Disorders - Psychosis Disorders
Kahn, R.
Background: Very few prospective, sequential studies are available that could guide decisions which have to be made in every day clinical routine. Some of the simplest questions of clinicians remain unanswered. For example: If the first antipsychotic used has not worked, is switching to another drug effective? Or should we perhaps increase the dose? And when should we start clozapine, the most efficacious drug? These questions are most urgent for patients with a first episode of psychosis. Methods: OPTiMiSE is an international clinical trial, conducted in 27 research centers located in 14 countries across Europe and Israel. Among other purposes, OPTiMiSE was designed to test a three-stage treatment algorithm. The 446 participants of OPTiMiSE were diagnosed with a first episode of schizophrenia, schizophreniform or schizoaffective disorder. Each participant started with a 4-week open label amisulpride treatment. After these 4 weeks, non-remitters are randomized to switch to another antipsychotic versus continuation of amisulpride for 6 weeks, in a double-blind fashion (phase 2). After these additional 6 weeks, non-remitters were switched to clozapine for another 12 weeks. Results: Description of the sample: Mean age at inclusion was 26 years, 30% of the patient sample was female. The median duration of illness was 4 months and none of the participants had been using antipsychotic medication for more than 2 weeks. All patients were treated on a voluntarily basis. The patient sample was moderately ill at baseline, with a mean score on the Positive And Negative Syndrome Scale (PANSS) of 78 (sd 19). Phase 1 Patients started on 200-800 mg/day amisulpride treatment, with a target dose of 400 mg/day. Drop-out rate was 20%. Out of the 446 patients who were initiated on amisulpride, 56% met remission criteria, based on the eight remission items of the PANSS. Side effects were mild, with a mean weight increase of 2.7 kg (sd 3.3). Phase 2 At the end of phase 1, 121 patients did not meet remission criteria. Out of the 93 patients who continued into the double-blind treatment phase, 72 patients completed the 6-week treatment phase. Remission rate in phase 2 was 35%. There was no significant difference between the two treatment arms regarding remission rate, nor regarding the drop out rate. Patients randomized to olanzapine gained significantly more weight compared to amisulpride. Phase 3 At the end of phase 2, 40 patients did not meet remission criteria. Out of the 28 patients who continued into the open-label clozapine treatment phase, 18 patients completed this 12-week treatment from which only 5 patients met remission criteria, translating into a remission rate of only 18%. Non-remitters generally did improve to a great extent but failed to meet the stringent remission criteria. Discussion: Amisulpride is confirmed to be a good option for initiating pharmacotherapy in first episode patients, resulting in a high remission rate. There was no advantage related to remission rates or drop out rates for switching non-responders after 4 week of treatment to another antipsychotic versus continuing the initiated antipsychotic for another 6 weeks; continuing the first antipsychotic may have the benefit of avoiding new side effects related to introducing a new antipsychotic. Despite a low remission rate following clozapine treatment, non-remitters generally did show a substantial reduction in symptoms, demonstrating that clozapine should be an option for non-responding psychotic patients early in the illness.
Schizophrenia Bulletin, 44 (Supplement 1) : S50
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Krynicki, C., Upthegrove, R., Suckling, J., Dazzan, P., Joyce, E., Lawrie, S., Husain, N., Chaudhry, I., Dunn, G., Jones, P., Lisiecka, D., Lewis, S., Barnes, T., Williams, S., Hopkins, S., Drake, R., Smallman, R., Giordano, A., Pariante, C., Deakin, B.
Background: Negative symptoms consist of impaired quality of life, social isolation, reduced emotional responsiveness, self-neglect and anhedonia, which have been categorised into avolition-apathy and expressive deficits sub-domains. The treatment of negative symptoms remains a challenge. Depression is commonly seen in schizophrenia and previous findings have suggested a relationship between depression and negative symptoms via the avolition-apathy sub-domain, (Barnes et al., 2016). It is possible this is the result of a common aetiology, distinct from expressive deficit or other symptoms of schizophrenia. Immune dysfunction has been implicated in both psychotic and depressive illnesses; increased circulating pro-inflammatory markers (such as IL-6, TNF-alpha & CRP). This suggests a novel target for treatments. A putative neuroprotective role of minocycline has been suggested via reducing microglial activation, and decrease in the production of cytokines including IL-6. Minocycline has been shown to be effective in the treatment of negative symptoms (Xiang et al., 2017) and depression (Soczynska et al., 2012). Within schizophrenia, we predict that that minocycline will lead to a longitudinal improvement in depression and the avolition-apathy sub-domain of negative symptoms Methods: Data from the BeneMin study will be presented. BeneMin recruited 207 patients with a current research diagnosis of schizophrenia within 5 years of onset and randomised to minocycline (300mg/day) or matching placebo for 12 months adjunctive to antipsychotic medication. For this analysis the primary outcome variable is the negative symptom subscale from the Positive and Negative Syndrome Scales (and broken down into avolition-apathy and expressive deficits sub-domains), Calgary Depression Scale in Schizophrenia (CDSS) and circulating IL-6, TNF-alpha and CRP over 4-time points 2, 6, 9, and 12 months. Results: At baseline, 40% were depressed (mean CDSS score = 5). The mean avolition-apathy PANSS score was 9.5 and expressive deficits was 9, and was comparable across placebo and minocycline arms. Preliminary results show that markers of inflammation were low in both treatment arms, compared with previous research (baseline CRP Md = 1.45, IL-6 Md = .57, TNF-alpha Md = 2.43) and this was comparable across depressed and nondepressed patients. TNF-alpha was significantly associated with expressivedeficits (B = .75, p = .005). Conversely, no marker of inflammation was associated with avolition-apathy or depression. However, in four linear mixed effect models across the 2, 6, 9 and 12-month follow-up assessments compared with placebo, minocycline had no effect on total negative symptoms, avolition-apathy, expressive deficits or depression. Further analysis stratifying patients by depression scores and markers of inflammation will be presented. Discussion: Preliminary results indicate that minocycline does not lead to a reduction in avolition-apathy or depression in early schizophrenia. This may be the result of a medicated, sample recruited within 5 years of illness onset, and low levels of depression. Future studies should target depression in psychosis as a primary aim with samples of individuals with increased inflammatory response to fully investigate minocycline's potential in targeted intervention.
Schizophrenia Bulletin, 44 (Supplement 1) : S131
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Other biological interventions
Lewis, S., Fraccaro, P., Ainsworth, J., Machin, M., Sanders, C., He, Z., Whelan, P., Stockton-Powdrell, C., Hopkins, R., Wykes, T.
Background: We developed a smartphone-based personalised technology to monitor symptoms in real time and showed good acceptability, reliability and validity for active remote monitoring of symptoms in previous published studies (www.clintouch.com). We report a randomised trial testing its efficacy in improving psychotic symptom control, and its potential as an early warning system for relapse when embedded into the ICT systems of mental health provider organisations, and as a tool for identifying new phenotypes for precision medicine. Methods: Participants with SMI receive a semi-random beep 2-4 times per day on their smartphone app and answer 14 key symptom rating items using a touchscreen slider. Responses are uploaded wirelessly in real time to a central server and build into a graphical readout on the handset, allowing active symptom monitoring and attempts at self-management. We built this into an end-to-end system in two NHS Hospital Trusts (Manchester and South London) to stream data into electronic care records and enable detection by the clinical team of early signs of relapse in people with SMI when key symptoms exceeded a personalised severity threshold. We conducted an open randomised controlled trial of this active symptom monitoring (ASM) using the smartphone app compared to usual management with the aim of assessing: (i) acceptability of continuous monitoring over 3 months; (ii) impact of active self-monitoring on PANSS positive symptoms and Empowerment Rating Scale score assessed at 6 and 12 weeks; (iii) efficiency of detecting early warning signs of relapse. Eligible participants with a DSM5 diagnosis of schizophrenia and related disorders and a history of relapse within the previous two years were included from an early intervention team (early psychosis group) and a community team (chronic psychosis group). Results: Of 181 eligible, 81 were randomised to either active symptom monitoring or management as usual. 90% stayed in the trial for 12 weeks. Of the 38 in the ASM arm who completed 12-week follow up, adherence defined as responding to >33% of alerts was 84%, >50% of alerts was 60%. At 12 weeks, ASM compared to usual management was associated with no difference on empowerment scale. PANSS positive subscale score showed a significant mean reduction in the ASM group over 12 weeks in the early psychosis group (n= 22, planned ANCOVA p<0.02), but no effect in the chronic psychosis group (n=19). Early warning sign alerts generated by the system occurred in 92% of cases and blind comparison with electronic case record data suggested good sensitivity and lower specificity, but with clear indications of how to adjust the gain of the system to improve future eventdetection efficiency. Multivariate analyses pointed to the ability of the system to identify clinical subtypes. Discussion: The active smartphone monitoring system is feasible and acceptable over three months in people with schizophrenia and related disorders. It was associated with psychotic symptom improvement in recent onset participants, supporting the notion of improved self-management. When built into clinical management workflows to enable personalised alerts of symptom deterioration, it was shown to have potential use in promoting earlier intervention for relapse.
Schizophrenia Bulletin, 44 (Supplement 1) : S106
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Technology, interventions delivered using technology (e.g. online, SMS)
Machielsen, M. W. J., Veltman, D. J., van-den-Brink, W., de-Haan, L.
OBJECTIVE: Cannabis use disorders (CUDs) are highly comorbid in patients with schizophrenia and associated with poor outcome. Clozapine has been put forward as the first choice antipsychotic in this patient group. However, little is known about the mechanisms underlying the assumed superiority of clozapine.
METHODS: A total of 38 patients with DSM-IV schizophrenia (30 with and 8 without a DSM-IV CUD) and 20 healthy comparison subjects were included between April 2009 and June 2012. Patients were randomized to antipsychotic treatment with clozapine or risperidone. At baseline and after 4weeks of medication, brain response to cannabis-related, positive and neutral images was measured using functional MRI. Neural correlates of cue reactivity were assessed in the following regions of interest: amygdala, ventral striatum, insula, thalamus, orbitofrontal cortex and anterior cingulate cortex. Subjective craving was assessed using self-report questionnaires (OCDUS and MCQ).
RESULTS: At baseline, patients with a comorbid CUD showed higher subjective craving and greater activation in response to cannabis-related images compared to patients without a CUD and healthy controls in most regions of interest. Clozapine treated patients reported a greater reduction in craving (F(1,28)=6.0, p=0.04) and showed a larger decrease in amygdala activation during cannabis-related images compared to risperidone treated patients (T=3.94, pFWE=0.006). In addition, significant correlations were found between subjective craving and thalamus and insula activation during cannabis-related images.
CONCLUSION: These findings provide evidence that clozapine is superior to risperidone in decreasing subjective craving and cue reactivity for cannabis-related images probably due to a differential effect on dopaminergic neurotransmission.
TRIAL REGISTRATION: 'Nederlands trial register' (http://www.trialregister.nl), nr NTR1761, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1761.
Schizophrenia Research, 194 : 32-38
- Year: 2018
- Problem: Psychosis Disorders, Cannabis Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
McGorry, P., Francey, S., Nelson, B., Jessica, G., Lara, B., Suzy, H., Pan-Yuen, H., Alex, F., Kelly, A., Mario, A. J., Brian, O.
Background: While antipsychotic medication (AP) is a very effective treatment for positive psychotic symptoms in first-episode psychosis (FEP), it is also associated with risks. These include adverse neurological and metabolic effects and measurable changes in brain structure. APs may even be associated with poorer functional recovery. Due to advances in the detection of, and psychosocial treatments for FEP, it is now ethically feasible to study the relative risks and benefits of offering AP as a first line treatment, and conversely, of withholding it, on a background of comprehensive evidence-based psychosocial care. This non-inferiority design randomised double blind placebo controlled study examines whether a (low-risk) 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. Methods: Young people with FEP were screened for study eligibility and invited to participate if they met stringent inclusion criteria indicating low-risk of harm to self or others, and adequate social support. Hence a large proportion of patients were assumed a priori to be too high risk to withhold antipsychotic medication. 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. Randomisation was stratified with three levels of DUP and gender creating six cells. Assessments of psychopathology, neurocognitive performance, and neuroimaging occurred regularly until two years after study entry. Results: 90 young people were randomised and 81 commenced trial medication. They were 44% male and mean age 18.5 years (SD = 2.7). Thirtyfour 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. Discussion: The results of this study demonstrate that it is feasible and acceptable to conduct AP-free research in carefully selected FEP to examine the risk-benefit ratio of current treatments under carefully controlled conditions that prioritise patient outcomes and safety. Although only one-third of the participants completed the six month trial intervention period, more of those on placebo completed the trial phase and they had higher mean, minimum and maximum time in the experimental intervention phase than those on medication. In addition, there were no differences between the groups on measures of psychopathology and functioning, suggesting that the intensive psychosocial intervention provided to all participants is complementary and may be more important than antipsychotic medication in the early phases of psychotic illness for a subgroup of young people. However this subgroup is very small as a % of total FEP patients treated during the study period. Further analysis of physical health and neuroimaging data and completion of the 24 month follow-up assessments will allow detailed examination of the risk-benefit ratio regarding antipsychotic medication in FEP.
Schizophrenia Bulletin, 44 (Supplement 1) : S162
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Medication dose reduction/discontinuation
, Psychological Interventions (any)
Morrison, A. P., Law, H., Carter, L., Sellers, R., Emsley, R., Pyle, M., French, P., Shiers, D., Yung, A. R., Murphy, E. K., Holden, N., Steele, A., Bowe, S. E., Palmier-Claus, J., Brooks, V., Byrne, R., Davies, L., Haddad, P. M.
BACKGROUND: Little evidence is available for head-to-head comparisons of psychosocial interventions and pharmacological interventions in psychosis. We aimed to establish whether a randomised controlled trial of cognitive behavioural therapy (CBT) versus antipsychotic drugs versus a combination of both would be feasible in people with psychosis.
METHODS: We did a single-site, single-blind pilot randomised controlled trial in people with psychosis who used services in National Health Service trusts across Greater Manchester, UK. Eligible participants were aged 16 years or older; met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service; were in contact with mental health services, under the care of a consultant psychiatrist; scored at least 4 on delusions or hallucinations items, or at least 5 on suspiciousness, persecution, or grandiosity items on the Positive and Negative Syndrome Scale (PANSS); had capacity to consent; and were help-seeking. Participants were assigned (1:1:1) to antipsychotics, CBT, or antipsychotics plus CBT. Randomisation was done via a secure web-based randomisation system (Sealed Envelope), with randomised permuted blocks of 4 and 6, stratified by gender and first episode status. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions. Choice and dose of antipsychotic were at the discretion of the treating consultant. Participants were followed up for 1 year. The primary outcome was feasibility (ie, data about recruitment, retention, and acceptability), and the primary efficacy outcome was the PANSS total score (assessed at baseline, 6, 12, 24, and 52 weeks). Non-neurological side-effects were assessed systemically with the Antipsychotic Non-neurological Side Effects Rating Scale. Primary analyses were done by intention to treat; safety analyses were done on an as-treated basis. The study was prospectively registered with ISRCTN, number ISRCTN06022197.
FINDINGS: Of 138 patients referred to the study, 75 were recruited and randomly assigned-26 to CBT, 24 to antipsychotics, and 25 to antipsychotics plus CBT. Attrition was low, and retention high, with only four withdrawals across all groups. 40 (78%) of 51 participants allocated to CBT attended six or more sessions. Of the 49 participants randomised to antipsychotics, 11 (22%) were not prescribed a regular antipsychotic. Median duration of total antipsychotic treatment was 44.5 weeks (IQR 26-51). PANSS total score was significantly reduced in the combined intervention group compared with the CBT group (-5.65 [95% CI -10.37 to -0.93]; p=0.019). PANSS total scores did not differ significantly between the combined group and the antipsychotics group (-4.52 [95% CI -9.30 to 0.26]; p=0.064) or between the antipsychotics and CBT groups (-1.13 [95% CI -5.81 to 3.55]; p=0.637). Significantly fewer side-effects, as measured with the Antipsychotic Non-neurological Side Effects Rating Scale, were noted in the CBT group than in the antipsychotics (3.22 [95% CI 0.58 to 5.87]; p=0.017) or antipsychotics plus CBT (3.99 [95% CI 1.36 to 6.64]; p=0.003) groups. Only one serious adverse event was thought to be related to the trial (an overdose of three paracetamol tablets in the CBT group).
INTERPRETATION: A head-to-head clinical trial of CBT versus antipsychotics versus the combination of the two is feasible and safe in people with first-episode psychosis.
FUNDING: National Institute for Health Research.
, 5(5) : 411-423
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
, Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
Nelson, B., Amminger, G. P., Yuen, H. P., Markulev, C., Lavoie, S., Schafer, M. R., Hartmann, J. A., Mossaheb, N., Schlogelhofer, M., Smesny, S., Hickie, I. B., Berger, G., Chen, E. Y. H., de-Haan, L., Nieman, D. H., Nordentoft, M., Riecher-Rossler, A., Verma, S., Thompson, A., Yung, A. R., McGorry, P. D.
This study reports a medium-term follow-up of a randomised, double-blind, placebo-controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk for psychosis (UHR) patients. Primary outcomes of interest were transition to psychosis and symptomatic and functional outcome. A secondary aim was to investigate clinical predictors of medium-term outcome. Three hundred four UHR participants were recruited across 10 specialised early psychosis services in Australia, Asia, and Europe. The intervention consisted of 1.4 g/daily of omega-3 PUFA or placebo, plus up to 20 sessions of cognitive-behavioural case management (CBCM), over the 6-month study period, with participants receiving further CBCM sessions on basis of need between months 6-12. Mean time to follow-up was 3.4 (median = 3.3; SD = 0.9) years. There was a modest increase in transitions between 12-month and medium-term follow-up (11-13%) and substantial improvement in symptoms and functioning between baseline and follow-up, with no differences between the treatment groups. Most improvement had been achieved by end of the intervention. 55% of the sample received mental health treatment between end of intervention and follow-up. Omega-3 PUFA did not provide additional benefits to good quality psychosocial intervention over the medium term. Although most improvement had been achieved by end of intervention the substantial rates of post-intervention mental health service use indicate longer-term clinical need in UHR patients. The post-intervention phase treatment or the longer-term effect of CBCM, or a combination of the two, may have contributed to maintaining the gains achieved during the intervention phase and prevented significant deterioration after this time.
npj Schizophrenia, 4(1) : 11
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Complementary & Alternative Interventions (CAM)
, Service Delivery & Improvement, Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
, Fish oil (Omega-3 fatty acids)
, Omega 3 fatty acids (e.g. fish oil, flax oil)
, Case management
Niendam, T., Loewy, R., Savill, M., Meyer, M., Rosenthal, A., Delucchi, K., Lesh, T., Skymba, H., Ragland, J. D., Goldman, H., Cress, R., Kravitz, R., Carter, C.,
Background: Reducing the duration of untreated psychosis (DUP) is essential to improve long-term outcome in young people with first episode of psychosis (FEP). The US "standard of FEP care" focuses on targeted provider education regarding FEP signs and symptoms to motivate referrals to FEP coordinated specialty care (CSC) services. However, a recent US multisite CSC trial showed a median DUP of 74.5 weeks, suggesting the current approach to engage referral sources is not sufficient to reduce DUP to proposed international standards of 12 weeks. This cluster-randomized controlled trial assesses whether standard targeted provider education plus novel technology-enhanced screening using the Prodromal Questionnaire- Brief version (PQ-B) identifies more individuals with FEP, earlier in their illness, compared to standard targeted provider education alone. Methods: Twenty-two sites were randomized within 3 strata [community mental health, CMH (N=10), middle/high schools, SCH (N=8), primary care, PC (N=4)] to 1 of 2 intervention arms [Education alone (TAU) vs Education + Electronic Screening (Active)]. Active sites screened eligible individuals ages 12-30 at initial presentation for mental health concerns and referred those who passed a liberal PQ-B cut off score for phone evaluation by the CSC clinic. TAU sites referred individuals for phone evaluation based on clinician judgment. Phone evaluations assessed eligibility for FEP services and DUP. Preliminary analyses examined the number of FEP referrals and length of DUP in each arm. Results: Active sites effectively implemented electronic screening within their settings. Of the 822 individuals electronically screened at Active sites between June 2015 and July 2017, 43.2% scored above the PQ-B cutoff (mean+/-SD PQ-B score=21.25 +/- 20.75; median=15; range = 0-95; IQR = 3-35). One in 8 individuals who completed the tablet were identified as experiencing threshold psychosis. Across both Active and TAU sites, 511 individuals were identified, 422 individuals agreed to be referred, and 319 completed a phone interview to determine eligibility: 33.23% reported attenuated and 36.68% fully psychotic symptoms. Active sites identified significantly more individuals with threshold psychosis (p<.001) than TAU. No difference in median days of DUP was observed across arms. Discussion: Preliminary results show the feasibility of electronic screening across various community settings and showed a 3.5 times higher identification rate for electronic screening of self-reported psychosis spectrum symptoms than clinician-based identification alone. Reasons for the lack of difference in DUP will be discussed. While the screening method may shorten the time from entry into mental health care and referral to specialty care treatment, significant DUP reduction may require interventions to reduce time to the first mental health contact. The next phase of the project will examine impact of clinic-based versus community-based treatment engagement to reduce barriers to initiating CSC care.
Schizophrenia Bulletin, 44 (Supplement 1) : S4
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Other service delivery and improvement interventions
Nishida, A., Ando, S., Yamasaki, S., Koike, S., Ichihashi, K., Miyakoshi, Y., Maekawa, S., Nakamura, T., Natsubori, T., Ichikawa, E., Ishigami, H., Sato, K., Matsunaga, A., Smith, J., French, P., Harima, H., Kishi, Y., Fujita, I., Kasai, K., Okazaki, Y.
The first episode of psychosis represents a critical period wherein comprehensive early intervention in psychosis (EIP) may alter the course of illness. However, evidence from randomized controlled trials that have examined the impact of comprehensive EIP care on clinical and functional recovery assessed by independent blinded raters is limited. The objective of this study was to conduct a single-blinded multicenter trial comparing comprehensive EIP care and standard care in young patients with first-episode psychosis (FEP) in Japan (J-CAP Study). A total of 77 participants with FEP (aged 15-35 years) were randomized to receive standard care or specialized comprehensive EIP care and were followed up for 1.5 years (trial no.: UMIN000005092). Function (measured with the Global Assessment of Functioning) and clinical remission (defined by internationally standardized criteria proposed by the Remission in Schizophrenia Working Group) were evaluated by independent raters who were blinded to group assignment. Dropout rate and other secondary outcomes were also examined. The specialized EIP care group had a higher clinical remission rate (odds ratio, 6.3; 95% confidence interval, 1.0-37.9) and lower treatment dropout rate (odds ratio, 0.038; 95% confidence interval, 0.002-0.923) than the standard care group, even after adjusting for baseline characteristics. Functional improvement in the specialized EIP care group was slightly higher than that in the standard care group, but this difference was not statistically significant (p=0.195). From the results, we conclude that comprehensive EIP care may provide advantages over standard care in patients with FEP.
Journal of Psychiatric Research, 102 : 136-141
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Service Delivery & Improvement, Other service delivery and improvement interventions
Nuechterlein, K., McEwen, S., Ventura, J., Subotnik, K., Turner, L., Boucher, M., Casaus, L., Hayata, J.
Background: The search for treatments to remediate cognitive deficits and their functional outcome consequences remains a critical frontier in schizophrenia. Cognitive training and aerobic exercise both show promising moderate impact on cognition and everyday functioning. Aerobic exercise is hypothesized to increase brain-derived neurotrophic factor (BDNF) and thereby stimulate neurogenesis and synaptic plasticity, leading to increased learning capacity. Systematic cognitive training should take advantage of increased learning capacity and be more effective when combined with aerobic exercise. Methods: In a recently completed randomized controlled trial, we examined the impact of a 6-month program of Cognitive Training & Exercise (CT&E) compared to Cognitive Training alone (CT) in 47 first-episode schizophrenia outpatients. All participants were provided the same Posit Science computerized cognitive training, four hours/week, using BrainHQ and SocialVille programs. The CT&E group also participated in total body circuit training exercises to enhance aerobic conditioning. The exercise intensity was in the 60-80% of aerobic capacity range, combining clinic and home-based exercise for a target of 150 minutes per week. Results: Mixed model analyses demonstrate that the MATRICS Consensus Cognitive Battery Overall Composite improves significantly more by 3 months with CT&E than with CT alone (6.6 vs. 2.2 T-score points, p<.02). Work/school functioning improves substantially more with CT&E than with CT alone by 6 months (p<.001). BDNF is a promising mechanism of action, improving even after 2 weeks and predicting the amount of cognitive gain at 3 months. The magnitude of cognitive gain by 3 months predicts the amount of work/school functioning improvement at 6 months, suggesting a cascade of effects. Analyses by Dr. McEwen show differential increases in cortical thickness in the left dorsal lateral prefrontal gyrus (p=.02) and right superior frontal gyrus (p=.02) over 6 months and increased functional connectivity in the central executive network (p=.04) with CT&E compared to CT alone and correlations of these increases with cognitive and functional outcome gains. Discussion: We conclude that aerobic exercise significantly enhances the impact of cognitive training on cognition, functional outcome, and frontal cortical thickness in first-episode schizophrenia and that BDNF is a promising mechanism of action for these effects.
Schizophrenia Bulletin, 44 (Supplement 1) : S18
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Complementary & Alternative Interventions (CAM)
, Cognitive remediation therapy, Physical activity, exercise
Ochoa, S., Salas, M., Lopez-Carrilero, R., Pousa, E., Barajas, A., Grasa, E., Barrigon, M. L., Lorente, E., Cid, J., Gonzalez, F., Ruiz, I., Birules, I.
Background: The Meta-Cognitive Training (MCT) is a psychological intervention that combines psychoeducational components and cognitive behavioural therapies with a meta-cognitive approach. The MCT (Moritz and Woodward, 2007) focuses on different cognitive biases, theory of mind and attribution bias, as well as on the predictive value of depressed mood and low self-esteem on paranoid ideation. The MCT has result effective for people with schizophrenia in order to improve symptoms, cognitive insight, jumping to conclusions, memory and quality of life. However, less information is regarding the effectiveness of MCT in first episode psychosis. On the other hand, gender has an important role in psychosis, nevertheless the effect of gender in the effectiveness of MCT has not been proved. The aim of the study is to assess the effectiveness of MCT regarding symptoms and cognitive insight in people with first episode psychosis, considering the effect of gender. Methods: A multicenter, randomized, controlled clinical trial was performed. A total of 122 patients were randomized to an MCT or a psychoeducational intervention. The sample was composed of people with a recent onset of psychosis, recruited from 9 public centers in Spain. The treatment consisted of 8 weekly sessions for both groups. Patients were assessed at three time-points: baseline, post-treatment, and at six months of follow-up. The evaluator was blinded to the condition of the patient. Symptoms were assessed with the PANSS and cognitive insight with the BCIS. A regression model for repeated measures was performed with the SPSS by gender. Results: The sample was composed by 85 men and 37 women, although 53 men and 21 women completed the treatment and the follow-up. Both psychoeducational and MCT group improved in positive symptoms at post-treatment and follow-up (p<0.05-0.001) with higher effect sizes in the MCT group (0.53 versus 0.38). Regarding negative symptoms the MCT group improved in the follow-up (p<0.001) and general symptoms MCT improved in the post-treatment and follow-up (p<0.001). Cognitive insight was higher in people who attended the MCT, in self-certainty in the posttreatment (p<0.05), self-reflectiveness in the follow-up (p<0.05) and the composite index in both assessments (p<0.05). Considering the results by gender, men of both groups improve more in positive, negative and disorganized symptoms of the PANSS (p<0.001- 0.046) while women improve in positive symptoms. A tendency of interaction between group and affective symptoms was found only in women (p=0.062), improving more women of the MCT group. Regarding cognitive insight, women of the MCT group improve more in self certainty and total BCIS compared with the psychoeducational group (p<0.001-0.022). Discussion: MCT could be an effective psychological intervention for people with a recent-onset of psychosis for the improvement of cognitive insight and psychotic symptoms. It seems that women could benefit more from the MCT intervention than men in reduction of affective symptoms and in the improvement of cognitive insight.
Schizophrenia Bulletin, 44 (Supplement 1) : S238
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage:
-
Treatment and intervention: Psychological Interventions (any)
, Cognitive remediation therapy, Psychoeducation
ONeill, A., Wilson, R., Blest-Hopley, G., Annibale, L., Colizzi, M., Bhattacharyya, S.
Background: Global neurocognitive impairments are a central feature of psychosis. Deficits in verbal memory in particular are the most consistently reported of these impairments from the first-episode of psychosis (FEP). Neuroimaging studies in psychosis have largely identified reductions in neural activation during various memory and learning related tasks, particularly in the medial temporal lobe, compared to healthy controls. Tetrahydrocannabinol (THC) and cannabidiol (CBD), both components of the cannabis plant that act through the endocannabinoid (eCB) system in the brain, have been found to induce direct and opposite neural effects during similar tasks in healthy samples, when compared to each other. Additionally, CBD has been shown to have antipsychotic properties, and may suppress THC induced psychotic symptoms and their directly associated functional abnormalities in healthy individuals. Thus far, the effects of CBD on the neural substrates implicated in memory and learning, and those underlying psychotic symptoms in FEP cohorts is unknown. Methods: 17 FEP patients were initially recruited to the study. A double- blind, randomized, placebo controlled, repeated measures, within subject cross over design, with at least a one-week washout period between scans was employed. Participants were given identical capsules of either CBD (600mg), or placebo (PLB), then scanned using a block design fMRI paradigm, while performing a verbal paired associate learning task. 13 participants completed scanning, and were included in the analysis of the data. An ROI mask of the hippocampus, striatum, and parahippocampal gyrus was used in the data analysis, and all results were thresholded for less than one false positive over the whole map. Results: A CBD related decrease in activity was observed in the left hippocampus (p = 0.0024) and the right parahippocampal gyrus (p = 0.0024) during the recall condition, within the FEP group. No significant differences between PLB and CBD functional activity were observed during the encoding condition. No significant differences were observed between FEP participant performances on the CBD and PLB study days. Discussion: These findings provide robust evidence of the modulatory effect of an acute dose of CBD on the neural substrates underlying learning and memory, supporting a role for the eCB system in the abnormalities observed in psychosis, and its potential as a target for treatment.
Schizophrenia Bulletin, 44 (Supplement 1) : S384
- Year: 2018
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
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Stage: First episode (psychosis only)
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Treatment and intervention: Biological Interventions (any)
, Other biological interventions