Long-term treatment with antipsychotic drugs in conventional doses prolonged QTc dispersion, but did not increase ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease

SummaryThere is a debate about long-term treatment of schizophrenia with antipsychotic drugs, with some experts suggesting that these drugs should be discontinued. In this issue, Takeuchi et al demonstrated by a meta-analysis of 11 trials that antipsychotic drugs maintained their efficacy for relapse prevention for 1 year, whereas patients on placebo kept getting worse. We consider these findings in the light of the current discussion about possible dose-related brain volume loss, supersensitivity psychosis, the high variability of results in long-term follow-up studies and recent approaches to discontinue antipsychotics in patients with a first-episode. The new findings speak in favour of continuing antipsychotics at the same dose, at least in patients whose condition is chronic, but the topic is complex.

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Reduction of QT and QTc Dispersion During Long-Term Treatment of Systemic Hypertension With Enalapril

The American Journal of Cardiology ◽

10.1016/s0002-9149(97)00869-2 ◽

1998 ◽

Vol 81 (2) ◽

pp. 170-174 ◽

Cited By ~ 44

Author(s):

José Ramón González-Juanatey ◽

José Marı́a Garcı́a-Acuña ◽

Antonio Pose ◽

Alfonso Varela ◽

Carlos Calvo ◽

...

Keyword(s):

Term Treatment ◽

Systemic Hypertension ◽

Qtc Dispersion ◽

Long Term Treatment

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New insights into the mechanism of drug-induced dyskinesia

CNS Spectrums ◽

10.1017/s1092852912000752 ◽

2012 ◽

Vol 18 (1) ◽

pp. 15-20 ◽

Cited By ~ 58

Author(s):

Anton J. M. Loonen ◽

Svetlana A. Ivanova

Keyword(s):

Antipsychotic Drugs ◽

Term Treatment ◽

Medium Spiny Neurons ◽

Indirect Pathway ◽

Drug Induced ◽

Disease Research ◽

Spiny Neurons ◽

Long Term Treatment ◽

Cortical Circuit

Dyskinesia is an extrapyramidal movement disorder characterized by involuntary, repetitive, irregular motions that affect the mouth and face and/or the limbs and trunk. Tardive dyskinesia (TD) is a well-known complication of long-term treatment with antipsychotic drugs. Dyskinesia is also induced with levodopa, a treatment for Parkinson's disease, and it occurs spontaneously as a symptom of Huntington's disease. Research on the pathogenesis of TD has focused on a dysfunction of either the dopaminergic or serotonergic system. However, recent evidence has suggested that we should focus on the possible damage of GABAergic medium spiny neurons (MSNs). MSNs are the first station in the cortico-striato-thalamo-cortical circuit that regulates the amplitude and velocity of movements. Two pathways can be distinguished in this circuit: a direct pathway, which increases movements (hyperkinesia), and an indirect pathway, which decreases movements (hypokinesia). Both pathways are activated by glutamatergic corticostriatal neurons. Here, we discuss some evidence that supports the hypothesis that indirect pathway MSNs are damaged in dyskinesia.

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Metabolic side effects of antipsychotic drugs in individuals with schizophrenia during medium- to long-term treatment: protocol for a systematic review and network meta-analysis of randomized controlled trials

Systematic Reviews ◽

10.1186/s13643-021-01760-z ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Johannes Schneider-Thoma ◽

Angelika Kapfhammer ◽

Dongfang Wang ◽

Irene Bighelli ◽

Spyridon Siafis ◽

...

Keyword(s):

Systematic Review ◽

Side Effects ◽

Antipsychotic Drugs ◽

Meta Analysis ◽

Density Lipoprotein ◽

Term Treatment ◽

Controlled Trials ◽

Metabolic Side Effects ◽

Long Term Treatment

Abstract Background Antipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking. Methods We will conduct a systematic review and network meta-analysis (NMA). We will include randomized controlled trials (RCTs) in which participants received either placebo or an antipsychotic (i.e. placebo-controlled trials and head-to-head comparisons of drugs). We will include studies in individuals with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) at any stage of the disease (acute episode; maintenance phase). We will include studies with a duration of more than 3 months (medium- to long-term treatment). The primary outcome will be the change in body weight. Secondary outcomes will be the further metabolic parameters: fastening glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. We will search for eligible studies (independent of the publication status) in Cochrane Schizophrenia Group’s Study-Based Register of Trials, which is compiled by regular searches in trial registries and multiple electronic databases from their inception onwards including MEDLINE, EMBASE and PsycINFO. Additionally, we will search previously published systematic reviews and websites of pharmaceutical companies for eligible studies. At least two reviewers will independently conduct the process of study selection and data extraction. We will use the Cochrane Risk of Bias 2 tool to evaluate the risk of bias in studies. We will conduct random-effects NMA within a Bayesian framework to synthesize all evidence for each outcome. We will conduct sensitivity and subgroup analyses to assess the robustness of the findings and to explore heterogeneity. The confidence in the results will be evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework. Discussion This systematic review and network meta-analysis will provide a synthesis of the existing evidence from RCTs how antipsychotic drugs differ in terms of metabolic side effects during medium- to long-term treatment. The findings have the potential to influence the choice of antipsychotic medication made by individuals with schizophrenia and their physicians. Systematic review registration PROSPERO CRD42020175414

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Long-term treatment with naproxcinod significantly improves skeletal and cardiac disease phenotype in the mdx mouse model of dystrophy

Human Molecular Genetics ◽

10.1093/hmg/ddu033 ◽

2014 ◽

Vol 23 (12) ◽

pp. 3239-3249 ◽

Cited By ~ 29

Author(s):

K. Uaesoontrachoon ◽

J. L. Quinn ◽

K. S. Tatem ◽

J. H. Van Der Meulen ◽

Q. Yu ◽

...

Keyword(s):

Mouse Model ◽

Cardiac Disease ◽

Term Treatment ◽

Mdx Mouse ◽

Disease Phenotype ◽

Long Term Treatment

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Washout of long-term treatment with flecainide and propafenone in patients with complex ventricular arrhythmias and cardiac disease

American Heart Journal ◽

10.1016/0002-8703(92)90600-z ◽

1992 ◽

Vol 124 (2) ◽

pp. 374-380

Author(s):

Antonio Vincenti ◽

Maurizio Landolina ◽

Roberto Latini ◽

Augusto Cavalli ◽

Fiorenzo Gaita ◽

...

Keyword(s):

Cardiac Disease ◽

Ventricular Arrhythmias ◽

Term Treatment ◽

Long Term Treatment

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Olanzapine in the long-term treatment of schizophrenia

The British Journal of Psychiatry ◽

10.1192/s000712500029363x ◽

1999 ◽

Vol 174 (S37) ◽

pp. 26-29 ◽

Cited By ~ 14

Author(s):

John Kane

Keyword(s):

Antipsychotic Drugs ◽

Antipsychotic Agent ◽

Term Treatment ◽

Term Therapy ◽

Therapeutic Benefits ◽

Maintenance Medication ◽

Long Term Treatment ◽

Long Term Therapy ◽

The Cost

The primary aim of the long-term treatment of patients with schizophrenia is to prevent relapse, which is costly both in psychological and economic terms. Although with conventional antipsychotic drugs relapse may occur despite compliance with maintenance regimens, the rate of relapse is reduced in compliant patients. However, this benefit is achieved at the cost of side-effects and the risk of developing tardive dyskinesia, even among patients who have taken these drugs for only a year or two. To provide the therapeutic benefits of maintenance medication without its drawbacks, intermittent dosing and long-term therapy with reduced doses of conventional medications have been explored. The atypical antipsychotic agent, olanzapine, has been shown to be effective maintenance medication and has an improved safety profile.

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