (35 of 89, 39%) had poor clinical
outcome than patients in the maintenance group (19 of 89, 21%) (P<0.01). Relapse during the randomized trial had partly mediated the significant
relationship between early medication discontinuation and poor outcome (P = 0.003). In first episode psychosis with a full initial response to
antipsychotic treatment, continued need for maintenance medication is important for the first three years after starting treatment, so as to prevent
relapse, and to decrease the risk for a poor long-term outcome.
Early Intervention in Psychiatry, 12 (Supplement
1) : 46
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Relapse prevention
-
Treatment and intervention: Biological Interventions
(any), Medication dose
reduction/discontinuation
MacDougall, A. G., Price, E., Vandermeer, M. R. J., Lloyd,
C., Bird, R., Sethi, R., Shanmugalingam, A., Carr, J., Anderson, K. K., Norman, R. M. G.
Aim: To assess the
feasibility of a randomized pilot trial that evaluated the acceptability and potential clinical utility of the Mindfulness Ambassador Program (MAP),
a unique, standardized 12-session facilitated group mindfulness-based intervention (MBI) for youth experiencing early psychosis. Method(s): Twenty-
one patients of an early psychosis intervention program were randomized to receive MAP (n = 11) or treatment as usual (n = 10). Acceptability was
measured by group attendance rate and client satisfaction; feasibility of the study design was measured by the recruitment and retention rate. The
means, standard deviations, and 95% confidence intervals were described for outcomes of interest. Result(s): MAP is associated with a high degree of
acceptability and has beneficial effects for depression and fatigue. The randomized trial design is feasible. Conclusion(s): This study provides
important pilot data supporting a larger randomized trial of effectiveness for MAP as a group MBI for early psychosis. Details of MAP and study
limitations are discussed. Copyright © 2018 John Wiley & Sons Australia, Ltd
Early intervention in
psychiatry., :
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder), First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Mindfulness based
therapy, Other service delivery and improvement
interventions
Okhuijsen-
Pfeifer, C., Huijsman, E. A. H., Hasan, A., Sommer, I. E. C., Leucht, S., Kahn, R. S., Luykx, J. J.
OBJECTIVE: No consensus exists on whether clozapine should be prescribed
in early stages of psychosis. This systematic review and meta-analysis therefore focus on the use of clozapine as first-line or second-line treatment
in non-treatment-resistant patients.\rMETHODS: Articles were eligible if they investigated clozapine compared to another antipsychotic as a first- or
second-line treatment in non-treatment-resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We
performed random-effects meta-analyses.\rRESULTS: Fifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800
on other antipsychotics). Our meta-analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of
clozapine (Hedges' g = 0.220, P = 0.026, 95% CI = 0.026-0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a
significant benefit of clozapine over risperidone (Hedges' g = 0.274, P = 0.030, 95% CI = 0.027-0.521).\rCONCLUSION: The few eligible trials on this
topic suggest that clozapine may be more effective than other antipsychotics when used as first- or second-line treatment. Only large clinical trials
may comprehensively probe disease stage-dependent superiority of clozapine and investigate overall tolerability.
Acta Psychiatrica Scandinavica, 138(4) : 281-
288
- Year: 2018
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Marchira, C. R., Suprianto, I., Subandi, M. A., Del-Vecchio-Good, M.
J., Good, B. J.
Psychoeducation of persons living with psychotic illness and their family caregivers is a long-standing and effective means of
providing information and support that benefits both families and those living with illness. However, cultural adaptation of psychoeducation and
integration into routine care in settings with very low mental health resources is rare. Purpose(s): This presentation aims to describe outcomes of
an investigation of the effectiveness of a culturally-adapted, brief interactive psychoeducation intervention for family caregivers in Java, and to
study the feasibility of integrating such interventions into routine mental health services provided by primary health care providers. Method(s): An
experimental study was conducted with pre-test and post-test assessments with 100 persons living with first episode psychotic illness and their
family caregivers. Families were randomly assigned to intervention and control groups, and psychiatric residents were trained to administer 4 weekly
interactive psychoeducation sessions with modules adapted for the local cultural setting. When the intervention was found to be feasible and
effective, a program was developed to train staff in three primary health centers to provide a similar intervention for individuals and families
registered with the primary health care center. Finding(s): The initial intervention was found to be feasible and effective, particularly in
increasing Knowledge of Schizophrenia of family members and reducing rehospitalization. Training of primary health care workers was found to be
feasible and effective. Conclusion(s): Adapting psychoeducation for individuals with psychotic illness and family caregivers is feasible and can be
integrated into primary health services in low resource settings.
Early Intervention in Psychiatry, 12 (Supplement
1) : 28
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder), First episode (psychosis only)
-
Treatment and intervention: Psychological Interventions
(any), Psychoeducation
Omachi, Y., Sumiyoshi, T.
Backgrounds: There is a debate regarding the optimal timing of
discontinuation of antipsychotic drugs in patients with first episode psychosis (FEP) or schizophrenia. We aimed to provide a review of the
literature on which strategy (medication maintenance vs. dose reduction/discontinuation) is more likely to maximize outcomes, such as cognition and
social function. Method(s): Using PubMed, the Cochrane Library and systematic reviews, articles published between 2007 and 2018 were reviewed, which
investigated the effect of dose reduction/discontinuation vs. maintenance treatment on measures of cognition and/or social function in FEP and
schizophrenia. Result(s): Six studies were identified; 2 studies reported on cognition while 4 studies concern social function. All studies except
one reported that improvement of functional outcomes in remitted patients with FEP or schizophrenia allocated to a dose reduction/discontinuation arm
was equal to or better than that in patients for whom medication doses were maintained. One trial of social function with a 1-year follow-up period
found a greater improvement in the medication maintenance group, while no group difference was observed with 3-year and 10-year follow-up periods. On
the other hand, a 7-year follow-up study found a superiority for the dose reduction/discontinuation regimen in terms of social outcome. Two studies
on cognition with a short follow-up period reported a greater improvement for the dose reduction/discontinuation group. Conclusion(s): Information on
cognition and social function has been relatively sparse. These measures of functional outcome should be considered in deciding which strategy of
antipsychotic treatments is beneficial in individual cases with FEP or schizophrenia. Copyright © 2007 - 2018 Frontiers Media S.A. All Rights
Reserved.
Frontiers in Psychiatry, 9 (SEP) (no
pagination)(447) :
- Year: 2018
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder), First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Medication dose
reduction/discontinuation
Breier, A., Vohs, J., Leonhardt, B., Mehdiyoun, N., Hummer, T., Liffick, E., Francis, M.
Background: Negative and cognitive symptoms are core features of
schizophrenia and contribute to the marked functional deficits and poor quality of life associated with this illness. Currently approved medications
for schizophrenia, however, are relatively ineffective for these symptom domains. N-Acetyl Cysteine (NAC) is a neuroprotective agent that mitigates
the deleterious effects of oxidative stress, inflammation and glutamatergic toxicity. Because of its unique mechanisms of action, NAC has been
investigated in several clinical trials in schizophrenia. While there is agreement that NAC appears ineffective for positive symptoms, the outcomes
data for negative symptoms and cognitive impairment are conflicting. Method(s): In this paper, we assessed the effects NAC (3600 mg/day) in a 52-
week, double-blind, placebo controlled trial in early phase schizophrenia spectrum disorders (N = 60). Result(s): NAC significantly improved (time x
group) PANSS negative symptoms (F = 5.1, p = 0.024), as well as PANSS total (F = 14.7, p<0.001) and disorganized thought (F = 13.7, p<0.001) symptom
scores. NAC failed to improve BACS cognitive total composite and individual cognitive test scores, as well as PANSS positive symptom scores. 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 symptom scores. Conclusion(s): These results replicate some but not all previous findings of NAC efficacy. The
discrepancies among NAC studies for negative and cognitive symptom results will be addressed with suggestions to reconcile these differences.
Early Intervention in Psychiatry, 12 (Supplement
1) : 69
- Year: 2018
- Problem: Psychosis Disorders
- Type: Controlled clinical trials
-
Stage: First episode (psychosis only), Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Other biological interventions