American journal of therapeutics最新文献

Background: Benzodiazepines have long held a leading position in medical therapeutics, known for their multiple common therapeutic properties and primarily being prescribed for anxiety and insomnia. However, their lack of specificity and various side effects have led to a reevaluation of their long-term use, resulting in a rapid growth in the literature focusing on targeted therapies.

Areas of uncertainty: Despite many efforts, uncertainties persist and there are heterogeneous findings across studies regarding the pharmacological effects attributed to gamma-aminobutyric acid type A (GABAA) receptor subunits. Selective compounds targeting GABAA receptor alpha subunits are currently under active research and definitive conclusions have not been reached yet. Some compounds have not progressed to clinical trials, while others, if advanced, have been halted. These challenges emphasize the difficulty in translating preclinical findings into clinical use.

Data sources: A literature review was conducted using the PubMed database, searching for articles discussing GABAA receptor subunits. The search was refined by including only selective compounds with potential anxiolytic and cognitive enhancement properties.

Results: Findings reveal compounds with promising anxiolytic and antidepressant effects with minimal sedation and absence of tolerance development. Moreover, some compounds show potential in alleviating cognitive dysfunction. There is a broad spectrum of potential therapeutic applications for selective compounds, ranging from neurological disorders such as epilepsy and neuropathic pain to cognitive dysfunction-related conditions. Currently, the leading selective compounds with the most promising results in ongoing clinical trials are basmisanil and darigabat. Basmisanil holds further exploration potential in the treatment of cognitive impairment and related conditions, while darigabat shows progress in the advancement of adjunctive therapy of focal onset seizures and for the treatment of panic disorder, respectively.

Conclusions: Future drug discovery efforts are encouraged to focus on positive allosteric modulators that selectively target the α2, α3 subunits and negative/positive allosteric modulators that target the α5 subunit of the GABAA receptor. The pursuit of ligands possessing only anxiolytic effects or those enhancing cognition continues to be an important focus for future research, with promising advancements depicted in recent studies.

Background: The nocebo effect is often disregarded in medical practice and is certainly much less known than the placebo effect, although, in reality, both can influence therapeutic decision making and the quality of life of patients. However, the nocebo effect raises a number of issues not only of a practical nature related to clinical activity but also ethical dilemmas related to the observance of the patient's autonomy, nonmaleficence, or informed consent and the information on which it is based.

Areas of uncertainty: The ethical dilemmas raised by the nocebo effect revolve around how informed consent can be achieved, the accuracy and volume of information that is transmitted to the patient, and how to report negative side effects of therapeutic treatment.

Data sources: In September 2023, a narrative analysis of the literature was conducted using a combination of keywords such as nocebo, placebo, ethics, therapeutic relationship from PubMed, Scopus, Google Scholar, and so on, as well as from official documents developed at an international level (World Health Organization), for a period of 10 years (2012-2021).

Results: Analyzing the articles that remarked upon the significant impact of ethics in nocebo research or in the therapeutic relationship, we can state that the existence of several relevant issues of interest have been detected regarding the ethical use of nocebo and its impact in research or in clinics and thus the need for proper knowledge and management of the impact of nocebo effects. The ethical paradox of obtaining informed consent with the 2 goals, first, the need for complete information and second, the preservation of the autonomy of the patient, respectively, that of "primum non-nocere" and of avoiding unnecessary harm by revealing probable adverse effects is a point of interest for numerous studies. The potential for a nocebo effect is present when we inform patients about the risks and benefits of treatment, there being a clear link between the moral and ethical duty to inform patients and the need to avoid situations that increase the nocebo impact on how the disease or the adverse effects of the treatment are perceived. Adapting information about the side effects of medicines should focus on ensuring a balance between transparency and caution, especially in patients with a high potential for nocebo effect.

Conclusions: The nocebo effect had for a long time been unknown or denied, although it can interfere with the results of the treatment used. As the nocebo phenomenon becomes increasingly known in medical practice, the clinical and ethical implications are identified by medical staff, and nocebo's adverse responses are no longer ignored.