Disorders - Psychosis Disorders
Kishi,
T., Oya, K., Iwata, N.
This meta-analysis of randomized controlled trials (RCTs) investigated the advantages of long-acting injectable antipsychotics (LAI-APs)
over oral antipsychotics (OAPs) with regard to efficacy and safety for patients with recent-onset psychotic disorders. Effect sizes and 95%
confidence intervals (95%CIs) were calculated. We identified five RCTs (1022 patients, mean study duration = 18 +/- 7.59 months) that compared LAI-
APs (paliperidone or risperidone) with OAPs. Pooled LAI-APs did not outperform OAPs in terms of the preventing of relapse (N = 3, n = 875). However,
there was significant heterogeneity (I2 = 76%), with one study showing no superiority of LAI-APs over OAPs [Malla 2013: risk ratio (RR) = 1.83, 95%CI
= 0.70-4.77, n = 77] and the other two studies showing LAI-APs to be superior [Schreiner 2015: [RR = 0.71, 95%CI = 0.51-0.97, number needed to treat
(NNT) = -17, n = 715, Subotnik 2015: RR = 0.15, 95%CI = 0.04-0.63, NNT = -4, n = 83]. Pooling the studies, there were no significant differences
between LAI-APs and OAPs in the improvement of Positive and Negative Syndrome Scale scores or in discontinuation due to all-cause, adverse events
(AEs), and death, but LAI-APs outperformed OAPs in terms of discontinuation due to inefficacy (RR = 0.34, NNT = -50) and nonadherence (RR = 0.30, NNT
= -33). However, the LAI-APs were associated with a higher incidence of at least one AE (RR = 1.13) and tremor (RR = 2.38) compared with OAPs.
(PsycINFO Database Record (c) 2017 APA, all rights reserved)
Psychiatry Research, 246 : 750-
755
- Year: 2016
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Typical Antipsychotics (first generation), Atypical Antipsychotics (second
generation), Service Delivery & Improvement
Malla, A., Chue, P., Jordan, G., Stip, E., Koczerginski, D., Milliken, H., Joseph, A., Williams, R., Adams, B., Manchanda, R., Oyewumi, K., Roy, M. A.
Few studies have examined effectiveness
and tolerability of risperidone long-acting injections (RLAI) in the early phase of a schizophrenia spectrum (SS) disorder using a randomized
controlled trial (RCT) design. Eighty-five patients in early phase of an SS disorder were randomized to receive either oral second-generation
antipsychotics (SGAs; n=41) or RLAI (n=44) over two years. Analyses were conducted on eligible participants (n=77) for the stabilization (maximum 18
weeks) and maintenance phases (up to Week 104) on primary outcome measures of time to stabilization and relapse, change in symptoms and safety, and
comparisons made across the two groups. Both groups showed improvement on Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global
Impression-Severity (CGI-S) scores. There were no time X group interactions on any of the primary outcome measures. Post hoc examination revealed
that the RLAI group showed greater change on CGI-S and PANSS negative symptom scores during the stabilization phase, while the oral group reached the
same level of improvement during the maintenance phase. The current exploratory study suggests that-within an RCT design-RLAI and oral SGAs are
equally effective and have similar safety profiles in patients in the early phase of SS disorders. Thus, RLAI offers no advantage to patients in
early phase of SS disorders, but is likely to be effective and safe for those who may have problems with adherence and may either choose to take it
or be prescribed under conditions of external control such as community treatment orders.
Clinical Schizophrenia & Related Psychoses, 9(4) : 198-
208
- Year: 2016
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only), Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Service Delivery & Improvement, Other service delivery and improvement
interventions
Loewy, R., Fisher, M., Schlosser, D. A., Biagianti, B., Stuart, B., Mathalon, D.
H., Vinogradov, S.
OBJECTIVE: Individuals at clinical high risk (CHR) for psychosis demonstrate cognitive impairments that predict later psychotic transition
and real-world functioning. Cognitive training has shown benefits in schizophrenia, but has not yet been adequately tested in the CHR population.
\rMETHODS: In this double-blind randomized controlled trial, CHR individuals (N = 83) were given laptop computers and trained at home on 40 hours of
auditory processing-based exercises designed to target verbal learning and memory operations, or on computer games (CG). Participants were assessed
with neurocognitive tests based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS) battery and
rated on symptoms and functioning. Groups were compared before and after training using a mixed-effects model with restricted maximum likelihood
estimation, given the high study attrition rate (42%).\rRESULTS: Participants in the targeted cognitive training group showed a significant
improvement in Verbal Memory compared to CG participants (effect size = 0.61). Positive and Total symptoms improved in both groups over time.
\rCONCLUSIONS: CHR individuals showed patterns of training-induced cognitive improvement in verbal memory consistent with prior observations in
schizophrenia. This is a particularly vulnerable domain in individuals at-risk for psychosis that predicts later functioning and psychotic
transition. Ongoing follow-up of this cohort will assess the durability of training effects in CHR individuals, as well as the potential impact on
symptoms and functioning over time. Clinical Trials Number: NCT00655239. URL: https://clinicaltrials.gov/ct2/show/NCT00655239?
term=vinogradov&rank=5.
Schizophrenia Bulletin, 42(Suppl 1) : S118-26
- Year: 2016
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions
(any), Cognitive remediation
therapy
Karson, C., Duffy, R., Eramo, A., Nylander, A., Offord, S.
Background: Treatment during
first-episode psychosis (FEP) or early schizophrenia may affect the rates of relapse and remission, as well as cognitive functioning, over time.
Prolonged duration of psychosis is associated with a poor prognosis, but the effects of treatment in patients with FEP or early schizophrenia on the
long-term outcomes are not well defined. Objective: To understand the long-term effects of treatment with antipsychotic agents on remission, relapse,
and cognition in patients with FEP or early schizophrenia. Methods: Using PubMed and Scopus databases, a systematic review was undertaken of articles
published between January 1, 2000, and May 20, 2015, that reported randomized and nonrandomized prospective clinical trials on the long-term effects
of oral or long-acting injectable antipsychotics on measures of relapse, remission, or cognition in patients with FEP or early schizophrenia. For
comparative purposes, trials reporting the effects of later intervention with antipsychotics in patients with longer disease history were also
evaluated. Titles, abstracts, and full-text articles were independently screened for eligibility by all the authors based on the predefined criteria.
Results: Nineteen studies met inclusion criteria: 13 reported long-term outcomes of relapse, remission, or cognition following antipsychotic
treatment in patients with FEP and six reported on patients with a longer disease history. Antipsychotic treatment in patients with FEP produced high
rates of remission in the year following treatment initiation, and untreated FEP reduced the odds of later achieving remission. Maintenance therapy
was more effective than treatment discontinuation or intermittent/guided discontinuation in preventing relapse. Initiating antipsychotic treatment in
patients with FEP also produced sustained cognitive improvement for up to 2 years. Antipsychotic therapy also reduced the risk or rate of relapse in
patients with a longer disease history, with outcomes in one study favoring a long-acting injectable formulation over an oral antipsychotic.
Conclusion: Treatment of patients with FEP is associated with benefits in the long-term outcomes of remission, relapse, and cognition. More long-term
studies of treatment in patients with FEP are needed to confirm these findings. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
Neuropsychiatric Disease and Treatment, 12 : 57-67
- Year: 2016
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Typical Antipsychotics (first generation), Atypical Antipsychotics (second
generation)
Mayoral-Van-Son, J., Ortiz-Garcia-De-La-Foz, V., Martinez-Garcia, O., Moreno, T., Parrilla-Escobar, M., Valdizan, E. M., Crespo-Facorro, B.
Objective: The timing of antipsychotic discontinuation in patients who have
fully recovered from their initial episode of psychosis is still open to discussion. We aimed to evaluate the risk of symptom recurrence during the 3
years after antipsychotic discontinuation in a sample of functionally recovered first-episode nonaffective psychosis (FEP) patients (DSM-IV criteria)
with schizophrenia spectrum disorder. Method: Participants in this open-label, nonrandomized, prospective study were drawn from an ongoing
longitudinal intervention program of FEP from a university hospital setting in Spain. From July 2004 to February 2011, functionally recovered FEP
individuals were eligible if they met the inclusion criteria of (1) a minimum of 18 months on antipsychotic treatment, (2) clinical remission for at
least 12 months, (3) functional recovery for at least 6 months, and (4) stabilization at the lowest effective doses for at least 3 months. Forty-six
individuals who were willing to discontinue medication were included in the discontinuation group (target group). Twenty-two individuals opted to
stay on the prescribed antipsychotic medication and therefore were included in the maintenance group (control group). Primary outcome measures were
relapse rate at 18 and 36 months and time to relapse. Results: The rates of relapse over the 3-year period were 67.4% (31 of 46) in the
discontinuation group and 31.8% (7 of 22) in the maintenance group. The mean time to relapse was 209 (median = 122) days and 608 (median = 607) days,
respectively (log rank = 10.106, P = .001). The resumption of antipsychotic medication after the relapse occurred was associated with clinical
stability and lack of further relapses. When the overall group of relapsed individuals from the 2 conditions (N = 38) was compared to those who
remained asymptomatic after 3 years (N = 30), there were significant differences (P < .05) in total scores on the Scale for the Assessment of
Negative Symptoms, the Clinical Global Impressions scale, and the Disability Assessment Schedule. Conclusions: Antipsychotic treatment
discontinuation in individuals who had accomplished a functional recovery after a single psychotic episode was associated with a high risk of symptom
recurrence. Relapsed individuals had a greater severity of symptoms and lower functional status after 3 years. © Copyright 2016 Physicians
Postgraduate Press, Inc.
Journal of Clinical Psychiatry, 77(4) : 492-
500
- Year: 2016
- Problem: Psychosis Disorders
- Type: Controlled clinical trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Medication dose
reduction/discontinuation
Harvey, R., James, A., Shields, G.
Introduction: Early-onset schizophrenia (EOS) is a serious debilitating disorder with considerable morbidity and a reduced life
expectancy; therefore, early diagnosis and effective treatments are particularly important. Negative symptoms are more prominent in adolescents and
children (compared with adults), and are key predictors of worse functional and clinical outcomes in EOS. Therefore, this study aimed to explore the
relative efficacy of antipsychotics used in the treatment of EOS, with a focus on studies reporting effectiveness using the Positive and Negative
Syndrome scale (PANSS), a scale that includes an overall symptom measure, in addition to separate subscales for positive and, importantly, negative
symptoms. Methods: A systematic literature review was conducted using the MEDLINE and Cochrane Central Register of Controlled Trials databases to
identify trials conducted in children and adolescents with schizophrenia, and symptom control was reported using the PANSS. A Bayesian random-effects
network meta-analysis was performed, synthesising data for a number of outcomes, including mean change from baseline in PANSS scores, treatment
discontinuation and weight gain. Results: Eleven studies were included in the evidence synthesis, comprising 1714 patients across eight active
interventions (aripiprazole, haloperidol, molindone, olanzapine, paliperidone, quetiapine, risperidone and ziprasidone) and placebo. All treatments
showed a greater reduction in total PANSS scores vs placebo; however, only three interventions (molindone, olanzapine and risperidone) were
associated with a statistically significant reduction in total PANSS scores at 6 weeks vs placebo. Haloperidol had the greatest reduction vs placebo;
however, this result was not statistically significant [mean difference, -15.6, 95 % credible interval (-35.4, 4.1)]. Haloperidol, olanzapine and
risperidone showed a statistically significant reduction in positive PANSS scores vs placebo; however, whilst all interventions showed a trend of
reduction in negative PANSS scores vs placebo, no comparisons were statistically significant. Conclusions: Many of the treatments are efficacious in
controlling symptoms, and all showed a trend of superiority vs placebo for total, positive and negative PANSS scores, although only olanzapine and
risperidone yielded statistically significant results vs placebo for both total and positive PANSS scores. Varying results for discontinuation and
weight gain demonstrate a need to balance efficacy with side-effect profiles. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
CNS
Drugs, 30(1) : 27-39
- Year: 2016
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder), First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Typical Antipsychotics (first generation), Atypical Antipsychotics (second
generation)
Ising, H., Kraan, T., Rietdijk, J., Dragt, S., Klaassen, R., Boonstra, N., Nieman,
D., Willebrands-Mendrik, M., van-den-Berg, D., Linszen, D., Wunderink, L., Veling, W., Smit, F., van-der-Gaag, M.
Background: Previously, we demonstrated that cognitive behavior therapy for ultra-high risk (called CBTuhr)
halved the incidence of psychosis over an 18-month period. Follow-up data from the same study are used to evaluate the longer-term effects at 4 years
post-baseline. Method: The Dutch Early Detection and Intervention Evaluation study was a randomized controlled trial of 196 UHR patients comparing
CBTuhr with treatment-as-usual (TAU) for comorbid disorders with TAU only. Of the original 196 patients, 113 consented to a 4-year follow-up (57.7%;
CBTuhr = 56 vs TAU = 57). Over the study period, psychosis incidence, remission from UHR status, and the effects of transition to psychosis were
evaluated. Results: The number of participants in the CBTuhr group making the transition to psychosis increased from 10 at 18-month follow- up to 12
at 4-year follow-up whereas it did not change in the TAU group (n = 22); this still represents a clinically important (incidence rate ratio [IRR] =
12/22 = 0.55) and significant effect (F(1,5) = 8.09, P = .03), favoring CBTuhr. The odds ratio of CBTuhr compared to TAU was 0.44 (95% CI: 0.24-0.82)
and the number needed to treat was 8. Moreover, significantly more patients remitted from their UHR status in the CBTuhr group (76.3%) compared with
the TAU group (58.7%) [t(120) = 2.08, P = .04]. Importantly, transition to psychosis was associated with more severe psychopathology and social
functioning at 4-year follow-up. Conclusions: CBTuhr to prevent a first episode of psychosis in persons at UHR of developing psychosis is still
effective at 4-year follow-up. Our data also show that individuals meeting the formal criteria of a psychotic disorder have worse functional and
social outcomes compared with non-transitioned cases. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
Schizophrenia Bulletin, 42(5) : 1243-1252
- Year: 2016
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions
(any), Cognitive & behavioural therapies (CBT)
Kane, J., Robinson, D., Schooler, N., Mueser, K., Penn,
D., Rosenheck, R., Addington, J., Brunette, M., Correll, C., Estroff, S., Marcy, P., Robinson, J., Meyer-Kalos, P., Gottlieb, J., Glynn, S., Lynde, D., Pipes, R., Kurian, B., Miller, A., Azrin, S., Goldstein, A., Severe,
J., Lin, H., Sint, K., John, M., Heinssen, R.
Objective: The primary aim of this study was to
compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for
implementation in the U.S. health care system, with community care on quality of life. Method: Thirty-four clinics in 21 states were randomly
assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by
remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and <= 6 months
of antipsychotic treatment (N = 404) were enrolled and followed for >= 2 years. The primary outcome was the total score of the Heinrichs-Carpenter
Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in
regular activities. Results: The 223 recipients of NAVIGATE remained in treatment longer, experienced greater improvement in quality of life and
psychopathology, and experienced greater involvement in work and school compared with 181 participants in community care. The median duration of
untreated psychosis was 74 weeks. NAVIGATE participants with duration of untreated psychosis of < 74 weeks had greater improvement in quality of life
and psychopathology compared with those with longer duration of untreated psychosis and those in community care. Rates of hospitalization were
relatively low compared with other first-episode psychosis clinical trials and did not differ between groups. Conclusions: Comprehensive care for
first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes. Effects are more pronounced for
those with shorter duration of untreated psychosis. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
The American Journal of Psychiatry, 173(4) : 362-
372
- Year: 2016
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Family therapy, Psychoeducation, Other Psychological Interventions, Individual placement and support (IPS), vocational
interventions, Other service delivery and improvement
interventions
Deas, G., Kelly, C., Hadjinicolaou, A. V., Holt, C., Agius, M., Zaman, R.
Introduction: There are now many existing studies which assess the
treatments available for 'at risk mental states', as patients who are believed to be in the prodromal phase of psychotic illness are referred to.
However, concerns regarding side effects of possible treatments remain. We here conduct a meta-analysis of the studies available up to July 2016. The
aim of this study is to decide what would be the best treatment for 'at high risk patients'. Results: 18 studies were selected for inclusion; 12
showed significance, 5 did not and one tended towards significance. Both antipsychotic medication and psychological intervention show mixed results
with cognitive behavioral therapy and olanzapine/amisulpride coming out on top. Omega 3 poly-unsaturated acid also shows promising and consistent
results. Discussion: Treatments appear promising but a balance needs to be kept between adverse events and effectiveness of preventing psychosis.
Conclusion: It is necessary to search further for treatments in order to identify effective treatments with fewer adverse side-effects in this phase
of psychotic illness. Copyright © Medicinska naklada - Zagreb, Croatia.
Psychiatria Danubina, 28(Suppl
1) : 31-38
- Year: 2016
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions
(any), Service Delivery & Improvement, Psychological Interventions
(any)
Grano, N., Karjalainen, M., Ranta, K., Lindgren, M., Roine, M., Therman, S.
The aim of the present study was to compare change in
functioning, affective symptoms and level of psychosis-risk symptoms in symptomatic adolescents who were treated either in an early intervention
programme based on a need-adapted Family- and Community-orientated integrative Treatment Model (FCTM) or in standard adolescent psychiatric treatment
(Treatment As Usual, TAU). 28 pairs were matched by length of follow-up, gender, age, and baseline functioning. At one year after the start of
treatment, the matched groups were compared on change in functioning (GAF-M), five psychosis-risk dimensions of the Structured Interview for
Psychosis-Risk Syndromes (SIPS), and self-reported anxiety, depression, and hopelessness symptoms (BAI, BDI-II, BHS). FCTM was more effective in
improving functioning (20% vs. 6% improvement on GAF-M), as well as self-reported depression (53% vs. 14% improvement on BDI-II) and hopelessness
(41% vs. 3% improvement on BHS). However, for psychosis-risk symptoms and anxiety symptoms, effectiveness differences between treatment models did
not reach statistical significance. To conclude, in the present study, we found greater improvement in functioning and self-reported depression and
hopelessness among adolescents who received a need-adapted Family- and Community-orientated integrative Treatment than among those who were treated
in standard adolescent psychiatry.\rCopyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Psychiatry Research, 237 : 9-
16
- Year: 2016
- Problem: Psychosis Disorders
- Type: Controlled clinical trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Cognitive & behavioural therapies (CBT), Family therapy, Other service delivery and improvement
interventions
Kasoff, L. I., Ahn, K., Gochman, P., Broadnax,
D. D., Rapoport, J. L.
Objective: Childhood-onset
schizophrenia (COS) is a rare but severe form of the disorder, which is often treatment refractory. Short-term studies have indicated a greater
differential efficacy, evident through effect sizes, favoring clozapine over other agents in alleviating negative symptoms in COS patients compared
with adult-onset patients (AOS). There have been no data for COS patients on long-term compliance with clozapine treatment. Therefore, we wanted to
know, over a span of up to 24 years, how many of our COS cohort had remained on clozapine for at least 2 years. We review short-term treatment data
and present updated long-term data on compliance and functioning for our patients. Methods: We present the results for long-term medication
maintenance over a 24 year observation period for our cohort of 131 patients. Of this cohort, 91.6% (120) were available for follow-up information
from either in-person or telephone contact with the patient and/or family members. We defined clozapine compliance as >=2 years receiving this
medication and doing well. Results: We were able to contact 120 of the 131 patients. In spite of the additional cost and inconvenience of regular
blood monitoring, 87 patients (72.5%, 87/120) adhered to long-term clozapine maintenance therapy with dosages ranging from 50 to 900 mg, and a median
dosage of 500 mg. This rate exceeds the long-term clozapine maintenance rates reported for AOS patients. Conclusions: Short-term data on differential
efficacy and long-term maintenance data suggest a possibly greater efficacy of clozapine, relative to other antipsychotics, in COS than in AOS. Our
overall findings indicate that very early-onset schizophrenic patients may be more responsive to clozapine. This extends other support for clozapine
as an option in the treatment of early-onset schizophrenia. Copyright © Mary Ann Liebert, Inc. 2016.
Journal of Child and
Adolescent Psychopharmacology, 26(5) : 428-435
- Year: 2016
- Problem: Psychosis Disorders
- Type: Controlled clinical trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Typical Antipsychotics (first generation), Atypical Antipsychotics (second
generation)
Crespo-Facorro, B., Pelayo-Teran, J.
M., Mayoral-van Son, J.
Implementing the most
suitable treatment strategies and making appropriate clinical decisions about individuals with a first episode of psychosis (FEP) is a complex and
crucial task, with relevant impact in illness outcome. Treatment approaches in the early stages should go beyond choosing the right antipsychotic
drug and should also address tractable factors influencing the risk of relapse. Effectiveness and likely metabolic and endocrine disturbances differ
among second-generation antipsychotics (SGAs) and should guide the choice of the first-line treatment. Clinicians should be aware of the high risk of
cardiovascular morbidity and mortality in schizophrenia patients, and therefore monitoring weight and metabolic changes across time is mandatory.
Behavioral and counseling interventions might be partly effective in reducing weight gain and metabolic disturbances. Ziprasidone and aripiprazole
have been described to be least commonly associated with weight gain or metabolic changes. In addition, some of the SGAs (risperidone, amisulpride,
and paliperidone) have been associated with a significant increase of plasma prolactin levels. Overall, in cases of FEP, there should be a clear
recommendation of using lower doses of the antipsychotic medication. If no or minimal clinical improvement is found after 2 weeks of treatment, such
patients may benefit from a change or augmentation of treatment. Clinicians should provide accurate information to patients and relatives about the
high risk of relapse if antipsychotics are discontinued, even if patients have been symptom free and functionally recovered on antipsychotic
treatment for a lengthy period of time. Copyright © 2016, The Author(s).
Neurology and Therapy, 5(2) : 105-130
- Year: 2016
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)