Disorders - psychosis disorders
Alphs,
L., Brown, B., Turkoz, I., Baker, P., Fu, D. J., Nuechterlein, K. H.
We report primary results of the Disease
Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial designed to compare the effectiveness of
paliperidone palmitate (PP) versus oral antipsychotics (OAP) in delaying time to first treatment failure (TtFTF) in participants with recent-onset
schizophrenia or schizophreniform disorder. DREaM included: Part I, 2-month oral run-in; Part II, 9-month disease progression phase (PP or OAP); Part
III, 9 months of additional treatment (PP/PP; OAP rerandomized: OAP/OAP or OAP/PP). PP/PP and OAP/OAP comprised the 18-month extended disease
progression (EDP) analysis. A total of 235 participants were randomized to PP (n = 78) or OAP (n = 157) in Part II. No statistically significant
differences in TF between treatment groups were identified during Part II (PP 29.5%, OAP 24.8%; P = 0.377), Part III (PP/PP 14.3%, OAP/PP 15.8%,
OAP/OAP 28.6%; P = 0.067) or the EDP analysis (PP/PP 28.6%, OAP/OAP 44.4%; NNT = 6; P = 0.080). Using a modified definition of TF excluding treatment
supplementation with another antipsychotic, a common approach to managing dose adjustments, significant differences were observed between treatment
groups in Part III (PP/PP 4.1%, OAP/PP 14.0%, OAP/OAP 27.0%; P = 0.002) and EDP (PP/PP 14.3%, OAP/OAP 42.9%; P = 0.001). Safety results were
consistent with the known safety profile of PP. Although significant treatment differences were not observed during the first 9 months of DREaM,
numerical differences favoring PP emerged in the last 9 months and significant differences were observed when TF criteria were limited to their most
impactful components. These results highlight the potential benefit of initiating PP early in the course of schizophrenia and provide valuable
insights for future clinical trials in recent-onset schizophrenia or schizophreniform disorder. Clinicaltrials.gov identifier: NCT02431702. Copyright
© 2022 Janssen Scientific Affairs, LLC
, 243 : 86-97
- Year: 2022
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Service Delivery & Improvement, Other service delivery and improvement
interventions
Allott, K., Yuen, H. P., Baldwin, L., O'Donoghue, B., Fornito, A., Chopra, S., Nelson, B., Graham, J., Kerr, M. J., Proffitt, T., Ratheesh, A., Alvarez-Jimenez, M., Harrigan, S., Brown, E., Thompson, A. D., Pantelis, C., Berk, M., McGorry, P. D., Francey, S. M., Wood, S.
J.
Objective: Cognitive
impairment occurs in antipsychotic-naive first-episode psychosis (FEP), but antipsychotics confound interpretation of the longitudinal course of
cognition. The primary aim was to disentangle the effects of illness from antipsychotics on cognition over the first 6-months of FEP treatment.
Method(s): Randomised, triple-blind placebo-controlled trial (Staged Treatment and Acceptability Guidelines in Early Psychosis; STAGES), where
cognition was a secondary outcome. Antipsychotic-naive FEP patients were allocated to receive risperidone/paliperidone (N=38) or placebo (N=40) in
addition to intensive psychosocial therapy for 6-months. A healthy control group (N=42) was also recruited. A cognitive battery assessing attention,
working memory, processing speed, verbal fluency, cognitive control and verbal paired-associate learning and memory was administered at baseline and
6-months. Twelve- and 24-month follow-up was also conducted. Result(s): Over the 6-month trial period, cognitive performance remained stable (working
memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. The exception was
for verbal paired-associate learning and memory, where a significant group-by-time interaction was observed. The placebo and healthy control groups
improved, and the medication group deteriorated on immediate paired-associate recall (p=0.039) and delayed cued recall (p=0.005); effect sizes were
medium-to-large. Findings were similar when only trial completers were included in the analysis. Conclusion(s): Risperidone/paliperidone may cause
progression of memory impairment in the early months of FEP. Replication is needed in confirmatory trials. The findings support the need for careful
consideration of the risks and benefits of various antipsychotics and the importance of accounting for their cognitive effects in longitudinal
research. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in
perpetuity. All rights reserved. No reuse allowed without permission.
medRxiv., 21 :
- Year: 2022
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Psychological Interventions
(any)
Adnan, Mahwish, Motiwala, Fatima, Trivedi, Chintan, Sultana, Tania, Mansuri, Zeeshan, Jain,
Shailesh
Background: Schizophrenia at a young age deserves
investigation because of the greater severity and burden of illness on individuals and health care than its adult onset. For this study, we included
both childhood-onset schizophrenia and early-onset schizophrenia. We used the common term \"childhood and adolescent-onset schizophrenia (CAOS)\" for
either type. This systematic review provides an overview of the clinical use, efficacy, and safety of clozapine treatment in managing CAOS.\rMethods:
We conducted a systematic literature search in PubMed, Embase, and PsycINFO databases. We searched for randomized controlled trials (RCTs), open-
label studies (OLSs), review articles, meta-analytic and observational studies. Our literature search resulted in 1242 search results. After the
title, abstract, and full article review, 18 studies qualified (double-blind RCTs n?=?4; OLS n?=?4; observational studies n?=?7; case reports n?=?
3).\rResults: Clozapine use in CAOS was generally well tolerated and not associated with any fatalities. Clozapine use in the short term (6 weeks)
and long term (2 - 9 years) was superior in efficacy than other antipsychotics in CAOS management. Improvement in overall symptoms was maintained
during long-term follow-up over the years in OLSs. Clozapine appeared to have a favorable clinical response and shorter hospital stays. Sedation and
hypersalivation were commonly reported (90%), constipation was next in frequency (13% - 50%). Neutropenia was seen in 6% - 15% of cases and
agranulocytosis (<0.1%). Although weight gain was common (up to 64%), followed by metabolic changes (8% - 22%), treatment-onset diabetes was less
frequent (<6%). Akathisia, tachycardia, and blood pressure changes were less commonly seen.\rConclusions: Limited studies indicate that clozapine is
a safe and efficacious option for CAOS management. We need large-scale and well-designed long-term RCTs for the use of clozapine in the management of
CAOS.
Journal of Child and Adolescent Psychopharmacology, 32(1) : 2-
11
- Year: 2022
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Weijers, J, Ten-Kate, C, Viechtbauer, W, Rampaart, L. J. A, Eurelings, E. H. M, Selten, J.
P.
BACKGROUND: Impaired mentalizing ability - an impaired ability to understand one's own and other people's behavior in terms of mental
states - is associated with social dysfunction in non-affective psychotic disorder (NAPD). We tested whether adding mentalization-based treatment for
psychotic disorder (MBTp) to treatment as usual (TAU) results in greater improvement in social functioning. METHOD(S): Multicenter, rater-blinded,
randomized controlled trial. Eighty-four patients with NAPD were assigned to TAU or MBTp plus TAU. Patients in the MBTp group received 18 months of
MBTp, consisting of weekly group sessions and one individual session per 2 weeks. Social functioning was measured using the Social Functioning Scale.
We conducted ANCOVAs to examine the difference between treatment conditions directly after treatment and at 6-month follow-up and performed
moderation and mediation analyses. RESULT(S): Intention-to-treat analyses showed no significant differences between groups post-treatment (p = 0.31)
but revealed the MBTp group to be superior to TAU at follow-up (p = 0.03). Patients in the MBTp group also seemed to perform better on measures of
mentalizing ability, although evidence of a mediation effect was limited (p = 0.06). Lastly, MBTp treatment was less effective in chronic patients
than in recent-onset patients (p = 0.049) and overall symptoms at baseline were mild, which may have reduced the overall effectiveness of the
intervention. CONCLUSION(S): The results suggest that MBTp plus TAU may lead to more robust improvements in social functioning compared to TAU,
especially for patients with a recent onset of psychosis.
Psychological medicine, 51(16) : 2846-
2855
- Year: 2021
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions
(any), Mentalization-based
therapy
Tocco, M, Pikalov, A, Deng, L, Goldman, R.
Introduction: Compared with adult onset, early onset schizophrenia is
typically characterized by greater illness severity and less favorable prognosis. Objective(s): To evaluate the proportion of adolescent patients
with schizophrenia who achieved sustained remission and recovery during 2 years of treatment with lurasidone. Method(s): Patients aged 13-17 years
with a DSM-IV-TR diagnosis of schizophrenia, and a Positive andNegative Symptom Scale (PANSS) total score >=70 and <120, were randomized to 6 weeks
of doubleblind (DB), fixed-dose treatment with lurasidone (37 or 74 mg/d) or placebo. Patients who completed 6 weeks of DB treatment were eligible to
enroll in a 2-year, open-label (OL), flexible dose extension study of lurasidone (18.5-74 mg/d). Criteria for sustained remission, were the 6-month
consensus criteria summarized by Andreasen (Am J Psych 2005;162:441-9). Criteria for sustained recovery consisted of meeting sustained remission
criteria with a Children's Global Assessment Scale (CGAS) score >=70 for at least 6-months indicating no clinically significant functional
impairment. Result(s): A total of 271 patients completed the 6-week DB study and entered the extension study, and 186 (68.6%) and 156 (57.6%)
completed 52 weeks and 104 weeks of treatment, respectively. During OL treatment with lurasidone, 52.8% met sustained remission criteria, with a
Kaplan-Meier (KM) estimate of 64.1 weeks for median time to sustained remission; and 28.8% met sustained recovery criteria, KM estimate of 104.6
weeks for median time to sustained recovery. Conclusion(s): For adolescents with schizophrenia, treatment with lurasidone was associated with high
rates of sustained remission and sustained recovery over a two-year period.
European Psychiatry, 64(Supplement
1) : S165-S166
- Year: 2021
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Mei, C., Van-Der-Gaag, M., Nelson, B., Smit, F., Yuen, H. P., Berger, M., Krcmar, M., French, P., Amminger,
G. P., Bechdolf, A., Cuijpers, P., Yung, A. R., McGorry, P.
D.
Intervention at the earliest illness stage, in ultra or clinical high-risk
individuals, or indicated prevention, currently represents the most promising strategy to ameliorate, delay or prevent psychosis. We review the
current state of evidence and conduct a broad-spectrum meta-analysis of various outcomes: transition to psychosis, attenuated positive and negative
psychotic symptoms, mania, depression, anxiety, general psychopathology, symptom-related distress, functioning, quality of life, and treatment
acceptability. 26 randomized controlled trials were included. Meta-analytically pooled interventions reduced transition rate (risk ratio [RR] = 0.57,
95%CI 0.41-0.81) and attenuated positive psychotic symptoms at 12-months (standardized mean difference = -0.15, 95%CI = -0.28--0.01). When stratified
by intervention type (pharmacological, psychological), only the pooled effect of psychological interventions on transition rate was significant.
Cognitive behavioral therapy (CBT) was associated with a reduction in incidence at 12-months (RR = 0.52, 95%CI = 0.33-0.82) and 18-48-months (RR =
0.60, 95%CI = 0.42-0.84), but not 6-months. Findings at 12-months and 18-48-months were robust in sensitivity and subgroup analyses. All other
outcomes were non-significant. To date, effects of trialed treatments are specific to transition and, a lesser extent, attenuated positive symptoms,
highlighting the future need to target other symptom domains and functional outcomes. Sound evidence supports CBT in reducing transition and the
value of intervening at this illness stage. Study registration: Research Registry ID: reviewregistry907. Copyright © 2021 Elsevier Ltd
Clinical Psychology Review, 86 (no pagination) :
- Year: 2021
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions
(any), Complementary & Alternative
Interventions (CAM), Psychological Interventions
(any)
McGorry, Patrick D., Mei, Cristina, Hartmann, Jessica, Yung, Alison R., Nelson, Barnaby
Over a quarter of a
century ago, the formulation of the \"at risk mental state\" and operational criteria to prospectively identify individuals at \"clinical\" or
\"ultra-high risk\" (UHR) for psychosis created a global wave of research momentum aimed at predicting and preventing first-episode psychosis. A
substantial number of randomized controlled trials (RCTs) were conducted to determine if transition to psychosis could be delayed or even prevented.
The efficacy of a range of interventions was examined, with standard meta-analyses clearly indicating that these could at least delay transition for
1-2 years and that outcomes improve. Recently, network meta-analyses have attempted to identify the most effective intervention. These highlighted
the fact that no one form of intervention is superior to the rest, a finding interpreted in such a way as to create doubts concerning the value of
intervening. These doubts have been reinforced by a subsequent Cochrane review which judged the quality of the evidence as low or very low. Here, we
report a narrative review of findings from RCTs and meta-analyses on the efficacy of interventions in UHR. We also critique the network meta-analyses
and the Cochrane review, and indicate that many of the trials were of the highest possible quality for such research, and were published in top
ranked psychiatry journals, which demand such quality. Although outcomes vary, and the UHR group is clearly heterogeneous, we highlight the clinical
benefits of psychosocial treatment. The next generation of clinical trials seek to elucidate the optimal type, duration and sequence of
interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
, 228 : 344-356
- Year: 2021
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Complementary & Alternative
Interventions (CAM), Psychological Interventions
(any), Cognitive & behavioural therapies (CBT), Cognitive remediation
therapy, Fish oil (Omega-3 fatty acids), Omega 3 fatty
acids (e.g. fish oil, flax oil)
Li, Huijun, Yang,
Shuwen, Chi, Hongmei, Xu, Lihua, Zhang, Tianghong, Singleton, Gwendolyn, Tang, Yingying, Stone, William S., Wang, Jijun
Background: Cognitive impairment
has adverse impact on the social and role functions of those at clinical high risk for psychosis and it has become an important target for
intervention. Mobile health applications are user-friendly, real-time, personalized and portable in administering cognitive training and have
promising application prospects in the field of mental health.\rMethods: Eighty CHR subjects were randomized into an intervention group and a control
group. CHR subjects of the intervention group performed attention and memory training via a Specific Memory Attention Resource and Training (SMART)
application in their smart phones for 10 min per day, five days per week for three months. Both groups were followed up for three months. At baseline
and follow-up phases, cognitive function was measured using the MATRICS Consensus Cognitive Battery (MCCB). In the follow-up, the intervention group
completed the Mobile Application Rating Scale (MARS) to provide feedback to improve SMART.\rResults: There is a significant group by time interaction
effect in the Attention/Vigilance domain, which is significantly better in the intervention group than in the control group at 3- month follow-up.
The improvement in Attention/Vigilance in the intervention group is significantly related to the amount of cognitive training time. Global Assessment
of Function (GAF) reduction rate at baseline could predict the improvement of Attention/Vigilance. MARS results indicate that CHR subjects were
receptive of SMART.\rConclusion: Mobile technology can be applied to improve cognitive function of CHR individuals, especially in the
Attention/Vigilance domain.
Asian Journal of Psychiatry Vol 58 2021, ArtID
102587, 58 :
- Year: 2021
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Cognitive remediation
therapy, Technology, interventions delivered using technology (e.g. online, SMS)
Kim, D. D., Barr, A. M., Lian,
L., Yuen, J. W. Y., Fredrikson, D., Honer, W. G., Thornton, A. E., Procyshyn, R. M.
Early
intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how
best to choose between dopamine D2 receptor (D2R) partial agonists and D2R antagonists in early stages of
schizophrenia. The aim of this meta-analysis was to directly compare D2R partial agonists with D2R antagonists for efficacy and
tolerability, using randomized controlled trials (RCTs) that involved participants diagnosed with first-episode psychosis, schizophrenia, or related
psychotic disorders with a duration of illness <=5 years. Fourteen RCTs, involving 2494 patients, were included in the meta-analysis. Aripiprazole
was the only identified D2R partial agonist, and was not significantly different from pooled D2R antagonists for overall
symptom reduction or all-cause discontinuation. However, aripiprazole was more favorable than pooled D2R antagonists for depressive
symptoms, prolactin levels, and triglyceride levels. Specifically, aripiprazole was more favorable than paliperidone for triglyceride levels and more
favorable than risperidone and olanzapine, but less favorable than ziprasidone, for weight gain. In addition, aripiprazole was less favorable for
akathisia compared with second-generation D2R antagonists, in particular olanzapine and quetiapine, and less favorable for discontinuation
due to inefficacy than risperidone. Lastly, aripiprazole was more favorable than haloperidol for various efficacy and tolerability outcomes. In
conclusion, aripiprazole's efficacy did not differ substantially from D2R antagonists in the early course of schizophrenia, whereas
differential tolerability profiles were noted. More double-blind RCTs are required comparing the efficacy and tolerability of aripiprazole as well as
other D2R partial agonists with D2R antagonists in early stages of schizophrenia. Copyright © 2021, The Author(s).
npj Schizophrenia, 7(1) (no pagination) :
- Year: 2021
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder), First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Halverson, Tate
F., Meyer-Kalos, Piper S., Perkins, Diana O., Gaylord, Susan A., Palsson, Olafur S., Nye, Lana, Algoe, Sara B., Grewen, Karen, Penn, David L.
Individuals with schizophrenia spectrum disorders (SSD) are at heightened risk for exposure to stressful life events which can lead to
increased sensitivity to stress and a dysregulated stress response, which are in turn associated with poor long-term functioning. Stress reactivity
is thus a promising treatment target in the early stages of SSD. Integrated-Coping Awareness Therapy (I-CAT) is a manualized intervention integrating
mindfulness and positive psychology to target a dysregulated stress response in SSD. The current study is a preliminary randomized-controlled trial
(RCT) comparing I-CAT (n = 18) with treatment as usual (TAU; n = 18) in individuals in the early stages of SSD. I-CAT was hypothesized to be more
effective than TAU on primary outcomes: increasing positive emotions, decreasing negative emotions, reducing stress, and improving functioning and
quality of life; and secondary outcomes: reducing symptoms, increasing mindfulness, and improving overall well-being. Excellent therapy attendance
rates, low study attrition, and positive participant feedback demonstrated that I-CAT was a feasible and well-tolerated psychosocial intervention.
Results suggest I-CAT led to greater reduction in symptoms (i.e., overall, negative, and disorganized symptoms), increased observational mindfulness,
increased endorsement of a sense of purpose in life, and preservation of work abilities and school social functioning compared with TAU. Future work
should replicate and extend these findings in a larger-scale RCT. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
, 235 : 91-101
- Year: 2021
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions
(any)
Haahr, Ulrik Helt, Jansen, Jens Einar, Lyse-Nielsen, Hanne-Grethe, Pedersen, Marlene Buch, Trauelsen, Anne Marie, Bachmann Ostergaard,
Lise, Simonsen, Erik
Background: The evidence for
manualized psycho-educative family intervention (FI) in first-episode psychosis (FEP) is well-established to reduce relapse and caregiver distress.
Less is known, however, about type and duration of FI.\rAim: To compare two different types of manualized family interventions for FEP: Multi-Family
Groups (MFG) and Single-Family Intervention (SFI).\rMethods: This was a prospective, quasi-experimental cohort study of all participants of an early
psychosis service (OPUS) with an ICD-10 diagnosis of F20 to F29 (excl. F21), aged 18 to 35 years, in Psychiatry Region Zealand, Denmark, during a 2-
year period. All service users and their relatives are offered FI, either MFG or SFI. Assessment of level of participation, psychopathology measured
by The Positive and Negative Syndrome Scale (PANSS), remission status and relapses was carried out at 3-year follow up.\rResults: We found no
differences between the service users participating in SFI (N = 25) or MFG (N = 18) on number of readmissions or relapses after baseline or
psychopathology. A binary logistic regression analysis on remission status at follow up showed a trend in favour of MFG. A surprisingly high
proportion of the families did not receive an FI.\rConclusions: SFI and MFG seem equally effective in an FEP programme. The low attendance of FI may
be due to several issues-among others, the probability that the FI did not sufficiently match the needs of the service users. Further studies
involving larger samples are needed, included randomized controlled trials and implementation studies.
Early Intervention in Psychiatry, 15(4) : 983-
992
- Year: 2021
- Problem: Psychosis Disorders
- Type: Controlled clinical trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Psychological Interventions
(any)
Griffiths, Sian Lowri, Wood, Stephen J., Fowler, David, Freemantle, Nick, Hodgekins, Joanne, Jones, Peter B., Singh, Swaran, Sharma, Vimal, Birchwood, Max
There is a need to develop and refine psychosocial interventions to improve functioning in First Episode Psychosis (FEP).
Social cognition and neurocognition are closely linked to functioning in psychosis; examinations of cognition pre- and post- psychosocial
intervention may provide insights into the mechanisms of these interventions, and identify which individuals are most likely to benefit.\rMethod
\rCognition was assessed within a multi-site trial of Social Recovery Therapy (SRT) for individuals with FEP experiencing poor functioning (<30 h
weekly structured activity). Fifty-nine participants were randomly allocated to the therapy group (SRT + Early intervention), and 64 were allocated
to treatment as usual group (TAU - early intervention care). Social cognition and neurocognition were assessed at baseline and 9 months; assessors
were blind to group allocation. It was hypothesized that social cognition would improve following therapy, and those with better social cognition
prior to therapy would benefit the most from SRT.\rResults\rThere was no significant impact of SRT on individual neurocognitive or social cognitive
variables, however, joint models addressing patterns of missingness demonstrate improvement across a number of cognitive outcomes following SRT.
Further, regression analyses showed those who had better social cognition at baseline were most likely to benefit from the therapy ( ß = 0 .350; 95%
CI = 0.830 to 8.891; p = .019).\rConclusion\rIt is not clear if SRT impacts on social cognitive or neurocognitive function, however, SRT may be
beneficial in those with better social cognition at baseline.
, 228 : 249-
255
- Year: 2021
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Case management