Seizure Disorders in Psychiatric Patients: Mimics, Comorbidity, and Medication Risks
This is Part 4 in our series on Medical History.
Read Part 3: Head Injury History: Recognizing Traumatic Brain Injury in Psychiatric Evaluation
In Part 1 we reviewed general medical red flags that should prompt suspicion for organic etiologies of psychiatric symptoms. This part focuses specifically on seizure disorders as both mimics of psychiatric illness and conditions with high psychiatric comorbidity. Seizures, particularly complex partial seizures and temporal lobe epilepsy, can present with symptoms that closely resemble panic disorder, dissociation, psychosis, and other psychiatric conditions.
Understanding seizure history and recognizing ictal and interictal psychiatric symptoms is essential for accurate diagnosis, avoiding misdiagnosis of epilepsy as psychiatric illness (and vice versa), selecting psychiatric medications that do not exacerbate seizures, and coordinating care with neurology to optimize both seizure control and mental health. The stakes are high: misdiagnosing psychogenic events as epilepsy leads to unnecessary antiseizure medications with significant side effects, while misdiagnosing epilepsy as a psychiatric disorder delays appropriate treatment and places patients at risk for status epilepticus and sudden unexpected death in epilepsy (SUDEP).
Learning Objectives
After reading this section, you should be able to:
- Conduct a comprehensive seizure history assessment including seizure semiology, aura, postictal symptoms, and witness descriptions
- Differentiate seizure events from panic attacks, dissociative episodes, and psychogenic nonepileptic seizures based on clinical features and temporal patterns
- Recognize psychiatric presentations of temporal lobe epilepsy and complex partial seizures, including episodic fear, derealization, and perceptual disturbances
- Understand the bidirectional relationship between epilepsy and psychiatric disorders, including the causal impact of untreated seizures on psychiatric risk
- Select psychiatric medications appropriately in patients with seizure disorders, avoiding pro-convulsant agents and coordinating with neurology
- Identify when EEG, neuroimaging, or neurology consultation is indicated in patients with episodic psychiatric symptoms
Start With Chart Review
Before interviewing the patient, review the medical record for documentation of seizures and neurological evaluation.
Key elements to review:
- Neurology notes: Look for diagnosis of epilepsy, seizure type classification, last seizure date, seizure frequency, and treatment recommendations.
- EEG reports: Review for epileptiform activity, focal slowing, or other abnormalities. Note that normal EEG does not rule out epilepsy (routine EEG sensitivity ~50%).
- Neuroimaging: Check for brain MRI findings that may be epileptogenic foci (mesial temporal sclerosis, cortical dysplasia, old infarcts, tumors).
- Medication list: Note all antiseizure medications (ASMs), doses, and recent changes. Check for medications that lower seizure threshold.
- Antiseizure medication levels: Review recent levels to assess adherence and therapeutic dosing.
- Emergency department records: Look for ED visits for seizures, status epilepticus, or seizure-related injuries.
- Seizure logs: Some patients maintain seizure diaries tracking frequency and triggers.
- Video-EEG monitoring results: Gold standard for characterizing seizures. Note seizure semiology descriptions from monitoring reports.
💡 Clinical Pearl: If a patient has documented epilepsy but psychiatric symptoms seem atypical for primary psychiatric illness (stereotyped episodic features, brief duration, automatic behaviors, postictal confusion), review EEG reports for seizure type. Complex partial seizures with psychiatric features may be misattributed to anxiety or psychosis. Conversely, if a patient has been diagnosed with epilepsy but EEGs are repeatedly normal and events don’t respond to ASMs, consider psychogenic nonepileptic seizures.
Why this matters: Many patients with epilepsy have co-occurring psychiatric disorders that may or may not be related to their seizures. Chart review helps you distinguish interictal psychiatric symptoms (occurring between seizures) from ictal symptoms (during seizures) from postictal symptoms (immediately after seizures), and identifies seizure frequency and control status which affect psychiatric risk.
Interview the Patient
Screening for Seizure History
Opening questions:
- “Have you ever had a seizure or been told you might have had one?”
- “Have you ever had spells where you lose awareness, black out, or can’t remember what happened?”
- “Has anyone ever told you that you had unusual movements, staring spells, or episodes where you didn’t seem like yourself?”
Follow-up and context questions:
- “Tell me more about what happens during these spells.”
- “How often do these spells occur?”
- “How long do they typically last?”
💡 Clinical Pearl: Many people associate “seizure” only with generalized tonic-clonic convulsions. Use multiple terms: “seizures, spells, blackouts, episodes, attacks” to capture various presentations. Specifically ask about staring spells, “absence” episodes, and brief lapses, as these may not be recognized by patients as seizures.
Characterizing Seizure Semiology
Follow-up questions:
- “Before the spell starts, do you have any warning signs? Like a strange feeling, unusual smell, déjà vu, rising sensation in your stomach, or sense of fear?”
- “What happens during the spell? Can you hear people talking? Can you respond? Do you move or make sounds?”
- “What have other people told you they observe during these spells?”
- “After the spell, how do you feel? Are you confused, tired, or unable to speak normally? How long does it take you to feel back to normal?”
Why This Information Matters
Aura (warning before seizure): Many seizures, particularly those arising from temporal or frontal lobes, begin with an aura. The aura itself is actually a focal aware seizure. Common auras include:
- Epigastric rising sensation: Often associated with temporal lobe epilepsy
- Fear or panic: Can be indistinguishable from panic attack
- Déjà vu or jamais vu: Strong sense of familiarity or unfamiliarity
- Olfactory or gustatory hallucinations: Unusual smells or tastes
- Visual distortions: Micropsia, macropsia, visual hallucinations
- Derealization or depersonalization: Feeling detached from reality or self
🚩 Red Flag: Episodic fear or anxiety that is stereotyped (always feels the same), brief (seconds to 1-2 minutes), and associated with epigastric rising sensation, olfactory hallucinations, or déjà vu should raise suspicion for temporal lobe epilepsy rather than panic disorder.
Ictal behaviors: What happens during the seizure helps classify seizure type:
- Focal aware seizures (formerly “simple partial”): Patient remains conscious and can describe experience. May have motor (jerking of one limb), sensory (numbness, tingling), autonomic (flushing, piloerection), or psychic (fear, déjà vu) symptoms.
- Focal impaired awareness seizures (formerly “complex partial”): Patient has altered consciousness, may stare blankly, have automatisms (lip smacking, picking at clothes, walking aimlessly), and cannot respond appropriately to questions.
- Focal to bilateral tonic-clonic: Starts as focal seizure, then generalizes to full convulsion.
- Absence seizures: Brief (seconds) staring spells with abrupt onset and offset, no postictal confusion.
Automatisms: Repetitive, purposeless movements during seizure (lip smacking, chewing, swallowing, picking, fumbling, walking) are characteristic of temporal lobe epilepsy.
Postictal state: The period immediately after seizure provides diagnostic clues:
- Postictal confusion: Disorientation and confusion lasting minutes to hours is typical after complex partial and generalized seizures, but NOT after panic attacks or psychogenic events.
- Postictal aphasia: Inability to speak normally suggests seizure arising from language-dominant hemisphere.
- Todd’s paralysis: Temporary weakness of a limb after focal seizure from that cortical region.
- Postictal psychosis: Delirium-like state with hallucinations and delusions that can last hours to days after seizure or cluster of seizures.
💡 Clinical Pearl: The postictal state is one of the most useful features for distinguishing seizures from psychiatric events. True seizures are typically followed by confusion, fatigue, and sometimes sleep, while panic attacks resolve abruptly without confusion, and psychogenic nonepileptic seizures often have immediate return to normal consciousness or dramatic emotional displays immediately afterward.
Timing, Frequency, and Precipitants
Follow-up questions:
- “When did these spells start? How old were you when you had your first one?”
- “How often do they happen now? Daily, weekly, monthly?”
- “Do you notice anything that seems to trigger the spells? Like stress, lack of sleep, flashing lights, or missing medications?”
- “Do the spells happen at any particular time of day?”
Why This Information Matters
Age of onset: Seizure disorders can begin at any age, but age of onset provides diagnostic clues:
- Childhood/adolescent onset: Genetic epilepsies, developmental abnormalities
- Young adult onset: Head trauma, substance use, brain tumors, autoimmune
- Late adult onset (>60): Stroke, neurodegenerative disease, tumors
Frequency: Seizure frequency affects psychiatric risk. Frequent uncontrolled seizures are associated with higher rates of psychiatric comorbidity than well-controlled epilepsy.
Precipitants: Common seizure triggers include:
- Sleep deprivation
- Alcohol use or withdrawal
- Medication nonadherence
- Stress (though less reliable than patients often believe)
- Photic stimulation (flashing lights) in photosensitive epilepsy
- Menstrual cycle (catamenial epilepsy)
Circadian patterns: Some seizure types have characteristic timing (frontal lobe seizures often occur during sleep, juvenile myoclonic epilepsy seizures often occur upon awakening).
Treatment History and Current Control
Follow-up questions:
- “Have you been evaluated by a neurologist? Have you had an EEG or brain imaging?”
- “Are you taking any medications for seizures? If so, which ones and what doses?”
- “Are you able to take your seizure medications consistently?”
- “How well controlled are your seizures with your current treatment? When was your last seizure?”
- “Have you tried other seizure medications in the past? How did they work?”
Why This Information Matters
Neurological evaluation: Documented epilepsy diagnosis with EEG and imaging provides confidence in diagnosis. However, many patients have epilepsy suspected clinically without confirmatory EEG.
Antiseizure medication regimen: Knowledge of current ASMs is essential for assessing drug interactions with psychiatric medications and understanding seizure control. Some ASMs have psychiatric side effects:
- Phenobarbital: Sedation, depression, cognitive impairment
- Topiramate: Cognitive dulling (“Dopamax”), word-finding difficulty, mood symptoms
- Levetiracetam: Irritability, aggression, mood lability (10-15% of patients)
- Zonisamide: Depression, psychosis (rare)
Adherence: Nonadherence to ASMs is a major cause of breakthrough seizures and status epilepticus. Psychiatric illness, cognitive impairment, substance use, and chaotic lifestyle contribute to nonadherence.
Seizure control: Well-controlled epilepsy (seizure-free for months to years) has lower psychiatric risk than poorly controlled epilepsy with frequent seizures.
Psychiatric Symptoms Related to Seizures
Follow-up questions:
- “Have you noticed any mood changes, anxiety, or changes in your thinking around the time of seizures?”
- “Do your psychiatric symptoms get worse before seizures, during seizures, or after seizures?”
- “Between seizures, how is your mood and anxiety?”
Why This Information Matters
Periictal psychiatric symptoms: Psychiatric symptoms can occur at different times relative to seizures:
- Preictal (hours to days before seizure): Irritability, depression, anxiety, psychosis may herald impending seizure
- Ictal (during seizure): Fear, déjà vu, derealization, visual hallucinations, paranoia
- Postictal (hours to days after seizure): Depression, psychosis, confusion
Interictal psychiatric symptoms: Psychiatric symptoms occurring between seizures, not temporally related to seizure events. These are the most common psychiatric manifestations of epilepsy and represent co-occurring psychiatric disorders that may or may not be causally related to epilepsy.
Distinguishing periictal from interictal symptoms is important because periictal symptoms may improve with better seizure control alone, while interictal symptoms require separate psychiatric treatment.
Seizures as Psychiatric Mimics
Temporal Lobe Epilepsy and Panic Disorder
Temporal lobe epilepsy (TLE), particularly arising from mesial temporal structures, can present with symptoms nearly identical to panic disorder:
- Sudden onset of intense fear or terror
- Epigastric rising sensation
- Palpitations, flushing
- Derealization, depersonalization
- Sense of impending doom
Key differentiating features:
| Feature | Panic Attack | TLE Seizure |
|---|---|---|
| Duration | 10-20 minutes (sometimes longer) | 30 seconds to 2 minutes (rarely >2 min) |
| Onset/offset | Gradual buildup and resolution | Abrupt onset and offset |
| Consciousness | Fully aware, can interact | May have altered awareness |
| Postictal state | None (immediate return to baseline) | Confusion, fatigue, often needs to sleep |
| Aura features | None, or anticipatory anxiety | Stereotyped aura (same every time): déjà vu, olfactory hallucination, rising epigastric sensation |
| Automatisms | None | Lip smacking, picking, fumbling |
| Amnesia | Full memory of event | Partial or complete amnesia for event |
| Response to treatment | Responds to SSRIs, benzodiazepines, CBT | No response to psychiatric treatment, responds to ASMs |
🚩 Red Flag: Brief (1-2 minute), stereotyped episodes of fear with epigastric sensation, olfactory hallucinations, or automatisms should prompt EEG evaluation for temporal lobe epilepsy, not treatment for panic disorder.
Derealization and Dissociation
Ictal derealization (feeling that the world is unreal) and depersonalization (feeling detached from oneself) can be misdiagnosed as dissociative disorders. Key differences:
- Epileptic: Brief (seconds to 1-2 minutes), stereotyped, often with other TLE features (déjà vu, automatisms), postictal confusion
- Dissociative: Longer duration (minutes to hours), variable triggers, no postictal state, often associated with trauma history
Psychosis
Postictal psychosis can present with hallucinations and delusions that are indistinguishable from primary psychotic disorders. However, postictal psychosis has characteristic features:
- Occurs after seizure or cluster of seizures (usually within 24-72 hours)
- Self-limited (typically resolves within days to 1-2 weeks)
- Lucid interval between seizure and psychosis onset
- Often includes confusion, disorientation (delirium-like)
Interictal psychosis (between seizures) can resemble schizophrenia and requires chronic antipsychotic treatment.
Seizures and Psychiatric Comorbidity
High Rates of Psychiatric Disorders in Epilepsy
Epilepsy is associated with substantially elevated rates of psychiatric disorders:
- Depression: 20-55% prevalence (2-5x general population)
- Anxiety disorders: 20-25% prevalence
- ADHD: 20-30% in children with epilepsy
- Psychosis: 2-7% (higher in TLE)
- Autism spectrum disorder: 20-30% co-occurrence
- Suicidal ideation: 11-12% (5x general population)
The relationship is bidirectional. Epilepsy increases risk for psychiatric disorders, AND psychiatric disorders increase risk for seizures.
Untreated Epilepsy Causally Increases Psychiatric Risk
Emerging evidence suggests that untreated epilepsy, particularly temporal lobe epilepsy, can causally increase risk for psychiatric disorders through:
- Recurrent seizures causing progressive neuronal damage
- Chronic neuroinflammation
- Disruption of mood-regulating circuits
- Psychosocial impact (stigma, driving restrictions, employment difficulties)
This means that optimal seizure control is not just about preventing seizures, it may also reduce psychiatric risk.
Treatment Implications
Medication Selection in Patients with Seizure Disorders
Pro-convulsant psychiatric medications to avoid or use with caution:
- Bupropion: Contraindicated in seizure disorders. Dose-dependent seizure risk (0.4% at 300mg/day, higher at >450mg).
- Clozapine: Dose-dependent seizure risk (1-2% at 300mg/day, 5% at 600mg/day). If used, requires slow titration, seizure monitoring, and often concurrent ASM.
- Tricyclic antidepressants: Lower seizure threshold at high doses (>200mg).
- Tramadol: Lowers seizure threshold.
- High-dose theophylline: Pro-convulsant.
- Rapid benzodiazepine withdrawal: Can precipitate seizures.
Generally safe psychiatric medications in epilepsy:
- SSRIs and SNRIs (except possibly high-dose venlafaxine)
- Mirtazapine
- Lamotrigine (ASM with mood-stabilizing properties)
- Most antipsychotics (though high-dose clozapine and possibly high-dose chlorpromazine have seizure risk)
ASMs with mood-stabilizing properties: Some antiseizure medications are also effective mood stabilizers and may be preferred in patients with epilepsy and mood disorders:
- Lamotrigine: Effective for bipolar depression, generally well-tolerated
- Valproate: Effective for mania, but cognitive side effects and teratogenicity limit use
- Carbamazepine: Effective for mania, but drug interactions and tolerability issues
Drug Interactions
Many ASMs are hepatic enzyme inducers or inhibitors, creating significant drug interaction potential:
Enzyme inducers (decrease levels of other medications):
- Carbamazepine, phenytoin, phenobarbital: Induce CYP450 enzymes, decreasing levels of many psychiatric medications, oral contraceptives, and other drugs
Enzyme inhibitors (increase levels of other medications):
- Valproate: Inhibits metabolism of lamotrigine (requires lamotrigine dose reduction)
Protein binding interactions: Valproate displaces other highly protein-bound drugs, increasing their free levels.
Coordination with neurology is essential when starting or changing psychiatric medications in patients on complex ASM regimens.
Treating Interictal Psychiatric Disorders
Interictal psychiatric disorders in epilepsy are treated similarly to psychiatric disorders in general population, with medication adjustments for seizure risk and drug interactions:
- Depression/anxiety: SSRIs first-line (sertraline, escitalopram). Avoid bupropion.
- Bipolar disorder: Lamotrigine preferred (already an ASM). Valproate if already on it for seizures. Avoid carbamazepine if patient already on multiple ASMs (drug interactions).
- Psychosis: Antipsychotics generally safe. Avoid very high dose clozapine.
- ADHD: Stimulants generally safe in well-controlled epilepsy. Use caution in poorly controlled seizures.
Psychotherapy is important and has no seizure risk. CBT effective for depression and anxiety in epilepsy.
When to Pursue Further Evaluation
Indications for EEG:
- Episodic symptoms suggestive of seizures (stereotyped, brief, with postictal confusion)
- First unprovoked seizure
- Suspected breakthrough seizures in diagnosed epilepsy
- Distinguishing seizures from psychogenic events (may require video-EEG monitoring)
Indications for neurology referral:
- Any suspected new-onset seizures
- Poor seizure control despite ASM treatment
- Need for ASM adjustment or polytherapy
- Psychiatric symptoms temporally related to seizures (periictal)
- Treatment-resistant psychiatric symptoms in context of epilepsy
Indications for neuroimaging (MRI brain):
- First unprovoked seizure (to identify structural etiology)
- Focal seizures
- Treatment-resistant epilepsy
- Change in seizure pattern
Psychogenic Nonepileptic Seizures (PNES)
Clinical features: Events that resemble seizures but are not caused by abnormal electrical activity. Associated with psychological factors, trauma history, and conversion disorder. Common features:
- Prolonged duration (minutes to >30 minutes)
- Pelvic thrusting, side-to-side head movements, asynchronous limb movements (atypical for epileptic seizures)
- Eyes forcefully closed (eyes open in true seizures)
- Crying or talking during event
- No postictal confusion (may have dramatic emotional display)
- Suggestibility (events triggered by suggestion)
- Elevated prolactin NOT seen after PNES (elevated 15-20 min after generalized tonic-clonic seizure)
Diagnosis: Requires video-EEG monitoring capturing typical event with no epileptiform activity.
Treatment: Psychotherapy (CBT, trauma-focused therapy), not ASMs. Important to communicate diagnosis empathetically to avoid implying patient is “faking.”
Complication: 10-20% of patients have both epileptic seizures AND PNES, making diagnosis challenging.
What to Document
| Documentation Level | What to Include | Example | When to Use This Level |
|---|---|---|---|
| Minimal | Basic seizure screening: history of seizures, current treatment, last seizure | “Patient denies history of seizures or unexplained loss of consciousness.” | No seizure history |
| Standard | Above + seizure type, frequency, aura, ASM regimen, adherence, relationship to psychiatric symptoms | “Patient has history of complex partial seizures, diagnosed age 18, arising from left temporal lobe per EEG. On levetiracetam 1500mg BID with good control (last seizure 6 months ago). Patient reports no aura. Seizures characterized by staring, lip smacking, and confusion for ~5 minutes after. Denies any relationship between seizures and current depressive symptoms. No ASM side effects noted. Medication adherence excellent per patient and confirmed by therapeutic levetiracetam level. Given seizure disorder, will avoid bupropion and use sertraline for depression.” | Any seizure history |
| Detailed | Above + detailed semiology, temporal relationship between psychiatric symptoms and seizures, periictal vs interictal distinction, medication interaction analysis, coordination plan with neurology | “Patient is a 32-year-old woman with temporal lobe epilepsy presenting with episodic fear, anxiety, and brief periods of ‘zoning out.’ Epilepsy diagnosed age 15, currently on lamotrigine 200mg BID. Describes two types of spells: (1) Seizures: occur monthly, last 1-2 minutes, begin with rising epigastric sensation and intense fear, then patient ‘zones out’ and doesn’t remember what happens, afterward feels confused and tired for 30 minutes; witnesses report lip smacking and staring; and (2) Panic-like episodes: occur weekly, last 10-20 minutes, no epigastric aura, patient remains aware throughout, no postictal confusion, associated with worry about work stress. Given clear distinction between ictal fear (brief, stereotyped, with aura and postictal state) and separate panic attacks (longer, variable, no postictal state), formulation is (1) inadequately controlled TLE with ictal fear, and (2) co-occurring panic disorder. Plan: (1) Coordinated with neurology today; neurologist will uptitrate lamotrigine to 250mg BID and obtain repeat EEG, (2) For panic symptoms, will initiate sertraline 50mg daily (safe in epilepsy) and refer for CBT, (3) Patient declines additional ASM given past side effects with levetiracetam (rage attacks). Will reassess panic symptoms after seizure control optimized, as ictal fear may be contributing to anticipatory anxiety. F/u in 2 weeks to monitor lamotrigine uptitration and sertraline response.” | Epilepsy with psychiatric symptoms, need to distinguish ictal from interictal symptoms, complex medication regimens requiring coordination |
Why This Information Matters
Diagnostic accuracy: Seizures, particularly temporal lobe epilepsy, can present with symptoms nearly identical to panic disorder, dissociative disorders, and psychosis. Misdiagnosing epilepsy as a psychiatric disorder delays appropriate treatment, places patients at risk for status epilepticus and SUDEP, and subjects them to ineffective psychiatric interventions. Conversely, misdiagnosing psychogenic nonepileptic seizures or panic attacks as epilepsy leads to unnecessary ASMs with significant side effects and potential harm.
Patient safety and medication selection: Using pro-convulsant psychiatric medications in patients with seizure disorders can precipitate seizures and status epilepticus. Bupropion is absolutely contraindicated in seizure disorders but is commonly prescribed for depression and smoking cessation. Knowledge of seizure history prevents this dangerous error. Similarly, high-dose clozapine in uncontrolled epilepsy creates unacceptable seizure risk.
Recognizing seizure control affects psychiatric risk: Emerging evidence suggests that untreated or poorly controlled epilepsy, particularly temporal lobe epilepsy, may causally contribute to development of mood and anxiety disorders. This means that optimizing seizure control through collaboration with neurology is not just about treating epilepsy, it may also reduce psychiatric symptom burden and prevent progression of psychiatric illness.
Periictal vs interictal distinction matters for treatment: Psychiatric symptoms that are temporally related to seizures (periictal) may improve with better seizure control alone, while interictal psychiatric symptoms require separate psychiatric treatment. Failure to make this distinction may result in over-treatment (adding psychiatric medications for periictal symptoms that would resolve with ASM optimization) or under-treatment (attributing interictal psychiatric symptoms solely to “stress of having epilepsy” and failing to provide effective psychiatric treatment).
Drug interactions and coordination: Many ASMs significantly interact with psychiatric medications through hepatic enzyme induction or inhibition. Carbamazepine can decrease levels of many antidepressants and antipsychotics, potentially leading to psychiatric breakthrough. Valproate increases lamotrigine levels, requiring dose reduction. These interactions necessitate close coordination between psychiatry and neurology and careful monitoring when medication changes are made.
Psychosocial impact: Epilepsy carries significant psychosocial burden: driving restrictions, employment discrimination, seizure-related injuries, fear of seizures in public, and stigma. These factors contribute to psychiatric morbidity independent of direct neurobiological effects. Comprehensive treatment addresses both neurological and psychosocial aspects of living with epilepsy.
Suicidal risk: Epilepsy is associated with 3-5 fold increased risk of suicide, with even higher risk in temporal lobe epilepsy and in the period shortly after epilepsy diagnosis. All patients with epilepsy and psychiatric symptoms require careful suicide risk assessment and safety planning.
The assessment of seizure history in psychiatric patients and recognition of seizures as potential mimics of psychiatric illness is essential for diagnostic accuracy, patient safety, and effective treatment. The brain’s electrical activity and its psychological manifestations are inseparable, and competent psychiatric practice requires understanding this fundamental relationship.
Next in this series: Part 5 – Overview of psychiatric disorders due to medical conditions
Previous post: Part 3 – Head Injury History: Recognizing Traumatic Brain Injury in Psychiatric Evaluation
