ReviewNature reviews. Drug discovery2013
50 years of hurdles and hope in anxiolytic drug discovery.
Review in Nature reviews. Drug discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 191 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Y-3 Injection in the Treatment of Acute Ischemic Stroke Phase II Clinical Trial -- Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Phase II Clinical Trial
A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Y-3 in Chinese Subjects With Acute Ischemic Stroke
Who cites it
191 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Pharmacological modulation of conditioned fear in the fear-potentiated startle test: a systematic review and meta-analysis of animal studies.Psychopharmacology · 2023Pooled it
- Efficacy of Silexan in patients with anxiety disorders: a meta-analysis of randomized, placebo-controlled trials.European archives of psychiatry and clinical neuroscience · 2023Pooled it
- Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration-effect relations using the IB-de-risk tool.Journal of psychopharmacology (Oxford, England) · 2022Pooled it
- The Overlapping Neurobiology of Induced and Pathological Anxiety: A Meta-Analysis of Functional Neural Activation.The American journal of psychiatry · 2021Pooled it
- A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models.Molecules (Basel, Switzerland) · 2015Pooled it
- Placebo Effects Are Small on Average in the 7.5% CO2 Inhalational Model of Generalized Anxiety.The international journal of neuropsychopharmacology · 2024Trial
- Trial
- The randomized clinical trial results of the anxiety treatment in patients with somatoform dysfunction and neurotic disorders.Scientific reports · 2021Trial
- The novel vasopressin receptor (V1aR) antagonist SRX246 reduces anxiety in an experimental model in humans: a randomized proof-of-concept study.Psychopharmacology · 2021Trial
- Effect of valproate and pregabalin on human anxiety-like behaviour in a randomised controlled trial.Translational psychiatry · 2018Trial
- A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder.The international journal of neuropsychopharmacology · 2018Trial
- Amygdala Lesions Reduce Anxiety-like Behavior in a Human Benzodiazepine-Sensitive Approach-Avoidance Conflict Test.Biological psychiatry · 2017Trial
- Sustained hyperactivity of parasubthalamic nucleus by PACAP signaling mediates stress-induced anxiety.Molecular psychiatry · 2026Article
- Diazepam selectively biases approach during threat-reward conflict while sparing reactive avoidance.Psychopharmacology · 2026Article
- Circuit-informed modulation of traumatic memory in PTSD: integrating extinction, suppression, and reconsolidation.Molecular psychiatry · 2026Review
- The Timing of Attentional Distraction Matters in Facilitating Extinction of Trace Fear Memory.Experimental neurobiology · 2026Article
- Anxiolytic Effects ofInternational journal of general medicine · 2026Article
- Neuromodulatory Effects of Arecoline on Anxiety-like Behavior in Mice Exposed to Chronic Unpredictable Mild Stress.International journal of molecular sciences · 2025Article
- Article
- Comprehensive Evaluation of Methanolic Fruits Extract of Jatropha gossypifolia L.: Neuropharmacological, Cytotoxic, Anthelmintic, GC-MS Profiling, and Molecular Docking Studies.Pharmacology research & perspectives · 2025Article
131 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Anxiety disorders are the most prevalent group of psychiatric diseases, and have high personal and societal costs. The search for novel pharmacological treatments for these conditions is driven by the growing medical need to improve on the effectiveness and the side effect profile of existing drugs. A huge volume of data has been generated by anxiolytic drug discovery studies, which has led to the progression of numerous new molecules into clinical trials. However, the clinical outcome of these efforts has been disappointing, as promising results with novel agents in rodent studies have very rarely translated into effectiveness in humans. Here, we analyse the major trends from preclinical studies over the past 50 years conducted in the search for new drugs beyond those that target the prototypical anxiety-associated GABA (γ-aminobutyric acid)-benzodiazepine system, which have focused most intensively on the serotonin, neuropeptide, glutamate and endocannabinoid systems. We highlight various key issues that may have hampered progress in the field, and offer recommendations for how anxiolytic drug discovery can be more effective in the future.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.