AAN Guideline: Management of Functional Seizures (Tolchin et al., 2025)
This topic summarizes the 2025 AAN practice guideline on the management of functional seizures, published in Neurology by Tolchin, Goldstein, Reuber, Stone, Perez, LaFrance and colleagues. The guideline is based on a systematic review of 12 Class II–III studies with 28 recommendation statements developed through a modified GRADE and Delphi process.
🔹 Bottom Line
- Guideline: AAN 2025 practice guideline — systematic review through Feb 2025; 12 Class II–III studies identified; modified GRADE + Delphi process
- Diagnosis: VEEG is the gold standard for "documented" functional seizures; when not feasible, diagnosis can be based on history, semiology, ambulatory EEG, interictal EEG, and smartphone video (Level B)
- Psychological interventions (especially seizure-specific CBT) possibly increase seizure freedom (pooled RR 1.87, 95% CI 1.36–2.56), decrease seizure frequency (SMD −0.81), and reduce anxiety (SMD −0.68)
- CBT sub-analysis: Functional seizure–specific CBT → RR 1.76 for seizure freedom (95% CI 1.10–2.80, I² = 0%)
- Do NOT prescribe benzodiazepines or ASMs for functional seizures alone — no efficacy, risk of adverse effects including intubation for prolonged episodes (Level B)
- Taper ASMs in patients with functional seizures without co-occurring epilepsy or another indication (Level B)
- Co-occurring epilepsy: Up to 12% of people with epilepsy and up to 20% of adults with functional seizures have both → VEEG to differentiate seizure types for targeted treatment (Level B)
- Communication: Provide a specific diagnostic label, rationale, and treatment plan; avoid stigmatizing behavior; involve family/caregivers in treatment (Level B)
- Psychiatric comorbidities: Mood disorders, anxiety, PTSD co-occur at high frequency → evaluate and treat concurrently (Level B)
Guideline Overview
Source & Scope
- Organization: AAN Guidelines Subcommittee (multidisciplinary panel)
- Published: Neurology 2026;106:e214466 (approved June 13, 2025; accepted October 31, 2025)
- Authors: Tolchin B, Goldstein LH, Reuber M, Stone J, Perez DL, LaFrance WC Jr, Fobian AD, Dorman J, Hua LH, et al.
- Evidence base: 12 Class II–III studies (systematic review of first published articles through February 25, 2025)
- Databases searched: Medline, Embase, PsychINFO, CINAHL
- Method: Modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) + modified Delphi process
- 6 Recommendations with 28 sub-statements total, all Level B or C
Four Clinical Questions Addressed
- Efficacy of psychological interventions on frequency & bothersomeness of functional seizures vs SMC?
- Efficacy of psychological interventions on health-related QoL, psychosocial functioning, & psychiatric comorbidities vs SMC?
- Efficacy of psychopharmacologic interventions on frequency & bothersomeness vs placebo/active treatment?
- Efficacy of psychopharmacologic interventions on health-related QoL, psychosocial functioning, & psychiatric comorbidities vs placebo/active treatment?
Definition & Terminology
- Functional seizures: Transient episodes of altered consciousness or involuntary movements resembling epileptic seizures or syncope, driven by episodic dissociation or other cognitive-affective mechanisms
- Previously labeled as: dissociative seizures, psychogenic nonepileptic seizures (PNES), psychogenic nonepileptic attacks, conversion disorder with attacks
- Classified in DSM-5-TR as a subtype of functional neurologic symptom disorder
- Do NOT conflate with malingering or factitious disorder (which are much less common)
- Diagnosis delayed an average of 7–8 years after symptom onset
- Characterized by biopsychosocial complexity: predisposing vulnerabilities, acute precipitants, perpetuating factors
- Co-occurring psychiatric disorders and adverse life experiences are common but not required for diagnosis
🔹 Clinical Pearl
Functional seizures are NOT malingering. They are classified in DSM-5-TR as a functional neurologic symptom disorder. The diagnosis is delayed an average of 7–8 years. VEEG is the gold standard for definite ("documented") diagnosis, but a clinical diagnosis based on history, semiology, and available video is acceptable when VEEG is not feasible.
Included Studies & Demographics
Study Selection
- Initial search: 223 citations retrieved → 206 abstracts reviewed → 87 full text → 32 graded for bias → 12 included
- Updated search: 126 records identified → 87 screened → 13 full text → 0 additional studies included
- Total: 12 studies (1 Class II, 11 Class III)
Study Participant Demographics
| Study | N | Mean Age | % Female | Co-occurring Epilepsy | Psych Comorbidities | % Dx by VEEG |
|---|
| Aboukasm 1998 | 100 | 43.3 | 90 | Y | Not available | 100 |
| Ataoglu 2003 | 30 | 23 (range 16–30) | 97 | N | Not available | 0 |
| Chen 2014 | 64 | 50.7 | 25 | N | 39% PTSD | 100 |
| Fobian 2020 | 29 | 15.1 (SD 2.5) | 57 | Y if free >6 mo | 52% anxiety/depression | 100 |
| Goldstein 2010 | 66 | 37.4 (SD 12.6) | 76 | N | 47% any psychiatric | 92 |
| Goldstein 2020 | 368 | 37.5 (SD 14.3) | 72 | Y if free >12 mo | 69% any psychiatric | 53 |
| Goldstein 2022 | 368 | 37.5 (SD 14.3) | 72 | Y if free >12 mo | 69% any psychiatric | 53 |
| Khattak 2006 | 100 | 24.3 (SD 8.76) | 88 | N | Not available | 0 |
| LaFrance 2010 | 38 | 34.4 (SD 12.6) | 76.3 | Y if distinguished | 61% mood, 87% anxiety | 100 |
| LaFrance 2014 | 38 | 37.9 (SD 11.5) | 81.6 | N | 68% mood, 79% anxiety | 100 |
| Senf-Beckenbach 2022 | 53 | 34.7 (SD 17.9) | 70.5 | N | Not available | Not available |
| Tolchin 2019 | 55 | 39.6 (SD 16.8) | 82.7 | N | 42% depression, 58% anxiety | 100 |
Psychological Interventions — Evidence Summary
Types of Psychological Interventions Studied
- Functional seizure–specific CBT (Goldstein 2010, 2020, 2022) — 12 weekly sessions over 4–5 mo + 1 booster at 9 mo
- Retraining and Control Therapy (ReACT) (Fobian 2020) — 8 weekly sessions
- Neurobehavioral therapy (NBT) (LaFrance 2014) — 12 weekly sessions
- Behavioral therapy (Khattak 2006) — daily sessions while admitted + 4 weekly follow-up
- Motivational interviewing + psychotherapy (Tolchin 2019) — motivational interview then 12 weekly sessions
- Group psychoeducation (Chen 2014) — 3 monthly 1.5-hour group sessions
- Body-focused group therapy (CORDIS) (Senf-Beckenbach 2022) — 10 weekly sessions
- Psychotherapy with protocolized review of videotaped seizures (Aboukasm 1998) — ≥5 sessions
- Sessions typically ranged 3–12 sessions; long-term outcome data beyond 1 year not available
Seizure Freedom (Primary Outcome)
| Analysis | Studies | Pooled RR (95% CI) | I² | Confidence |
|---|
| All psychological interventions | 7 Class III | 1.87 (1.36–2.56) | 3% | Low |
| CBT-specific sub-analysis | 2 Class III (Goldstein 2010, 2020) | 1.76 (1.10–2.80) | 0% | Low |
- Comparators: SMC, routine clinical care, nondirective supportive therapy, informational interviews, diazepam, no therapy
- Exclusion of the nonrandomized study (Aboukasm 1998) did not change the magnitude or significance of the RR
- Conclusion: Psychological interventions possibly increase the probability of achieving freedom from functional seizures
Individual Study RRs for Seizure Freedom
| Study | RR | LCL | UCL | Weight (%) |
|---|
| Aboukasm (1998) | 5.29 | 0.35 | 79.34 | 1.3 |
| Fobian (2020) | 8.43 | 1.87 | 38.03 | 4.3 |
| Goldstein (2010) | 2.42 | 0.85 | 6.85 | 8.8 |
| Goldstein (2020) | 1.58 | 0.92 | 2.71 | 30.8 |
| Tolchin (2019) | 2.87 | 0.85 | 9.68 | 6.5 |
| Ataoglu (2002) | 1.56 | 1.01 | 2.40 | 45.9 |
| LaFrance (2014) | 2.33 | 0.30 | 17.88 | 2.3 |
| Summary | 1.87 | 1.37 | 2.56 | I² 3 |
Seizure Frequency (SMD)
| Analysis | Studies | Pooled SMD (95% CI) | I² | Confidence |
|---|
| All psychological interventions | 3 Class III | −0.81 (−1.58 to −0.05) | 86% | Low |
| CBT-specific sub-analysis | 2 Class III | −0.38 (−0.81 to 0.04) | 60% | Very low |
- High heterogeneity (I² = 86%) for overall analysis
- CBT sub-analysis crossed zero (95% CI −0.81 to 0.04) → insufficient evidence for CBT alone on seizure frequency
- Conclusion: Psychological interventions possibly decrease functional seizure frequency
Seizure Severity & Bothersomeness
- Based on 2 Class III studies: pooled SMD = −0.64, favoring psychological interventions (95% CI −1.41 to 0.13, I² = 69%)
- Confidence is very low → insufficient evidence to determine whether interventions change severity/bothersomeness
🔹 Clinical Pearl
Seizure-specific CBT is the best-studied psychological intervention for functional seizures. The CODES trial (Goldstein 2020, n=368) is the largest RCT. Pooled RR for seizure freedom with CBT = 1.76 (95% CI 1.10–2.80). All evidence is Class III with low confidence — no Class I studies exist. Typical protocol: 12 weekly CBT sessions + booster at 9 months.
Psychological Interventions — Secondary Outcomes
Health-Related Quality of Life
| Analysis | Studies | Pooled SMD (95% CI) | I² | Confidence |
|---|
| All psychological interventions | 3 Class III | 0.37 (0.16–0.57) | 0% | Low |
- Favors psychological interventions (higher SMD = better QoL)
- CBT sub-analysis (1 Class III study, Goldstein 2022): estimated mean difference on EQ-5D VAS = 6.16 (95% CI 1.48–10.84, p = 0.010), favoring CBT — very low confidence
- Conclusion: Psychological interventions possibly increase health-related quality of life
Psychosocial Functioning (WSAS)
| Analysis | Studies | Pooled SMD (95% CI) | I² | Confidence |
|---|
| All psychological interventions | 3 Class III | −0.44 (−0.64 to −0.24) | 0% | Low |
| CBT-specific sub-analysis | 2 Class III | −0.40 (−0.61 to −0.19) | 0% | Low |
- Negative SMD = improved psychosocial functioning (lower WSAS scores are better)
- Conclusion: Psychological interventions, including CBT, possibly improve psychosocial functioning
Anxiety
| Analysis | Studies | Pooled SMD (95% CI) | I² | Confidence |
|---|
| All psychological interventions | 5 Class III | −0.68 (−1.30 to −0.07) | 87% | Low |
| CBT-specific sub-analysis | 2 Class III | −0.19 (−0.40 to 0.02) | 0% | Low |
- Overall psychological interventions possibly decrease anxiety (SMD −0.68)
- CBT alone: 95% CI crosses zero (−0.40 to 0.02) → possibly no change in anxiety with CBT vs SMC
Depression
| Analysis | Studies | Pooled SMD (95% CI) | I² | Confidence |
|---|
| All psychological interventions | 4 Class III | −0.43 | — | Low |
- 95% CI includes zero → insufficient evidence to determine change in depression
🔹 Clinical Pearl
Psychological interventions improve QoL (SMD 0.37) and psychosocial functioning (SMD −0.44) with low heterogeneity (I² = 0% for both). These are more robust findings than seizure frequency reduction (I² = 86%). CBT specifically improves psychosocial functioning (WSAS scores) with SMD −0.40. Evidence for depression reduction is insufficient.
Pharmacologic Interventions — Evidence Summary
Sertraline (2 Studies)
| Outcome | Studies | Pooled Estimate | 95% CI | Confidence |
|---|
| Seizure freedom | 1 Class II + 1 Class III | RR 2.34 | 0.34–16.09 (I² = 49%) | Very low |
| Seizure rate change | 1 Class II (LaFrance 2010) | RR 0.51 | 0.25–1.05, p = 0.29 | Very low |
| HRQoL (QOLIE-31) | 1 Class II (LaFrance 2010) | RMD 9.80 | −9.17 to 28.77, p = 0.311 | Very low |
| Psychosocial functioning (LIFE-RIFT) | 1 Class II (LaFrance 2010) | RMD −2.00 | −5.22 to 1.22, p = 0.223 | Very low |
| Anxiety (DTS) | 1 Class II (LaFrance 2010) | RMD −3.10 | −32.68 to 26.48, p = 0.837 | Very low |
| Depression (HRSD) | 1 Class II (LaFrance 2010) | RMD −1.70 | −8.43 to 5.03, p = 0.621 | Very low |
- LaFrance 2010 (Class II): Sertraline 25–200 mg flexible dosing over 12 wk vs placebo; n = 38
- LaFrance 2014 (Class III): 4-arm trial — sertraline alone, NBT alone, combined NBT + sertraline, treatment as usual; n = 38
- All results nonsignificant → insufficient evidence that sertraline changes seizure freedom, frequency, QoL, anxiety, or depression
Diazepam (1 Study)
- Ataoglu 2003 (Class III): 3 wk of twice-daily paradoxical diazepam 5–15 mg vs routine clinical care; n = 30
- Seizure freedom: Paradoxical therapy group achieved greater freedom from functional seizures (1 Class III, t = 2.27, p = 0.034) — very low confidence
- Anxiety (HRSA): RMD = −3.73 (95% CI −6.96 to −0.50, p = 0.024), favoring paradoxical therapy — very low confidence
- Conclusion: Insufficient evidence that diazepam changes seizure freedom or anxiety in functional seizures
Overall Pharmacologic Conclusions
- No pharmacologic intervention has demonstrated efficacy for directly treating functional seizures
- Evidence for sertraline and diazepam is insufficient across all outcomes
- Psychopharmacologics may still be appropriate for co-occurring psychiatric conditions (mood disorders, anxiety, PTSD)
🔹 Clinical Pearl
There is NO evidence supporting any medication for the direct treatment of functional seizures. Sertraline (the only SSRI studied in a controlled trial for functional seizures) showed nonsignificant results across all outcomes. Benzodiazepines have potential harms (habit-forming, cognitive impairment, motor vehicle accident risk, intubation risk for prolonged functional seizures). Medications should only be prescribed for co-occurring psychiatric disorders or epilepsy, NOT for functional seizures themselves.
Recommendation 1: Diagnosis of Functional Seizures
Rationale
- Diagnosis is delayed an average of 7–8 years after symptom onset
- Semiological features positively associated with functional seizures help guide accurate diagnosis
- Historical and semiological information from both patients and witnesses improves accuracy
- VEEG = gold standard for "documented" diagnosis; captures typical event + shows no epileptiform correlate
- VEEG: inpatient EMU (30–60 min), continuous inpatient monitoring, or home-video EEG
- When VEEG not feasible: ambulatory EEG, interictal EEG, smartphone video, history + semiology, tilt-table testing
- Clinicians with greater experience diagnose functional seizures more accurately
Recommendation 1 Statements
| # | Statement | Level |
|---|
| 1A | Clinicians should include functional seizures in the differential diagnosis of seizure-like or syncope-like episodes | B |
| 1B | When evaluating seizure-like episodes, clinicians should seek historical and semiological information from both patients and witnesses | B |
| 1C | In emergency settings with prolonged seizure-like episodes, clinicians should perform a brief ictal physical examination | B |
| 1D | When diagnostic ambiguity exists between epileptic and functional seizures (after reviewing history, semiology, video, and EEG), clinicians may obtain VEEG of typical seizure-like episodes where feasible | C |
| 1E | When ambiguity between syncope and functional seizures remains, clinicians should evaluate blood pressure, cardiac rhythm (ECG monitoring), and/or tilt-table testing | B |
| 1F | Where VEEG/ECG/tilt-table capture of typical episodes is not feasible, clinicians should use ambulatory EEG, interictal EEG, interictal ECG, smartphone video, and history/semiology | B |
| 1G | When diagnosing functional seizures, clinicians should screen and evaluate for other functional neurologic symptoms | B |
| 1H | When diagnosis or management is beyond clinician's scope, should refer to appropriate specialist | B |
Key Diagnostic Points for Boards
- Serum prolactin, lactate, and creatine kinase: may be elevated after bilateral tonic-clonic epileptic seizures but have significant false-positive and false-negative rates — not reliable for distinguishing functional from epileptic seizures
- Smartphone videos of seizure-like episodes reviewed by a neurologist can facilitate semiology evaluation and allow accurate diagnosis in most cases
- Patients with functional seizures frequently have multiple functional neurologic symptoms
Recommendation 2: Assessment of Psychiatric Comorbidities & Epilepsy
Rationale
- Mood disorders, anxiety disorders, and PTSD co-occur at high frequency with functional seizures
- Substance use disorders also co-occur at elevated rates
- Adverse life experiences (abuse, neglect) are 3–5× more common than in general population and 2× more common than in other psychiatric disorders
- Greater psychiatric symptom severity → higher rates of treatment nonadherence
- Adherence to psychotherapy is associated with better outcomes for seizure frequency and QoL
- Treatment of co-occurring psychiatric disorders may facilitate functional seizure treatment
Co-occurring Epilepsy
- Functional seizures co-occur with epilepsy in up to 12% of people with epilepsy
- Co-occur in up to 20% of adults with functional seizures
- Co-occur in 30%–40% of children with functional seizures
- Co-occur in up to 50% of individuals with intellectual disabilities and functional seizures
- VEEG + clinical history + semiology = gold standard to differentiate seizure types for targeted treatment
Recommendation 2 Statements
| # | Statement | Level |
|---|
| 2A | Clinicians should evaluate patients with functional seizures for co-occurring psychiatric disorders (affective, trauma-related, personality, substance use) to treat both conditions | B |
| 2B | Clinicians should offer patients with functional seizures and co-occurring psychiatric disorders (who are not already receiving mental health care) referral to a mental health specialist | B |
🔹 Clinical Pearl
Co-occurring epilepsy rates to remember: 12% of epilepsy patients, 20% of adults with functional seizures, 30–40% of children, 50% of those with intellectual disability. VEEG is essential to differentiate seizure types. Adverse life experiences are 3–5× more common than in the general population. Psychiatric comorbidities are present in 42–69% of studied populations.
Recommendation 3: Co-occurring Epilepsy Management
Rationale
- Treating co-occurring epileptic and functional seizures requires accurately identifying and differentiating the seizure types
- ASMs are effective for epileptic seizures but have no evidence of efficacy for functional seizures
- Patients need counseling about the risks/benefits of ASMs for epileptic vs functional seizures
Recommendation 3 Statements
| # | Statement | Level |
|---|
| 3A | Clinicians should evaluate patients with functional seizures for co-occurring epilepsy to deliver appropriate treatment | B |
| 3B | Clinicians should use history, semiology, and VEEG (where feasible) to distinguish functional from epileptic seizure types | B |
| 3C | Clinicians should counsel patients about ASM risks/benefits for epileptic seizures and their lack of efficacy for functional seizures | B |
| 3D | Clinicians should prescribe appropriate ASM treatments for epileptic seizures in patients with both functional seizures and epilepsy | B |
Recommendation 4: General Principles of Management
Rationale
- Functional seizures are diagnosed based on history, physical examination, semiology, and evaluation of alternative diagnoses
- Psychological interventions may be effective — can be provided by mental health specialists; neurologists can facilitate through effective communication and motivational interviewing
- Common clinical practices can harm patients through stigmatization, humiliation, or inflicting pain
- Patients with functional seizures are entitled to the same dignity and respect as other patients
- Provision of a clear explanation of the diagnosis and treatment plan is an essential platform for further treatment
- Effective self-management has been linked to improvements in health outcomes for chronic conditions
Recommendation 4 Statements
| # | Statement | Level |
|---|
| 4A | Neurologists and mental health clinicians should collaborate in the assessment and treatment of functional seizures | B |
| 4B | Clinicians should adhere to universal standards of care: speak respectfully, refrain from unnecessary harm, avoid stigmatizing behavior | B |
| 4C | Clinicians should provide a specific diagnostic label and rationale for the diagnosis in a clear, empathetic, supportive manner, accounting for the patient's cultural context | B |
| 4D | Clinicians should engage in shared decision making regarding the treatment plan | B |
| 4E | Clinicians should counsel patients and caregivers on how to manage an acute functional seizure episode | B |
| 4F | Clinicians should ask patients about driving and provide advice per regional regulations | B |
| 4G | Clinicians should ask about the impact of functional seizures on occupational and social functioning | B |
| 4H | Clinicians should direct patient and caregivers to resources for learning and support (e.g., advocacy organizations) | B |
| 4I | Clinicians should provide continuity of care to facilitate treatment and increase patient satisfaction | B |
🔹 Clinical Pearl
How to deliver the diagnosis (board favorite): Use a specific diagnostic label (e.g., "functional seizures"), explain the rationale clearly, account for cultural context, and engage in shared decision making. Do NOT use potentially stigmatizing terms. Development of a seizure action plan can enhance patient control and decrease vulnerability. Many driving restrictions apply to functional seizures, similar to epilepsy.
Recommendation 5: Psychological Interventions
Rationale
- Psychological interventions studied include: NBT, paradoxical therapy, behavioral therapy, ReACT, CBT, motivational interviewing + psychotherapy, group psychoeducation, body-focused group therapy
- These interventions possibly increase seizure freedom, decrease seizure frequency, reduce anxiety, improve HRQoL, and improve psychosocial functioning
- Psychological interventions are generally safe and well tolerated
- Family/caregiver involvement improves treatment outcomes, especially in children
- Shared decision making is critical when recommending psychological interventions
Recommendation 5 Statements
| # | Statement | Level |
|---|
| 5A | When psychological interventions are indicated and accessible, clinicians should counsel patients about potential benefits and risks to facilitate shared decision making | B |
| 5B | When scope of practice does not include counseling, clinicians should refer patients to a knowledgeable clinician for evidence-based psychological treatment | B |
| 5C | Clinicians should refer interested and appropriate patients to psychological interventions for treatment of functional seizures | B |
| 5D | Clinicians should, with patient permission, involve family, caregivers, or social support network in the psychological treatment of adults | B |
| 5E | Clinicians should involve family in the psychological treatment of children with functional seizures | B |
Recommendation 6: Pharmacologic Interventions
Rationale
- Many patients are initially misdiagnosed with epilepsy and treated with ASMs before the correct diagnosis is made
- Even after diagnosis, many patients continue to receive ASMs and/or benzodiazepines despite no evidence of benefit
- Although ASMs treat co-occurring epilepsy and psychopharmacologics treat co-occurring psychiatric disorders, there is no evidence that either class directly treats functional seizures
Risks of Benzodiazepines in Functional Seizures
- Habit-forming
- Cognitive impairment
- Increased risk of motor vehicle accidents
- In the acute setting, administration for prolonged functional seizures can result in intubation and iatrogenic harm
- Benzodiazepines may provide anxiolysis and can sometimes abort prolonged functional seizures in the short term, but long-term harms outweigh benefits
ASM Tapering
- ASMs cause adverse effects ranging from common mild effects (fatigue, dizziness) to severe/life-threatening effects (Stevens-Johnson syndrome, aplastic anemia, hepatic failure)
- In patients with functional seizures without co-occurring epilepsy who were previously treated with ASMs, immediate tapering leads to improved outcomes compared with delayed withdrawal
- Other indications for ASMs (besides epilepsy) may include: mood disorders, anxiety disorders, migraine, neuropathic pain
Recommendation 6 Statements
| # | Statement | Level |
|---|
| 6A | Clinicians should counsel patients with functional seizures without co-occurring epilepsy or another indication about the potential risks and lack of benefit of benzodiazepines | B |
| 6B | Clinicians should not prescribe benzodiazepines for acute abortive treatment of functional seizures in patients without co-occurring epilepsy, anxiety disorders, or another indication | B |
| 6C | Clinicians should counsel patients about the lack of benefit and potential risks of ASMs for functional seizures | B |
| 6D | Clinicians should not prescribe ASMs to patients with functional seizures without co-occurring epilepsy or another indication | B |
| 6E | Clinicians should taper off ASMs for patients with functional seizures without another indication, to reduce adverse effects | B |
🔹 Clinical Pearl
Two "should not" recommendations (6B and 6D) are critical for boards: Do NOT prescribe benzodiazepines for acute abortive treatment of functional seizures (risk of intubation), and do NOT prescribe ASMs for functional seizures without epilepsy or another indication. For patients already on ASMs without another indication, taper them off. Always check for co-occurring epilepsy (up to 20% of adults) before tapering.
Key Clinical Trials
CODES Trial (Goldstein et al., 2020 & 2022)
CODES — Cognitive Behavioural Therapy for Dissociative Seizures
- Design: Pragmatic, multicentre, randomised controlled trial (Class III)
- N: 368 (largest RCT in functional seizures)
- Population: Adults with dissociative seizures; 72% female; mean age 37.5; 69% with any psychiatric comorbidity; 53% diagnosed by VEEG
- Intervention: CBT + SMC (12 sessions over 4–5 mo + 1 booster at 9 mo) vs SMC alone
- SMC: Neurologist meeting including guidance on diagnosis + information booklets + regular outpatient psychiatrist care (no psychotherapy)
- Outcomes at 12 months:
- Seizure freedom: RR 1.58 (95% CI 0.92–2.71) — favored CBT but CI crossed 1
- Seizure frequency: SMD −2.22 (95% CI −0.60 to 0.00) — not statistically significant
- Psychosocial functioning (WSAS): SMD −0.36 (95% CI −0.60 to −0.13) — significant, favoring CBT
- Anxiety (GAD-7): SMD = −0.18 (95% CI −0.41 to 0.05) — not significant
- 6-month outcomes (Goldstein 2022): Similar pattern; CBT had greatest weight in pooled analyses (30.8–80% in different meta-analyses)
LaFrance Sertraline RCT (2010)
LaFrance et al. — Pilot Pharmacologic RCT
- Design: Randomized, double-blind, placebo-controlled (Class II — highest class in this guideline)
- N: 38; mean age 34.4; 76.3% female; 61% mood disorders, 87% anxiety disorders
- Intervention: Sertraline 25–200 mg flexible dosing over 12 wk vs placebo
- Results: All outcomes nonsignificant (seizure freedom, frequency, QoL, anxiety, depression)
- Seizure rate: RR 0.51 (95% CI 0.25–1.05, p = 0.29)
ReACT Trial (Fobian et al., 2020)
Fobian et al. — Retraining and Control Therapy for Pediatric Functional Seizures
- Design: Randomized controlled trial (Class III)
- N: 29 children; mean age 15.1; 57% female; 52% anxiety and/or depression
- Intervention: 8 weekly sessions of ReACT vs 8 weekly sessions of nondirective supportive therapy
- Results: RR for seizure freedom = 8.43 (95% CI 1.87–38.03), strongly favoring ReACT
- Note: Small sample size; weight in meta-analysis = 4.3%
Summary of Recommendations by Evidence Level
Level B Recommendations ("Should")
| Rec # | Key Statement |
|---|
| 1A | Include functional seizures in the differential of seizure-like/syncope-like episodes |
| 1B | Seek history and semiology from patients AND witnesses |
| 1C | Perform brief ictal exam in emergency settings with prolonged episodes |
| 1E | Evaluate BP, cardiac rhythm, tilt-table when syncope vs functional seizures ambiguity exists |
| 1F | Use ambulatory EEG, interictal EEG, ECG, smartphone video, history/semiology when VEEG not feasible |
| 1G | Screen for other functional neurologic symptoms |
| 1H | Refer when diagnosis/management is beyond scope |
| 2A | Evaluate for co-occurring psychiatric disorders |
| 2B | Refer to mental health specialist for co-occurring psychiatric disorders |
| 3A–3D | Evaluate for co-occurring epilepsy; use history/semiology/VEEG to differentiate; counsel on ASMs; prescribe ASMs for epileptic seizures |
| 4A–4I | Collaborate neuro + mental health; universal care standards; provide diagnostic label & rationale; shared decision making; counsel on acute episodes; driving; occupational impact; resources; continuity of care |
| 5A–5E | Counsel on psychological interventions; refer for evidence-based treatment; involve family/social support |
| 6A | Counsel about risks/lack of benefit of benzodiazepines for functional seizures alone |
| 6B | Should not prescribe benzodiazepines for acute abortive treatment of functional seizures without another indication |
| 6C | Counsel about lack of benefit and risks of ASMs for functional seizures |
| 6D | Should not prescribe ASMs for functional seizures without co-occurring epilepsy or another indication |
| 6E | Taper off ASMs when no other indication exists |
Level C Recommendation ("May")
| Rec # | Key Statement |
|---|
| 1D | Clinicians may obtain VEEG of typical seizure-like episodes when diagnostic ambiguity exists between epileptic and functional seizures |
Evidence Confidence Summary
| Outcome | Direction | Confidence |
|---|
| Psychological interventions → seizure freedom | Favors intervention (RR 1.87) | Low |
| Psychological interventions → seizure frequency | Favors intervention (SMD −0.81) | Low |
| Psychological interventions → HRQoL | Favors intervention (SMD 0.37) | Low |
| Psychological interventions → psychosocial functioning | Favors intervention (SMD −0.44) | Low |
| Psychological interventions → anxiety | Favors intervention (SMD −0.68) | Low |
| Psychological interventions → depression | Nonsignificant (SMD −0.43) | Low |
| CBT → seizure freedom | Favors CBT (RR 1.76) | Low |
| CBT → seizure frequency | Nonsignificant (SMD −0.38) | Very low |
| CBT → psychosocial functioning | Favors CBT (SMD −0.40) | Low |
| CBT → anxiety | Nonsignificant (SMD −0.19) | Low |
| Sertraline → seizure freedom | Nonsignificant (RR 2.34) | Very low |
| Sertraline → all other outcomes | Nonsignificant | Very low |
| Diazepam → seizure freedom | Insufficient evidence | Very low |
🔹 Clinical Pearl
Key numbers for the RITE exam: Pooled RR for seizure freedom with psychological interventions = 1.87 (CI 1.36–2.56). CBT-specific RR = 1.76 (CI 1.10–2.80). All 28 recommendation statements are Level B except 1D (Level C). There are NO Level A recommendations. Two "should not" statements: do not prescribe benzodiazepines for acute abortive treatment (6B) and do not prescribe ASMs (6D) for functional seizures without another indication. Co-occurring epilepsy prevalence: 12% of epilepsy patients have functional seizures; 20% of adults with functional seizures have epilepsy. Diagnosis delay averages 7–8 years.
