Lurasidone HCL for PNES: Not Recommended
Lurasidone HCL is not an appropriate treatment for Psychogenic Non-Epileptic Seizures (PNES), as PNES is a dissociative/conversion disorder requiring psychotherapy as the primary intervention, not antipsychotic medication. Lurasidone is FDA-approved only for schizophrenia and bipolar disorder, conditions fundamentally different from PNES 1.
Understanding PNES as a Distinct Disorder
PNES are paroxysmal events that resemble epileptic seizures but are caused by psychological processes rather than abnormal electrical brain activity 2. Key characteristics include:
- PNES is classified as a dissociative disorder (ICD-10) or somatoform disorder (DSM-IV), not a psychotic disorder 2
- Video-EEG monitoring is the gold standard for diagnosis, distinguishing PNES from true epileptic seizures 2
- PNES can manifest as an immunization stress-related response (ISRR), representing a stress-induced phenomenon rather than a neurological condition 3
Why Antipsychotics Like Lurasidone Are Inappropriate
Lurasidone targets dopamine and serotonin receptors to treat psychotic symptoms and mood episodes in schizophrenia and bipolar disorder 1. PNES patients do not have psychosis or primary mood disorder as their core pathology—they have a dissociative/conversion mechanism triggered by psychological distress 2, 4.
The Evidence Gap
- No clinical trials exist evaluating lurasidone or any antipsychotic specifically for PNES 2, 5, 6
- Antipsychotics carry significant risks including metabolic syndrome, extrapyramidal symptoms, and sedation that would not be justified without evidence of benefit 1
- Misdiagnosing PNES as epilepsy leads to inappropriate anticonvulsant treatment—similarly, treating PNES as a psychotic disorder with antipsychotics represents a fundamental misunderstanding of the condition 2
Evidence-Based Treatment for PNES
Psychotherapy, particularly cognitive behavioral therapy (CBT), represents the only intervention with demonstrated efficacy for PNES 6. The treatment algorithm should follow this sequence:
Step 1: Diagnostic Communication
- Present the PNES diagnosis clearly to the patient, explaining that seizures are real but not caused by epilepsy 2, 6
- Emphasize that PNES is a treatable condition requiring psychological intervention rather than neurological medication 5
Step 2: Primary Psychotherapeutic Intervention
- Cognitive behavioral therapy has the strongest evidence, including one pilot randomized controlled trial showing superiority over standard medical care 6
- Augmented psychodynamic interpersonal psychotherapy showed efficacy in uncontrolled trials 6
- Group psychodynamic psychotherapy and group psychoeducation demonstrated benefit in open-label studies 6
Step 3: Address Psychiatric Comorbidities
PNES patients have high rates of depression, anxiety, PTSD, and dissociative disorders that require treatment 2, 4. When comorbid psychiatric conditions exist:
- For comorbid depression/anxiety: Consider sertraline, which showed pre- versus post-treatment decrease in seizure frequency in a pilot randomized controlled trial, though it did not differ significantly from placebo 6
- For comorbid anxiety: SSRIs or venlafaxine (which showed efficacy in uncontrolled trials for PNES) may be appropriate 6
- Treat the psychiatric comorbidity, not the PNES itself, as the seizures are a manifestation of underlying psychological distress 2
Step 4: Multidisciplinary Follow-Up
- Neurologist involvement remains essential post-diagnosis to monitor for any true epileptic seizures and coordinate care 2
- Psychiatrist involvement is necessary to manage comorbid psychiatric conditions and coordinate psychotherapy 2
Critical Pitfalls to Avoid
Do not prescribe antipsychotics like lurasidone for PNES unless the patient has a separate, comorbid psychotic disorder (e.g., schizophrenia or bipolar disorder with psychotic features) that independently warrants antipsychotic treatment 1. The presence of PNES alone does not justify antipsychotic use.
Do not assume seizure freedom is the only outcome measure—nearly half of patients who become seizure-free remain functionally impaired, emphasizing the need to address quality of life, psychosocial functioning, and underlying psychiatric comorbidities 2, 5.
Do not discontinue neurological follow-up after diagnosis—ongoing monitoring is essential to detect any development of true epilepsy (which occurs at higher rates in PNES patients than the general population) and to support treatment adherence 2.
When Lurasidone Might Be Appropriate
Lurasidone would only be indicated if the patient has a separate, comorbid psychiatric condition for which it is FDA-approved 1:
- Schizophrenia with concurrent PNES: Lurasidone 40-160 mg/day once daily with food for psychotic symptoms 1
- Bipolar disorder (if approved for this indication in your jurisdiction) with concurrent PNES: Treat the bipolar disorder according to standard guidelines 7
In these scenarios, treat the psychotic or mood disorder with lurasidone while simultaneously addressing PNES with psychotherapy 5, 6.
Prognosis and Realistic Expectations
Even with appropriate treatment, many PNES patients continue to have seizures and disability 2, 5. However, quality of life can be improved with evidence-based psychotherapy and treatment of psychiatric comorbidities 5. A holistic, multidisciplinary approach focusing on functional recovery rather than seizure freedom alone produces the best outcomes 5, 6.