How Benzodiazepines Affect the EEG

Overview

Benzodiazepines, once a mainstay of anxiety treatment, are now prescribed more cautiously, particularly for long-term use. Over the past two decades, their role in managing chronic anxiety has increasingly been replaced by antidepressants such as SSRIs and SNRIs, due to concerns about tolerance, dependence, withdrawal, cognitive impairment, and interaction with other CNS depressants (Baldwin et al., 2014). Antidepressants, despite their slower onset, are preferred for maintenance treatment because they lack the addictive potential and sedative burden that characterize benzodiazepines.

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 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 anxiety?" the Clinician Detective asks, "What kind of brain is experiencing this anxiety? Are there functional causes driving this symptom? How will a specific drug interact with it?"

Case Example

Kara, a 32-year-old elementary school teacher with no prior psychiatric history, presented with a 4-month history of persistent anxiety, sleep disturbances, and difficulty concentrating. She had always been high-functioning, both socially and professionally, and was known for her emotional resilience and energy in the classroom. The anxiety appeared suddenly, without an identifiable psychological trigger. It was not focused on specific thoughts or situations, but rather felt like a pervasive internal unease. She described feeling “wired but tired,” with frequent early awakenings, physical tension, and an inability to settle her mind.

Her primary care provider initially diagnosed her with generalized anxiety disorder and prescribed escitalopram. Within days, she experienced worsening sleep, increased jitteriness, and a feeling of detachment. After discontinuing the medication, she was started on sertraline, but this too made her feel overstimulated and emotionally flattened. When cognitive behavioral therapy provided little benefit and her symptoms persisted, she was referred for a more in-depth evaluation.

Kara underwent assessment with a clinician using Dr. Swatzyna’s EEG-informed psychiatry approach, which emphasizes the use of electroencephalography (EEG) to identify functional brain abnormalities that may underlie psychiatric symptoms. During the interview, she noted that her symptoms began soon after she moved to a newly renovated classroom. She recalled a persistent synthetic odor but had not considered it relevant.

Her EEG revealed several abnormalities. A prominent feature was spindling excessive beta (SEB), a pattern of high-amplitude, rhythmic beta activity between 20 and 25 Hz over the frontocentral scalp regions. SEB is often associated with hyperarousal, trauma-related dysregulation, and poor tolerance for stimulatory or serotonergic medications. Additionally, her EEG revealed intermittent delta bursts in the left temporal region, indicating localized cortical irritability. The posterior dominant alpha rhythm, typically a marker of relaxed wakefulness, was attenuated and unstable, pointing to disturbed thalamocortical regulation.

These findings suggested that Kara’s symptoms were likely secondary to environmental effects on cortical function rather than a primary anxiety disorder. Based on the temporal relationship between her symptom onset and the relocation to the classroom, an environmental assessment was initiated. Air sampling revealed elevated levels of formaldehyde, benzene, and toluene—compounds commonly released during renovation from adhesives, insulation, and flooring. Formaldehyde levels exceeded 100 parts per billion, a concentration known to provoke neurologic and respiratory symptoms in sensitive individuals. A urinary mycotoxin panel identified low-level ochratoxin A exposure, consistent with mild mold contamination.

The working diagnosis was environmentally induced cortical hyperexcitability, resulting in neurophysiological dysregulation and anxiety-like symptoms. Kara was placed on temporary leave from her classroom and moved to a low-exposure environment. Her treatment plan was designed to support neural recovery. It included daily supplementation with N-acetylcysteine to promote glutathione production, omega-3 fatty acids to reduce neuroinflammation, and behavioral interventions to regulate autonomic activity. She also began neurofeedback focused on reducing excessive beta activity in the frontocentral region.

No psychotropic medications were reintroduced during this period. Within four weeks, her anxiety diminished significantly, her sleep returned to normal, and her cognitive clarity improved. A repeat EEG performed 6 weeks after environmental withdrawal showed resolution of SEB, normalization of the posterior alpha rhythm, and absence of temporal delta bursts. Her EEG was now consistent with a regulated resting state.

Kara returned to work after 3 months, reassigned to a different building. She resumed teaching without difficulty and remained symptom-free in follow-up. Her case highlights the importance of identifying nonpsychiatric factors that contribute to emotional and cognitive symptoms. Her anxiety, initially presumed to be a primary mood disorder, was a manifestation of neurotoxic exposure.

From the Clinician Detective perspective, this case underscores a fundamental tenet of EEG-informed psychiatry: psychiatric symptoms often reflect functional brain disturbance, not necessarily primary mental illness. The EEG was not simply a confirmation tool—it was a clinical compass that redirected her care. In complex or refractory cases, evaluating the brain’s electrical function can uncover root causes that medications alone cannot resolve. For patients like Kara, EEG-guided inquiry into environmental and physiological contributors can mean the difference between chronic misdiagnosis and full recovery.

Clinical Presentation 

Benzodiazepines are grouped into four pharmacokinetic subtypes based on elimination half-life and receptor specificity: long-acting, intermediate-acting, short-acting, and benzodiazepine receptor agonist (BZRA) hypnotics. This classification informs both clinical decisions and expectations about EEG changes.

For example, longer-acting agents accumulate over time and may cause daytime sedation or confusion, while short-acting agents can produce abrupt shifts in cortical activation, sometimes worsening the very symptoms they aim to treat.

The diversity in EEG effects across this class reinforces the need for individualized, biomarker-informed prescribing.

The ✽ symbol identifies adverse effects associated with serious clinical risk.

Long-Acting Benzodiazepines

Diazepam (Valium) and clonazepam (Klonopin) are commonly used for their extended duration of action and broad-spectrum efficacy in anxiety, seizures, spasticity, and alcohol withdrawal. Their sedative and anxiolytic effects are sustained by active metabolites, making them useful in acute and chronic conditions. However, their long half-lives also increase the risk of cognitive dulling, delayed psychomotor recovery, and next-day sedation, especially in older adults or those with underlying cognitive impairment.

In patients with EEG evidence of cortical slowing or impaired thalamocortical regulation, long-acting benzodiazepines may suppress neural networks excessively, leading to disorientation, slowed reaction time, or worsening of attention. Paradoxical reactions such as emotional dysregulation or behavioral disinhibition have also been observed, particularly in patients with frontotemporal instability, trauma history, or prefrontal EEG abnormalities.

Intermediate-Acting Benzodiazepines

Lorazepam (Ativan) and oxazepam (Serax) provide a balance between rapid onset and moderate duration, making them ideal for short-term use in agitation, procedural sedation, and alcohol withdrawal. Because they lack active metabolites, these agents are often preferred in older adults and those with hepatic dysfunction.

Though generally well-tolerated, intermediate-acting benzodiazepines can still produce confusion, memory interference, and attentional narrowing, particularly in individuals with temporal slowing or diffuse EEG suppression. Paradoxical effects—such as increased impulsivity or irritability—are not uncommon in neurologically vulnerable populations. In such cases, careful EEG review prior to prescribing can identify patients at risk for adverse responses.

Short-Acting Benzodiazepines

Alprazolam (Xanax) and triazolam (Halcion) have fast onset and short half-lives, which makes them useful for panic disorder and sleep-onset insomnia, respectively. However, their brief duration increases the risk of rebound symptoms, physiological dependence, and withdrawal-related mood instability.

Clinicians frequently encounter patients who experience emotional lability, agitation, or cognitive impairment during dose tapering or missed doses. These reactions are especially pronounced in individuals with elevated cortical excitability, as evidenced by intermittent beta spindling or sharp wave discharges on EEG. In such cases, these drugs may exacerbate rather than relieve symptoms.

BZRA Hypnotics

BZRA hypnotics like zolpidem (Ambien), eszopiclone (Lunesta), and zaleplon (Sonata) selectively bind the α1 subunit of the GABA-A receptor, inducing sedation with minimal anxiolytic or muscle relaxant effects. While marketed as safer alternatives for insomnia, they are associated with anterograde amnesia, impaired motor coordination, and complex sleep behaviors, including sleepwalking, driving, and eating during sleep.

These effects are particularly concerning in older patients and those with slowed cortical rhythms or frontal dysregulation, where sleep-related disinhibition may lead to falls, disorientation, or hallucinations. In EEG-informed practice, BZRAs should be prescribed cautiously in patients with pre-existing diffuse slowing, thalamocortical disruption, or impaired alpha rhythm organization.

EEG Effects

Long-Acting Benzodiazepines

EEG studies of long-acting benzodiazepines such as diazepam reveal widespread effects on cortical rhythms. These include suppression of alpha activity, increased frontocentral beta power, and attenuated coherence between hemispheres, particularly in the temporal and parietal regions. One study noted significant reductions in 1–6 Hz, 8–12 Hz, and 19–35 Hz EEG power bands, alongside disrupted temporal coupling, suggesting that long-acting benzodiazepines dampen both excitatory and integrative functions of the cortex (Muñoz-Torres et al., 2011).

In clinical terms, these changes correlate with slowed cognition, flattened affect, and impaired working memory. For individuals with baseline EEG slowing, long-acting benzodiazepines may push cortical networks into a state of functional underactivation, resembling encephalopathy.

Intermediate-Acting Benzodiazepines

Lorazepam typically increases low-amplitude beta activity while moderately suppressing alpha rhythm, especially in frontal leads. These effects are symmetrical and dose-dependent, generally preserving EEG integrity in healthy individuals. However, in patients with pre-existing temporal lobe slowing, lorazepam may further depress network synchrony, leading to mild to moderate cognitive and executive dysfunction.

Prolonged use or high cumulative dosing may shift the EEG toward a mixed theta-beta state, a marker of inefficient cortical regulation often associated with slowed processing speed and mental fog.

Short-Acting Benzodiazepines

EEG changes observed with alprazolam and triazolam include increased sigma (12–15 Hz) and high-frequency beta, often accompanied by reduced delta and theta power, particularly during early sleep stages (Tan et al., 2003). These agents enhance spindle activity, which may improve sleep initiation, but often at the expense of deep restorative sleep, particularly in vulnerable populations such as the elderly.

REM suppression and altered REM onset latency have been reported with triazolam, potentially exacerbating mood instability in patients with depressive or bipolar disorders. In patients with SEB, the further increase in beta activity may elevate emotional reactivity, contradicting the intended sedative effect.

BZRA Hypnotics

BZRA hypnotics like zolpidem increase frontal beta and sigma activity, while suppressing slow-wave (delta and theta) oscillations during non-REM sleep. This EEG profile supports sleep initiation but may interfere with memory consolidation, emotional regulation, and homeostatic plasticity, especially in individuals with reduced baseline alpha power or diffuse EEG slowing.

In patients with traumatic brain injury, IEDs, or executive dysfunction, zolpidem has been linked to episodes of delirium, perceptual distortion, or emotional flattening. EEG during these events often reveals frontal desynchronization and low-amplitude polymorphic theta, resembling toxic-metabolic or limbic encephalopathic patterns.

An EEG-Informed Psychiatry Perspective

In Dr. Swatzyna’s EEG-informed model, the decision to prescribe benzodiazepines is based not just on symptom clusters, but on the brain’s capacity to tolerate or benefit from GABAergic modulation. This requires attention to EEG biomarkers that signal cortical instability, inhibitory network dysfunction, or subclinical excitability.

For example, patients with spindling excessive beta—a high-amplitude, spindle-shaped beta rhythm often found in trauma-exposed or hypervigilant individuals—may paradoxically worsen when exposed to benzodiazepines that amplify beta. Instead of sedation, these patients often report increased anxiety, vigilance, or emotional dysregulation. Similarly, patients with intermittent epileptiform discharges may be temporarily stabilized by benzodiazepines, but there is a risk of worsening instability upon abrupt withdrawal.

In contrast, patients with excess frontal theta, low beta, and hypoarousal may respond favorably to moderate, carefully titrated doses of intermediate-acting benzodiazepines like lorazepam. These cases benefit from reduced overactivity in limbic circuits and a temporary enhancement of thalamocortical rhythmicity.

The worst outcomes often result from prescribing without EEG data, particularly in populations with known vulnerability: elderly patients, individuals with head injury, or those with chronic insomnia and mood instability. By integrating EEG findings into prescribing decisions, clinicians can prevent adverse reactions, tailor medication choices, and reduce reliance on trial-and-error methods.

Benzodiazepines remain powerful and effective tools when used judiciously. However, without EEG insight, they risk destabilizing already fragile neural networks. The future of safe prescribing lies in aligning medication selection with cortical function, bringing neurophysiology back into the heart of psychiatric decision-making.​

Key Takeaways

1. Benzodiazepines vary widely in EEG and clinical effects—Subtypes differ by half-life and receptor affinity, influencing sedation, rebound symptoms, and cortical modulation.

   
   

2. EEG biomarkers predict benzodiazepine tolerance and risk—Spindling beta, diffuse slowing, or epileptiform discharges help identify patients likely to experience paradoxical reactions, cognitive decline, or withdrawal instability.

   
   

3. Short-acting agents pose higher risk for rebound and destabilization—Drugs like alprazolam and triazolam may amplify cortical excitability in vulnerable individuals, especially without EEG guidance.

   
   

4. BZRA hypnotics are not universally safer—Zolpidem and similar agents can cause disorientation, sleep disturbances, and EEG desynchronization, particularly in older adults or those with frontal dysfunction.

   
   

5. EEG-informed prescribing is essential for safe use—Dr. Swatzyna’s Clinician Detective model emphasizes matching benzodiazepine type and dose to the brain’s functional profile, reducing adverse outcomes and enhancing precision in psychiatric care.

Glossary

alpha rhythm: an EEG frequency range of 8–12 Hz typically associated with relaxed wakefulness. Benzodiazepines commonly reduce alpha power, particularly over posterior regions.

anterograde amnesia: the impaired ability to form new memories after drug administration, often associated with benzodiazepines and BZRA hypnotics.

benzodiazepine receptor agonist (BZRA) hypnotics: non-benzodiazepine drugs that bind to the benzodiazepine site on the GABA-A receptor, primarily targeting the α1 subunit to induce sedation (e.g., zolpidem, eszopiclone).

beta activity: an EEG frequency band (13–30 Hz) associated with alertness and cognitive engagement. Benzodiazepines typically increase beta activity, especially in the 20–30 Hz range.

cortical excitability: a measure of how easily the cerebral cortex responds to stimuli. Elevated excitability may increase the risk for seizures, mood lability, or paradoxical drug reactions.

diffuse slowing: generalized EEG slowing, often indicating widespread cerebral dysfunction, commonly seen in metabolic encephalopathy or advanced age.

disinhibition: a behavioral phenomenon where inhibitory control is reduced, leading to impulsivity or aggression. It can be a side effect of benzodiazepines, particularly in patients with frontal lobe dysfunction.

epileptiform discharges: transient EEG patterns such as spikes or sharp waves that reflect cortical hyperexcitability, even in the absence of clinical seizures.

frontotemporal instability: a disruption in the function or connectivity of the frontal and temporal lobes, often associated with impulsivity, mood instability, or altered cognition.

gamma activity: high-frequency EEG oscillations (>30 Hz) associated with cognitive processing and perceptual integration. Not typically enhanced by benzodiazepines.

GABA-A receptor: a ligand-gated chloride channel that mediates inhibitory neurotransmission in the brain. Benzodiazepines enhance the receptor's function, increasing neural inhibition.

half-life: the time required for the concentration of a drug in the plasma to decrease by half. Determines the duration of action and accumulation potential of benzodiazepines.

interhemispheric coherence: a measure of synchronized EEG activity between the brain’s hemispheres. Benzodiazepines may reduce coherence, especially in temporal regions.

lorazepam: an intermediate-acting benzodiazepine with minimal hepatic metabolism, commonly used for agitation, seizures, and alcohol withdrawal.

Muñoz-Torres pattern: an EEG signature seen with diazepam involving suppression of alpha, beta, and delta bands, along with impaired temporal coupling.

paradoxical agitation: an adverse reaction where a sedative agent induces increased agitation, irritability, or aggression rather than calming effects.

posterior dominant rhythm (PDR): the dominant alpha rhythm seen over occipital areas in relaxed wakefulness. Often diminished by sedative medications.

REM suppression: a reduction in rapid eye movement sleep duration, which may be induced by certain benzodiazepines or hypnotics, affecting mood and memory.

rebound anxiety: the worsening of anxiety symptoms following abrupt discontinuation or missed doses of short-acting benzodiazepines.

spindling excessive beta (SEB): an EEG biomarker characterized by rhythmic, spindle-shaped beta activity, often indicating cortical hyperarousal or trauma-related dysregulation.

sigma activity: EEG activity in the 12–15 Hz range associated with sleep spindles during stage 2 non-REM sleep. Often increased by benzodiazepines.

sleep architecture: the structure and progression of sleep stages throughout the night. Benzodiazepines and BZRAs can alter sleep architecture by reducing deep sleep and REM.

spindles: short bursts of sigma-frequency EEG activity during stage 2 sleep, associated with memory consolidation and sleep stability.

thalamocortical dysrhythmia: disruption in rhythmic signaling between the thalamus and cortex, associated with slow-wave abnormalities and cognitive impairment.

theta activity: EEG activity in the 4–8 Hz range, associated with drowsiness and early sleep stages. It may be increased by sedatives or in cognitive disorders.

withdrawal syndrome: a constellation of symptoms—including anxiety, tremors, insomnia, and seizures—that can occur when benzodiazepines are abruptly discontinued.

References

Baldwin, D. S., Aitchison, K., Bateson, A., Curran, H. V., Davies, S., Leonard, B., Nutt, D. J., Stephens, D. N., Wilson, S., & Young, A. H. (2014). Benzodiazepines: Risks and benefits. British Journal of Psychiatry, 205(2), 97–101. https://doi.org/10.1192/bjp.bp.113.141937

Brienza, M., Cianflone, F., & Bonanni, L. (2019). EEG alterations induced by psychotropic drugs: A review. Clinical EEG and Neuroscience, 50(1), 6–17. https://doi.org/10.1177/1550059418786447

Demos, J. N. (2019). Getting started with neurofeedback (2nd ed.). W. W. Norton & Company.

Muñoz-Torres, C., Walter, M., Dierks, T., & Koenig, T. (2011). Diazepam-induced EEG changes in healthy volunteers: Topographical distribution and source localization analysis. Neuropsychobiology, 63(4), 203–209. https://doi.org/10.1159/000323526

Stahl, S. M. (2017). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). Cambridge University Press. https://doi.org/10.1017/9781108235936

Swatzyna, R. J., Morrow, L. M., Collins, D. M., Barr, E. A., Roark, A. J., & Turner, R. P.(2024). Evidentiary significance of routine EEG in refractory cases: A paradigm shift in psychiatry. Clinical EEG and Neuroscience. Advance online publication. https://doi.org/10.1177/15500594231221313

Tan, X., Campbell, I. G., Palagini, L., & Feinberg, I. (2003). High dose benzodiazepine effects on sleep EEG power spectra in healthy young adults. Journal of Psychopharmacology, 17(2), 189–194. https://doi.org/10.1177/026988110301700201