scholarly journals Do antipsychotic drugs lose their efficacy for relapse prevention over time?

2017 ◽  
Vol 211 (3) ◽  
pp. 127-129 ◽  
Author(s):  
Stefan Leucht ◽  
John M. Davis
Keyword(s):  
Relapse Prevention ◽  
Antipsychotic Drugs ◽  
Meta Analysis ◽  
Term Treatment ◽  
First Episode ◽  
Brain Volume Loss ◽  
New Findings ◽  
Long Term Treatment ◽  
Long Term Follow Up

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.

scholarly journals 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

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

scholarly journals Pharmacogenetic association between NAT2 gene polymorphisms and isoniazid induced hepatotoxicity: trial sequence meta-analysis as evidence

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Saif Khan ◽  
Raju K. Mandal ◽  
Abdulbaset Mohamed Elasbali ◽  
Sajad A. Dar ◽  
Arshad Jawed ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Term Treatment ◽  
Wild Type ◽  
Severe Problem ◽  
Trial Sequence ◽  
Increased Risk ◽  
Long Term Treatment ◽  
Nat2 Gene

Abstract Hepatotoxicity is a severe problem generally faced by tuberculosis (TB) patients. It is a well-known adverse reaction due to anti-TB drugs in TB patients undergoing long-term treatment. The studies published previously have explored the connection of N-acetyltransferase 2 (NAT2) gene polymorphisms with isoniazid-induced hepatotoxicity, but the results obtained were inconsistent and inconclusive. A comprehensive trial sequence meta-analysis was conducted employing 12 studies comprising 3613 controls and 933 confirmed TB cases using the databases namely, EMBASE, PubMed (Medline) and Google Scholar till December 2017. A significant association was observed with individuals carrying variant allele at position 481C>T (T vs. C: P = 0.001; OR = 1.278, 95% CI = 1.1100–1.484), at position 590G>A (A vs. G: P = 0.002; OR = 1.421, 95% CI = 1.137–1.776) and at position 857G>A (A vs. G: P = 0.0022; OR = 1.411, 95% CI = 1.052–1.894) to higher risk of hepatotoxicity vis-à-vis wild-type allele. Likewise, the other genetic models of NAT2 gene polymorphisms have also shown increased risk of hepatotoxicity. No evidence of publication bias was observed. These results suggest that genetic variants of NAT2 gene have significant role in isoniazid induced hepatotoxicity. Thus, NAT2 genotyping has the potential to improve the understanding of the drug–enzyme metabolic capacity and help in early predisposition of isoniazid-induced hepatotoxicity.

scholarly journals What does the latest meta-analysis really tell us about antidepressants?

2018 ◽  
Vol 27 (5) ◽  
pp. 430-432 ◽  
Author(s):  
J. Moncrieff
Keyword(s):  
Meta Analysis ◽  
Term Treatment ◽  
Significant Other ◽  
Brain Abnormality ◽  
Antidepressant Effects ◽  
Long Term Treatment ◽  
Clinically Significant ◽  
Meta Analyses ◽  
Chemical Imbalance

A recent meta-analysis of antidepressant trials is the largest conducted to date. Although it claims to prove antidepressant effectiveness beyond dispute, the main outcome is response rates, which are derived from continuous data in a process that can inflate differences between groups. The standardised mean difference of 0.3 is in line with other meta-analyses that show small differences between antidepressants and placebo that are unlikely to be clinically significant. Other factors likely to exaggerate the effects are discussed, and evidence on associations between antidepressant effects and severity and outcomes of long-term treatment is considered. Clinicians need to have open discussions with patients about the limitations of antidepressant research, the lack of evidence that antidepressants correct a chemical imbalance or other brain abnormality, and the range of adverse effects and mental and physical alterations they can produce.

Pharmacotherapy of dysthymia: review and new findings

1998 ◽  
Vol 13 (4) ◽  
pp. 203-209 ◽  
Author(s):  
M Versiani ◽  
AE Nardi ◽  
I Figueira
Keyword(s):  
Monoamine Oxidase ◽  
Reuptake Inhibitor ◽  
Serotonin Reuptake ◽  
Response Rate ◽  
Term Treatment ◽  
Reversible Inhibitors ◽  
Benefit Ratio ◽  
New Findings ◽  
Long Term Treatment

SummaryOpen trials with tricyclics, classical monoamine oxidase inhibitors (MAOIs) or lithium in dysthymia yielded a response rate in 45% of subjects. A long-term treatment of dysthymia with 276 patients treated during 4 years with either moclobemide, tranylcypromine or a combination of amitryptiline plus chlordiazepoxide is described. After discontinuation there was a relapse rate of 89.1%. The controlled studies with tricyclics, MAOIs, reversible inhibitors of monoamine oxidase (RIMAs), specific serotonin reuptake inhibitor (SSRIs) or benzamides showed that drugs well-tolerated work better in dysthymia, due to the fact that the treatment must be long-term. Sertraline was studied vs placebo or imipramine in primary dysthymia. Moclobemide, imipramine and placebo were also studied in 315 patients. Mean doses were 650 mg/d of moclobemide and 203.2 mg/d of imipramine. Moclobemide and sertraline were both efficacious and well tolerated. In a long term treatment the clinician should assess the risk-benefit ratio. Dysthymic patients are very sensitive to unwanted effects and compliance is a serious issue.

Efficacy of Thyroid Hormone Suppression for Benign Thyroid Nodules: Meta-Analysis of Randomized Trials

2005 ◽  
Vol 133 (3) ◽  
pp. 391-396 ◽  
Author(s):  
Matthew T. Sdano ◽  
Mercedes Falciglia ◽  
Jeffrey A. Welge ◽  
David L. Steward
Keyword(s):  
Thyroid Nodule ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Term Treatment ◽  
Volume Reduction ◽  
Benign Thyroid Nodule ◽  
Long Term Treatment ◽  
Nodule Volume ◽  
Benign Thyroid

OBJECTIVE: To determine the efficacy of thyroid hormone suppressive therapy (THST) to decrease benign thyroid nodule volume. DESIGN: Meta-analysis. METHODS: Systematic search using electronic databases (PubMed, Medline, Cochrane Library) through August 2004, paper review, and contacting experts and drug manufacturers. Only randomized controlled studies of THST vs no treatment or placebo, for reduction of benign thyroid nodule volume, were included. Exclusion criteria were: >6-month treatment, lack of ultrasound volume measurement, and region of endemic goiter. Primary outcome was clinically relevant nodule volume reduction (>50%), with a random effects model (RevMan4.2). RESULTS: Nine randomized trials were included (609 subjects). Subjects were 88% more likely to experience >50% nodule volume reduction with THST than placebo or no treatment (relative risk = 1.88; 95% CI = 1.18-3.01; P = 0.008). However, 8 subjects must be subjected to the risk of cardiac and skeletal side effects from THST, for one to benefit from therapy (number needed to treat = 8, risk difference = 0.13; 95% CI = 0.06-0.19; P = 0.0003). Sensitivity analysis reveals that 15 null studies would have to have been missed to reverse statistical significance (fail-safe N = 15). Review of the only study with long-term treatment (5 years) suggests no significant difference in nodule volume reduction between THST and placebo. Further, studies with follow-up after THST withdrawal demonstrate rapid increase in thyroid nodule and goiter volumes. CONCLUSION: THST appears more likely than placebo or no treatment to significantly reduce benign thyroid nodule volume, but long-term treatment may be less effective and regrowth is likely following cessation of therapy. Given the risks of THST, routine use is not recommended for benign nodules.

The Role of Long Acting Antipsychotics in Bipolar Disorder

2017 ◽  
Vol 41 (S1) ◽  
pp. S15-S15
Author(s):  
E. Vieta
Keyword(s):  
Bipolar Disorder ◽  
Meta Analysis ◽  
Term Treatment ◽  
Patient Profile ◽  
Long Term Treatment ◽  
Short And Long Term ◽  
Competing Interest ◽  
Long Acting

Antipsychotics are widely used for the short and long-term treatment of bipolar disorder. Depot and long-acting injectable formulations (LAIs) can be particularly useful for certain subgroups of patients. This lecture will discuss the available data from randomized controlled trials of LAIs in bipolar disorder. A recently published meta-analysis and individual studies assessing depot medications, as well as modern LAIs such as risperidone, paliperidone and aripiprazole, will be reviewed, looking carefully into the prevention of either pole of illness and tolerability. Potential indications and patient profile, based on data and clinical experience, will be discussed.Disclosure of interestThe author has not supplied his declaration of competing interest.

United States open-label glatiramer acetate extension trial for relapsing multiple sclerosis: MRI and clinical correlates

2001 ◽  
Vol 7 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Jerry S Wolinsky ◽  
Ponnada A Narayana ◽  
Kenneth P Johnson ◽  
Keyword(s):  
Glatiramer Acetate ◽  
Term Treatment ◽  
Open Label ◽  
Clinical Correlates ◽  
Long Term Treatment ◽  
Open Label Extension ◽  
Long Term Follow Up ◽  
Relapsing Multiple Sclerosis

After the placebo-controlled extension of the pivotal US trial of glatiramer acetate for the treatment of relapsing multiple sclerosis ended, 208 participants entered an open-label, long-term treatment protocol. Magnetic resonance imaging (MRI) was added to the planned evaluations of these subjects to determine the consequences of long-term treatment on MRI-defined pathology and evaluate its clinical correlates. Of the 147 subjects that remained on long-term follow-up, adequate images were obtained on 135 for quantitative MRI analysis. The initial imaging sessions were performed between June 1998 and January 1999 at 2447+61 days (mean+standard deviation) after the subject's original randomization. Clinical data from a preplanned clinical visit were matched to MRI within 3+51 days. At imaging, 66 patients originally randomized to placebo (oPBO) in the pivotal trial had received glatiramer acetate for 1476+63 days, and 69 randomized to active treatment with glatiramer acetate (oGA) were on drug for 2433+59 days. The number of documented relapses in the 2 years prior to entering the open-label extension was higher in the group originally randomized to placebo (oPBO=1.86+1.78, oGA=1.03+1.28; P=0.002). The annualized relapse rate observed during the open-label study was similar for both groups (oPBO=0.27, +0.45 oGA=0.28+0.40), but the reduction in rate from the placebo-controlled phase was greater for those beginning therapy with GA (oPBO reduced by 0.66+0.71, oGA reduced by 0.23+0.58; P=0.0002). One or more gadolinium enhancing lesions were found in 27.4% of all patients (number of distinct enhancements=1.16+2.52, total enhanced tissue volume=97+26 ml). The risk of having an enhancement was higher in those with relapses during the open-label extension (odds ratio 4.65, 95% confidence interval (CI) 2.0 to 10.7; P=0.001). The odds for finding an enhancement was 2.5 times higher for those patients originally randomized to placebo (CI 1.1 to 5.4; P=0.02) compared to those always on glatiramer acetate. MRI-metrics indicative of chronic pathology, particularly measures of global cerebral tissue loss (atrophy), were uniformly worse for those originally on placebo. These observations enrich our long-term follow up of the clinical consequences of treatment with glatiramer acetate to include its apparent effects on MRI-defined pathology. They show that the effect of glatiramer acetate on enhancements is definite, but modest, consistent with the drug's described mechanisms of action, and that a delay in initiating treatment results in progression of MRI-measured pathology that can be prevented.

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