Disorders - Psychosis Disorders
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.\rMETHODS: 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.\rRESULTS: 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.\rCONCLUSIONS: 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
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.\rMETHODS: 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).\rRESULTS: 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.\rCONCLUSION: 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.\rTRIAL 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.\rMETHODS: 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.\rFINDINGS: 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).\rINTERPRETATION: 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.\rFUNDING: 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
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Service Delivery & Improvement, Other service delivery and improvement
interventions