Discussion
To our knowledge, this is the first national study of BZD prescribing in a cohort of people with PNES, and our findings have important implications for informing future research efforts to improve care and treatment for PNES. Overall, in a nationwide sample of privately-insured adults, we observed that approximately one-third of those with a new PNES diagnosis had been prescribed a BZD in the year prior to their diagnosis. 18.1% received BZDs in the month following a PNES diagnosis, with a median days’ supply of 30 days, and clonazepam, alprazolam and lorazepam representing the most common BZDs prescribed after PNES diagnosis. While our data cannot precisely show why people were being prescribed BZDs, we found that nearly 90% received scripts exceeding 7 days, suggesting that few individuals were receiving BZDs purely for symptomatic treatment of acute PNES. While the potential for risks associated with continued BZD prescribing is potentially heightened by co-occurring opioid use (nearly 40% of the sample at baseline), the percentage receiving both opioids and BZDs was lower (17.3% in prior year; 3.5% in 30 days prior to PNES).
This study does not directly address whether correctly diagnosing PNES will reduce BZD use in the management of seizures; however, our data suggests that the deprescribing of BZDs after PNES diagnosis—among people already receiving BZDs is not the most common treatment course in current practice. Our data shows that BZD fills following a PNES diagnosis were heavily dependent on prior BZD use, a pattern that was even seen among people without common indications for BZDs (ie, diagnoses of epilepsy, anxiety and insomnia). Specifically, the majority of people who received BZDs in the month prior to PNES diagnosis remained on BZDs in the 1-month follow-up period. This practice may be at odds with standard clinical practice, which encourages the deprescribing of anticonvulsant medication in PNES. LaFrance and colleagues noted that, according to international surveys of clinicians in the USA, South America and Europe, ‘current standard medical care’ (treatment as usual) for PNES involves the tapering of antiseizure medications and the deferring of psychotropic medication initiation to a mental health specialist.23 Many neurologists and epileptologists may feel uncomfortable tapering BZDs, deferring to mental health professionals, a process that can be hindered by inadequate availability of collaborative care. It is possible that neurologists may not be the physicians prescribing the BZDs and may also feel uncomfortable initiating a taper. Additionally, community physicians may refer patients with suspected PNES to tertiary epilepsy centres for video electroencephalogram, another potential reason for deprescribing of BZDs to be delayed.
The high prevalence of co-occurring psychiatric disorders in the PNES cohort may mean these individuals experience anxiolytic and/or antidepressant benefits from BZDs. Poor quality sleep and anxiety are common problems in people with PNES.24 25 Historically, BZDs were commonly prescribed as a front-line long-term therapy for anxiety disorders and insomnia in the general population; while recent literature has raised concerns about the long-term risks of BZD treatment outweighing short-term mental health benefits,26 there is limited data to guide clinical practice on the use of BZDs to treat anxiety and sleep problems specifically in people with PNES. While a study of BZD prescribing in the immediate post-PNES period showed that BZD treatment did not reliably terminate seizure activity among people misdiagnosed with status epilepticus,11 there remains a dearth of studies investigating the use of BZDs for prophylactic treatment or acute management of PNES. Overall the risk/benefit ratio for both short-term and long-term use of BZDs in PNES remains poorly understood.
While most of our nationwide sample was not prescribed a BZD in the month after PNES diagnosis, single-site studies have suggested this practice may be common at certain institutions,10 suggesting there is heterogeneity in BZD prescribing patterns across different institutions and healthcare systems. Especially since BZD tapering among people prescribed for stable long-term treatment can be associated with anticipated harms,27 these results should not be taken as a call to rapidly deprescribe BZDs in people with PNES. While examining subsequent patient outcomes was outside the scope of this study, further work is needed to determine whether, and how, BZD treatment should be prescribed in this population with many psychiatric comorbidities and complex treatment needs, which could help inform treatment decisions.
There are several key limitations to consider. First, we are only able to capture PNES events that culminate in healthcare encounters; we cannot rule out the possibility of PNES being misdiagnosed and/or missing in these administrative data.28 Second, because the sample included adults with stable enrolment in private insurance, findings may not be generalisable to children and those with less stable insurance coverage.29 30 Third, our study only evaluates potential BZD prescribing during the 30 days following a new PNES diagnosis and may not capture more delayed prescribing changes that are, nevertheless, related to the incident PNES. Finally, we are unable to determine the validity of epilepsy diagnoses, and it is possible that some epilepsy diagnoses were re-evaluated in adults later presenting with PNES. Epilepsy diagnoses may be inaccurate in many cases, and it may be difficult to correct a misdiagnosis; studies found that 41% of people with PNES without ES were still prescribed antiseizure medications 4 years after diagnosis.31 In a systematic review of ICD-10 codes for ES, the positive predictive value of ES diagnoses was estimated to range from 62 to 90+%, with a specificity of 69.6%32; validation studies have not been done for ES codes using national claims data and thus we are unable to definitively deduce if the epilepsy diagnosis reflects a PNES with baseline epilepsy or potential misdiagnosis. Future research with enhanced clinical data is needed to untangle the diagnosing and misdiagnosing of epilepsy in patients newly diagnosed with PNES.
Despite these limitations, this study is strengthened by its use of multistate population-level data to evaluate potential unmet treatment needs among patients with PNES, a highly stigmatised and understudied condition. As evidence-based psychological and multimodal interventions are lacking,33 future research is needed to understand prescribing decisions and patient outcomes. Estimates on the use of BZD treatment in adults with PNES may help physicians and policymakers devise targeted intervention to address treatment gaps in people with PNES.