Head-to-Head Comparison of Sedation and Somnolence Among 37 Antipsychotics in Schizophrenia, Bipolar Disorder, Major Depression, Autism Spectrum Disorders, Delirium, and Repurposed in COVID-19, Infectious Diseases, and Oncology From the FAERS, 2004–2020

Abstract

Objective: Antipsychotic compounds are known to induce sedation somnolence and have expanded clinical indications beyond schizophrenia to regulatory approval in bipolar disorder, treatment-resistant depression, and is being repurposed in infectious diseases and oncology. However, the medical sciences literature lacks a comprehensive association between sedation and somnolence among a wide-range of antipsychotic compounds. The objective of this study is to assess the disproportionality of sedation and somnolence among thirty-seven typical and atypical antipsychotics.Materials and Methods: Patient adverse drug reactions (ADR) cases were obtained from the United States Food and Drug Administration Adverse Events Reporting System (FAERS) between January 01, 2004 and September 30, 2020 for a wide-array of clinical indications and off-label use of antipsychotics. An assessment of disproportionality were based on cases of sedation and somnolence and calculated using the case/non-case methodology. Statistical analysis resulting in the reporting odds-ratio (ROR) with corresponding 95% confidence intervals (95% CI) were conducted using the R statistical programming language.Results: Throughout the reporting period, there were a total of 9,373,236 cases with 99,251 specific ADRs reporting sedation and somnolence. Zuclopenthixol (n = 224) ROR = 13.3 (95% CI, 11.6–15.3) was most strongly associated of sedation and somnolence and haloperidol decanoate long-acting injection (LAI) was not statistically associated sedation and somnolence. Further, among atypical antipsychotic compounds, tiapride and asenapine were the top two compounds most strongly associated with sedation and somnolence. Comprehensively, the typical antipsychotics ROR = 5.05 (95%CI, 4.97–5.12) had a stronger association with sedation and somnolence when compared to atypical antipsychotics ROR = 4.65 (95%CI, 4.47–4.84).Conclusion: We conducted a head-to-head comparison of thirty-seven antipsychotics and ranked the compounds based on the association of sedation and somnolence from ADR data collected throughout 16 years from the FAERS. The results are informative and with recent interests in repurposing phenothiazine antipsychotics in infectious disease and oncology provides an informative assessment of the compounds during repurposing and in psychopharmacology.

Tackling the Behavior of Cancer Cells: Molecular Bases for Repurposing Antipsychotic Drugs in the Treatment of Glioblastoma

“…If we add that most of the medications described here are inexpensive when compared with the astounding costs of the new generation of cancer drugs, and that their times to reach the GBM patient’s bed can be drastically shortened, clinical trials involving the addition of selected antipsychotics to the state-of-art Stupp regimen should be particularly welcome. On the other hand, it should be considered that these drugs are not devoid of well-known and sometimes severe but drug-specific, dose-dependent and mostly reversible side effects, i.e., sedation and extrapyramidal syndrome [ 154 ].…”

Adverse Events During Pregnancy Associated With Entecavir and Adefovir: New Insights From a Real-World Analysis of Cases Reported to FDA Adverse Event Reporting System

“…professionals ( Sakaeda et al, 2013 ). The analysis of the FAERS database has been exploited in pharmacovigilance for drug safety assessments, not only to detect drug-AE associations unidentified in pre-market clinical trials, but also protect patients from potential harms ( Chen et al, 2021 ; Eugene et al, 2021 ; Ma et al, 2021 ). It is worth noting that whether a drug is the causative agent of an AE occurring during its use, is something that can only be accurately judged through a rigorous causality assessment by healthcare professionals, while non-healthcare professional reports on their own appear to increase the risk of erroneous information ( Andreaggi et al, 2020 ).…”

“…The FAERS database, established for national post-market surveillance for drug safety, is a spontaneous reporting system for healthcare professionals, consumers, and drug manufacturers ( Sakaeda et al, 2013 ). As FAERS case reports have been increasing annually, the database is largely used to identify novel drug-associated AEs not previously observed in clinical trials ( Chen et al, 2021 ; Eugene et al, 2021 ; Ma et al, 2021 ). Moreover, data-mining of drug-related case reports from spontaneous reporting systems can provide us with a valuable source of information about the safety of specific drugs in real-life, especially for frail populations such as pregnant women ( Tkachenko et al, 2019 ; Carnovale et al, 2020 ).…”

The More, the Merrier…? Antipsychotic Polypharmacy Treatment Strategies in Schizophrenia From a Pharmacology Perspective

“…Thus, whereas the poor D2 affinity of CLZ may be complemented by the higher D2 affinity of RIS, the latter agent (together with its active metabolite paliperidone; PAL) is more liable to cause EPS and hyperprolactinemia. Moreover, as both agents possess significant alpha1-adrenoceptor and H1-receptor antagonism, a CLZ + RIS APP intervention may result in an enhanced acute (orthostatic) hypotensive action as well as risk for accentuated sedation [see, e.g., ( 40 )]. A similar reasoning may apply to the OLA + RIS combination, where any possible benefits of supplemented D2 receptor blockade may be potentially outweighed by an increased AE liability mediated by the very same site (e.g., prolactin rise, increased EPS risk), but also by other targets—as in the CLZ + RIS discussion above.…”

“…This also applies regarding the propensity to induce weight gain and accompanying metabolic AE, with the SGA OLA and CLZ displaying the most, and TGA agents like ARI and CAR the least, harmful profiles ( 55 ). Additionally, marked antipsychotic drug heterogeneity in prolactin-raising and sedation-inducing properties occur ( 40 , 56 ). From the APP perspective it is notable that add-on treatment with TGA can significantly attenuate OLA- and CLZ-induced AE like the aforementioned ( 57 – 60 ).…”