Transdiagnostic Psychopharmacology: Bridging Mechanisms Across Mental Disorders

A special issue of Future Pharmacology (ISSN 2673-9879).

Deadline for manuscript submissions: 31 August 2026 | Viewed by 16514

Special Issue Editor


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Guest Editor
Department of Psychiatry and Legal Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
Interests: psychiatry; addiction; substance abuse; psychiatry comorbidities; psychotherapy and psychopharmacology

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to this Special Issue on Transdiagnostic Psychopharmacology: Bridging Mechanisms Across Mental Disorders, an area of growing relevance at the intersection of clinical neuroscience, psychopharmacology, and psychiatric nosology. Traditional diagnostic frameworks such as the DSM and ICD have guided the classification of mental disorders and the indication of psychotropic medications. However, accumulating evidence from genetics, neurobiology, and translational research suggests that many psychiatric symptoms and underlying mechanisms transcend these categorical boundaries.

Medications originally developed for one disorder frequently demonstrate efficacy across multiple conditions—such as antipsychotics, which can be used to treat mood disorders, and antidepressants, which are often also used to treat anxiety disorders—highlighting the limitations of diagnosis-specific prescribing. This Special Issue aims to consolidate research that supports a symptom- and mechanism-based approach to psychopharmacological treatment. It reflects a paradigm shift toward personalized psychiatry, grounded in shared neurobiological substrates, and aligned with dimensional models such as the Research Domain Criteria (RDoC).

We aim to gather cutting-edge research and theoretical contributions on transdiagnostic psychopharmacology, emphasizing pharmacological strategies that target core domains of psychopathology—such as affect regulation, cognitive control, reward processing, and stress reactivity—across traditional diagnostic categories. The issue aligns with the journal’s scope by integrating neurobiological insights with clinical applications, advancing the development of mechanism-based, individualized treatments.

By focusing on shared dimensions of mental disorders and exploring pharmacological interventions that span diagnostic classifications, this Special Issue supports the journal’s mission to disseminate innovative and interdisciplinary research in psychiatric science and neuropsychopharmacology. The goal is to encourage submissions that contribute to refining clinical practice and developing new frameworks for drug development, repurposing, and biomarker-driven interventions.

Original research articles and reviews are welcome. Potential topics may include (but are not limited to) the following:

  • Neurobiological and genetic mechanisms underlying shared psychopathology across diagnostic boundaries.
  • Pharmacological modulation of dimensional constructs (e.g., anhedonia, impulsivity, affective instability).
  • Mechanism-based prescribing strategies and clinical trial designs.
  • Transdiagnostic applications of existing psychotropics (e.g., antidepressants, antipsychotics, mood stabilizers).
  • Drug repurposing based on transcriptomic or neuroimaging findings.
  • Translational models aligning with RDoC or other dimensional diagnostic systems.
  • Clinical studies addressing polypharmacy in comorbid or mixed presentations.
  • Conceptual or critical reviews that address the limitations of traditional diagnostic systems in psychopharmacology.
  • Integrative approaches combining pharmacology with digital phenotyping, biomarkers, or AI-based prediction models.

We look forward to receiving your contributions.

Prof. Dr. Felix Kessler
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Future Pharmacology is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • transdiagnostic
  • psychopharmacology
  • psychiatry
  • treatment
  • neurobiological
  • pharmacotherapy
  • pharmacogenomics

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Published Papers (3 papers)

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Review

36 pages, 2556 KB  
Review
Transdiagnostic Pharmacology of Addictions: Current Evidence and Future Perspectives
by Sofia Perez Lopes da Silveira, Bruna Barros Aguiar, Andressa Goldman Ruwel, Patrícia Furtado Martins, Douglas G. Lewis, Helena Moura, Maurício Timm Peglow, Lisia Von Diemen, Alexei Gil and Félix Henrique Paim Kessler
Future Pharmacol. 2026, 6(2), 19; https://doi.org/10.3390/futurepharmacol6020019 - 30 Mar 2026
Viewed by 419
Abstract
Background: Addictive disorders are highly heterogeneous and frequently comorbid, limiting the clinical utility of categorical diagnoses. Transdiagnostic pharmacology seeks to address these limitations by targeting symptom dimensions and shared neurobiological processes across addictions. Methods: We conducted a theory-driven narrative review of studies indexed [...] Read more.
Background: Addictive disorders are highly heterogeneous and frequently comorbid, limiting the clinical utility of categorical diagnoses. Transdiagnostic pharmacology seeks to address these limitations by targeting symptom dimensions and shared neurobiological processes across addictions. Methods: We conducted a theory-driven narrative review of studies indexed in MEDLINE, PubMed, LILACS, and Web of Science (October–November 2025), integrating clinical, mechanistic, and dimensional evidence. Findings were organized using the Dysregulation Phenomena of the Three Main Modes of the Predostatic Mind and the Advanced Cognitive Emotional Regulation Therapy (DREXI3/ACERT) framework, which conceptualizes addiction as dysregulation across three interacting systems—Alarm, Seeking, and Balance—and six transdiagnostic symptom dimensions, with a proposed expansion into twenty clinically observable domains (TDPM-20). Results: Pharmacological interventions consistently target neurobiological systems related to stress, reward, impulsivity, and compulsivity. Across studies, the most clinically relevant outcomes remain abstinence, reduction in substance use, and treatment retention. While these outcomes are essential, expanding outcome frameworks to incorporate dimensional and mechanistically informed measures may enhance the identification of clinically meaningful subgroups. Across studies, multiple pharmacological classes show transdiagnostic potential, but their clinical application remains variably aligned with dimensional clinical profiles. Conclusions: A dimensionally oriented approach grounded in neurobiological principles may improve alignment between clinical processes and therapeutic strategies. The DREXI3/ACERT model provides a structured framework for individualized treatment planning and research integration. This approach should be understood as complementary to, rather than a replacement for, established evidence-based treatments for specific substance use disorders, particularly in contexts where therapeutic options remain limited or insufficient. Advancing transdiagnostic pharmacology will require broader dimensional stratification, expanded outcome frameworks capable of capturing patient heterogeneity, and integrative trial designs to strengthen precision psychiatry in addictive disorders. Full article
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25 pages, 2047 KB  
Review
Pharmacogenetics in Attention-Deficit/Hyperactivity Disorder (ADHD)
by Ana Cabetas, Antonio del Bosque, María Sainz-Gil and Zoraida Verde
Future Pharmacol. 2026, 6(1), 5; https://doi.org/10.3390/futurepharmacol6010005 - 7 Jan 2026
Cited by 1 | Viewed by 1540
Abstract
Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental condition, and pharmacogenetic studies aim to clarify interindividual variability in treatment responses and adverse effects. Despite increasing research, the field remains fragmented. This review provides a bibliometric analysis of ADHD pharmacogenetics (2005–2025), identifying [...] Read more.
Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental condition, and pharmacogenetic studies aim to clarify interindividual variability in treatment responses and adverse effects. Despite increasing research, the field remains fragmented. This review provides a bibliometric analysis of ADHD pharmacogenetics (2005–2025), identifying its intellectual foundations, thematic structure, and global distribution. Methods: A bibliometric search was conducted in Scopus and Web of Science, retrieving 711 documents published between 2005 and July 2025. Data were analyzed with the Bibliometrix R package and Biblioshiny interface, applying bibliometric mapping, Bradford’s Law, co-word analysis, and thematic mapping. Only peer-reviewed journal articles, books, and book chapters were included to ensure scientific rigor. Results: The dataset shows a modest annual growth rate but strong impact, with an average of 29.6 citations per article. Highly cited works converge into four domains: (i) clinical guidelines and pharmacological treatments; (ii) cognitive heterogeneity and subtypes; (iii) neurodevelopmental and genetic mechanisms; (iv) environmental and health-related influences. Geographically, the United States leads with 24.8% of publications, followed by Brazil, China, and European countries. Keyword analysis reveals two main clusters: a clinical–therapeutic pole (methylphenidate, atomoxetine, child) and a genetic–molecular pole (dopamine transporter, SNPs, genotype). Conclusions: ADHD pharmacogenetics shows consolidation with strong clinical and genetic cores but limited integration of comorbidity, adult populations, and non-stimulant treatments. Future research should prioritize multi-center cohorts, multi-omic designs, and stronger international collaboration to advance precision medicine in ADHD. Full article
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33 pages, 640 KB  
Review
Future Pharmacotherapy for Bipolar Disorders: Emerging Trends and Personalized Approaches
by Giuseppe Marano, Francesco Maria Lisci, Gianluca Boggio, Ester Maria Marzo, Francesca Abate, Greta Sfratta, Gianandrea Traversi, Osvaldo Mazza, Roberto Pola, Gabriele Sani, Eleonora Gaetani and Marianna Mazza
Future Pharmacol. 2025, 5(3), 42; https://doi.org/10.3390/futurepharmacol5030042 - 4 Aug 2025
Cited by 3 | Viewed by 13847
Abstract
Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse [...] Read more.
Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article
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