Dataset Information

Brain Networks Reveal the Effects of Antipsychotic Drugs on Schizophrenia Patients and Controls.

ABSTRACT: The study of brain networks, including those derived from functional neuroimaging data, attracts a broad interest and represents a rapidly growing interdisciplinary field. Comparing networks of healthy volunteers with those of patients can potentially offer new, quantitative diagnostic methods and a framework for better understanding brain and mind disorders. We explore resting state functional Magnetic Resonance Imaging (fMRI) data through network measures. We construct networks representing 15 healthy individuals and 12 schizophrenia patients (males and females), all of whom are administered three drug treatments: i) a placebo; and two antipsychotic medications ii) aripiprazole and iii) sulpiride. We compare these resting state networks to a performance at an "N-back" working memory task. We demonstrate that not only is there a distinctive network architecture in the healthy brain that is disrupted in schizophrenia but also that both networks respond to antipsychotic medication. We first reproduce the established finding that brain networks of schizophrenia patients exhibit increased efficiency and reduced clustering compared with controls. Our data then reveal that the antipsychotic medications mitigate this effect, shifting the metrics toward those observed in healthy volunteers, with a marked difference in efficacy between the two drugs. Additionally, we find that aripiprazole considerably alters the network statistics of healthy controls. Examining the "N-back" working memory task, we establish that aripiprazole also adversely affects their performance. This suggests that changes to macroscopic brain network architecture result in measurable behavioral differences. This is one of the first studies to directly compare different medications using a whole-brain graph theoretical analysis with accompanying behavioral data. The small sample size is an inherent limitation and means a degree of caution is warranted in interpreting the findings. Our results lay the groundwork for an objective methodology with which to calculate and compare the efficacy of different treatments of mind and brain disorders.

SUBMITTER: Towlson EK

PROVIDER: S-EPMC6752631 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Brain Networks Reveal the Effects of Antipsychotic Drugs on Schizophrenia Patients and Controls.

Towlson Emma K EK Vértes Petra E PE Müller-Sedgwick Ulrich U Ahnert Sebastian E SE

Frontiers in psychiatry 20190912

The study of brain networks, including those derived from functional neuroimaging data, attracts a broad interest and represents a rapidly growing interdisciplinary field. Comparing networks of healthy volunteers with those of patients can potentially offer new, quantitative diagnostic methods and a framework for better understanding brain and mind disorders. We explore resting state functional Magnetic Resonance Imaging (fMRI) data through network measures. We construct networks representing 15 ...[more]

PMID: 31572229

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Project description:BACKGROUND:Aripiprazole is a relatively new antipsychotic drug, said to be the prototype of a new third generation of antipsychotics; the so-called dopamine-serotonin system stabilisers. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of typical antipsychotics. OBJECTIVES:To evaluate the effects of aripiprazole compared with other typical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY:We searched the Cochrane Schizophrenia Group Trials Register (November 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA:We included all randomised trials comparing aripiprazole with typical antipsychotics in people with schizophrenia or schizophrenia-like psychosis. DATA COLLECTION AND ANALYSIS:We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. We have contacted representatives of Bristol Myers Squibb pharmaceuticals (UK) for additional data. MAIN RESULTS:We included nine randomised trials involving 3122 people comparing aripiprazole with typical antipsychotic drugs. None of the studies reported on relapse - our primary outcome of interest. Attrition from studies was high and data reporting poor. Participants given aripiprazole were comparable to those receiving typical drugs in improving global state and mental state. Aripiprazole provided a significant advantage over typical antipsychotics in terms of fewer occurrences of extra-pyramidal symptom (n=968, 3 RCT, RR 0.46 CI 0.3 to 0.9, NNT 13 CI 17 to 10), and particularly akathisia (n=897, 3 RCT, RR 0.39 CI 0.3 to 0.6, NNT 11 CI 14 to 9). Fewer participants given aripiprazole developed hyperprolactinaemia (n=300, 1 RCT, RR 0.07 CI 0.03 to 0.2, NNT 2 CI 3 to 1). Aripiprazole presented a lesser risk of sinus tachycardia (n=289, 1 RCT, RR 0.09 CI 0.01 to 0.8, NNT 22 CI 63 to 13) and blurred vision (n=308, 1 RCT, RR 0.19 CI 0.1 to 0.7, NNT 14 CI 25 to 10); but enhanced risk of occurrence of dizziness (n=957, 3 RCT, RR 1.88 CI 1.1 to 3.2, NNH 20 CI 33 to 14) and nausea (n=957, 3 RCT, RR 3.03 CI 1.5 to 6.1, NNH 17 CI 25 to 13). Attrition rates were high in both groups, although significantly more participants in the aripiprazole group completed the study in the long term (n=1294, 1 RCT, RR 0.81 CI 0.8 to 0.9 NNT 8 CI 5 to 14). AUTHORS' CONCLUSIONS:Aripiprazole differs little from typical antipsychotic drugs with respect to efficacy, however it presents significant advantages in terms of tolerability. Clearly reported pragmatic short, medium and long term randomised controlled trials are required to replicate and validate these findings and determine the position of aripiprazole in everyday clinical practice.

Dataset Information

Brain Networks Reveal the Effects of Antipsychotic Drugs on Schizophrenia Patients and Controls.

Publications

Brain Networks Reveal the Effects of Antipsychotic Drugs on Schizophrenia Patients and Controls.

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