Disorders - Psychosis Disorders
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
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Stage: First episode (psychosis only)
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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
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Stage: Treatment resistant/treatment refractory
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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
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Stage: First episode (psychosis only)
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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
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Stage: Treatment resistant/treatment refractory
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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
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Stage: At risk (indicated or selected prevention)
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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
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Stage: Disorder established (diagnosed disorder)
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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
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Stage: At risk (indicated or selected prevention)
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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
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Stage: Disorder established (diagnosed disorder)
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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
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Stage: First episode (psychosis only)
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Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
Keefe, Richard S., Seidman, Larry J., Christensen, Bruce K., Hamer, Robert M., Sharma, Tonmoy, Sitskoorn, Margriet M., Rock, Stephanie L., Woolson, Sandra, Tohen, Mauricio, Tollefson, Gary D., Sanger, Todd M., Lieberman, Jeffrey A.
Background: Neurocognitive deficits are severe in first-episode psychosis. Methods: Patients (N = 263) with first-episode psychosis (schizophrenia, schizoaffective, or schizophreniform disorders) were randomly assigned to double-blind treatment with olanzapine (mean 11.30 mg/day) or haloperidol (mean 4.87 mg/day) for 104 weeks. A neurocognitive battery was administered at baseline (n = 246) and 12 (n = 167), 24 (n = 126), 52 (n = 89), and 104 (n = 46) weeks during treatment. Weighted principal component and unweighted composite scores were derived from individual tests. Results: Both treatment groups demonstrated significant improvement on both composite scores. On the basis of the weighted composite score, olanzapine had greater improvement than haloperidol only at 12 (p = .014) and 24 (p = .029) weeks. For the unweighted composite, olanzapine had significantly better improvement compared with haloperidol only at week 12 (p = .044). At week 12 only, olanzapine improved performance on the Digit Symbol and Continuous Performance Test significantly more than haloperidol. Conclusions: Both antipsychotic agents appeared to improve neurocognitive functioning among first-episode psychosis patients with schizophrenia. A significantly greater benefit in terms of neurocognitive improvement was found with olanzapine than with haloperidol at weeks 12 and 24. (PsycINFO Database Record (c) 2007 APA, all rights reserved) (journal abstract).
Biological Psychiatry, 59(2) : 97-105
- Year: 2006
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
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Stage: First episode (psychosis only)
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Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
Edwards, J., Elkins, K., Hinton, M., Harrigan, S. M., Donovan, K., Athanasopoulos, O., McGorry, P. D.
OBJECTIVE: To evaluate a cannabis-focused intervention (cannabis and psychosis therapy: CAP) for patients continuing to use cannabis following initial treatment for first-episode psychosis (FEP). METHOD: Consecutive admissions to an early psychosis program were screened and consenting individuals using cannabis in the 4 weeks prior to assessment participated. A single-blind randomized controlled trial compared CAP (n = 23) with a clinical control condition (psychoeducation, PE; n = 24). There were no significant differences between the CAP and PE groups on cannabis use at end of treatment and 6 months post-intervention. RESULTS: There were no significant group differences on psychopathology and functional ratings at follow-up. A significant reduction in cannabis use was observed for both groups over time. CONCLUSION: PE and specific cannabis-focused intervention are associated with similar reductions in cannabis use in an FEP cohort. Simple interventions may therefore be worth considering prior to intensive psychotherapeutic efforts with this population.
Acta Psychiatrica Scandinavica, 114(2) : 109-17
- Year: 2006
- Problem: Psychosis Disorders, Cannabis Use
- Type: Randomised controlled trials
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Stage: First episode (psychosis only)
, At risk (indicated or selected prevention)
, Disorder established (diagnosed disorder)
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Treatment and intervention: Psychological Interventions (any)
, Psychoeducation, Other Psychological Interventions
Armenteros, Jorge L., Davies, Mark
BACKGROUND: To develop an evidence base for using antipsychotic medications for schizophrenia in children and adolescents. METHOD: Data sources were identified in PsychINFO (1872-2003), MEDLINE (1966-2003), and articles in reference lists. Study selection criteria: (1) treatment with antipsychotics; (2) ages were between 5 and 18 years; (3) sample diagnosed with schizophrenia; (4) prospective design; (5) rating instruments used. Fifteen studies met inclusion criteria and were rated. Study quality was independently rated. RESULTS: Average response rate among 8 studies employing atypicals was 55.7% compared to 72.3% among 13 studies employing typicals. The difference was statistically different at the trend level (z = 1.65, P < 0.10). The effect size on a continuous measure was 0.36 in favor of typicals. When study quality was included in the model, the effect of medication type remained unchanged. Average weight gain in patients treated with typicals was 1.4 Kg. compared to 4.5 Kg for those treated with atypicals. Sedation was more common among those on atypicals. The rate of extrapyramidal side effects was similar among the two groups CONCLUSIONS: Antipsychotic medications seem effective for schizophrenia treatment in children and adolescents. Typicals appear to be more effective and cause less weight gain than atypicals. However, more rigorous clinical trials are necessary. [References: 36]
European Child & Adolescent Psychiatry, 15(3) : 141-8
- Year: 2006
- Problem: Psychosis Disorders
- Type: Systematic reviews
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)