A newly unveiled case study published in BMC Psychiatry reveals an alarming sensitivity of dementia with Lewy bodies (DLB) patients to gabapentinoids, even at remarkably low doses. This groundbreaking report details how low-dose administration of mirogabalin and pregabalin—both widely prescribed gabapentinoid medications—induced acute psychotic episodes in an elderly patient. The revelations challenge existing assumptions about the safety thresholds of these drugs in vulnerable neurodegenerative populations, suggesting that hypersensitivity in DLB may extend beyond antipsychotics to other pharmacological agents affecting neural pathways.
Dementia with Lewy bodies is characterized by cognitive decline, fluctuating attention, visual hallucinations, and parkinsonian motor symptoms. One of its hallmark features is the pronounced sensitivity to antipsychotic drugs, often causing severe adverse reactions including worsened motor symptoms and increased mortality risk. Historically, clinical caution has predominantly revolved around traditional antipsychotics. However, this recent case strongly implicates gabapentinoids, a class of anticonvulsant and neuropathic pain medications, as potent triggers of psychosis in DLB, even at doses significantly lower than those previously associated with such effects.
The subject of the case was a woman in her late seventies diagnosed with mild dementia and subtle parkinsonism. For neuropathic pain management, she was prescribed mirogabalin at a modest dose of 15 mg daily. Shortly after treatment initiation, she began to experience vivid hallucinations accompanied by delusional misidentification—a well-documented psychotic manifestation linked with dementia with Lewy bodies. Remarkably, these symptoms emerged rapidly, underscoring an acute neuropsychiatric response to the drug rather than a gradual side effect.
Following discontinuation of mirogabalin, the patient’s psychotic symptoms substantially abated but did not fully resolve, suggesting residual neurochemical imbalances. Investigations including dopamine-transporter scintigraphy revealed bilateral striatal uptake reduction, consistent with dopaminergic deficit—a pathological hallmark of DLB. Subsequent administration of donepezil, an acetylcholinesterase inhibitor, facilitated further mitigation of her psychosis, highlighting the interplay between cholinergic pathways and psychotic symptomatology in this disorder.
The clinical course took another unexpected turn when pregabalin, another gabapentinoid, was introduced at an equally low dose of 25 mg daily to manage a resurgence of neuropathic pain. Almost mirroring the prior episode, the patient’s psychosis rapidly re-emerged, reinforcing the suspected causative relationship between gabapentinoid exposure and neuropsychiatric exacerbations in DLB. Discontinuation once again led to symptom resolution, cementing the causal link.
Traditionally, pregabalin-associated psychosis has been documented predominantly at substantially higher doses, ranging from 300 to 450 mg daily, and predominantly in populations without underlying neurodegenerative disease. This report’s novel finding that psychotic episodes can be instigated at minuscule dosages in DLB patients underscores a unique hypersensitivity profile for gabapentinoids within this group. The pathophysiological basis may involve an exaggerated modulation of glutamatergic and GABAergic neurotransmission, already disrupted in Lewy body dementia.
Neuropharmacologically, gabapentinoids act primarily by binding to the α2δ subunit of voltage-gated calcium channels, reducing excitatory neurotransmitter release. While neuroprotective in some contexts, in DLB, where neuronal circuits are already compromised, this modulation may inadvertently destabilize the delicate neurotransmitter balance. This disruption may precipitate hallucinations, delusions, and other psychotic phenomena that mirror or exacerbate the natural symptom profile of the disease.
The clinical implications of these observations cannot be overstated. Gabapentinoids are frequently employed in neuropathic pain management due to their relatively favorable side effect profiles and minimal abuse potential. However, this case signals the urgent need for healthcare providers to exercise heightened vigilance when prescribing these medications to patients with Lewy body dementia, regardless of dose. Regular monitoring for emergence or worsening of psychiatric symptoms should be rigorous and perhaps necessitate alternative pain management strategies.
Furthermore, this case invites a broader reconsideration of pharmacotherapy paradigms in neurodegeneration-associated psychosis. The neuronal vulnerabilities in DLB may extend beyond dopaminergic hypersensitivity to include a profound susceptibility to agents influencing multiple neurotransmitter systems. Consequently, the development of targeted guidelines and protocols for gabapentinoid use in dementia populations is warranted to prevent inadvertent harm.
From a research standpoint, this report opens avenues for mechanistic studies into the molecular underpinnings of gabapentinoid-induced psychosis in neurodegenerative states. Delineating the specific receptor-level interactions, calcium channel subtypes involved, and downstream signaling cascades may reveal new therapeutic targets that either mitigate adverse effects or exploit these pathways beneficially. Additionally, longitudinal cohort studies to ascertain prevalence and risk factors for gabapentinoid sensitivity in DLB could refine clinical risk stratification.
Moreover, the pharmacodynamic interactions between gabapentinoids and cholinesterase inhibitors like donepezil, which appeared to alleviate psychosis in this patient, merit rigorous examination. Enhancing cholinergic transmission may represent a compensatory mechanism counteracting gabapentinoid-induced disruptions. These findings hint at possible combination therapies or dosage adjustments tailored specifically for vulnerable dementia subsets.
In conclusion, this remarkable case throws a spotlight on an underrecognized yet critical dimension of dementia with Lewy bodies management. Low-dose gabapentinoids, long considered safe in general populations, may invoke acute and severe psychosis in those with Lewy body pathology. The neuropsychiatric safety profiles of these common medications require urgent reevaluation in the context of neurodegeneration. Clinicians and researchers alike must grapple with these findings to optimize patient outcomes and avoid precipitating profound neuropsychiatric crises under the guise of symptom palliation.
As the global burden of dementia rises inevitably, such nuanced insights into drug-disease interactions will become increasingly pivotal. This case serves both as a cautionary tale and a catalyst for deeper inquiry into pharmacovigilance in complex neurological disorders. The evolving landscape of neurodegenerative treatment demands that therapeutic innovations be balanced with meticulous attention to the unique susceptibilities of affected individuals.
Subject of Research: Psychosis induced by low-dose gabapentinoids in a patient with dementia with Lewy bodies.
Article Title: A case of dementia with Lewy bodies with psychosis induced by low-dose gabapentinoids.
Article References:
Kanemoto, H., Akiyama, T., Taomoto, D. et al. A case of dementia with Lewy bodies with psychosis induced by low-dose gabapentinoids. BMC Psychiatry 25, 491 (2025). https://doi.org/10.1186/s12888-025-06937-7
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