Disorders - Psychosis Disorders
Subotnik, K. L., Ventura, J., Gretchen-Doorly, D., Casaus, L. R., Luo, J. S., Turner, L., DeTore, N. R., Hellemann, G. S., Marder, S. R., Amano, J. E., Kaiser, S. K., Nuechterlein, K. H.
Background: Long-acting injectable antipsychotic medication is typically reserved for periods of schizophrenia in which adherence with oral medication has been repeatedly poor. In addition, the use of higher cost long-acting injectable second-generation antipsychotic medication needs to be justified by research demonstrating clear clinical advantages for the long-acting medications over daily oral medication. Methods: At the UCLA Aftercare Research Program, we compared the clinical efficacy of the long-acting injectable formulation of risperidone (RLAI) to the oral form (RisO) in a 12-month randomized controlled trial in schizophrenia patients with a recent first psychotic episode. Analyses were conducted with 82 recent-onset schizophrenia patients who were randomized to RLAI vs. RisO. Each patient's adherence was rated on a 1-5 scale based on timeliness of injections for RLAI, and on pill counts, plasma levels, patient reports, and psychiatrist judgments for oral medication. Frequency of breakthrough positive psychotic symptoms and psychotic relapse during follow up were the outcome variables. Results: To date, only 3 patients (7%) have refused to continue treatment at the time of randomization to RLAI. There were clear clinical advantages of RLAI. The rate of psychotic relapse was lower (5% versus 33%) for the RLAI group compared to the RisO group, and breakthrough psychotic symptoms were rarer for the patients treated with RLAI. In general, the occurrence of side effects did not differ between medication conditions. Discontinuations on RisO were more common due to inadequate clinical response than for RLAI, but the rate of discontinuation due to intolerable side effects was similar for both medications. Adherence with RisO did not differ prior to randomization, but adherence was much better for injectable compared to oral medication during the randomized treatment (p < .001). The rating of medication adherence across both medication conditions was significantly associated with both prevention of relapse and control of breakthrough positive psychotic symptoms. Conclusion: These data document that long-acting RLAI has very clear advantages for the promotion of adherence and the consistent administration over time in the initial period of schizophrenia. The clinical advantages of RLAI appear to be more pronounced in this first-episode schizophrenia sample than in prior studies of chronically ill patients, supporting the increased use of RLAI in the early course of schizophrenia.
Schizophrenia Bulletin, 39 : S353-S354
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Service Delivery & Improvement, Other service delivery and improvement interventions
VanDerGaag, M., Smit, F., Bechdolf, A., French, P., Linszen, D. H., Yung, A. R., McGorry, P., Cuijpers, P.
Over the last decade many studies were conducted to assess the feasibility of early detection of people at risk of developing psychosis and intervention to prevent or delay a first psychotic episode. Most of these studies were small and underpowered. A meta-analysis can demonstrate the effectiveness of the efforts to prevent or postpone a first episode of psychosis.A search conducted according the PRISMA guideline identified 10 studies reporting 12-month follow-up data on transition to psychosis, and 5 studies with follow-ups varying from 24 to 48. months. Both random and fixed effects meta-analyses were conducted.The quality of the studies varied from poor to excellent. Overall the risk reduction at 12. months was 54% (RR. = 0.463; 95% CI. = 0.33-0.64) with a Number Needed to Treat (NNT) of 9 (95% CI. = 6-15). Although the interventions differed, there was only mild heterogeneity and publication bias was small. All sub-analyses demonstrated effectiveness. Also 24 to 48-month follow-ups were associated with a risk reduction of 37% (RR. = .635; 95% CI. = 0.44-0.92) and a NNT of 12 (95% CI. = 7-59). Sensitivity analysis excluding the methodologically weakest study showed that the findings were robust.Early detection and intervention in people at ultra-high risk of developing psychosis can be successful to prevent or delay a first psychosis. Antipsychotic medication showed efficacy, but more trials are needed. Omega-3 fatty acid needs replication. Integrated psychological interventions need replication with more methodologically sound studies. The findings regarding CBT appear robust, but the 95% confidence interval is still wide. (copyright) 2013 Elsevier B.V.
Schizophrenia Research, 149(1-3) : 56-62
- Year: 2013
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions (any)
, Complementary & Alternative Interventions (CAM)
, Psychological Interventions (any)
Wunderink, L., Nieboer, R. M., Wiersma, D., Sytema, S., Nienhuis, F. J.
IMPORTANCE: Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis (FEP) showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before. OBJECTIVE: To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation (DR) vs maintenance treatment (MT) trial. DESIGN: Seven-year follow-up of a 2-year open randomized clinical trial comparingMT and DR. SETTING: One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million-population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission. PARTICIPANTS: After 7 years, 103 patients (80.5%) of 128 patients who were included in the original trial were located and consented to follow-up assessment. INTERVENTION: After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician. MAIN OUTCOMES AND MEASURES: Primary outcomewas rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy (MT or DR) was controlled for baseline parameters. RESULTS: The DR patients experienced twice the recovery rate of the MT patients (40.4%vs 17.6%). Logistic regression showed an odds ratio of 3.49 (P = .01). Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates. CONCLUSIONS AND RELEVANCE: Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16228411.
JAMA Psychiatry, 70(9) : 913-920
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
, Relapse prevention
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
, Medication dose reduction/discontinuation
, Service Delivery & Improvement, Other service delivery and improvement interventions
Stafford, M. R., Jackson, H., Mayo-Wilson, E., Morrison, A. P., Kendall, T.
Objective To determine whether any psychological, pharmacological, or nutritional interventions can prevent or delay transition to psychotic disorders for people at high risk. Design Systematic review and meta-analysis. Data sources Embase, Medline, PreMedline, PsycINFO, and CENTRAL were searched to November 2011 without restriction to publication status. Review methods Randomised trials comparing any psychological, pharmacological, nutritional, or combined intervention with usual services or another treatment. Studies of participants with a formal diagnosis of schizophrenia or bipolar disorder were excluded. Studies were assessed for bias, and relevant limitations were considered in summarising the results. Results 11 trials including 1246 participants and eight comparisons were included. Median sample size of included trials was 81 (range 51-288). Meta-analyses were performed for transition to psychosis, symptoms of psychosis, depression, and mania; quality of life; weight; and discontinuation of treatment. Evidence of moderate quality showed an effect for cognitive behavioural therapy on reducing transition to psychosis at 12 months (risk ratio 0.54 (95% confidence interval 0.34 to 0.86); risk difference -0.07 (-0.14 to -0.01). Very low quality evidence for omega-3 fatty acids and low to very low quality evidence for integrated psychotherapy also indicated that these interventions were associated with reductions in transition to psychosis at 12 months. Conclusions Although evidence of benefits for any specific intervention is not conclusive, these findings suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the potential for benefit of psychological interventions in the treatment of people at high risk of psychosis. (copyright) BMJ Publishing Group Ltd 2013.
British Journal of Psychiatry, 346(7892) :
- Year: 2013
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions (any)
, Complementary & Alternative Interventions (CAM)
, Psychological Interventions (any)
, Fish oil (Omega-3 fatty acids)
, Omega 3 fatty acids (e.g. fish oil, flax oil)
Taylor, M., Ng, K. Y. B.
Background: The relapse rate after a first episode of schizophrenia is high, often due to non-adherence with medication. Long-acting injections of antipsychotics (LAI) are used to promote adherence to medication. Objective: To review the literature on the use of LAIs in first-episode and early schizophrenia. Method: A systematic electronic search of all original data containing peer-reviewed studies published in English using EMBASE, MEDLINE, Cochrane and PsychINFO from the onset of records. Reference lists from retrieved articles were examined for further relevant studies. Results: Ten studies were identified: two cohort studies; three randomised controlled trials; and five open studies. These studies, although limited, demonstrated the effectiveness of LAI in early schizophrenia. Seven of the 10 studies had risperidone long-acting injection as the only LAI. Conclusion: LAIs may be useful in the treatment of early schizophrenia in terms of symptom control and relapse reduction, particularly if chosen by the patient or when medication adherence is a priority. There is a need for a large-scale, randomised controlled trial comparing oral and LAI antipsychotics to assess long-term outcomes. (copyright) The Royal Australian and New Zealand College of Psychiatrists 2012.
Australian & New Zealand Journal of Psychiatry, 47(7) : 624-630
- Year: 2013
- Problem: Psychosis Disorders
- Type: Systematic reviews
-
Stage: First episode (psychosis only)
, Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
, Service Delivery & Improvement, Other service delivery and improvement interventions
Sanz-Fuentenebro, J., Taboada, D., Palomo, T., Aragues, M., Ovejero, S., Del-Alamo, C., Molina, V.
In first-episode patients with psychosis, clozapine may be potentially valuable as an initial treatment seeking to limit early on clinical and cognitive deterioration. Nevertheless, until recently its restricted use has limited the study of this possibility. Our research group is developing a non-commercial, multicentric and open label study on the differential efficacy between clozapine and risperidone in first-episode schizophrenia. In this paper, we present the results related to clinical variables after a one-year follow-up. So far, we have recruited 30 patients diagnosed with schizophrenia or schizophreniform disorder with illness duration of less than two years. The patients had not received any previous treatment and they were randomized to treatment with clozapine or risperidone. Our results indicate that on average, patients on clozapine adhered to their original treatment for a longer time period than patients on risperidone. By last observation carried forward (LOCF) analysis, patients on clozapine and risperidone displayed similar clinical improvements, although marginally greater improvements in positive and total symptoms scores were found in the clozapine group. At the 12-month point we observed a marginal improvement in negative symptom scores in patients on clozapine. Subjective secondary effects, as measured with the Udvalg for KliniskeUndersogelser (UKU) scale, correlated negatively with negative symptoms at follow-up. Our data, although preliminary, suggest that clozapine may have a slightly superior efficacy in the initial year of treatment of first-episode treatment-naive patients with schizophrenia, and this can be explained for the most part by greater adherence to this treatment. (copyright) 2013 Elsevier B.V.
Schizophrenia Research, 149(1-3) : 156-161
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Sigrunarson, V., Grawe, R. W., Morken, G.
Background: The aim of this study is to compare the 12-year follow-up effects on in- and outpatient services of 2 years of integrated treatment for recent-onset schizophrenia versus treatment as usual in a randomized controlled trial. Methods: 50 patients aged 18-35 years were randomized to Integrated Treatment (IT) (N = 30) or Treatment-as-Usual (TAU) (N = 20) for two years. TAU comprised optimal pharmacotherapy and outreach assertive treatment, while IT also included cognitive-behavioural family treatment, skills training, strategies for residual psychotic and non-psychotic problems and home-based crisis management. Results: There were no differences in number of days in hospital, time to readmission, number of admittances to psychiatric wards, number of involuntarily psychiatric admissions or number of outpatient contacts over a period of 12 years following the initial 2-year treatment trial. Fewer patients in the IT group were, however, involuntary admitted to hospital in the period. Conclusions: The intensive two-year psychosocial intervention seemed to have little long-term effects on use of in- and outpatient services. Trial registration: Current Controlled Trials: NCT00184509. (copyright) 2013 Sigrunarson et al.; licensee BioMed Central Ltd.
BMC Psychiatry, 13 :
- Year: 2013
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
, Skills training, Other Psychological Interventions, Case management
, Other service delivery and improvement interventions
Scoriels, Linda, Barnett, Jennifer H., Soma, Praveen K., Sahakian, Barbara J., Jones, Peter B.
Rationale: Cognitive impairments are important determinants of functional outcome in psychosis, which are inadequately treated by antipsychotic medication. Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy population and in patients with schizophrenia.; Objectives: We aimed to establish modafinil's role in the adjunctive treatment of cognitive impairments in the first episode of psychosis, a time when symptoms may be more malleable than at chronic stages of the disease.; Methods: Forty patients with a first episode of psychosis participated in a randomised, double-blind, placebo-controlled crossover design study assessing the effects of a single dose of 200 mg modafinil on measures of executive functioning, memory, learning, impulsivity and attention.; Results: Modafinil improved verbal working memory (d = 0.24, p = 0.04), spatial working memory errors (d = 0.30, p = 0.0004) and strategy use (d = 0.23, p = 0.03). It also reduced discrimination errors in a task testing impulsivity. Modafinil showed no effect on impulsivity measures, sustained attention, attentional set-shifting, learning or fluency.; Conclusions: Modafinil selectively enhances working memory in first episode psychosis patients, which could have downstream effects on patients' social and occupational functioning.;
Psychopharmacology, 220(2) : 249-258
- Year: 2012
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Other biological interventions
Secher, R. G., Nordentoft, M., Austin, S., Mors, O.
In the OPUS trial, 547 people with a first diagnose within the schizophrenic spectrum were randomized to either two years of intensive, early, psychosocial intervention (OPUS treatment) or treatment as usual (TAU). OPUS treatment included social skills training, multi family groups, own case manager, optional house calls and more. TAU generally offered none of the treatment elements mentioned above. After the intervention the OPUS patients showed significantly lower psychopathology, rates of hospitalization and improved social functioning as compared to the TAU patients. After 5 years, the only significant difference between the two interventions was that the former OPUS patients had significantly fewer days in supported housing. Study Focus: The 10-year follow-up compares clinical, psychological and social outcomes in the OPUS-group with the TAU-group. Methods and Materials: All the original participants were invited to complete a series of interviews and questionnaires measuring levels of psychopathology, quality of life, social functioning, meta-cognitive beliefs, perceived ability to cope with everyday life and symptoms and cognitive functioning. Results: A total of 347 participants were interviewed, giving a follow-up rate of over 70%, of those of the former patients who were not emigrated or dead. Results comparing the OPUS-treatment and the TAU will be presented. Perspectives: The OPUS trial is the worlds' largest randomized controlled trial comparing intensive, early, psychosocial intervention with TAU for schizophrenia spectrum disorders. Data gathered 10 years after the commencement of the interventions will inform us about the long term effects of psychosocial treatments for this group of patients.
Early Intervention in Psychiatry, 6 : 21
- Year: 2012
- Problem: Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions (any)
, Skills training, Other Psychological Interventions, Case management
San, L., Arranz, B., Perez, V., Safont, G., Corripio, I., Ramirez, N., Duenas, R., Alvarez, E.
The aim of this study was to compare the 12-month effectiveness of several second-generation antipsychotic drugs, with that of haloperidol in never-treated patients with first-episode psychosis. In total, 114 patients without life time exposure to any psychotropic medication were randomized to haloperidol, olanzapine, risperidone, quetiapine or ziprasidone. Primary outcome was time to all-cause discontinuation. Secondary outcomes included discontinuation rates and symptom change as measured by the Positive and Negative Syndrome Scale (PANSS). The overall discontinuation rate 64%. At 12 months, the proportion of patients discontinuing treatment was 40.0% for olanzapine, 56.5% for quetiapine, 64.0% for risperidone, 80.0% for ziprasidone and 85.7% for haloperidol. Mean time to antipsychotic discontinuation was higher in patients randomized to second-generation antipsychotics than in those taking haloperidol. Significantly lower discontinuation was noted in patients on olanzapine than on haloperidol, or ziprasidone. Our results suggest that olanzapine might lead to longer treatment continuation in treatment naive FEP patients than haloperidol and, possibly ziprasidone. Global psychopathology was significantly less reduced by haloperidol than with each individual SGA in this earliest phase of treatment. (copyright) 2012 Elsevier Ireland Ltd.
Psychiatry Research, 200(2-3) : 693-701
- Year: 2012
- 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)
Thomas, S. P., Nandhra, H. S., Singh, S. P.
Objective: To review the evidence base for the efficacy and tolerability of antipsychotic medication for the treatment of the first episode of schizophrenia. Data Source: MEDLINE databases were searched for published articles in English over the last 25 years, from January 1986 to January 2011, on choice of antipsychotic treatment for the first episode of schizophrenia, with an emphasis on efficacy and tolerability of antipsychotic drugs in the acute phase of psychotic illness. Study Selection: The keywords antipsychotic drugs and schizophrenia were used in combination with drug treatment, pharmacologic treatment, efficacy, and tolerability in addition to atypical antipsychotics, first-generation antipsychotics, second-generation antipsychotics, first-episode psychosis, and acute psychotic episode. Data Synthesis: At present, there is no convincing evidence to guide clinicians in choosing a single first-line antipsychotic that is effective in treating the positive and negative symptoms of the first episode of schizophrenia. Even though second-generation antipsychotic drugs offer potential benefits in terms of less extrapyramidal side effects and some benefits in treating negative, affective, and cognitive symptoms, these drugs are not without their own side effects. Conclusions: With the introduction of a number of second-generation antipsychotic drugs there have been significant advances in antipsychotic drug treatment over the last decade. Despite these advances, there are still a number of limitations in continued use of some antipsychotic medications due to their efficacy and tolerability issues in the acute and early maintenance phases of psychosis. Active research in this area would provide more promising results of improved efficacy and tolerability of antipsychotic medication. (copyright) 2012 Physicians Postgraduate Press, Inc.
Primary Care Companion to the Journal of Clinical Psychiatry, 14(1) :
- Year: 2012
- 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)
Rosenbaum, B., Harder, S., Knudsen, P., Koster, A., Lajer, M., Lindhardt, A., Valbak, K., Winther, G.
During recent decades, the field of treatment of schizophrenia has lacked empirical, systematic outcome studies that support psychodynamic psychotherapy as an evidence-based intervention for patients with schizophrenia. The Danish schizophrenia project (DNS) compared psychodynamic psychotherapy for psychosis with standard treatment in patients with a first-episode schizophrenia spectrum disorder. The study was designed as a prospective, comparative, longitudinal multi-site investigation of consecutively referred patients who were included during two years. The patients were treated with either manualized individual supportive psychodynamic psychotherapy (SPP) in addition to treatment as usual or with treatment as usual alone (TaU). Symptoms and functional outcomes were measured using the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning scale (GAF). The study included 269 consecutively admitted patients, age 18-35, of whom 79% remained in the study after two years. The intervention group improved significantly on measures of both PANSS and GAF scores, with large effect sizes at two years follow-up after inclusion. Further, improvement on GAFfunction (p = 0.000) and GAFsymptom (p = 0.010) significantly favored SPP in combination with TaU over TaU alone. In spite of limitations, this study speaks in favor of including supportive psychodynamic psychotherapy in the treatment for patients with schizophrenic first-episode psychoses. (copyright) 2012 Washington School of Psychiatry.
Psychiatry, 75(4) : 331-341
- Year: 2012
- Problem: Psychosis Disorders
- Type: Controlled clinical trials
-
Stage: First episode (psychosis only)
-
Treatment and intervention: Psychological Interventions (any)
, Psychodynamic/Psychoanalysis