Disorders - Psychosis Disorders
Saksa, John R., Cohen, Shuki J., Srihari, Vinod H., Woods, Scott W.
Several recent studies of individually administered cognitive behavior therapy (CBT) for early psychosis have reported only modest treatment benefits. The purpose of the current study was to review the literature to determine how outcomes of group CBT differ from outcomes of individually administered CBT among early cases. Our findings suggest that group CBT for early psychosis may be a more effective modality for this group of patients. We speculate that patients' uncertainty about illness in general may impair the effectiveness of individually administered CBT for early cases and that group CBT may be more effective for these young patients by better addressing those factors with the aid of peer-to-peer interactions, identification, and modeling.
International Journal of Group Psychotherapy, 59(3) : 357-383
- Year: 2009
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
Salimi, Kayvon, Jarskog, L. Fredrik, Lieberman, Jeffrey A.
Increasingly, it is recognized that first-episode schizophrenia represents a critical stage of illness during which the effectiveness of therapeutic interventions can affect long-term outcome. In this regard, the advent of clozapine and subsequent atypical antipsychotic drugs held promise for improved outcomes in patients with first-episode schizophrenia, given the expectation of improved therapeutic efficacy and a more benign side effect burden compared with typical antipsychotic drugs. A growing number of large clinical trials have evaluated the merits of atypical antipsychotic drugs in the early stages of psychosis. A number of conclusions can be drawn from studies completed to date, with the caveat that data are either limited or unavailable for the antipsychotic drugs most recently approved by the US FDA. Studies of atypical antipsychotic drugs support data obtained with typical agents indicating that positive symptoms of psychosis are very treatment responsive and generally at lower doses than in chronic illness. It also appears that first-episode patients tend to stay on atypical antipsychotic drugs longer than on typical agents when all-cause discontinuation criteria are considered as the primary outcome measure. However, there are few differential advantages of clinical efficacy among the individual atypical antipsychotic drugs and there is little evidence to support distinct therapeutic advantages for negative symptoms or cognitive symptoms for atypical agents. Furthermore, while new-onset psychosis patients are particularly susceptible to extrapyramidal symptoms, they are also prone to gain weight and related metabolic adverse effects associated with many, but not all, atypical antipsychotic drugs. Recent data indicating that certain atypical antipsychotic drugs may have a sparing effect on cortical grey matter loss in first-episode schizophrenia is intriguing, given the potential long-term benefits. In summary, atypical antipsychotic drugs represent an incremental advance for patients in first-episode schizophrenia, especially in the area of neurological tolerability. However, metabolic concerns associated with many atypical agents along with limited benefits in cognition and negative symptom domains highlight the persistent therapeutic needs of these patients.
CNS Drugs, 23(10) : 837-855
- Year: 2009
- 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)
Moller, Hans-Jürgen, Riedel, Michael, Jager, Markus, Wickelmaier, Florian, Maier, Wolfgang, Kuhn, Kai-Uwe, Buchkremer, Gerhard, Heuser, Isabella, Klosterkotter, Joachim, Gastpar, Markus
Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics, and to be more
sensitive to developing extrapyramidal side-effects. The authors therefore compared in such patients the
efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone
and of the conventional neuroleptic haloperidol. Risperidone was hypothesized to have better extrapyramidal
tolerability and efficacy in treating negative symptoms. Patients were randomly assigned under
double-blind conditions to receive risperidone (n=143) or haloperidol (n=146) for 8 wk. The primary
efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom
Scale (PANSS) negative score between treatment groups; secondary efficacy criteria were changes on the
PANSS total score and other PANSS subscores, and several other measures of psychopathology and general
functioning. The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of
extrapyramidal side-effects measured with the Simpson - Angus Scale (SAS) compared between treatment
groups. The main hypothesis was that risperidone would be superior in terms of improving negative
symptoms and lowering the risk of extrapyramidal symptoms. Secondary tolerability criteria were the other
extrapyramidal symptoms, measured with the Hillside Akathisia Scale (HAS) and the Abnormal Involuntary
Movement Scale (AIMS). The average mean daily doses were 3.8 mg (S.D.=1.5) for risperidone and
3.7 mg (S.D.=1.5) for haloperidol. There were similar, significant improvements in both treatment groups in
the primary and secondary efficacy criteria. At week 8 nearly all scores of extrapyramidal side-effects
indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with
risperidone [SAS: risperidone 36.5% of patients ; haloperidol 51.5% of patients ; likelihood ratio test,
x2(1)=7.8, p=0.005]. There were significantly fewer drop-outs [risperidone n=55, drop-out rate=38.5%;
haloperidol n=79, drop-out rate=54.1%, x2(1)=7.1, p=0.009] and a longer non-discontinuation time
[risperidone: average of 50.8 d to drop-out ; haloperidol : average of 44.0 d to drop-out ; log rank test,
x2(1)=6.4, p=0.011] in the risperidone group. Risperidone and haloperidol appear to be equally effective in
treating negative and other symptoms of first-episode schizophrenia. Risperidone has better extrapyramidal
tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients.
International Journal of Neuropsychopharmacology, 11(07) : 985-997
- Year: 2008
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
Kumra, S., Oberstar, J. V., Sikich, L., Findling, R. L., McClellan, J. M., Vinogradov, S., Charles Schulz, S.
Early-onset schizophrenia-spectrum (EOSS) disorders (onset of psychotic symptoms before 18 years of age) represent a severe variant associated with significant chronic functional impairment and poor response to antipsychotic treatment. All drugs with proven antipsychotic effects block dopamine D 2 receptors to some degree. The ongoing development of the dopamine and other neurotransmitter receptor systems during childhood and adolescence may affect clinical response and susceptibility to side effects in youth. A literature search was conducted of clinical trials of antipsychotics in children and adolescents with EOSS disorders between 1980 and 2007 from the Medline database, reference lists, and conference proceedings. Trials were limited to double-blind studies of duration of 4 or more weeks that included 15 or more patients. Ten clinical trials were identified. Antipsychotic medications were consistently found to reduce the severity of psychotic symptoms in children and adolescents when compared with placebo. The superiority of clozapine has been now demonstrated relative to haloperidol, standard-dose olanzapine, and "high-dose" olanzapine for EOSS disorders. However, limited comparative data are available regarding whether there are differences among the remaining second-generation antipsychotics (SGAs) in clinical effectiveness. The available data from short-term studies suggest that youth might be more sensitive than adults to developing antipsychotic-related adverse side effects (eg, extrapyramidal side effects, sedation, prolactin elevation, weight gain). In addition, preliminary data suggest that SGA use can lead to the development of diabetes in some youth, a disease which itself carries with it significant morbidity and mortality. Such a substantial risk points to the urgent need to develop therapeutic strategies to prevent and/or mitigate weight gain and diabetes early in the course of treatment in this population. copyright 2007 The Authors.
Schizophrenia Bulletin., 34(1) : 60-71
- Year: 2008
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
Kumra, Sanjiv, Kranzler, Harvey, Gerbino-Rosen, Ginny, Kester, Hana M., DeThomas, Courtney, Kafantaris, Vivian, Correll, Christoph U., Kane, John M.
BACKGROUND: The present study evaluated the effectiveness and safety of clozapine versus "high-dose" olanzapine in treatment-refractory adolescents with schizophrenia. METHODS: Children, ages 10-18 years, who met DSM-IV criteria for schizophrenia and who were resistant or intolerant to at least two antipsychotic drugs were randomized to receive 12 weeks of double-blind flexibly dosed treatment with clozapine (n = 18) or "high-dose" olanzapine (up to 30 mg/day) (n = 21). The primary efficacy measure was response (improvement), defined as a decrease of 30% or more in total Brief Psychiatric Rating Scale score from baseline and a Clinical Global Impression Scale improvement rating of "1" (very much improved) or "2" (much improved). RESULTS: Significantly more clozapine-treated adolescents met response criteria (66%) compared with olanzapine-treated subjects (33%). Clozapine was superior to olanzapine in terms of reduction of the psychosis cluster scores and negative symptoms from baseline to end point. However, both treatments were associated with significant weight-gain and related metabolic abnormalities. CONCLUSIONS: This double-blind randomized comparison of two second-generation antipsychotic drugs for treatment-refractory adolescents with schizophrenia supports clozapine as the agent of choice. The development of interventions to limit weight gain and metabolic side effects are needed to enhance the risk-benefit profile for both study treatments.
Biological Psychiatry, 63(5) : 524-9
- Year: 2008
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Treatment resistant/treatment refractory
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Lecomte, Tania, Leclerc, Claude, Corbiere, Marc, Wykes, Til, Wallace, Charles J., Spidel, Alicia
This study aimed at determining the effectiveness of group cognitive behavior therapy (CBT) for recent onset psychosis in comparison with a recognized intervention for individuals with severe mental illness-social skills training. One hundred twenty-nine participants took part in a single-blind randomized controlled trial with repeated measures (baseline, 3 months, and 9 months). Participants were randomized to 1 of 3 conditions: group CBT, group social skills training for symptom management, or a wait-list control group. Both interventions were delivered by mental health staff with minimal training. Both treatments resulted in improvements on positive and negative symptoms compared with the waitlist control group, with the CBT group having significant effects over time on overall symptoms, and post-treatment effects on self-esteem, and active coping skills compared with the wait-list control group and lower drop-out rates than the skills training group. Therapist fidelity was adequate for both treatment conditions. Group CBT for psychosis is a promising intervention for individuals with recent onset of psychosis and their mental health professionals. (PsycINFO Database Record (c) 2009 APA, all rights reserved) (journal abstract).
Journal of Nervous & Mental Disease, 196(12) : 866-875
- Year: 2008
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
, Skills training
Kahn, Rene S., Fleischhacker, W. Wolfgang, Boter, Han, Davidson, Michael, Vergouwe, Yvonne, Keet, Ireneus P. M., Gheorghe, Mihai D., Rybakowski, Janusz K., Galderisi, Silvana, Libiger, Jan, Hummer, Martina, Dollfus, Sonia, Lopez-Ibor, Juan J., Hranov, Luchezar G., Gaebel, Wolfgang, Peuskens, Joseph, Lindefors, Nils, Riecher-Rossler, Anita, Grobbee, Diederick E., EufestStudyGroup
BACKGROUND: Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia; however, their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated. We aimed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol, in first-episode schizophrenia. METHODS: We did an open randomised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites, in 14 countries. Eligible patients were aged 18-40 years, and met diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. 498 patients were randomly assigned by a web-based online system to haloperidol (1-4 mg per day; n=103), amisulpride (200-800 mg per day; n=104), olanzapine (5-20 mg per day; n=105), quetiapine (200-750 mg per day; n=104), or ziprasidone (40-160 mg per day; n=82); follow-up was at 1 year. The primary outcome measure was all-cause treatment discontinuation. Patients and their treating physicians were not blinded to the assigned treatment. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN68736636. FINDINGS: The number of patients who discontinued treatment for any cause within 12 months was 63 (Kaplan-Meier estimate 72%) for haloperidol, 32 (40%) for amisulpride, 30 (33%) for olanzapine, 51 (53%) for quetiapine, and 31 (45%) for ziprasidone. Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride (hazard ratio [HR] 0.37, [95% CI 0.24-0.57]), olanzapine (HR 0.28 [0.18-0.43]), quetiapine (HR 0.52 [0.35-0.76]), and ziprasidone (HR 0.51 [0.32-0.81]). However, symptom reductions were virtually the same in all the groups, at around 60%. INTERPRETATION: This pragmatic trial suggests that clinically meaningful antipsychotic treatment of first-episode of schizophrenia is achievable, for at least 1 year. However, we cannot conclude that second-generation drugs are more efficacious than is haloperidol, since discontinuation rates are not necessarily consistent with symptomatic improvement.
Lancet, 371(9618) : 1085-97
- Year: 2008
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
, Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
Jackson, H. J., McGorry, P. D., Killackey, E., Bendall, S., Allott, K., Dudgeon, P., Gleeson, J., Johnson, T., Harrigan, S.
BACKGROUND: The ACE project involved 62 participants with a first episode of psychosis randomly assigned to either a cognitive behaviour therapy (CBT) intervention known as Active Cognitive Therapy for Early Psychosis (ACE) or a control condition known as Befriending. The study hypotheses were that: (1) treating participants with ACE in the acute phase would lead to faster reductions in positive and negative symptoms and more rapid improvement in functioning than Befriending; (2) these improvements in symptoms and functioning would be sustained at a 1-year follow-up; and (3) ACE would lead to fewer hospitalizations than Befriending as assessed at the 1-year follow-up. METHOD: Two therapists treated the participants across both conditions. Participants could not receive any more than 20 sessions within 14 weeks. Participants were assessed by independent raters on four primary outcome measures of symptoms and functioning: at pretreatment, the middle of treatment, the end of treatment and at 1-year follow-up. An independent pair of raters assessed treatment integrity. RESULTS: Both groups improved significantly over time. ACE significantly outperformed Befriending by improving functioning at mid-treatment, but it did not improve positive or negative symptoms. Past the mid-treatment assessment, Befriending caught up with the ACE group and there were no significant differences in any outcome measure and in hospital admissions at follow-up. CONCLUSIONS: There is some preliminary evidence that ACE promotes better early recovery in functioning and this finding needs to be replicated in other independent research centres with larger samples.
Psychological Medicine, 38(5) : 725-35
- Year: 2008
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
, Other Psychological Interventions
Killackey, E., Jackson, H., & McGorry, P.
Unemployment is a major problem for people with first-episode psychosis and schizophrenia. This has repercussions for the economy, social functioning and illness prognosis.
Aims
To examine whether a vocational intervention - individual placement and support (PS) - which has been found to be beneficial in populations with chronic schizophrenia, was a useful intervention for those with first-episode psychosis.
Method
A total of 41 people with first-episode psychosis were randomised to receive either 6 months of IPS + treatment as usual (TAU) (n=20) or TAU alone (n=21).
Results
The IPS group had significantly better outcomes on level of employment (13 v. 2, P<0.001), hours worked per week (median 38 v. 22.5, P=0.006), jobs acquired (23 v. 3) and longevity of employment (median 5 weeks v. 0, P=0.021). The IPS group also significantly reduced their reliance on welfare benefits.
Conclusions
Individual placement and support has good potential to address the problem of vocational outcome in people with first-episode psychosis. This has economic, social and health implications.
British Journal of Psychiatry, 193(2) : 114-120
- Year: 2008
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Individual placement and support (IPS), vocational interventions
Findling, Robert, Robb, Adelaide, Nyilas, Margaretta, Forbes, Robert, Jin, Na, Ivanova, Svetlana, Marcus, Ronald, McQuade, Robert, Iwamoto, Taro, Carson, William
Aripiprazole is a dopamine partial agonist approved for use in adults for short- and long-term treatment of schizophrenia and bipolar disorder. This study was designed to examine the acute efficacy, safety, and tolerability of aripiprazole for adolescents with schizophrenia. METHOD: This was a 6-week multicenter, double-blind, randomized, placebo-controlled trial. Subjects 13 to 17 years old with a DSM-IV diagnosis of schizophrenia and a Positive and Negative Syndrome Scale (PANSS) total score of 70 or more were randomly assigned (1:1:1 ratio) to placebo or 10 or 30 mg/day of aripiprazole. The primary endpoint was mean change from baseline to endpoint (last observation carried forward) in PANSS total score. Assessments of safety and tolerability included spontaneously reported adverse events, extrapyramidal symptom scores, serum prolactin concentration, body weight, and metabolic measures. RESULTS: Of 302 patients, 85% completed the 6-week study. The mean baseline PANSS score was 94.1. At the end of the study, both aripiprazole doses showed statistically significant differences from placebo in reduction in PANSS total score. Adverse events occurring in more than 5% of either aripiprazole group and with a combined incidence at least twice the rate for placebo were extrapyramidal disorder, somnolence, and tremor. Mean changes in prolactin were -8.45, -11.93, and -15.14 ng/ml for placebo and 10 mg and 30 mg of aripirazole, respectively. Mean body weight changes were -0.8, 0.0, and 0.2 kg for placebo and 10 mg and 30 mg of aripiprazole, respectively. CONCLUSION: Both 10- and 30-mg/day doses of aripiprazole were superior to placebo in the acute treatment of adolescents with schizophrenia. Aripiprazole was generally well tolerated.
American Journal of Psychiatry, 165(11) : 1432-1441
- Year: 2008
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Bertelsen, Mette, Jeppesen, Pia, Petersen, Lone, Thorup, Anne, Ohlenschlæger, Johan, leQuach, Phuong, Christensen, Torben Østergaard, Krarup, Gertrud, Jorgensen, Per, Nordentoft, Merete
CONTEXT:
Intensive early treatment for first-episode psychosis has been shown to be effective. It is unknown if the positive effects are sustained for 5 years.
OBJECTIVE:
To determine the long-term effects of an intensive early-intervention program (OPUS) for first-episode psychotic patients.
DESIGN:
Single-blinded, randomized, controlled clinical trial of 2 years of an intensive early-intervention program vs standard treatment. Follow-up periods were 2 and 5 years.
SETTING:
Copenhagen Hospital Corporation and Psychiatric Hospital, Aarhus, Denmark. Patients A total of 547 patients with a first episode of psychosis. Of these, 369 patients were participating in a 2-year follow-up, and 301 were participating in a 5-year follow-up. A total of 547 patients were followed for 5 years.
INTERVENTIONS:
Two years of an intensive early-intervention program vs standard treatment. The intensive early-intervention treatment consisted of assertive community treatment, family involvement, and social skills training. Standard treatment offered contact with a community mental health center.
MAIN OUTCOME MEASURES:
Psychotic and negative symptoms were recorded. Secondary outcome measures were use of services and social functioning.
RESULTS:
Analysis was based on the principles of intention-to-treat. Assessment was blinded for previous treatment allocation. At the 5-year follow-up, the effect of treatment seen after 2 years (psychotic dimension odds ratio [OR], -0.32; 95% confidence interval [CI], -0.58 to -0.06; P = .02; negative dimension OR, -0.45; 95% CI, -0.67 to -0.22; P = .001) had equalized between the treatment groups. A significantly smaller percentage of patients from the experimental group were living in supported housing (4% vs 10%, respectively; OR, 2.3; 95% CI, 1.1-4.8; P = .02) and were hospitalized fewer days (mean, 149 vs 193 days; mean difference, 44 days; 95% CI, 0.15-88.12; P = .05) during the 5-year period.
CONCLUSIONS:
The intensive early-intervention program improved clinical outcome after 2 years, but the effects were not sustainable up to 5 years later. Secondary outcome measures showed differences in the proportion of patients living in supported housing and days in hospital at the 5-year follow-up in favor of the intensive early-intervention program.
Archives of General Psychiatry, 65(7) : 762-771
- Year: 2008
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Other service delivery and improvement interventions
Berger, Gregor E., Proffitt, Tina-Marie, McConchie, Mirabel, Kerr, Melissa, Markulev, Connie, Yuen, Hok Pan, O'Donnell, Colin, Lubman, Dan, Polari, Andrea, Wood, Stephen, Amminger, Paul G., McGorry, Patrick D.
OBJECTIVE: To assess dosing, efficacy, and tolerability of quetiapine fumarate in drug-naive first-episode psychosis. METHOD: We present a prospective, randomized, controlled, single-center, double-blind, fixed-dose, 4-week comparison study of 200 mg/day versus 400 mg/day of quetiapine in 141 drug-naive acutely ill first-episode psychosis patients (diagnosed according to DSM-IV) aged 15 to 25 years. The double-blind 4-week trial (Part 1) was followed by a single-blind, naturalistic, flexible-dose 8-week period (Part 2). The main outcome measures were symptomatic change, functioning, and tolerability. Data were collected from July 2003 until January 2006. RESULTS: The estimated time trends of the linear mixed-effects modeling indicated that efficacy between the 2 treatment groups in Part 1 was similar for most outcome measures except for 5 measures: the Scale for the Assessment of Negative Symptoms (SANS) anhedonia-asociality subscale (p = .011), the Social and Occupational Functioning Assessment Scale (p = .020), the Global Assessment of Functioning scale (p = .070), the SANS affective flattening or blunting subscale (p = .051), and the Udvalg for Kliniske Undersogelser total (p = .056), suggesting that the 200-mg group improved more for the SANS anhedonia-asociality subscale, whereas the 400-mg group showed a slight deterioration. Social and global functioning also improved more in the 200-mg group than in the 400-mg group. Part 2 of the study revealed that, independent of the initial target dose, when clinicians were able to adjust the dose flexibly, the dose at 12 weeks was similar between groups and averaged 268 mg/day. CONCLUSION: Our study in acutely ill drug-naive first-episode psychosis patients suggests that quetiapine is a safe and well-tolerated antipsychotic medication. In contrast to multiepisode patients, dosing should be more conservative in untreated new-onset cases. An initial dose of 250 to 300 mg/day of quetiapine is proposed as a primary target dose in drug-naive first-episode psychosis patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00449397. Copyright 2008 Physicians Postgraduate Press, Inc.
Journal of Clinical Psychiatry, 69(11) : 1702-14
- Year: 2008
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)