Clinical specificity profile for novel rapid acting antidepressant drugs

Scala, Mauro; Fanelli, Giuseppe; De Ronchi, Diana; Serretti, Alessandro; Fabbri, Chiara

doi:10.1097/yic.0000000000000488

Cited by 41Treatment of Major DepressionBipolar Disorder and TreatmentTryptophan and brain disorders

Clinical specificity profile for novel rapid acting antidepressant drugs

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Scala, Mauro, Fanelli, Giuseppe, De Ronchi, Diana, Serretti, Alessandro, Fabbri, Chiara·2023·International Clinical Psychopharmacology

DOI 10.1097/yic.0000000000000488PMC PMC10373854

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Abstract

Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants are not effective in all patients and often show a relevant response latency, with a range of adverse events, including weight gain and sexual dysfunction. Novel rapid agents were developed with the aim of overcoming at least in part these issues. Novel drugs target glutamate, gamma-aminobutyric acid, orexin, and other receptors, providing a broader range of pharmacodynamic mechanisms, that is, expected to increase the possibility of personalizing treatments on the individual clinical profile. These new drugs were developed with the aim of combining a rapid action, a tolerable profile, and higher effectiveness on specific symptoms, which were relatively poorly targeted by standard antidepressants, such as anhedonia and response to reward, suicidal ideation/behaviours, insomnia, cognitive deficits, and irritability. This review discusses the clinical specificity profile of new antidepressants, namely 4-chlorokynurenine (AV-101), dextromethorphan-bupropion, pregn-4-en-20-yn-3-one (PH-10), pimavanserin, PRAX-114, psilocybin, esmethadone (REL-1017/dextromethadone), seltorexant (JNJ-42847922/MIN-202), and zuranolone (SAGE-217). The main aim is to provide an overview of the efficacy/tolerability of these compounds in patients with mood disorders having different symptom/comorbidity patterns, to help clinicians in the optimization of the risk/benefit ratio when prescribing these drugs.

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Psilocybin has a sexually and metabolically safe profile.
“and the drug has a sexually and metabolically safe profile. 8”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [8]
The Results section (‘Adverse events, safety, and tolerability’; page unavailable) describes a low tendency for the drugs reviewed, including psilocybin, to cause sexual dysfunction, weight gain, or metabolic changes. But it says the observation period was too limited for firm conclusions and that these drugs *may* be sexually and metabolically friendly. Calling psilocybin sexually and metabolically safe omits that uncertainty. (LLM, conf=0.88)
Experimental — accuracy not yet measured
In medical and research settings there is no risk of withdrawal symptoms for psilocybin.
“for example, in medical and research settings there is no risk of withdrawal symptoms for psilocybin”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [8]
The Discussion (page unavailable) refers to a lack of psilocybin-induced withdrawal and rebound symptoms, supporting the claim in the studied settings. But the Conclusion (page unavailable) says withdrawal symptoms need longer follow-up to be reliably assessed, so the categorical assertion of no risk goes beyond the paper. (LLM, conf=0.85)
Experimental — accuracy not yet measured

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Symptoms of maternal depression immediately after delivery predict unsuccessful breast feeding: Figure 1
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Bipolar Disorder
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Self-citation
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Effect of as-needed use of intranasal PH94B on social and performance anxiety in individuals with social anxiety disorder: L<scp>iebowitz et al.</scp>
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Authors: Scala, M., Fanelli, G., De Ronchi, D., Serretti, A., & Fabbri, C.
Affiliations: University of Bologna (IT)
Radboud University Medical Center (NL)
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
King's College London (GB)
Corresponding author: Serretti, Alessandro
ORCID: Scala, Mauro
Fanelli, Giuseppe
Serretti, Alessandro
Fabbri, Chiara
Venue: International Clinical Psychopharmacology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2023-06-30
Volume: 38
Issue: 5
Pages: 297-328
ISSN: 0268-1315 (ISSN-L)
DOI: 10.1097/yic.0000000000000488
PMC: PMC10373854
OpenAlex: W4382502499
Cited by: 41
References: 119
Citations by year: 2026: 3 · 2025: 17 · 2024: 18 · 2023: 3
FWCI: 1.49
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: International Clinical Psychopharmacology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Radboud Repository (Radboud University) (submittedVersion, cc-by)
Institutional Research Information System (University of Udine) (submittedVersion)
Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
Funders: NextGenerationEU
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: rapid-acting antidepressants, mood disorders, pimavanserin, psilocybin, zuranolone, glutamate receptor antagonists, GABA agonists, orexin receptor antagonists, anhedonia, suicidal ideation, insomnia, cognitive impairment, irritability, adverse events, personalized treatment
MeSH terms: Antidepressive Agents, Major Depressive Disorder, Depressive Disorder, Major, Humans, Sleep Initiation and Maintenance Disorders, Comorbidity, Bupropion

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