How Antipsychotics Affect the EEG

Antipsychotics are essential in treating primary psychotic disorders, including schizophrenia, schizoaffective disorder, and psychotic depression, and are increasingly prescribed for adjunctive use in bipolar disorder, agitation in dementia, irritability in autism, and treatment-resistant mood disorders.

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While most antipsychotics modulate dopamine transmission, their pharmacological diversity has led to the classification of antipsychotics into four functional groups: first-generation (typical), second-generation (atypical), third-generation, and a newly proposed fourth-generation class. The ✽ symbol identifies adverse effects associated with serious clinical risk.

The Clinician Detective

Dr. Ronald Swatzyna, Director and Chief Scientist of the Houston Neuroscience Brain Center, inspired our Clinician Detective series and the EEG-informed psychiatry perspective of this post. In his Association for Applied Psychophysiology and Biofeedback (AAPB) Distinguished Scientist address, he reminded his audience that the DSM-5 advises systematically ruling out general medical conditions before assigning a psychiatric diagnosis to ensure diagnostic validity and appropriate treatment planning.

He argued that in abrupt onset and refractory cases, EEG biomarkers should challenge neurofeedback providers and their medical colleagues to become detectives to identify their causes. This collaborative approach allows each professional to contribute to assessment while "staying in their lane."

Dr. Swatzyna generously mentors professionals in his investigative method, including raw EEG interpretation, to train the next generation of neurofeedback clinicians. Dr. Swatzyna and colleagues have highlighted the clinical importance of EEG biomarkers in explaining medication response and failure. Swatzyna et al. (2024) have shown that certain EEG patterns—such as spindling, excessive beta, focal slowing, diffuse encephalopathy, and isolated epileptiform discharges—predict poor response to specific drug classes.

Dr. Ronald Swatzyna’s Clinician Detective approach, grounded in EEG biomarker profiling, provides a biologically informed framework for understanding who benefits from benzodiazepines—and who may be harmed. In this model, the clinician moves beyond symptomatic labeling and evaluates the patient’s functional brain activity, using the EEG to identify patterns such as spindling excessive beta (SEB), diffuse slowing, or epileptiform discharges that can predict adverse drug reactions or paradoxical effects.

Rather than asking, "Which drug treats psychosis?" the Clinician Detective asks, "What kind of brain is experiencing these positive symptoms? Are there functional causes driving this symptom? How will a specific drug interact with it?"

Case Example: Reversing a Misdiagnosis of Schizophrenia Through EEG and Functional Medicine

Initial Presentation

Ben, a 28-year-old software engineer with no personal or family history of psychiatric illness, had been functioning at a high level both socially and professionally. He was cognitively intact, physically healthy, and emotionally stable.

Approximately 10 months before his decline, he experienced a mild flu-like illness following several weekends of hiking and camping in wooded areas. He recovered quickly and resumed his normal life, dismissing the episode as a seasonal cold.

Three months before referral, Ben began showing subtle but concerning changes. Initially, he complained of fatigue and insomnia. His sleep became fragmented, and he woke feeling unrefreshed.

Over the following weeks, these symptoms evolved into a progressive loss of cognitive sharpness, mild paranoia, and auditory perceptual anomalies. He became convinced that his employer was monitoring his webcam and that certain social media posts contained hidden references to him. He heard indistinct voices and began socially withdrawing. Despite early insight, his functional decline was rapid and uncharacteristic.

Deterioration Under Antipsychotic Treatment

Based on DSM-5 criteria, Ben was diagnosed with schizophrenia and started on antipsychotic therapy. He received three different medications over three months—risperidone, olanzapine, and aripiprazole—each from a different antipsychotic generation. Rather than improving, Ben’s symptoms worsened with each trial. Risperidone caused sedation and emotional flattening but left his paranoia untouched. Olanzapine added weight gain, headaches, and further cognitive dulling. Aripiprazole, expected to preserve cognition, led instead to agitation, pacing, and severe insomnia.

What was not yet known—but would soon become clear—is that Ben’s brain was already in a state of diffuse cortical dysfunction, and these medications—designed to suppress dopaminergic signaling—were further destabilizing his already compromised neurophysiology. His EEG would later reveal a pattern incompatible with primary psychosis, and in retrospect, each antipsychotic made matters worse: not because of resistance, but because they were pharmacologically misaligned with his underlying condition.

His psychiatrist, interpreting the lack of improvement as treatment resistance, began considering antipsychotic augmentation with mood stabilizers or benzodiazepines. This was the first step toward polypharmacy escalation. Fortunately, Ben’s partner requested a second opinion before this course was pursued further. He was referred for an EEG by a clinician trained in Dr. Swatzyna’s EEG-informed model.

EEG Evidence Consistent With Neuroinflammation

A resting-state 19-channel EEG was performed mid-morning under controlled conditions. The results were striking: diffuse theta and delta activity across the scalp, most prominently over frontal and temporal regions; poorly organized posterior alpha rhythm; intermittent frontal delta bursts; and globally reduced coherence.

These findings were not consistent with schizophrenia, which typically produces normal or mildly altered EEG patterns in early stages. Instead, Ben’s EEG resembled toxic-metabolic encephalopathy or neuroinflammatory dysfunction—conditions in which antipsychotics may worsen cortical suppression and delay appropriate care.

The absence of epileptiform activity ruled out seizure-driven psychosis, but the widespread low-frequency slowing signaled that the brain was struggling to maintain normal cortical communication. Alpha blocking was notably absent, suggesting thalamocortical desynchronization. In this context, Ben’s poor response to antipsychotics was no mystery—they were acting on a dysregulated system in ways that exacerbated its instability.

Functional Medicine Evaluation

Given the EEG findings, Ben underwent targeted functional medicine testing. He was found to be positive for both IgM and IgG antibodies to Borrelia burgdorferi, confirming active Lyme disease. Inflammatory markers (IL-6, TNF-alpha, C4a) were significantly elevated, consistent with central nervous system involvement—Lyme neuroborreliosis. Heavy metals, mold toxins, and autoimmune encephalitis markers were negative.

Correct Diagnosis and Reversal

The diagnosis shifted from schizophrenia to Lyme-associated neuroborreliosis, a known but often missed cause of acute-onset psychosis, cognitive impairment, and behavioral changes. The EEG had uncovered what three antipsychotics had masked: a reversible, inflammatory brain disorder.

Ben began a 6-week course of intravenous ceftriaxone, followed by oral doxycycline. Psychiatric medications were tapered and discontinued. Functional support included omega-3s, N-acetylcysteine, curcumin, and glutathione, with neurofeedback targeting alpha rhythm stabilization.

Recovery and EEG Normalization

By week 4 of antimicrobial therapy, paranoia had diminished. By week 6, auditory hallucinations ceased. Cognition steadily improved. At 3 months, Ben returned to part-time work. A repeat EEG at month 4 showed restoration of a 10 Hz posterior dominant alpha rhythm, normalized coherence, and complete resolution of delta intrusions. His electrophysiological and psychiatric recovery were complete.

Lessons Learned

Ben’s case illustrates that antipsychotics can worsen non-psychiatric brain disorders when misapplied, especially in cases of neuroinflammation or encephalopathy.

Each antipsychotic trial Ben underwent acted on an already dysregulated brain in ways that compounded his instability.

Risperidone, a dopamine-serotonin antagonist, initially caused sedation and emotional blunting but failed to suppress psychotic symptoms, likely due to its suppression of thalamocortical circuits in a brain already exhibiting diffuse slowing and reduced alpha coherence.

Olanzapine, with strong antihistaminergic and anticholinergic properties, further exacerbated cortical suppression, increasing slow-wave activity and cognitive fog while adding metabolic side effects that undermined neurological recovery.

Aripiprazole, a dopamine partial agonist considered cognitively neutral in typical cases, had a paradoxical effect in Ben's case—its mild dopaminergic stimulation likely interacted with his neuroinflammatory state to produce agitation, insomnia, and heightened limbic activation.

Rather than restoring balance, each medication introduced new stress to a cortex struggling with neuroimmune dysregulation, amplifying rather than relieving his symptoms. The worsening with each successive drug was not due to medication resistance but to the fundamental mismatch between pharmacologic targets and the actual pathophysiology revealed by the EEG.

Ben's case exemplifies the core insight of Dr. Swatzyna’s clinician detective model: that not all psychiatric symptoms are psychiatric in origin, and that functional abnormalities in brain activity—detectable on the EEG—can signal the presence of invisible, systemic pathology. Without the EEG findings that prompted a deeper search, Ben’s treating psychiatrist likely would have escalated to polypharmacy, adding mood stabilizers or a second antipsychotic in response to each failed trial. This strategy would have been not only ineffective but harmful, compounding side effects while failing to address the real cause of his illness.

In this case, the EEG was not used as a confirmatory test—it was a diagnostic pivot point. It redirected the trajectory of Ben’s care from a dead-end psychiatric protocol to precision, biologically informed treatment that cured the underlying infection and restored normal brain function.

The lesson is clear: in cases of sudden-onset psychiatric symptoms, particularly with poor response to treatment and unusual EEG findings, clinicians must be willing to ask not, “What drug should we try next?” but “What is this brain trying to tell us?” Without that shift in thinking, recovery would have remained out of reach.

Clinical Presentation

First-Generation Antipsychotics

First-generation antipsychotics (FGAs) such as haloperidol and chlorpromazine primarily block dopamine D2 receptors. These medications are effective at treating positive symptoms like hallucinations and delusions but are also known for their high risk of ✽ extrapyramidal side effects, including parkinsonism, dystonia, akathisia, and tardive dyskinesia. Other side effects include sedation, ✽ orthostatic hypotension, and, at high doses, ✽ seizure risk, particularly in vulnerable populations (Stahl, 2017).

Second-Generation Antipsychotics

Second-generation antipsychotics (SGAs) include drugs such as clozapine, olanzapine, and risperidone. These agents antagonize both dopamine D2 and serotonin 5-HT2A receptors, reducing EPS risk and offering efficacy against both positive and negative symptoms. However, they are associated with weight gain, insulin resistance, and lipid abnormalities, particularly in drugs like clozapine and olanzapine. Clozapine also carries the highest risk of ✽ seizure among SGAs, particularly at doses above 500 mg/day (Baik et al., 2011).

Third-Generation Antipsychotics

Third-generation antipsychotics (TGAs) such as aripiprazole, brexpiprazole, and cariprazine act as partial agonists at dopamine D2 and serotonin 5-HT1A receptors, with antagonism at 5-HT2A. These agents are generally well tolerated, with lower sedation and metabolic risk profiles, and are favored in patients requiring maintenance treatment with fewer cognitive and metabolic side effects. Some patients may experience akathisia, restlessness, or impulse control problems, particularly during early titration (Stahl, 2017).

Fourth-Generation Antipsychotics

Fourth-generation antipsychotics (4GAs), represented by xanomeline-trospium (Cobenfy), represent a mechanistic departure. Xanomeline is a muscarinic M1/M4 receptor agonist, while trospium is a peripheral anticholinergic added to limit peripheral cholinergic side effects. Unlike prior generations, Cobenfy does not act directly on dopamine receptors. It has shown promise for both positive and negative symptoms of schizophrenia, with early clinical trials suggesting minimal EPS and metabolic burden (Brannan et al., 2021). Potential side effects include nausea, excessive salivation, and insomnia, though cognitive benefits have also been reported.

EEG Effects of Antipsychotics

EEG studies in humans show that antipsychotics exert class-specific and dose-dependent effects on brain rhythms. These effects reflect pharmacologic action on neurotransmitter systems, including dopamine, serotonin, acetylcholine, histamine, and GABA. EEG changes may predict cognitive side effects, sedation, seizure risk, and even treatment response. By integrating EEG findings into clinical decision-making, psychiatrists can better align medication with the patient’s neurophysiological state.

First-Generation Antipsychotics 

FGAs are associated with widespread slowing of EEG activity, particularly with sedating phenothiazines like chlorpromazine. Studies show increased delta and theta power and decreased alpha and beta activity, consistent with cortical sedation (Hughes et al., 2001; McClelland et al., 1990). Chlorpromazine also slows the posterior dominant rhythm (PDR) and increases frontal theta transients (Demos, 2019). These changes align with clinical observations of cognitive dulling and sedation.

In contrast, haloperidol, a high-potency, nonsedating FGA, has been shown to increase frontal theta transients, with a posterior shift in beta distribution (Merlotti et al., 2007; Yoshimura et al., 2007). Haloperidol’s EEG effects suggest a more focused modulation of subcortical circuits, though it has been associated with epileptiform activation in rare cases, particularly with high doses or in predisposed individuals (Blume, 2006).

Second-Generation Antipsychotics 

SGAs demonstrate variable EEG effects due to differing receptor profiles. Clozapine is notable for producing significant EEG slowing, with increased delta and theta, and reduced alpha and beta power. These changes are most pronounced over frontal and central regions and have been correlated with cognitive impairment and increased seizure risk (Knott et al., 2001; Yoshimura et al., 2007). Joutsiniemi et al. (2001) found clozapine produces distinct frontal and parietal slow-wave topographies, consistent with its sedative and neurophysiologically destabilizing effects. Clozapine has also been associated with paroxysmal activity, including spike-wave discharges in patients at risk (Baik et al., 2011).

Other SGAs such as risperidone and olanzapine produce more modest changes. Risperidone is associated with mild reductions in alpha and increases in frontal theta, especially at higher doses (Brienza et al., 2019). Olanzapine has been shown to slightly increase frontal beta and delta, likely reflecting its anticholinergic and antihistaminergic profile (Yoshimura et al., 2007). These EEG patterns are typically symmetric and reversible, but in sensitive individuals may reflect mild cognitive slowing.

Third-Generation Antipsychotics 

TGAs, including aripiprazole, show minimal EEG disruption. Aripiprazole has been reported to increase low beta power without significantly altering alpha or delta activity (Yoshimura et al., 2007). It preserves posterior alpha rhythm, which is typically associated with alertness and cognitive readiness. EEG findings are consistent with aripiprazole’s clinical reputation for cognitive neutrality. In rare cases, especially with polypharmacy or rapid titration, TGAs have been linked to transient EEG instability, such as beta bursts or subtle epileptiform features in vulnerable patients (Swatzyna et al., 2024).

Fourth-Generation Antipsychotics 

4GAs, such as xanomeline-trospium (Cobenfy), have not yet been extensively studied with EEG in humans. However, based on its central cholinergic activity, it is expected to enhance alpha and beta synchrony, particularly in frontal and parietal areas. Cholinergic stimulation is known to support attentional processing, executive function, and thalamocortical integration, and it has been associated with increased phase locking and coherence in the alpha band during cognitive tasks (Klinkenberg et al., 2011). While cholinergic agonism may improve network coordination, excessive stimulation could, theoretically, lead to REM suppression or paradoxical arousal in patients with trauma or autonomic dysregulation. Trospium, which limits peripheral cholinergic effects, likely has little EEG impact due to its inability to cross the blood–brain barrier.

As clinical use of Cobenfy expands, systematic EEG studies will be essential to clarify its neurophysiological impact and guide its use in populations with baseline cortical dysregulation. Early observations suggest favorable cognitive effects and minimal sedative burden, which may make it a preferred option in patients with cognitive vulnerability or post-antipsychotic EEG suppression.

An EEG-Informed Psychiatry Perspective on Antipsychotic Use

Dr. Ronald Swatzyna’s clinician detective model offers a transformative perspective on antipsychotic prescribing by placing the brain’s functional status—rather than only the patient’s symptoms—at the center of clinical decision-making. His work demonstrates that treatment-resistant psychiatric symptoms often correlate with identifiable EEG abnormalities, and that these electrophysiological findings can reveal systemic, inflammatory, or neurological dysfunctions that mimic psychiatric illness but do not respond to antipsychotic medication (Swatzyna et al., 2024). In this framework, the presence of certain EEG biomarkers may indicate the need for functional medical evaluation before considering psychopharmacological intervention.

One critical EEG biomarker is diffuse slowing, which manifests as elevated delta and theta power across widespread cortical regions and diminished alpha coherence. This pattern is common in patients who present with hallucinations, confusion, or bizarre behavior but lack the classical course or cognitive organization of schizophrenia. Rather than supporting a psychotic disorder diagnosis, diffuse slowing is often indicative of toxic-metabolic encephalopathy, neuroinflammation, or autoimmune brain dysfunction, particularly in elderly individuals or those with recent medical decompensation (Hughes et al., 2001; Swatzyna et al., 2024).

Prescribing antipsychotics in these cases—especially sedating second-generation agents like olanzapine or high-potency first-generation drugs—may worsen mental status, leading to increased risk for falls, aspiration, or catatonia-like states. Instead, such EEG findings should prompt testing for electrolyte imbalances, liver and renal function, thyroid panel, C-reactive protein, and autoimmune antibodies. In many cases, symptoms resolve with correction of the underlying medical cause—no antipsychotic required.

Focal slowing, characterized by a localized increase in theta or delta activity, often in temporal or frontal regions, suggests structural or functional impairment of specific cortical networks. In patients with new-onset psychosis or disorganized behavior, focal slowing on the EEG may indicate temporal lobe epilepsy, head trauma, or vascular anomalies, particularly when unilateral and consistent across recordings (Demos, 2019; Joutsiniemi et al., 2001).

Antipsychotics are frequently prescribed to such patients under the assumption of primary psychosis, but this may obscure the true etiology. Before committing to long-term dopamine blockade, clinicians should obtain high-resolution MRI, neurovascular studies, or, in some cases, lumbar puncture. These investigations can uncover silent infarcts, mass lesions, or inflammatory processes that account for focal slowing and psychiatric symptoms. Without the EEG, these patients may be misdiagnosed and exposed to years of inappropriate pharmacotherapy.

Epileptiform discharges, such as spikes, sharp waves, or polyspike bursts, are also frequently misinterpreted or minimized in psychiatric populations. However, studies have shown that such patterns, especially when arising from temporal or frontotemporal leads, are strongly associated with episodic aggression, affective lability, and brief psychotic episodes (Baik et al., 2011; Knott et al., 2001). These events are sometimes subclinical seizures or forms of limbic irritability, not schizophrenia or mania.

Antipsychotics in these cases may be not only ineffective but dangerous—particularly agents like clozapine, which lower the seizure threshold (Yoshimura et al., 2007). Patients with EEG-confirmed epileptiform discharges are often better served by anticonvulsant therapy, sometimes with low-dose benzodiazepines or immunomodulatory treatment, depending on the underlying pathology. Swatzyna’s data show that a significant portion of patients labeled as treatment-resistant psychotic or bipolar disorder exhibit these biomarkers and improve only when treated for seizure-related or inflammatory neuropsychiatric conditions (Swatzyna et al., 2024).

A fourth EEG biomarker of importance is spindling excessive beta (SEB), a pattern of high-amplitude, rhythmic beta activity in the 20–25 Hz range, typically over frontal or frontocentral regions. SEB is frequently seen in patients with complex PTSD, developmental trauma, or autonomic dysregulation, where it reflects cortical hyperarousal and limbic overactivation (Swatzyna et al., 2024). These patients often present with agitation, paranoia, or dissociation and may be mistakenly diagnosed with mania or psychosis.

Prescribing dopamine antagonists to individuals with SEB can exacerbate insomnia, inner restlessness, and even dissociative states. Activating third-generation antipsychotics like aripiprazole can further amplify beta activity and precipitate emotional destabilization. Instead, the EEG points toward the need to evaluate HPA axis function, cortisol dysregulation, and chronic stress physiology. These patients often benefit more from trauma-informed interventions, limbic-calming neurofeedback, and autonomic retraining than from neuroleptic medication.

The utility of the EEG in these scenarios lies in its ability to signal when symptoms are downstream effects of systemic or environmental insults, not merely psychiatric phenomena.

When the EEG is abnormal in ways that suggest encephalopathy, focal compromise, seizure susceptibility, or trauma-related hyperarousal, the appropriate next step is often functional or integrative medical testing. These tests might include panels for mold exposure (e.g., mycotoxins), heavy metals (e.g., mercury, lead), mitochondrial function, vitamin and mineral status, and immune dysregulation (e.g., anti-NMDA receptor antibodies). Dr. Swatzyna’s clinical data demonstrate that pursuing these root causes often leads to resolution of psychiatric symptoms without the need for long-term pharmacotherapy.

In contrast, a normal EEG—characterized by stable posterior alpha, minimal slow-wave activity, and absence of epileptiform discharges—may support a primary psychiatric diagnosis, particularly when symptoms are chronic, non-cyclic, and without identifiable physiological correlates. In such cases, antipsychotic medications may be appropriate and effective, particularly when chosen based on individual tolerability and cognitive side effect profile.

An EEG-informed psychiatry perspective does not reject antipsychotics. It refines their use by identifying who is likely to respond, who may deteriorate, and who requires a different form of evaluation altogether. The EEG becomes the bridge between psychiatry and internal medicine, allowing clinicians to detect neurophysiological patterns that point beyond dopamine and into the broader terrain of brain-body interaction. By using the EEG not only as a monitoring tool but as a frontline diagnostic asset, clinicians can offer precision treatment, reduce iatrogenic harm, and unlock recovery pathways that would otherwise be missed.

What We Wish Clinicians Knew About Diagnosing Sudden-Onset Schizophrenia

Sudden-onset psychosis in an otherwise high-functioning individual is often interpreted through a narrow lens: if symptoms meet DSM-5 criteria for schizophrenia and no obvious medical etiology is found on basic lab work or imaging, a diagnosis of first-episode psychosis is assigned, and antipsychotic treatment initiated. While this may be appropriate in some cases, clinicians should recognize that de novo psychosis is not always primary. It may instead be the earliest manifestation of inflammatory, infectious, autoimmune, toxic, or metabolic brain dysfunction—syndromes that are not distinguishable by symptoms alone and are frequently misdiagnosed as schizophrenia (Endres et al., 2015; Swatzyna et al., 2024).

What many clinicians may not realize is that the EEG is often more sensitive than standard neuroimaging or labs in detecting early cortical dysfunction, particularly where psychosis is secondary to systemic illnesses like Lyme disease.

Studies show that patients with autoimmune encephalitis, neuroborreliosis, or paraneoplastic syndromes may present with hallucinations and delusions, but exhibit normal MRI and CT scans, while their EEGs reveal diffuse slowing, frontal delta bursts, or epileptiform discharges, pointing to underlying cortical irritability or encephalopathy (Baik et al., 2011; Kelley et al., 2017). In these cases, routine psychiatric evaluation and imaging may fail to identify the source of the dysfunction, while the EEG provides a functional readout of brain activity that can redirect the diagnostic pathway.

Additionally, we wish clinicians knew that the absence of prodromal symptoms—such as social withdrawal, cognitive decline, or attenuated psychotic features—should raise red flags. The typical developmental trajectory of schizophrenia involves a gradual deterioration in social and executive functioning during adolescence or early adulthood (van Os et al., 2010). When psychosis appears suddenly, in a neurologically intact individual with no psychiatric history, clinicians should expand their differential. Infections like Lyme disease, Herpes Simplex Virus, or Mycoplasma pneumoniae have all been implicated in neuroinflammatory psychosis, and respond not to dopamine blockade, but to antibiotic or immunosuppressive treatment (Fallon et al., 1997; Hansen et al., 2021).

Polypharmacy is another trap clinicians fall into when antipsychotics fail. Rather than re-evaluating the diagnosis, the instinct is to add a mood stabilizer, benzodiazepine, or a second antipsychotic, assuming treatment resistance. This approach compounds sedation and metabolic burden, often leading to iatrogenic worsening. Dr. Swatzyna’s EEG-guided model reveals that in many of these cases, the problem is not a lack of drug effect—but inappropriate treatment of the wrong condition. In his cohort of over a thousand refractory cases, patients who failed multiple psychiatric medications were frequently found to have one or more functional EEG biomarkers—such as diffuse slowing or epileptiform discharges—that suggested the need for functional medicine testing rather than pharmacologic escalation (Swatzyna et al., 2024).

We also wish more psychiatrists appreciated that psychosis is a symptom, not a disease, and that not all psychosis is schizophrenia. EEG findings like spindling beta, subclinical spikes, or impaired alpha rhythms provide objective evidence that the brain is dysregulated—but not necessarily in a way that corresponds to psychiatric disease categories. These patterns are better understood as signals of a functional brain in distress, whether due to trauma, inflammation, infection, or toxicity. When clinicians recognize this, they open the door to recovery pathways that conventional psychopharmacology alone cannot access.

Ultimately, what we wish clinicians knew is this: in sudden-onset psychosis, the EEG should be a standard part of the diagnostic process, and abnormal findings should prompt targeted investigations for underlying systemic contributors. Treating schizophrenia without confirming its biological plausibility risks not only prolonged suffering but also cementing incorrect diagnoses that shape a patient's life for years. EEG-informed psychiatry doesn’t reject medication—but it demands that treatment be guided by the brain’s actual function, not just the checklist of symptoms.

Key Takeaways

1. Sudden-onset psychosis is not always schizophrenia—When psychosis appears de novo in a high-functioning individual without prodrome, systemic or neurological causes should be investigated.

   
   

2. The EEG can detect cortical dysfunction missed by MRI or labs—Findings like diffuse slowing, frontal delta, or epileptiform discharges often reveal encephalopathy or neuroinflammation not evident on structural imaging.

   
   

3. Treatment resistance may signal misdiagnosis—Failure to respond to antipsychotics should prompt reassessment, not escalation to polypharmacy, especially when EEG abnormalities suggest an underlying infectious or inflammatory process.

   
   

4. Psychosis is a symptom, not a disease—The EEG helps differentiate between primary psychiatric illness and secondary causes such as Lyme disease or autoimmune encephalitis, guiding targeted intervention.

   
   

5. EEG-informed psychiatry expands diagnostic accuracy—Using the EEG as a frontline tool in first-episode psychosis allows clinicians to uncover hidden biological drivers and personalize treatment beyond standard psychiatric algorithms.

Glossary

affective lability: rapid, often unpredictable shifts in emotional state; may be associated with limbic dysregulation or epileptiform activity.

akathisia: a distressing sense of inner restlessness accompanied by excessive movement, often a side effect of antipsychotic medications.

anticonvulsant therapy: treatment using medications that stabilize neuronal membranes to reduce seizure activity and cortical hyperexcitability.

autoimmune antibodies: immune proteins targeting the body’s own tissues; their presence can indicate autoimmune encephalitis affecting the brain.

autoimmune brain dysfunction: neurological and psychiatric symptoms caused by the immune system attacking brain tissue, often mimicking primary psychiatric disorders.

brexpiprazole: a third-generation antipsychotic that acts as a partial dopamine D2 agonist with serotonin receptor modulation, generally preserving cognitive function.

cariprazine: a third-generation antipsychotic known for targeting dopamine D3 receptors, with use in schizophrenia and bipolar disorder.

cognitive neutrality: a pharmacological profile indicating minimal impact on attention, memory, or executive function, often desired in antipsychotic treatment.

complex PTSD: a trauma-related condition involving chronic emotional dysregulation and dissociation, often associated with cortical hyperarousal.

coherence in the alpha band: a measure of synchronized alpha activity between brain regions, reflecting functional network integrity.

cortical hyperarousal: a state of excessive beta activity in the EEG, often linked to anxiety, trauma, or stimulant use.

C-reactive protein: a blood marker of systemic inflammation; elevated levels can suggest underlying infection, autoimmune disease, or neuroinflammation.

developmental trauma: early-life adverse experiences that disrupt brain development and regulation, often reflected in abnormal EEG patterns.

dystonia: a movement disorder characterized by involuntary muscle contractions, often caused by dopamine-blocking medications.

episodic aggression brief, unprovoked outbursts of anger or violence that may be linked to limbic irritability or epileptiform discharges.

epileptiform discharges: abnormal EEG waveforms, such as spikes or sharp waves, indicating increased cortical excitability or seizure risk.

extrapyramidal side effects (EPS): a group of motor symptoms—including tremor, rigidity, and restlessness—caused by dopamine receptor antagonism.

first-generation antipsychotics (FGAs): dopamine D2 antagonists known for high EPS risk and EEG slowing; includes drugs like haloperidol and chlorpromazine.

frontal slow-wave topographies: EEG patterns showing excess delta or theta in frontal regions, often associated with cognitive impairment or drug effects.

frontal theta transients: brief bursts of theta activity over the frontal cortex, typically indicating sedation, encephalopathy, or disrupted executive function.

functional medical evaluation: a diagnostic approach assessing systemic contributors to neuropsychiatric symptoms, such as inflammation, infections, and endocrine disorders.

head trauma: physical injury to the brain that can cause focal EEG slowing, seizures, or neuropsychiatric symptoms.

insulin resistance: a metabolic state where cells respond poorly to insulin, commonly associated with weight gain from second-generation antipsychotics.

limbic irritability: a condition in which the limbic system becomes overactive, often leading to episodic mood swings, paranoia, or aggression.

neuroinflammation: inflammatory processes affecting the central nervous system, often leading to EEG slowing and cognitive symptoms.

orthostatic hypotension: a drop in blood pressure upon standing, common with antipsychotics, especially those with anticholinergic or alpha-blocking properties.

paradoxical arousal: a counterintuitive increase in alertness or agitation in response to sedative medications, often seen in trauma-affected patients.

parietal slow-wave topographies: excess low-frequency EEG activity over parietal regions, associated with sensory integration deficits or sedation.

parkinsonism: a cluster of symptoms—tremor, rigidity, bradykinesia—mimicking Parkinson’s disease, caused by dopamine blockade.

phase locking: a measure of neural synchrony, where different brain regions fire at consistent phases; enhanced by cholinergic modulation.

posterior shift in beta distribution: a movement of beta activity toward parietal regions on EEG, sometimes observed with high-potency antipsychotics like haloperidol.

restlessness: a subjective or observable inability to remain still, often a manifestation of akathisia or inner agitation.

REM suppression: reduction in rapid eye movement sleep, sometimes induced by antipsychotics or cholinergic drugs.

second-generation antipsychotics (SGAs): dopamine-serotonin antagonists with reduced EPS risk but increased metabolic side effects; includes clozapine and olanzapine.

spindling excessive beta (SEB): a pattern of rhythmic, high-amplitude beta activity suggesting cortical overarousal and poor tolerance for activating medications.

tardive dyskinesia: a late-onset movement disorder involving involuntary facial or limb movements, often irreversible and caused by long-term antipsychotic use.

temporal lobe epilepsy: a form of epilepsy originating in the temporal lobes, often presenting with mood instability, paranoia, or episodic psychosis.

thalamocortical integration: the coordinated activity between the thalamus and cortex, critical for attention and consciousness; disrupted in many neuropsychiatric conditions.

third-generation antipsychotics (TGAs):dopamine partial agonists like aripiprazole and brexpiprazole that balance dopaminergic tone with fewer cognitive side effects.

thyroid panel: a set of blood tests assessing thyroid function; abnormalities may contribute to psychiatric symptoms or EEG slowing.

toxic-metabolic encephalopathy: brain dysfunction resulting from toxins or metabolic imbalance; EEG typically shows diffuse slowing and disorganized rhythms.

transient EEG instability: temporary disruption of normal EEG rhythms, potentially indicating vulnerability to seizures, metabolic insult, or drug side effects.

vascular anomalies: abnormal blood vessels in the brain that may lead to localized EEG slowing, stroke, or seizure activity.

fourth-generation antipsychotics (4GAs): newer agents like xanomeline-trospium that act on muscarinic receptors rather than dopamine, aiming to reduce side effects and enhance cognition.

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