COMPREHENSIVE REVIEW OF ANTIPSYCHOTIC AGENTS: MECHANISMS OF ACTION, CLINICAL UTILITY, ADVERSE EFFECTS, TOXICITY MANAGEMENT, PHARMACOGENOMICS, PRECISION MEDICINE, PHARMACOVIGILANCE, THERAPEUTIC DRUG MONITORING, EVIDENCE-BASED CLINICAL PRACTICE AND EMERGING

Authors

  • Nodar Sulashvili MD, PhD, Doctor of Pharmaceutical and Pharmacological Sciences In Medicine, Professor of Faculty of Medicine at Georgian International University GIU; Professor of Pharmacology of Faculty of Medicine at Georgian National University SEU; Professor of Medical and Clinical Pharmacology of Faculty of Medicine at BAU International University Batumi, Georgia; Professor of Medical and Clinical Pharmacology of International School of Medicine at Alte University; Invited Professor/Lecturer of Scientific Research-Skills Center at Tbilisi State Medical University; Invited Lecturer of Clinical Pharmacology Department at Tbilisi State Medical University; Tbilisi, Georgia; https://orcid.org/0000-0002-9005-8577
  • Maka Buleishvili MD, PhD, Doctor of Medical Sciences, Professor, Dean of Faculty of Medicine at Georgian International University GIU, Tbilisi, Georgia; Professor of Faculty of Medicine at Georgian National University SEU, Professor of Faculty of Medicine at European University, Professor of Faculty of Medicine at Caucasus International University, Professor of Faculty of Medicine at Georgian-American University, Invited Lecturer of Tbilisi State Medical University, Tbilisi, Georgia; Professor of Faculty of Medicine at BAU International University Batumi, https://orcid.org/0009-0004-2657-8473
  • Mariam Darbaidze MD, PhD, Doctor of Biological Sciences, Professor of Georgian International University GIU, Vice Rector of Georgian International University GIU; Professor of Georgian National University SEU; Tbilisi, Georgia; https://orcid.org/0009-0005-0275-4222
  • Margarita Beglaryan MD, PhD, Doctor of Pharmaceutical Sciences, Academician, Professor of Yerevan State Medical University After Mkhitar Heratsi, Head of the Department of Pharmaceutical Management, Yerevan, Armenia; https://orcid.org/0000-0003-3697-6390
  • Nana Gorgaslidze MD, PhD, Doctor of Pharmaceutical Sciences, Academician, Professor of Tbilisi State Medical University, Head of The Department of Social and Clinical Pharmacy, Tbilisi, Georgia. https://orcid.org/0000-0002-4563-5224
  • Ada (Adel) Tadevosyan MD, PhD, Doctor of Medical Sciences, Academician, Professor of Yerevan State Medical University, Academician and Full Member of the International Academy of Sciences of Ecology and Life Safety (MANEB), Academician of the Republic Armenia Law Academy, Member of the Association of Psychiatrists of Armenia, World Association of Psychiatrists, International Association for Traumatic Stress, World Association for Biological Psychiatry, International Association "Stress and Behavior", Licensed Psychiatrist, Psychotherapist, Public Health Organizer; Tbilisi-Georgia, Yerevan-Armenia, Los Angeles-USA;
  • Magda Davitashvili PhD, Doctor of Biological Sciences, Professor, Academician, Georgian Academy of Ecological Sciences, Program Coordinator of Quality Assurance Office at Iakob Gogebashvili Telavi State University (TeSaU), Telavi, Georgia. https://orcid.org/0009-0005-4213-6533
  • Irina Imerlishvili PhD, Doctor of Law, Professor, Rector of BAU International University Batumi; Professor of BAU International University Batumi; Professor at the International Black Sea University, Batumi-Tbilisi, Georgia; https://orcid.org/0009-0008-6862-7025
  • Marina Giorgobiani MD, PhD, Doctor of Medical Sciences, Academician, Professor of Tbilisi State Medical University, Faculty of Public Health; Department of Hygiene and Medical Ecology, Tbilisi, Georgia. https://orcid.org/0000-0003-0686-5227
  • Vira Kravchenko MD, PhD, Doctor of Biological Sciences, Academician, Professor, Head of The Biological Chemistry Department at National University of Pharmacy of Ukraine, Kharkiv, Ukraine. https://orcid.org/0000-0001-6335-2490
  • Marika Sulashvili MD, Doctor of Family Medicine, Invited Lecturer of Tbilisi State Medical University, Lecturer of Department of Molecular and Medical Genetics, Invited Professor of Biochemistry and Molecular and Medical Genetics at The University of Georgia. Tbilisi, Georgia. https://orcid.org/0000-0002-6338-4262
  • David Aphkhazava PhD, Doctor of Biological Sciences, Professor of Biochemistry at The University of Georgia, Tbilisi, Georgia. Orcid: https://orcid.org/0000-0001-6216-6477
  • Igor Seniuk PhD, Doctor of Pharmaceutical Sciences, Dean of faculty of Pharmacy at National University of Pharmacy of Ukraine, Associate Professor of Biological Chemistry Department at National University of Pharmacy, Kharkiv, Ukraine. https://orcid.org/0000-0003-3819-7333
  • Lela Grigolia MD, PhD, Doctor of Medical Sciences, Professor of The Caucasus International University; Tbilisi, Georgia;
  • Kakhaber Robakidze MD, PhD, Doctor of Medical Sciences, Academician, Professor of The Caucasus International University; National Health Center named after Academician O. Gudushauri; Tbilisi, Georgia;
  • Shafiga Topchiyeva PhD, Doctor of Biological Sciences, Academician, Professor of Institute of Zoology, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan; https://orcid.org/0000-0002-6369-1414
  • Giorgi Pkhakadze MD, MPH, PhD, Doctor of Medical Sciences, Professor, Head of the School of Public Health at David Tvildiani Medical University, Chair of Public Health Institute of Georgia (PHIG), Tbilisi, Georgia; Member of the United Nations Secretary General’s Independent Accountability Panel, Geneva, Switzerland; President, Accreditation San Frontières, Paris, France, Lviv Ukraine. https://orcid.org/0000-0001-7609-4515
  • Olga Shapoval MD, PhD, Doctor of Pharmaceutical Sciences, Associate Professor of Department of Pharmacology and Medical Prescription at Kharkiv State Medical University, Kharkiv, Ukraine; https://orcid.org/0000-0002-1971-2863
  • Mohini Yadav International School of Medicine at Alte University; Tbilisi, Georgia;
  • Udgam Yaduvanshi International School of Medicine at Alte University; Tbilisi, Georgia;
  • Ukesh Pauldurai Pandian Caucasus Medicine School at Caucasus University; Tbilisi, Georgia;
  • Shamik Jethwa Faculty of Medicine at Georgian National University SEU, Tbilisi, Georgia;
  • Tauseef Jameel Mohammed International School of Medicine at Alte University; Tbilisi, Georgia;
  • Tanishq Sunil Thakur Faculty of Medicine at Georgian National University SEU, Tbilisi, Georgia;
  • Rohit Faculty of Medicine at Grigol Robakidze University, Tbilisi, Georgia;

Keywords:

Antipsychotic agents, Precision psychiatry, Pharmacogenomics, Therapeutic drug monitoring, Pharmacovigilance

Abstract

Antipsychotic agents remain the cornerstone of pharmacological management for schizophrenia spectrum disorders and are increasingly utilized in bipolar disorder, major depressive disorder, autism spectrum disorder-associated irritability, Tourette syndrome, delirium, dementia-related behavioral disturbances, and several off-label neuropsychiatric conditions. Over the past seven decades, substantial advances in psychopharmacology, molecular neuroscience, pharmacogenomics, and precision medicine have transformed the understanding of antipsychotic drug mechanisms, therapeutic applications, safety profiles, and individualized treatment strategies. Despite remarkable progress, antipsychotic therapy continues to present considerable clinical challenges, including treatment resistance, variable therapeutic response, metabolic complications, extrapyramidal symptoms, cardiovascular toxicity, neuroendocrine disturbances, cognitive impairment, and medication non-adherence. Consequently, optimizing antipsychotic therapy requires an integrated evidence-based approach that combines neurobiological understanding, pharmacokinetic monitoring, pharmacogenomic-guided prescribing, pharmacovigilance, and patient-centered clinical decision-making. This comprehensive review critically evaluates the current scientific evidence regarding conventional (first-generation) and atypical (second- and third-generation) antipsychotic medications, emphasizing their molecular pharmacology, receptor-binding characteristics, intracellular signaling pathways, neurochemical modulation, and mechanisms underlying therapeutic efficacy and adverse reactions. Particular attention is devoted to dopamine, serotonin, glutamate, gamma-aminobutyric acid (GABA), acetylcholine, histamine, adrenergic, and neuroinflammatory pathways that collectively contribute to psychosis pathophysiology and antipsychotic pharmacodynamics. The review further examines the expanding role of partial dopamine agonists, multimodal receptor modulators, long-acting injectable formulations, and novel investigational compounds designed to improve efficacy while minimizing toxicity. Clinical applications across schizophrenia, schizoaffective disorder, bipolar disorder, psychotic depression, treatment-resistant psychosis, pediatric psychiatry, geriatric psychiatry, and consultation-liaison psychiatry are comprehensively discussed. Comparative analyses of efficacy, relapse prevention, functional recovery, cognitive outcomes, quality of life, and long-term disease management are integrated with recommendations from contemporary international clinical practice guidelines. The review also explores individualized therapeutic selection according to patient-specific characteristics, psychiatric comorbidities, medical illnesses, age-related considerations, pregnancy, hepatic and renal dysfunction, and polypharmacy. A substantial focus is placed on adverse drug reactions and toxicity management, including extrapyramidal syndromes, tardive dyskinesia, neuroleptic malignant syndrome, metabolic syndrome, obesity, diabetes mellitus, dyslipidemia, hyperprolactinemia, QT interval prolongation, myocarditis, agranulocytosis, seizures, hepatic dysfunction, and anticholinergic toxicity. Current evidence regarding early recognition, prevention strategies, emergency management, supportive care, therapeutic drug monitoring, laboratory surveillance, and multidisciplinary interventions is critically synthesized. Special consideration is given to clozapine monitoring protocols, individualized dose optimization, drug-drug interactions mediated through cytochrome P450 enzymes, and strategies for minimizing preventable medication-related harm. The review additionally highlights emerging advances in pharmacogenomics, biomarker-guided therapy, artificial intelligence-assisted clinical decision support, digital psychiatry, real-world pharmacovigilance systems, population pharmacokinetic modeling, machine learning prediction of treatment response, and precision psychiatry. Genetic polymorphisms involving CYP2D6, CYP1A2, CYP3A4, CYP2C19, dopamine receptor genes, serotonin receptor genes, and transporter proteins are examined as potential determinants of efficacy, adverse events, and individualized dosing strategies. Furthermore, recent developments in therapeutic drug monitoring, pharmacometric modeling, personalized medicine, and translational neuroscience are evaluated for their potential to optimize treatment outcomes and reduce healthcare burden. The contemporary antipsychotic pharmacotherapy is evolving toward highly individualized, evidence-based, and precision-oriented clinical practice. Integration of neuropharmacology, pharmacogenomics, pharmacovigilance, therapeutic drug monitoring, and innovative therapeutic technologies provides unprecedented opportunities to enhance efficacy, improve long-term safety, reduce treatment-related morbidity, and promote functional recovery among individuals with severe mental illness. Continued multidisciplinary research, international collaboration, biomarker validation, and implementation of personalized treatment algorithms will be essential for advancing the next generation of antipsychotic therapeutics and improving global psychiatric care.

Published

2026-08-03

How to Cite

Nodar Sulashvili, Maka Buleishvili, Mariam Darbaidze, Margarita Beglaryan, Nana Gorgaslidze, Ada (Adel) Tadevosyan, Magda Davitashvili, Irina Imerlishvili, Marina Giorgobiani, Vira Kravchenko, Marika Sulashvili, David Aphkhazava, Igor Seniuk, Lela Grigolia, Kakhaber Robakidze, Shafiga Topchiyeva, Giorgi Pkhakadze, Olga Shapoval, Mohini Yadav, Udgam Yaduvanshi, Ukesh Pauldurai Pandian, Shamik Jethwa, Tauseef Jameel Mohammed, Tanishq Sunil Thakur, & Rohit. (2026). COMPREHENSIVE REVIEW OF ANTIPSYCHOTIC AGENTS: MECHANISMS OF ACTION, CLINICAL UTILITY, ADVERSE EFFECTS, TOXICITY MANAGEMENT, PHARMACOGENOMICS, PRECISION MEDICINE, PHARMACOVIGILANCE, THERAPEUTIC DRUG MONITORING, EVIDENCE-BASED CLINICAL PRACTICE AND EMERGING. Scientific Results, (14). Retrieved from https://ojs.publisher.agency/index.php/SR/article/view/9111

Issue

No. 14 (2026): Scientific Results

Section

Medical Sciences

License

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