Disorders - Psychosis Disorders
Green, Alan I., Tohen, Mauricio F., Hamer, Robert M., Strakowski, Stephen M., Lieberman, Jeffrey A., Glick, Ira, Clark, W. Scott, HgdhResearchGroup
BACKGROUND: Co-occurring substance use disorders, mostly involving alcohol, cannabis or cocaine, occur commonly in patients with schizophrenia and are associated with increased morbidity and mortality. Available but limited data suggest that substance use disorders (especially cannabis use disorders) may also be common in first-episode patients and appear linked to a poor outcome in these patients. Strategies to curtail substance use form an important dimension of the treatment program for both first-episode and chronic patients. We report on rates of co-occurring substance use disorders in patients within their first episode of schizophrenia-related psychosis from a multicenter, international treatment trial of olanzapine vs. haloperidol. METHODS: The study involved 262 patients (of 263 who were randomized and who returned for a post-randomization evaluation) within their first episode of psychosis (schizophrenia, schizoaffective disorder or schizophreniform disorder) recruited from 14 academic medical centers in North America and Western Europe. Patients with a history of substance dependence within 1 month prior to entry were excluded. RESULTS: Of this sample, 97 (37%) had a lifetime diagnosis of substance use disorder (SUD); of these 74 (28% of the total) had a lifetime cannabis use disorder (CUD) and 54 (21%) had a lifetime diagnosis of alcohol use disorder (AUD). Patients with SUD were more likely to be men. Those with CUD had a lower age of onset than those without. Patients with SUD had more positive symptoms and fewer negative symptoms than those without SUD, and they had a longer duration of untreated psychosis. The 12-week response data indicated that 27% of patients with SUD were responders compared to 35% of those without SUD. Patients with AUD were less likely to respond to olanzapine than those without AUD. DISCUSSION: These data suggest that first-episode patients are quite likely to have comorbid substance use disorders, and that the presence of these disorders may negatively influence response to antipsychotic medications, both typical and atypical antipsychotics, over the first 12 weeks of treatment.
Schizophrenia Research, 66(2-3) : 125-35
- Year: 2004
- 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)
Keefe, Richard S., Seidman, Larry J., Christensen, Bruce K., Hamer, Robert M., Sharma, Tonmoy, Sitskoorn, Margriet M., Lewine, Richard R., Yurgelun-Todd, Deborah A., Gur, Ruben C., Tohen, Mauricio, Tollefson, Gary D., Sanger, Todd M., Lieberman, Jeffrey A.
Objective: The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis. Method: Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment. Results: An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine. Conclusions: Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small. (PsycINFO Database Record (c) 2007 APA, all rights reserved) (journal abstract).
American Journal of Psychiatry, 161(6) : 985-995
- Year: 2004
- 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)
Kavanagh, David J., Young, Ross, White, Angela, Saunders, John B., Wallis, Jeff, Shockley, Natalie, Jenner, Linda, et-al
Substance misuse is common in early psychosis, and impacts negatively on outcomes. Little is known about effective interventions for this population. We report a pilot study of brief intervention for substance misuse in early psychosis (Start Over and Survive: SOS), comparing it with Standard Care (SC). Twenty-five in-patients aged 18-35 years with early psychosis and current misuse of non-opioid drugs were allocated randomly to conditions. Substance use and related problems were assessed at baseline, 6 weeks and 3, 6 and 12 months. Final assessments were blind to condition. All 13 SOS participants who proceeded to motivational interviewing reported less substance use at 6 months, compared with 58% (7/12) in SC alone. Effects were well maintained to 12 months. However, more SOS participants lived with a relative or partner, and this also was associated with better outcomes. Engagement remained challenging: 39% (16/41) declined participation and 38% (5/13) in SOS only received rapport building. Further research will increase sample size, and address both engagement and potential confounds.
Drug & Alcohol Review, 23(2) : 151-5
- Year: 2004
- Problem: Psychosis Disorders, Substance Use Disorders (any)
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Psychological Interventions (any)
, Motivational interviewing, includes Motivational Enhancing Therapy
Hafner, H., Maurer, K., Ruhrmann, S., Bechdolf, A., Klosterkotter, J., Wagner, M., Maier, W., Bottlender, R., Moller, H. J., Gaebel, W., Wolwer, W.
As effective and practical approaches to primary and universal prevention of psychosis are lacking, intervention efforts are targeted at the early stages of schizophrenia to prevent (by way of secondary prevention) or postpone psychosis onset, reduce severity of illness or at least ameliorate the social consequences involved. Early intervention requires early detection and early recognition (diagnosis) of persons at risk and early prediction of psychosis. Within the German Research Network on Schizophrenia (GRNS) awareness programmes are being carried out in several German cities, and these efforts are already improving utilisation of early-recognition and early-prediction services by at risk persons. The empirical basis of developing a two-step early-recognition inventory and strategies of application will be discussed. This instrument is supplemented by a set of cognitive tests, prospectively validated in the GRNS. Results from preliminary analysis of data covering a two-year period demonstrate that the inventory and the cognitive tests are readily accepted. When used for screening in non-specialist settings and at the next level, i. e. at early-recognition centres, they seem to permit identification of at-risk persons. Early intervention is being tested 1) in a randomised controlled multi-centre trial consisting of a specially developed cognitive-behavioural therapy in the early (prepsychotic) prodromal state and 2) on additional treatment with appropriate doses of amisulpride in the late prodromal (early psychotic) state. Preliminary data from Study 1 covering 16.3 months show significantly fewer transitions to psychosis and from Study 2 reduced positive and negative symptoms and improved global functioning compared with controls who had received normal clinical treatment. As a result, both the early-recognition inventory plus cognitive tests and the two therapy strategies are feasible. We hope that the favourable trend indicated by the preliminary data will be confirmed in the final analysis planned for 2005 and the objective of implementing effective and practical secondary prevention of psychosis and its consequences will be attained.
European Archives of Psychiatry & Clinical Neuroscience., 254(2) : 117-128
- Year: 2004
- 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)
, Cognitive & behavioural therapies (CBT)
Li, T. Y., Li, Y. Y., Wu, T. C., Yan, W. Y., Chen, Y. H., An, Y., Lu, C. Y., Zhu, H. L., Jiang, C. X.
Aim: To investigate the influence of early intervention on the quality of life (QOL) in first-episode schizophrenic patients. Methods: Totally 97 patients with first episode schizophrenia were randomly divided into study group(n = 49) and control group(n = 48). Patients in the study group received drug treatment and psychological and social interventions, while patients in the control group received drug treatment only. All the patients were evaluated with the positive and negative symptoms scale (PANSS) and WHO Quality of Life Survey (WHOQOL-100) before treatment and 1 year after discharge. Results: One year after discharge, the negative rating scale of PANSS in the study group was improved obviously better than that in the control group (9.04 +/- 1.80 vs 13.20 +/- 1.90), with significant difference(t = 11.24, P < 0.01), and QOL was remarkably enhanced except mental support, significantly different from before treatment (t = 3.85 - 26.41, P < 0.01. In the control group, physiological field, independent field and mental support were not greatly improved(t = 7.70, 6.45, 0.64, P > 0.05). Conclusion: Early intervention is good for the improvement of the QOL in first-episode schizophrenic patients. Copyright © 2008 Elsevier B. V., Amsterdam. All Rights Reserved.
Zhongguo Linchuang Kangfu, 8(18) : 3464-5
- Year: 2004
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Psychological Interventions (any)
Lieberman, Jeffrey A., Tollefson, Gary, Tohen, Mauricio, Green, Alan I., Gur, Raquel E., Kahn, Rene, McEvoy, Joseph, Perkins, Diana, Sharma, Tonmoy, Zipursky, Robert, Wei, Hank, Hamer, Robert M., HgdhStudyGroup
OBJECTIVE: Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial. METHOD: Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase. RESULTS: Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%). CONCLUSIONS: As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.
American Journal of Psychiatry, 160(8) : 1396-404
- Year: 2003
- 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)
McEvoy, J., Lieberman, J. A., Perkins, D., Hamer, R. M., Sharma, T., Zipursky, R., Kahn, R., Gur, R., Centorrino, F., Glick, I.
The aim of this study was to compare, in a large and well-controlled clinical trial, the acute and long-term effectiveness of haloperidol and olanzapine in first episode schizophrenia and schizoaffective dis- order patients. 262 first-episode subjects were randomly assigned under double-blind conditions to haloperidol or olanzapine and fol- lowed for up to 104 weeks. Domains measured included treatment continuation and adherence, psychopathology, psychosocial meas- ures, neurocognitive function, brain morphology and metabolism. Both haloperidol and olanzapine were associated with substantial and comparable reductions in symptom severity. Olanzapine treated subjects showed significantly greater symptom decreases in mixed model analysis, lower rates of treatment-emergent Parkinsonism and akathisia and greater weight gain. Treatment discontinuation rates were high overall with only 47 patients remaining in the study by 2 years. Retention was greater with olanzapine. Beginning by week 6, there were more dropouts with haloperidol than olanzapine, and this difference in dropout rates widened over the course of the study with 12% of haloperidol subjects and 24% of olanzapine subjects staying in the study at two years. The psychopathology and safety results of through 104 weeks will be presented and discussed.
Schizophrenia Research, 60 : 313
- Year: 2003
- 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)
Hamann, J., Kissling, W., Leucht, S., Rummel-Kluge, C.
BACKGROUND: The new generation antipsychotics are associated with a lower risk of adverse effects compared with drugs such as haloperidol. Many treatment guidelines recommend the use of new generation ('atypical') antipsychotic drugs for people with a first episode of schizophrenia. OBJECTIVES: To examine the effects of the new generation antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane Schizophrenia Group's register (March 2002) and the included and excluded studies tables of relevant Cochrane reviews, references of all relevant studies, contacted industry and authors of relevant studies to identify further trials. SELECTION CRITERIA: Randomised clinical trials comparing new generation antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, sulpiride, ziprasidone, zotepine) with conventional antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by three reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data but excluded them if loss to follow up was greater than 50%. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences (WMD). MAIN RESULTS: We include two short-term studies (total n=266), one of which was a report of a sub-group of a larger study. One compared risperidone with an average of 6 mg/day haloperidol and the other olanzapine with an average of 11 mg/day haloperidol. Compared with olanzapine, significantly more people receiving haloperidol left the study early (n=83, 1 RCT, RR 0.43 CI 0.3 to 0.7, NNH 3 CI 2 to 8). This was not so for the risperidone versus haloperidol comparison (n=183, 1 RCT, RR=0.7 CI 0.4 to 1.1). In terms of global effects, studies reported no differences between risperidone and haloperidol (n=183, RR not much improved 1.0 CI 0.6 to 1.5), and olanzapine and the same control (n=83, RR needing at least one dose of benzodiazepine 0.8 CI 0.5 to 1.1). More people allocated to olanzapine had clinically significant improvement in mental state compared with those given haloperidol (n=83, RR no 'clinically significant improvement' 0.45 CI 0.3 to 0.7, NNH 3 CI 2 to 6). In the risperidone study, however, no such difference was apparent (n=183, RR 'no clinically significant improvement in mental state' 0.85 CI 0.6 to 1.2). Significantly more people given haloperidol (4-16mg) experienced at least one adverse event when compared with risperidone (4-16mg) (n=183, RR 0.9 CI 0.8 to 0.98, NNH 8 CI 4 to 50). Use of anticholinergic medication for extrapyramidal adverse events was less prevalent for people allocated either olanzapine (n=83, RR 0.3 CI 0.2 to 0.7, NNH 4 CI 2 to 14) or risperidone (n=183, RR 0.7 CI 0.5 to 0.9, NNH 4 CI 3 to 9) compared with those given haloperidol.There are no data at all on outcomes such as compliance, cost, social and cognitive functioning, relapse, rehospitalisation, or quality of life. There are no medium to long-term data. Eight ongoing studies may provide more information. REVIEWER'S CONCLUSIONS: The results of this review are inconclusive. Whether the use of new generation antipsychotics really makes the treatment less off putting and enhances long-term compliance is unclear. Pragmatic, well-designed and reported long-term trials would be useful to answer this question. [References: 107]
Cochrane Database of Systematic Reviews, (4) : CD004410
- Year: 2003
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
DeHaan, L., VanBruggen, M., Lavalaye, J., Booij, J., Dingemans, P. M. A. J., Linszen, D.,
Objective: The authors tested the hypothesis that a dopamine D2 receptor occupancy level between 60% and 70% in patients with recent-onset schizophrenia would result in optimal subjective experience. In addition, they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol. Method: Subjects (N=24) who met DSM-IV criteria for schizophrenia were randomly assigned to 6 weeks of double-blind treatment with either olanzapine, 7.5 mg/day, or haloperidol, 2.5 mg/day. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed at baseline and at endpoint. After 6 weeks, D2 receptor occupancy was assessed with [123I]iodobenzamide single photon emission computed tomography. Results: The two study groups were similar at baseline. After 6 weeks, patients receiving olanzapine had a significantly lower mean dopamine D2 receptor occupancy (51.0%, range=36%-67%) than those given haloperidol (65.5%, range= 45%-75%). Receptor occupancy between 60% and 70% was associated with optimal subjective experience, and subjective experience improved significantly in the haloperidol group. Conclusions: A level of D2 receptor occupancy between 60% and 70% is optimal for subjective experience of patients with recent-onset schizophrenia. Substantial interindividual variation in D2 receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol. Olanzapine, 7.5 mg/day, showed no superior subjective response over haloperidol, 2.5 mg/day. Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia, and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy.
American Journal of Psychiatry., 160(2) : 303-309
- Year: 2003
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
Bola, John R., Mosher, Loren R.
The Soteria project (1971-1983) compared residential treatment in the community and minimal use of antipsychotic medication with "usual" hospital treatment for patients with early episode schizophrenia spectrum psychosis. Newly diagnosed DSM-II schizophrenia subjects were assigned consecutively (1971 to 1976, N = 79) or randomly (1976 to 1979, N = 100) to the hospital or Soteria and followed for 2 years. Admission diagnoses were subsequently converted to DSM-IV schizophrenia and schizophreniform disorder. Multivariate analyses evaluated hypotheses of equal or better outcomes in Soteria on eight individual outcome measures and a composite outcome scale in three ways: for endpoint subjects (N = 160), for completing subjects (N = 129), and for completing subjects corrected for differential attrition (N = 129). Endpoint subjects exhibited small to medium effect size trends favoring experimental treatment. Completing subjects had significantly better composite outcomes of a medium effect size at Soteria (+.47 SD, p =.03). Completing subjects with schizophrenia exhibited a large effect size benefit with Soteria treatment (+.81 SD, p =.02), particularly in domains of psychopathology, work, and social functioning. Soteria treatment resulted in better 2-year outcomes for patients with newly diagnosed schizophrenia spectrum psychoses, particularly for completing subjects and for those with schizophrenia. In addition, only 58% of Soteria subjects received antipsychotic medications during the follow-up period, and only 19% were continuously maintained on antipsychotic medications.
Journal of Nervous & Mental Disease, 191(4) : 219-29
- Year: 2003
- Problem: Psychosis Disorders
- Type: Controlled clinical trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Service Delivery & Improvement, Other service delivery and improvement interventions
vanBruggen, Johanna, Tijssen, Jans, Dingemans, Petrus, Gersons, Berthold, Linszen, Donald
The symptom response and side-effects of olanzapine and risperidone were compared in patients with recent onset schizophrenia. Actively symptomatic patients (n=44) randomly received olanzapine 15 mg (median dose) or risperidone 4 mg (median dose). Symptom response and side-effects were measured during a 6-10-week treatment study. No major differences were observed between the two treatment groups. Symptoms improved significantly on the Positive and Negative Syndrome Scale total score, positive subscale and general psychopathology subscale for both treatment groups. Using five symptom dimensions, both drugs were effective in treating positive symptoms and agitation/excitement symptoms, and neither olanzapine or risperidone influenced disorganization and depression symptoms. Results on the negative symptoms subscale and symptom dimension were inconclusive. No major differences were found in the frequency of the reported side-effects akathisia, parkinsonism and weight gain. These data indicate that the differences between olanzapine and risperidone in symptom response are small. In spite of the relatively low power of the study, we could exclude the presence of substantially different treatment effects between olanzapine and risperidone.
International Clinical Psychopharmacology, 18(6) : 341-6
- Year: 2003
- 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)
Woods, Scott W., Breier, Alan, Zipursky, Robert B., Perkins, Diana O., Addington, Jean, Miller, Tandy J., Hawkins, Keith A., et-al
BACKGROUND: The prodromal phase of schizophrenic disorders has been described prospectively. The present study aimed to determine the short-term efficacy and safety of olanzapine treatment of prodromal symptoms compared with placebo. METHODS: This was a double-blind, randomized, parallel-groups, placebo-controlled trial with fixed-flexible dosing conducted at four sites. Sixty patients met prodromal diagnostic criteria, including attenuated psychotic symptoms, as determined by structured interviews. Olanzapine 5-15 mg daily or placebo was prescribed for 8 weeks. RESULTS: In the mixed-effects, repeated-measures analysis, the treatment x time interaction for the change from baseline on the Scale of Prodromal Symptoms total score was statistically significant, and post hoc analyses revealed that the olanzapine-placebo difference reached p<.10 by week 6 and p<.05 at week 8. Ratings of extrapyramidal symptoms remained low in each group and were not significantly different. Olanzapine patients gained 9.9 lb versus.7 lb for placebo patients (p<.001). CONCLUSIONS: This short-term analysis suggests olanzapine is associated with significantly greater symptomatic improvement but significantly greater weight gain than is placebo in prodromal patients. Extrapyramidal symptoms with olanzapine were minimal and similar to those with placebo. Future research over the longer term with more patients will be needed before recommendations can be made regarding routine treatment.
Biological Psychiatry, 54(4) : 453-64
- Year: 2003
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)