New Information on Functional Neurological Disorder and Drug Therapy
Author(s): Sandisiwe Kema1, Lourdes de Fatima Ibanez Valdes2, Sibi Joseph2, Humberto Foyaca Sibat2*
Abstract
Introduction: Functional Seizures (FS), also referred to as functional dissociative seizures, are among the most prevalent manifestations of Functional Neurological Disorder (FND) in both adult and paediatric populations. FND and FS are associated with substantial healthcare utilization, frequent hospital admissions, repeated diagnostic investigations, and significant economic burden. Historically regarded as diagnoses of exclusion, FND and FS are now recognised as “rule-in” conditions based on characteristic clinical signs and positive diagnostic features. Recent advances in neurobiology have highlighted the role of altered brain network functioning, predictive processing abnormalities, neurotransmitter dysregulation, and central sensitization in symptom generation. In this context, neurological agents such as pregabalin, which modulate neuronal excitability and neurotransmitter release, have attracted increasing interest as potential adjunctive therapies for managing comorbid symptoms frequently observed in FND, including chronic pain, sensory disturbances, anxiety, sleep dysfunction, and heightened autonomic arousal. The primary objective of this review is to summarize current evidence regarding FND while exploring the potential therapeutic relevance of pregabalin within a multidisciplinary management framework. Objectives: This study aimed to review the contemporary medical literature on Functional Neurological Disorder (FND), including its pathophysiology, clinical manifestations, diagnosis, prognosis, and treatment strategies, with particular emphasis on the potential role of pregabalin in the management of associated neurological and neuropsychiatric symptoms.
Methods: PubMed, MEDLINE, and Cochrane Review databases were searched using the Boolean terms: (“functional neurological disorder” OR “functional neurological symptom disorder”) AND (“pathophysiology” OR “diagnosis” OR “treatment” OR “prognosis”). Additional searches were performed using: (“functional neurological disorder”) AND (“functional movement disorder” OR “functional non-epileptic seizures” OR “functional cognitive disorder” OR “pregabalin” OR “neuropathic pain” OR “anxiety”). The search included publications from January 2020 to June 2026. Eligible studies comprised peer-reviewed articles, systematic reviews, narrative reviews, and original research publications. Non-English articles, duplicate records, and studies not primarily focused on FND were excluded. The systematic review followed the PRISMA 2020 reporting guidelines.
Results: A total of 219 records were identified through the database search. Following title and abstract screening, 115 studies were excluded. After duplicate removal, 72 full-text articles were assessed for eligibility. Twenty-three studies were excluded because full-text access was unavailable, and eight were excluded because complete English translations could not be obtained. Additional studies were excluded due to limited relevance to FND. Ultimately, 24 studies met the inclusion criteria. The reviewed literature demonstrated that FND is a multifactorial disorder involving abnormalities in self-agency, emotional processing, attention, predictive coding, and sensorimotor integration. Several studies also highlighted the frequent coexistence of chronic pain, fatigue, anxiety disorders, sleep disturbances, and sensory symptoms. Although pregabalin is not currently established as a disease-specific treatment for FND, available evidence suggests that it may provide symptomatic benefit in selected patients by reducing central sensitization, modulating excitatory neurotransmission, improving sleep quality, alleviating anxiety symptoms, and contributing to the management of chronic pain syndromes frequently associated with FND.
Conclusions: Early diagnosis, effective communication, and multidisciplinary management remain fundamental to improving outcomes in patients with FND. Growing evidence supports a neurobiological framework that integrates functional brain network alterations, neurotransmitter dysregulation, and biopsychosocial factors. While pregabalin should not be considered a primary treatment for FND itself, it may serve as a valuable adjunctive pharmacological option for selected patients presenting with pain-related symptoms, sensory disturbances, anxiety, and sleep dysfunction. Further prospective clinical studies are required to clarify its therapeutic role, long-term safety, and potential impact on functional recovery. To the best of our knowledge, this review represents one of the first attempts to integrate contemporary FND pathophysiology with a drug-focused perspective highlighting the potential relevance of pregabalin within a comprehensive treatment mode.