Summary Background The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy ...based on the randomised evidence. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs. Methods We did a Bayesian-framework, multiple-treatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation. Findings We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0·88, 0·73–1·03; amisulpride 0·66, 0·53–0·78; olanzapine 0·59, 0·53–0·65; risperidone 0·56, 0·50–0·63; paliperidone 0·50, 0·39–0·60; zotepine 0·49, 0·31–0·66; haloperidol 0·45, 0·39–0·51; quetiapine 0·44, 0·35–0·52; aripiprazole 0·43, 0·34–0·52; sertindole 0·39, 0·26–0·52; ziprasidone 0·39, 0·30–0·49; chlorpromazine 0·38, 0·23–0·54; asenapine 0·38, 0·25–0·51; lurasidone 0·33, 0·21–0·45; and iloperidone 0·33, 0·22–0·43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug (haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76 (haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from −0·09 for the best drug (haloperidol) to −0·74 for the worst drug (olanzapine), for prolactin increase 0·22 (aripiprazole) to −1·30 (paliperidone), and for QTc prolongation 0·10 (lurasidone) to −0·90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in meta-regressions and sensitivity analyses. Interpretation Antipsychotics differed substantially in side-effects, and small but robust differences were seen in efficacy. Our findings challenge the straightforward classification of antipsychotics into first-generation and second-generation groupings. Rather, hierarchies in the different domains should help clinicians to adapt the choice of antipsychotic drug to the needs of individual patients. These findings should be considered by mental health policy makers and in the revision of clinical practice guidelines. Funding None.
Summary Background Because of the debate about whether second-generation antipsychotic drugs are better than first-generation antipsychotic drugs, we did a meta-analysis of randomised controlled ...trials to compare the effects of these two types of drugs in patients with schizophrenia. Methods We compared nine second-generation antipsychotic drugs with first-generation drugs for overall efficacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-effects, weight gain, and sedation. Findings We included 150 double-blind, mostly short-term, studies, with 21 533 participants. We excluded open studies because they systematically favoured second-generation drugs. Four of these drugs were better than first-generation antipsychotic drugs for overall efficacy, with small to medium effect sizes (amisulpride −0·31 95% CI −0·44 to −0·19, p<0·0001, clozapine −0·52 −0·75 to −0·29, p<0·0001, olanzapine −0·28 −0·38 to −0·18, p<0·0001, and risperidone −0·13 −0·22 to −0·05, p=0·002). The other second-generation drugs were not more efficacious than the first-generation drugs, even for negative symptoms. Therefore efficacy on negative symptoms cannot be a core component of atypicality. Second-generation antipsychotic drugs induced fewer extrapyramidal side-effects than did haloperidol (even at low doses). Only a few have been shown to induce fewer extrapyramidal side-effects than low-potency first-generation antipsychotic drugs. With the exception of aripiprazole and ziprasidone, second-generation antipsychotic drugs induced more weight gain, in various degrees, than did haloperidol but not than low-potency first-generation drugs. The second-generation drugs also differed in their sedating properties. We did not note any consistent effects of moderator variables, such as industry sponsorship, comparator dose, or prophylactic antiparkinsonian medication. Interpretation Second-generation antipsychotic drugs differ in many properties and are not a homogeneous class. This meta-analysis provides data for individualised treatment based on efficacy, side-effects, and cost. Funding National Institute of Mental Health.
Objective:The authors examined the safety and efficacy of antidepressants added to antipsychotic drugs in the treatment of schizophrenia.Method:Multiple databases and previous publications were ...searched through June 2015 to identify all randomized controlled trials of any add-on antidepressants compared with placebo or no-treatment in schizophrenia. Depressive and negative symptoms (primary outcomes), overall symptoms, positive symptoms, side effects, exacerbation of psychosis, and responder rates were examined. Subgroup, meta-regression, and sensitivity analyses were performed, as well as investigations of publication bias and risk of bias.Results:Eighty-two randomized controlled trials with a total of 3,608 participants were included. Add-on antidepressants appeared more efficacious than controls for depressive symptoms (standardized mean difference: –0.25, 95% CI=–0.38 to –0.12), negative symptoms (standardized mean difference: –0.30, 95% CI=–0.44 to –0.16), overall symptoms (standardized mean difference: –0.24, 95% CI=–0.39 to –0.09), positive symptoms (standardized mean difference: –0.17, 95% CI=–0.33 to –0.01), quality of life (standardized mean difference: –0.32, 95% CI=–0.57 to –0.06), and responder rate (risk ratio: 1.52, 95% CI=1.29 to 1.78; number-needed-to-treat-to-benefit: 5, 95% CI=4 to 7). The effects on depressive and negative symptoms appeared more pronounced when minimum thresholds of these symptoms were inclusion criteria (standardized mean difference: –0.34, 95% CI=–0.58 to –0.09 and standardized mean difference: –0.58, 95% CI=–0.94 to –0.21, respectively). There were no significant differences between antidepressants and controls in terms of exacerbation of psychosis, premature discontinuation, and the number of participants with at least one adverse event. More patients taking add-on antidepressants suffered from abdominal pain, constipation, dizziness, and dry mouth.Conclusions:Analysis of primary outcomes (depressive and negative symptoms) suggests small, beneficial effects of adjunctive antidepressants. It would appear that this augmentation can be accomplished with a low risk of exacerbation of psychosis and adverse effects. However, secondary and subgroup analyses should be interpreted cautiously and considered exploratory.
Previous research suggests a broad range of deficits in major depressive disorder. Our goal was to update the current assumptions and investigate the extent of cognitive impairment in depression in ...the acute and remitted state. A systematic review of the existing literature between 2009 and 2019 assessing the risk of bias within the included studies was performed. Of the 42 articles reviewed, an unclear risk of bias was shown overall. The risk of bias mainly concerned the sample selection, inadequate remedial measures, as well as the lack of blinding the assessors. In the acute phase, we found strong support for impairment in processing speed, learning, and memory. Follow-up studies and direct comparisons revealed less pronounced deficits in remission, however, deficits were still present in attention, learning and memory, and working memory. A positive correlation between the number of episodes and cognitive deficits as well as depression severity and cognitive deficits was reported. The results also demonstrate a resemblance between the cognitive profiles in bipolar disorder and depression. Comparisons of depression with schizophrenia led to unclear results, at times suggesting an overlap in cognitive performance. The main findings support the global deficit hypothesis and align with results from prior meta-analyses and reviews. Recommendations for future research are also presented.
The Hamilton Depression Rating Scale (HAM-D) and the Montgomery Asberg Depression Rating Scale (MADRS) are scales used frequently to rate the symptoms of depression. There are many situations in ...which it is important to know what a given total score or a percent reduction from baseline score of one scale means in relation to the other scale.
We used the equipercentile linking method to identify corresponding scores of simultaneous HAM-D and MADRS ratings in 4388 patients from 31 mirtazapine trials in major depressive disorder. Data were collected at baseline and at weeks 1, 2 and 4.
HAM-D scores of 10, 20, 30 and 40 roughly corresponded to MADRS scores of 13, 26, 39 and 52–53, respectively. An absolute HAM-D improvement of 10, 20, 25 points corresponded to a MADRS improvement of 12, 26, and 34. A percentage improvement from baseline of the HAM-D was approximately the same as a percentage improvement on the MADRS.
These results are important for the comparison of trials that used the HAM-D and MADRS. We present conversion tables for future research.
•The results provide guidance for clinicians and researchers in how to convert HAM-D scores to MADRS scores and vice versa.•HAM-D totals scores of 10, 20, 30 and 40 correspond to MADRS total scores of 13, 26, 39 and 52–53.•A percentage reduction from baseline on one scale is approximately the same as a percentage reduction on the other scale.
Abstract Background Little is known about the clinical relevance of the Montgomery Asberg Depression Rating Scale (MADRS) total scores. It is unclear how total scores translate into clinical ...severity, or how commonly used measures for response (reduction from baseline of ≥50% in the total score) translate into clinical relevance. Moreover, MADRS based definitions of remission vary. Methods We therefore compared: a/ the MADRS total score with the Clinical Global Impression – Severity Score (CGI-S) b/ the percentage and absolute change in the MADRS total scores with Clinical Global Impression – Improvement (CGI-I); c/ the absolute and percentage change in the MADRS total scores with CGI-S absolute change. The method used was equipercentile linking of MADRS and CGI ratings from 22 drug trials in patients with Major Depressive Disorder (MDD) (n=3,288). Results Our results confirm the validity of the commonly used measures for response in MDD trials: a CGI-I score of 2 (‘much improved’) corresponded to a percentage MADRS reduction from baseline of 48% to 57%, and a CGI-I score of 1 (‘very much improved’) to a reduction of 80% to 84%. If a state of almost complete absence of symptoms were required for a definition of remission, a MADRS total score would be < 8, because such scores corresponded to a CGI-S score of 2 (‘borderline mentally ill’). Limitations: Although our analysis is based on a large number of patients, the original trials were not specifically designed to examine our research question. Conclusions The results might contribute to a better understanding and improved interpretation of clinical trial results in MDD.
What does the PANSS mean? Leucht, Stefan; Kane, John M.; Kissling, Werner ...
Schizophrenia research,
11/2005, Letnik:
79, Številka:
2
Journal Article
Recenzirano
Despite the frequent use of the Positive and Negative Syndrome Scale (PANSS) for rating the symptoms of schizophrenia, the clinical meaning of its total score and of the cut-offs that are used to ...define treatment response (e.g. at least 20% or 50% reduction of the baseline score) are as yet unclear. We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions (CGI).
PANSS and CGI ratings at baseline (
n
=
4091), and after one, two, four and six weeks of treatment taken from a pooled database of seven pivotal, multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking.
Being considered “mildly ill” according to the CGI approximately corresponded to a PANSS total score of 58, “moderately ill” to a PANSS of 75, “markedly ill” to a PANSS of 95 and severely ill to a PANSS of 116. To be “minimally improved” according to the CGI score was associated with a mean percentage PANSS reduction of 19%, 23%, 26% and 28% at weeks 1, 2, 4 and 6, respectively. The corresponding figures for a CGI rating “much improved” were 40%, 45%, 51% and 53%.
The results provide a better framework for understanding the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations. Such studies may ideally use at least a 50% reduction from baseline cut-off to define response rather than lower thresholds. In treatment resistant populations, however, even a small improvement can be important, so that a 25% cut-off might be appropriate.
Initial environmental pyrosequencing studies suggested highly complex protistan communities with phylotype richness decisively higher than previously estimated. However, recent studies on individual ...bacteria or artificial bacterial communities evidenced that pyrosequencing errors may skew our view of the true complexity of microbial communities. We pyrosequenced two diversity markers (hypervariable regions V4 and V9 of the small-subunit rDNA) of an intertidal protistan model community, using the Roche GS-FLX and the most recent GS-FLX Titanium sequencing systems. After pyrosequencing 24 reference sequences we obtained up to 2039 unique tags (from 3879 V4 GS-FLX Titanium reads), 77% of which were singletons. Even binning sequences that share 97% similarity still emulated a pseudodiversity exceeding the true complexity of the model community up to three times (V9 GS-FLX). Pyrosequencing error rates were higher for V4 fragments compared with the V9 domain and for the GS-FLX Titanium compared with the GS-FLX system. Furthermore, this experiment revealed that error rates are taxon-specific. As an outcome of this study we suggest a fast and efficient strategy to discriminate pyrosequencing signals from noise in order to more realistically depict the structure of protistan communities using simple tools that are implemented in standard tag data-processing pipelines.
We identified empirical correlates for the 42 substantive scales of the German language version of the Minnesota Multiphasic Personality Inventory (MMPI)-2-Restructured Form (MMPI-2-RF): Higher ...Order, Restructured Clinical, Specific Problem, Interest, and revised Personality Psychopathology Five scales. We collected external validity data by means of a 177-item chart review form in a sample of 488 psychiatric inpatients of a German university hospital. We structured our findings along the interpretational guidelines for the MMPI-2-RF and compared them with the validity data published in the tables of the MMPI-2-RF Technical Manual. Our results show significant correlations between MMPI-2-RF scales and conceptually relevant criteria. Most of the results were in line with U.S. validation studies. Some of the differences could be attributed to sample compositions. For most of the scales, construct validity coefficients were acceptable. Taken together, this study amplifies the enlarging body of research on empirical correlates of the MMPI-2-RF scales in a new sample. The study suggests that the interpretations given in the MMPI-2-RF manual may be generalizable to the German language MMPI-2-RF.
Public Significance Statement
This study displays significant correlations between scale scores of the German language version of the MMPI-2-Restructured Form (MMPI-2-RF; a clinical self-assessment instrument) and the diagnostic clinical findings of a German inpatient sample. Furthermore, it compares the results with U.S. validation studies und suggests that the interpretations given in the MMPI-2-RF manual are generalizable to the German language MMPI-2-RF.
To understand what given scores of the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS) mean from a clinical point of view is important for the translation ...of research results into practice. We therefore (a) compared the absolute change of the BPRS/PANSS with the Clinical Global Impressions Ratings (CGI) -improvement score and the change of the CGI severity score, (b) analyzed whether the severity of illness at baseline had an impact on the latter association, and (c) attempted to replicate previous BPRS findings using a completely different data set based upon the PANSS-derived BPRS. The method used was equipercentile linking of BPRS and CGI ratings from 14 drug trials in acutely ill patients with schizophrenia (n=5970). An absolute reduction of the BPRS/PANSS by approximately 10/15 points corresponded to a CGI change of 'minimally improved' and to a change of the CGI severity score by one severity step. However, the latter associations depended on the severity of symptoms at baseline. Less severely ill patients required less BPRS/PANSS total score reduction to achieve the same CGI-improvement score than more severely ill patients. This effect of initial severity was attenuated using percentage rather than absolute BPRS/PANSS reduction scores. The linking analysis between the absolute BPRS/PANSS reduction and the CGI may have an implication for the interpretation of efficacy differences found in clinical trials, and for sample size estimations. Clinicians seem to base CGI ratings on relative change rather than on absolute change of symptoms.
PDF