Primidone: A New Hope for Psoriasis Treatment

In a groundbreaking development poised to transform the landscape of dermatological therapeutics, researchers have identified primidone, a long-standing anticonvulsant drug, as a promising candidate for the treatment of psoriasis. This revelation emerges from an extensive study led by Riebeling, Kolbrink, Philippsen, and colleagues, recently published in Cell Death Discovery. Their findings suggest that primidone’s mechanism of action may significantly alleviate the inflammatory and hyperproliferative processes underpinning psoriasis, offering new hope for millions affected by this chronic and often debilitating skin disease.

Psoriasis is characterized by rapid turnover of skin cells and persistent inflammation, conditions traditionally managed through a combination of topical therapies, systemic agents, and biologics. However, these treatments frequently carry the burden of side effects, immunosuppression, or limited efficacy in some patient populations. The prospect of repurposing primidone—a drug with a well-established safety profile originally designed to prevent seizures—introduces a novel therapeutic avenue that may circumvent many existing limitations.

At the molecular level, primidone appears to modulate key inflammatory pathways that become dysregulated during psoriatic flares. The researchers demonstrated that primidone can interfere with the signaling cascades of proinflammatory cytokines, which are central drivers in the recruitment and activation of immune cells in psoriatic lesions. By dampening these signals, primidone reduces the aberrant immune response that fuels both epidermal hyperproliferation and chronic inflammation.

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Cutting-edge in vitro experiments revealed that primidone not only attenuates the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17)—two pivotal cytokines implicated in psoriasis pathogenesis—but also inhibits downstream transcription factors that orchestrate keratinocyte proliferation. These results underscore primidone’s dual capability to target both immunological and epidermal components of the disease, an attribute that could translate into superior clinical outcomes.

Furthermore, this investigation highlights primidone’s intriguing role in modulating oxidative stress parameters within psoriatic keratinocytes. Oxidative stress, a critical contributor to cellular damage and inflammation in psoriasis, was markedly reduced upon treatment with primidone. The drug’s antioxidative properties appear to further enhance its therapeutic potential, by preserving cellular integrity and preventing the cascade of events that prolong psoriatic lesions.

Crucially, in vivo studies employing psoriasiform mouse models validated the efficacy observed in cellular assays. Primidone administration led to significant improvements in histological markers of psoriasis, including normalized epidermal thickness and decreased immune cell infiltration. These preclinical findings pave the way for upcoming clinical trials designed to assess the drug’s safety, dosage optimization, and therapeutic efficacy in human subjects.

One particularly compelling aspect of primidone’s repurposing lies in its pharmacokinetics and safety profile. Having been in clinical use for decades as an anticonvulsant, primidone’s absorption, metabolism, and tolerability are well documented, potentially expediting regulatory approval for dermatological applications. This contrasts favorably with newer biologic agents, which often require protracted development and carry higher treatment costs.

The research team also explored primidone’s effects on apoptotic pathways in keratinocytes. Dysregulated apoptosis contributes to excessive accumulation of skin cells in psoriatic plaques, and primidone was observed to restore apoptotic balance, promoting programmed cell death where it was previously impaired. This normalization of cellular turnover dynamics is critical for resolving psoriatic lesions and preventing their recurrence.

From a mechanistic standpoint, primidone’s action is multifaceted. Beyond its anticonvulsant properties linked to modulation of neuronal ion channels, it exerts anti-inflammatory effects by downregulating nuclear factor kappa B (NF-κB) signaling—a key transcription factor governing inflammatory gene expression. By inhibiting NF-κB activation, primidone effectively blunts one of the central pathways sustaining psoriatic inflammation.

The implications of this discovery extend beyond psoriasis itself. Since many chronic inflammatory diseases share overlapping molecular mechanisms, primidone might hold therapeutic promise for conditions such as atopic dermatitis, rheumatoid arthritis, and perhaps even certain autoimmune disorders. This raises exciting prospects for repositioning an established drug into a broader array of inflammatory indications.

Clinicians and patients alike stand to benefit from this advancement, particularly if primidone proves effective as a monotherapy or as part of combination regimens. The drug’s oral administration route offers an accessible alternative to biologic injections, enhancing patient compliance and quality of life. Moreover, it may provide a cost-effective solution, expanding access to effective psoriasis treatment worldwide.

The research team emphasizes the necessity of comprehensive clinical trials to establish dosing parameters, long-term safety, and comparative efficacy against current standard-of-care treatments. They advocate for multidisciplinary collaboration to refine the understanding of primidone’s molecular targets and optimize its integration into psoriasis management protocols.

This study underscores the growing trend of drug repurposing in biomedical research, wherein existing pharmaceuticals are investigated for new therapeutic applications. Such strategies accelerate drug development timelines and reduce costs, ultimately delivering novel treatments to patients more quickly. Primidone’s journey from anticonvulsant to potential psoriasis therapy exemplifies this innovative approach.

In conclusion, the identification of primidone as a clinically promising candidate for psoriasis treatment represents a significant stride forward. By targeting multiple pathogenic pathways—including inflammation, oxidative stress, and aberrant cell proliferation—primidone has the potential to fill existing gaps in psoriasis management and improve patient outcomes. As the field eagerly anticipates forthcoming clinical data, this discovery may herald a new era in dermatology where old drugs find new purpose through cutting-edge science.

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Article References:
Riebeling, T., Kolbrink, B., Philippsen, R. et al. Primidone: a clinically promising candidate for the treatment of psoriasis. Cell Death Discov. 11, 275 (2025). https://doi.org/10.1038/s41420-025-02552-3

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41420-025-02552-3

Keywords:

Tags: chronic skin disease treatmentsdermatological therapeutics innovationsimmune response in skin disordersinflammatory pathways in psoriasisnovel psoriasis therapiesprimidone clinical studiesPrimidone for psoriasis treatmentprimidone mechanism of actionpsoriasis inflammation managementpsoriasis research breakthroughspsoriasis treatment side effectsrepurposing anticonvulsants for dermatology