Disorders - Psychosis Disorders
Phillips, L. J., McGorry, P.
D., Yuen, H. P., Ward, J., Donovan, K., Kelly, D., Francey, S. M., Yung, A. R.
Valid criteria to identify young people who are believed to be at ultra high risk (UHR) of developing a psychotic episode were developed
over the last decade. The first randomized controlled trial of treatment in a UHR cohort indicated that specific pharmacotherapy and psychotherapy
delayed onset of disorder, and possibly reduced incidence. This paper reports results of follow-up of that trial. 41 of the 59 (69.5%) participants
in the original study agreed to follow-up. No differences were found in transition rate, level of symptomatology or functioning between participants
who received a combination of psychological treatment and anti-psychotic medication compared to those who received supportive therapy alone. A
significant proportion of both treatment groups reported moderate levels of psychiatric morbidity and a continuing need and desire for care at this
follow-up. Low levels of hospitalisation were noted for those who did progress to psychosis. Conclusions that can be drawn from this exploratory
study are limited by the relatively small number of participants in the original study and the failure to follow-up the entire cohort. Although
participants may have been treated too briefly to result in enduring positive effects, there appear to have been some cost savings in inpatient
mental health treatment required after the end of the trial for individuals in both treatment groups who developed psychosis. copyright 2007 Elsevier
B.V. All rights reserved.
Schizophrenia
Research., 96(1-3) : 25-33
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Psychological Interventions
(any), Supportive
therapy, Other Psychological Interventions
Ruhrmann,
S., Bechdolf, A., Kuhn, K. U., Wagner, M., Schultze-Lutter, F., Janssen,
B., Maurer, K., Hafner, H., Gaebel, W., Moller, H. J., Maier, W., Klosterkotter, J.
BACKGROUND: People in a putatively late prodromal state not only have an
enhanced risk for psychosis but already suffer from mental and functional disturbances. AIMS: To evaluate the acute effects of a combined supportive
and antipsychotic treatment on prodromal symptoms. METHOD: Putatively prodromal individuals were randomly assigned to a needs-focused intervention
without (n=59) or with amisulpride (n=65). Outcome measures at 12-weeks effects were prodromal symptoms, global functioning and extrapyramidal side-
effects. RESULTS: Amisulpride plus the needs-focused intervention produced superior effects on attenuated and full-blown psychotic symptoms, basic,
depressive and negative symptoms, and global functioning. Main side-effects were prolactin associated. CONCLUSIONS: Coadministration of amisulpride
yielded a marked symptomatic benefit. Effects require confirmation by a placebo-controlled study.
British Journal of Psychiatry, 51 : s88-
95
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Wykes, T., Newton, E., Landau, S., Rice, C., Thompson, N., Frangou, S.
Background:
Schizophrenia with an onset in adolescence is known to be associated with a poorer outcome and cognitive difficulties. These impairments have an
impact on quality of life and represent treatment targets. Cognitive remediation therapy (CRT) attempts to improve cognitive deficits by teaching
information processing strategies through guided mental exercises. The objective of this study is to evaluate the efficacy of CRT in alleviating
cognitive deficits compared to treatment as usual and explore the mediating and moderating effects of cognitive improvement. Method: Single-blind
randomized controlled trial with two groups, one receiving CRT (N21) and the other standard care (N19) assessed at baseline, 3 months (post therapy)
and follow-up (3 months post therapy). Participants were recruited from specialist inpatient and community mental health services and were young
patients with recent onset schizophrenia (average age of 18) and evidence of cognitive and social behavioural difficulties. The intervention was
individual cognitive remediation therapy delivered over a period of 3 months with at least three sessions per week. The main outcome measures were
cognition (memory, cognitive flexibility and planning) and secondary outcomes (symptoms, social contacts and self-esteem). Results: Compared to
standard care, CRT produced significant additional improvements in cognitive flexibility as measured by the Wisconsin Card Sort Test (WCST). Therapy
moderated the effects of improved planning ability on symptoms such that improvements only had a beneficial effect when they were achieved in the
context of CRT. Improvements in cognition in all domains had a direct effect on social functioning and improvements in WCST had a direct effect on
overall symptom improvement. Conclusions: Cognitive remediation therapy can contribute to the improvement in WCST even in adolescents. The changes in
cognitive outcomes also contributed to improvements in functioning either directly or solely in the context of CRT. Evidence of the mediator and
moderator effects of cognitive changes should lead to more effective therapy development. copyright 2007 Elsevier B.V. All rights reserved.
Schizophrenia Research., 94(1-3) : 221-230
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions
(any), Cognitive remediation
therapy
Welch, M., Welch, T.
Early psychosis (EP), in
which the terms first-episode psychosis or first-break psychosis are also considered, is an area of developing research intensity. Although it is
apparent that considerable progress has been made in establishing best practice criteria and protocols for EP in general, the particular issues
pertaining to rural areas have not received the same attention. The purpose of the present study was to conduct a systematic review of the literature
of early psychosis programmes, initiatives and research in rural areas in order to help establish the best available evidence. The authors conducted
a systematic search of major electronic databases, based on the NHMRC hierarchy of evidence, an established scale, for identified early psychosis
cross-referenced with multiple rural terms, between the years 1995 and 2005. A total of 637 articles met the initial search criteria; 206 were
identified as having primary significance; three dealt specifically with rural areas. There is a paucity of research findings or published literature
concerning the specific needs or characteristics of early psychosis practice or service delivery in rural areas. A number of inferences and
suggestions for further research, investigations and policy directions are put forward for consideration.
Australian & New
Zealand Journal of Psychiatry., 41(6) : 485-494
- Year: 2007
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement
Sporn, A. L., Vermani, A., Greenstein, D. K., Bobb, A. J., Spencer, E.
P., Clasen, L. S., Tossell, J. W., Stayer, C. C., Gochman, P. A, Lenane, M. C., Rapoport, J. L., Gogtay, N.
OBJECTIVE: Clozapine is a unique atypical antipsychotic with superior
efficacy in treatment-resistant schizophrenia. Plasma concentration of clozapine and its major metabolite N-desmethylclozapine (NDMC) as well as the
ratio of NDMC to clozapine have been reported to be predictors of clozapine response. Here we evaluate these as well as other measures in an effort
to find predictors of response to clozapine in our early-onset treatment-refractory population. METHOD: Fifty-four children and adolescents
participated in double-blind (n = 22) or open-label (n = 32) clozapine trials. Clinical evaluations took place at baseline, week 6 on clozapine, and
at 2- to 6-year follow-up. The data were analyzed in relation to demographics, age at onset, IQ, clozapine dose, and plasma concentrations of
prolactin, clozapine, NDMC, and NDMC/clozapine ratio. Stepwise regression and correlation analyses were performed to find predictors of treatment
response. RESULTS: Clinical improvement after 6 weeks of clozapine treatment, as measured by the percentage of improvement on the Brief Psychiatric
Rating Scale and the Scale for the Assessment of Positive Symptoms, was strongly associated with the NDMC/clozapine ratio at the 6-week time point
(Pearson correlation coefficient: r = 0.41; p < .01 for Brief Psychiatric Rating Scale and r = 0.43; p < .01 for Scale for the Assessment of Positive
Symptoms). Although the rate of side effects was higher than that typically found in the adult population, it did not appear to be related to
clozapine dose, clozapine or NDMC plasma concentrations, or NDMC/clozapine ratio. Outcome at long-term follow-up, as measured by Children's Global
Assessment Scale, was associated with lesser illness severity at baseline and with greater improvement during the initial 6 weeks of clozapine
treatment. CONCLUSIONS: The NDMC/clozapine ratio may be a valuable predictor of response to clozapine and may suggest new approaches to clozapine
treatment. Copyright 2007 copyright American Academy of Child and Adolescent Psychiatry.
Journal of the American Academy of Child &
Adolescent Psychiatry., 46(10) : 1349-1356
- Year: 2007
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Treatment resistant/treatment refractory
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Robinson, Delbert G., Woerner, Margaret G., Napolitano, Barbara, Patel, Raman C., Sevy, Serge M., Gunduz-Bruce, Handan, Soto-Perello, Jose M., Mendelowitz,
Alan, Khadivi, Ali, Miller, Rachel, McCormack, Joanne, Lorell, Beth S., Lesser, Martin L., Schooler, Nina
R., Kane,
John M.
OBJECTIVE: The
authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders.
METHOD: One hundred twelve subjects (70% male; mean age=23.3 years [SD = 5.1]) with first-episode schizophrenia (75%), schizophreniform disorder
(17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2.5-20 mg/day) or risperidone (1-6 mg/day). RESULTS:
Response rates did not significantly differ between olanzapine (43.7%, 95% CI=28.8%-58.6%) and risperidone (54.3%, 95% CI=39.9%-68.7%). Among those
responding to treatment, more subjects in the olanzapine group (40.9%, 95% CI=16.8%-65.0%) than in the risperidone group (18.9%, 95% CI=0%-39.2%) had
subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between
medications. Extrapyramidal symptom severity scores were 1.4 (95% CI=1.2-1.6) with risperidone and 1.2 (95% CI=1.0-1.4) with olanzapine.
Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was
17.3% (95% CI=14.2%-20.5%) with olanzapine and 11.3% (95% CI=8.4%-14.3%) with risperidone. Body mass index at baseline and at 4 months was 24.3 (95%
CI=22.8-25.7) versus 28.2 (95% CI=26.7-29.7) with olanzapine and 23.9 (95% CI=22.5-25.3) versus 26.7 (95% CI=25.2-28.2) with risperidone.
CONCLUSIONS: Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an
advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.
American Journal of Psychiatry, 163(12) : 2096-
102
- Year: 2006
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Shaw, P., Sporn, A., Gogtay, N., Overman, G. P., Greenstein, D., Gochman, P., Tossell, J. W., Lenane, M., Rapoport, J. L.
BACKGROUND: Childhood-onset schizophrenia is
a rare but severe form of the disorder that is frequently treatment resistant. The psychiatrist has a limited evidence base to guide treatment,
particularly as there are no trials in children comparing atypical antipsychotics, the mainstay of current treatment. OBJECTIVE: To compare the
efficacy and safety of olanzapine and clozapine, hypothesizing that clozapine would be more efficacious. DESIGN: Double-blind randomized 8-week
controlled trial, with a 2-year open-label follow-up. SETTING: National Institute of Mental Health study, January 1998 to June 2005. Patients
underwent reassessment 2 years after discharge. PATIENTS: Children and adolescents recruited nationally, aged 7 to 16 years, meeting unmodified DSM-
IV criteria for schizophrenia, and resistant to treatment with at least 2 antipsychotics. INTERVENTIONS: After drug washout and a 1- to 3-week
antipsychotic-free period, patients were randomized to treatment with clozapine (n = 12) or olanzapine (n = 13). MAIN OUTCOME MEASURES: The Clinical
Global Impression Severity of Symptoms Scale and Schedule for the Assessment of Negative/Positive Symptoms. RESULTS: Clozapine was associated with a
significant reduction in all outcome measures, whereas olanzapine showed a less consistent profile of clinical improvement. While there were moderate
to large differential treatment effects in favor of clozapine, these reached significance only in the alleviation of negative symptoms from an
antipsychotic-free baseline (P = .04; effect size, 0.89). Clozapine was associated with more overall adverse events. At 2-year follow-up, 15 patients
were receiving clozapine with evidence of sustained clinical improvement, but additional adverse events emerged, including lipid anomalies (n = 6)
and seizures (n = 1). CONCLUSIONS: While not demonstrating definitively the superiority of clozapine compared with olanzapine in treatment-refractory
childhood-onset schizophrenia, the study suggests that clozapine has a more favorable profile of clinical response, which is balanced against more
associated adverse events.
Archives of General Psychiatry, 63(7) : 721-30
- Year: 2006
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Treatment resistant/treatment refractory
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Nordentoft, Merete, Thorup, Anne, Petersen, Lone, Ohlenschlaeger, Johan, Melau, Marianne, Christensen, Torben Ostergaard, Krarup, Gertrud, Jorgensen, Per, Jeppesen, Pia
BACKGROUND: Only a few randomized clinical trials have tested the effect on transition
rates of intervention programs for patients with sub-threshold psychosis-like symptoms. AIM: To examine whether integrated treatment reduced
transition to psychosis for first-contact patients diagnosed with schizotypal disorder. METHODS: Seventy-nine patients were randomized to integrated
treatment or standard treatment. Survival analysis with multivariate Cox-regression was used to identify factors determinant for transition to
psychotic disorder. RESULTS: In the multivariate model, male gender increased risk for transition to psychotic disorder (relative risk=4.47,
(confidence interval 1.30-15.33)), while integrated treatment reduced the risk (relative risk=0.36 (confidence interval 0.16-0.85)). At two-year
follow-up, the proportion diagnosed with a psychotic disorder was 25.0% for patients randomized to integrated treatment compared to 48.3% for
patients randomized to standard treatment. CONCLUSION: Integrated treatment postponed or inhibited onset of psychosis in significantly more cases
than standard treatment.
Schizophrenia Research, 83(1) : 29-40
- Year: 2006
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Service Delivery & Improvement, Other service delivery and improvement
interventions
Mozes, T., Ebert, T., Michal, S. E., Spivak, B., Weizman, A.
BACKGROUND AND PURPOSE: Childhood-onset schizophrenia (COS) is a clinically severe form of schizophrenia, which causes severe impairment to
cognitive, linguistic, and social development. There are few prospective and retrospective open clinical trials of risperidone and olanzapine in COS.
In this open-label, randomized, prospective study, we compared the tolerability and effectiveness of risperidone versus olanzapine in the treatment
of COS patients. METHODS: The study population consisted of 25 children with COS (mean age 11.09 +/- 1.55 years). After an evaluation, patients
received risperidone (0.25-4.5 mg/day, mean dose 1.62 +/- 1.02 mg/day) or olanzapine (2.5-20 mg/day, mean dose 8.18 +/- 4.41 mg/day) for 12 weeks,
with weekly evaluations. RESULTS: Both groups showed comparable significant (p < 0.001) within-group improvement from baseline to endpoint (LOCF) in
Positive and Negative Symptoms Scale (PANSS) total and subscale scores. Of the olanzapine-treated children, 11 (91.7%) completed the 12 weeks of the
study, whereas in the risperidone-treated children only 9 (69.2%) did. No significant differences between risperidone-treated children and
olanzapine-treated children were observed on Barnes Akathisia Rating Scale (BAS) and Simpson-Angus Scale (SAS) rating scales. Both treatment groups
showed significant (p < 0.001) increase in weight from baseline to endpoint. CONCLUSION: Our open-label, small-scale comparative study suggests that
both risperidone and olanzapine appear to be efficacious antipsychotic medications in COS, with a slight nonsignificant advantage of olanzapine in
the dropout rate.
Journal of Child & Adolescent Psychopharmacology, 16(4) : 393-
403
- Year: 2006
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
McGlashan, Thomas H., Zipursky, Robert B., Perkins, Diana, Addington, Jean, Miller, Tandy, Woods, Scott W., Hawkins, Keith A., Hoffman, Ralph E., Preda, Adrian, Epstein, Irvin, Addington, Donald, Lindborg, Stacy, Trzaskoma, Quynh, Tohen,
Mauricio, Breier, Alan
OBJECTIVE: This study assessed the efficacy of olanzapine in
delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia. METHOD: This randomized
trial occurred at four North American clinics in the Prevention Through Risk Identification, Management, and Education project. Outpatients received
olanzapine (5-15 mg/day, N=31) or placebo (N=29) during a 1-year double-blind treatment period and no treatment during a 1-year follow-up period.
Efficacy measures included the conversion-to-psychosis rate and Scale of Prodromal Symptoms scores. RESULTS: During the treatment year, 16.1% of
olanzapine patients and 37.9% of placebo patients experienced a conversion to psychosis, a nearly significant difference. The hazard of conversion
among placebo patients was about 2.5 times that among olanzapine-treated patients, which also approached significance. In the follow-up year, the
conversion rate did not differ significantly between groups. During treatment, the mean score for prodromal positive symptoms improved more in the
olanzapine group than in the placebo group, and the mixed-model repeated-measures least-squares mean score showed significantly greater improvement
between weeks 8 and 28 with olanzapine. The olanzapine patients gained significantly more weight (mean=8.79 kg, SD=9.05, versus mean=0.30 kg,
SD=4.24). CONCLUSIONS: A significant treatment difference in the conversion-to-psychosis rate was not demonstrated. However, these results may be
influenced by low power. The nearly significant differences suggest that olanzapine might reduce the conversion rate and delay onset of psychosis.
Olanzapine was efficacious for positive prodromal symptoms but induced weight gain. Further treatment research in this phase of illness is
warranted.
American Journal of Psychiatry, 163(5) : 790-
9
- Year: 2006
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Grawe, R. W., Falloon, I. R. H., Widen, J. H., Skogvoll, E.
OBJECTIVE: This random-controlled study evaluated benefits derived from continued integrated biomedical and psychosocial
treatment for recent-onset schizophrenia. METHOD: Fifty cases of schizophrenia of less than 2 years duration were allocated randomly to integrated or
standard treatment (ST) for 2 years. ST comprised optimal pharmacotherapy and case management, while IT also included cognitive-behavioural family
treatment, that incorporated skills training, cognitive-behavioural strategies for residual psychotic and non-psychotic problems and home-based
crisis management. Psychopathology, functioning, hospitalisation and suicidal behaviours were assessed two monthly and a composite index, reflecting
overall clinical outcome was derived. RESULTS: IC proved superior to ST in reducing negative symptoms, minor psychotic episodes and in stabilising
positive symptoms, but did not reduce hospital admissions or major psychotic recurrences. The composite index showed that significantly more IC
patients (53%) had excellent 2-year outcomes than ST (25%). CONCLUSION: Evidence-based treatment achieves greater clinical benefits than
pharmacotherapy and case management alone for recent-onset schizophrenia.
Acta Psychiatrica Scandinavica, 114(5) : 328-
36
- Year: 2006
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Other Psychological Interventions, Case management, Other service delivery and improvement
interventions
Green,
A. I., Lieberman, J. A., Hamer, R. M., Glick, I. D., Gur, R. E., Kahn, R. S., McEvoy,
J. P., et-al, HgdhStudyGroup
Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic
medications in patients within their first episode of psychosis. This study examined the effectiveness of the atypical antipsychotic olanzapine and
the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year
treatment period. Two hundred and sixty-three patients were randomized to olanzapine or haloperidol in a doubleblind, multisite, international 2-year
study. Clinical symptoms and side effects were assessed at baseline and longitudinally following randomization for the duration of the study.
Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity (the primary outcome
measure) over the course of the study. However, the treatment groups differed on two secondary efficacy measures. Patients were less likely to
discontinue treatment with olanzapine than with haloperidol: mean time (in days) in the study was significantly greater for those treated with
olanzapine compared to haloperidol (322.09 vs. 230.38, p<0.0085). Moreover, remission rates were greater in patients treated with olanzapine as
compared to those treated with haloperidol (57.25% vs. 43.94%, p<0.036). While extrapyramidal side effects were greater in those treated with
haloperidol, weight gain, cholesterol level and liver function values were greater in patients treated with olanzapine. The data from this study
suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients, which must be weighed against those adverse
effects that are more likely with olanzapine.
Schizophrenia Research, 86(1-3) : 234-43
- Year: 2006
- 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)