Understanding Agitation: Causes and Symptoms

by Mazin A Mukhtar

You Have A New Patient!

A 35-year-old male was brought to the emergency department by police due to violent behavior, including damaging vehicles and threatening individuals in a public area. On initial assessment, he was highly agitated, hostile, and uncooperative, exhibiting signs of psychomotor agitation characterized by verbal outbursts, exaggerated hand gestures, and shouting phrases such as “Leave me!”

He demonstrated persecutory delusions, expressing a belief that law enforcement and medical personnel were conspiring to harm him by damaging his brain, which necessitated his transport to the hospital.

Despite stable vital signs, his aggressive and uncooperative behavior made a complete physical examination impractical. Efforts at verbal de-escalation and pharmacologic intervention with rapid tranquilization were ineffective. Given the severity of his agitation and the potential risk to himself and others, physical restraints were applied to ensure safety. Following stabilization, the patient was initiated on an oral antipsychotic regimen, which resulted in a gradual return to baseline functioning within three weeks.

Introduction

Psychosis is one of the most common presentations in hospital emergencies and can sometimes pose significant challenges for physicians. The main challenges in managing psychosis include the uncooperativeness of patients during the acute phase and the unavailability of collateral resources, particularly when the patient is brought in from the street [1]. Physicians must remain vigilant to avoid overlooking organic disorders that present with behavioral disturbances. Approximately three out of 100 people will experience at least one episode of psychosis during their lifetimes.

During psychosis, patients’ thoughts and perceptions are distorted, leading to difficulty in distinguishing what is real from what is unreal, which can result in violent behavior.

The symptoms of psychosis can be categorized into two dimensions [2]:

Positive symptoms: These involve the acquisition of new symptoms, including delusions, hallucinations, disorganized speech, and disorganized behavior.
Negative symptoms: These involve the loss of abilities or functions, such as alogia, avolition, flattening of affect (reduced facial expression), self-neglect, or social withdrawal.

Psychosis can occur in various psychiatric disorders, such as schizophrenia spectrum disorders, bipolar disorder, and major depressive disorder. It can also manifest as a result of substance use or other medical conditions [3].

General Approach and History Taking

Always ensure the safety of yourself and your staff. Be mindful of both verbal and nonverbal communication. Listen actively to your patient and demonstrate genuine interest in their story. Use open-ended questions to encourage the patient to express what’s on their mind. Maintain a neutral stance and avoid showing approval or disapproval unless absolutely necessary. Be honest and sincere to build a trusting relationship.

Remember, when there is a risk to the patient or others, confidentiality may need to be overridden. Ensure that you gather the highest-quality information to inform your decisions. Perform a thorough physical examination and order the necessary investigations. Always consider potential organic causes of psychiatric manifestations.

Document your assessment and decisions clearly and comprehensively. Do not hesitate to act immediately if the situation demands urgent intervention [4].

Evaluating an acutely agitated patient presents unique challenges, as obtaining a thorough history is often difficult [5,6]. Despite these limitations, gathering as much information as possible is critical, and collateral information from family, emergency personnel, or police can be invaluable. Key elements to obtain include the patient’s past medical and psychiatric history, including any current or past psychotropic medications and known allergies. A detailed review of home medications and social history—such as alcohol use, substance abuse, living situation, and caregiving arrangements—can provide important context. Recent health changes, such as headaches, which might suggest an intracranial process, or dysuria in elderly patients, which could indicate urosepsis, should also be explored. Establishing the patient’s baseline mental status is vital to differentiate acute changes from pre-existing conditions. While history is often a cornerstone of diagnosis, in cases of acute agitation, a thorough physical examination becomes even more essential due to the frequent limitations of the patient’s ability to provide accurate information.

Differential Diagnoses

When evaluating a patient presenting with acute agitation or psychosis, it is essential to consider a broad differential diagnosis encompassing both organic (medical) and inorganic (psychiatric) causes. Organic causes are often rooted in medical conditions such as hypercalcemia, hypercapnia, hypoxia, and infections like encephalitis, meningitis, or sepsis. Substance-related causes, including the use of alcohol, hallucinogens, steroids, stimulants, or synthetic marijuana, must also be considered. Other organic disorders, such as delirium, hypoglycemia, stroke, carbon dioxide poisoning, neurosyphilis, Wilson’s disease, AIDS, vitamin B12 deficiency, and drug overdose, should be ruled out early in the evaluation. Drug-related problems, including intoxication, withdrawal, or complications like Wernicke’s encephalopathy, also warrant investigation [5,6].

In contrast, inorganic causes are primarily psychiatric and include schizophrenia spectrum disorders, bipolar disorder, posttraumatic stress disorder (PTSD), psychotic depression, and mood disorders with psychotic features, such as major depressive disorder or bipolar affective disorder. Other psychiatric considerations include malingering, factitious disorders, personality disorders (e.g., schizoid, schizotypal, or borderline personality disorders), and autistic spectrum disorders [5,6].

Differentiating between organic and inorganic causes is critical, particularly in cases of acute, undifferentiated agitation where limited history and physical examination findings may complicate the assessment. Organic causes often present with abnormal vital signs, disorientation, fluctuating symptoms, or signs of trauma, indicating an underlying medical condition. In contrast, inorganic causes typically lack these features, suggesting a primary psychiatric etiology. A thorough evaluation of symptoms and key clinical features is essential to guide diagnosis and management effectively [5,6].

Physical Examination

In cases of acute agitation, a thorough physical examination is critical due to the typically limited history and review of systems. The examination should include a comprehensive neurologic evaluation and a head-to-toe inspection for signs of trauma or injury. Although a full neurologic examination may not always be feasible during the initial assessment, it should be completed as soon as possible and before final disposition [6].

The first priority in the physical examination is to assess and ensure the patient’s airway, breathing, and circulation (ABCs) are intact. This process begins with a focus on safety, as the patient may pose an immediate threat to themselves or medical staff. Factors such as the patient’s age, psychiatric history, suspected or known substance abuse, and the severity of their agitation should be considered when determining the need for intervention, including medication. The patient should be placed on monitors, and a complete set of vital signs, including temperature, should be obtained [6].

The primary survey of the patient can be guided by the mnemonic “ABCDE” [6]. A stands for airway, assessing its patency to ensure there are no obstructions. B involves evaluating respiratory effort and adequacy. C focuses on circulation, ensuring adequate perfusion and ruling out hypotension or arrhythmias. D addresses disability by assessing the patient’s level of consciousness and screening for reversible causes of altered mental status, such as hypoglycemia, hypoxemia, or abnormal pupil responses. Finally, E involves exposing the patient fully by changing them into a hospital gown to facilitate a rapid visual assessment for trauma or concealed items such as weapons.

A full neurologic examination should be performed as soon as possible to evaluate for underlying neurologic conditions contributing to the agitation [6]. Additionally, a head-to-toe inspection is essential to identify any signs of trauma or physical injury that may explain the presentation [6]. In cases of acute undifferentiated agitation, the examination findings can help differentiate between organic and inorganic causes. Organic causes are often associated with abnormal vital signs, disorientation, fluctuating symptoms, or signs of trauma. In contrast, inorganic causes, such as primary psychiatric conditions, typically lack these features. A systematic and detailed physical examination is crucial for identifying the underlying cause and guiding appropriate management.

A thorough physical examination is also important, as individuals with psychiatric disorders have a mortality rate 2-4 times higher than that of the general population. Deviations in vital signs may signal infections, while abnormalities in pupil size (constriction or dilation) can indicate substance use or withdrawal. Signs such as optic neuritis, neuropathy, and muscle weakness should prompt consideration of multiple sclerosis. A bull’s-eye rash suggests Lyme disease, while a malar rash may indicate systemic lupus erythematosus (SLE).

Dermatitis, particularly on exposed skin, may point to pellagra (vitamin B3 deficiency), and choreiform movements raise suspicion for Huntington’s disease. Findings such as a pill-rolling tremor and bradykinesia are characteristic of Parkinson’s disease, whereas tremor, dysarthria, and gait disturbances may suggest Wilson’s disease. Cognitive assessments revealing memory impairment and disorientation are consistent with dementia, while deficits in attention and orientation often indicate delirium [7].

Diagnostic Testing

The investigation of psychosis should be guided by findings from the physical examination, ensuring that potential underlying medical causes of behavioral disturbances are identified and addressed. A series of common tests are routinely performed to evaluate possible contributing factors.

Hematology screening is conducted to rule out anemia, which can impact mental and physical health. Urea and creatinine levels are measured to assess for uremia, a condition associated with kidney dysfunction that may present with altered mental status. Similarly, glucose levels are checked to exclude hypoglycemia or hyperglycemia, both of which can lead to behavioral disturbances or psychosis.

Urine screening plays a pivotal role in identifying substance abuse, a common and reversible cause of psychotic symptoms [8]. Additionally, urine analysis is performed to detect urinary tract infections or alterations in pH, which could indicate tampering, such as dilution with water, in cases of drug screening.

Inflammatory and autoimmune causes are considered through tests like ESR (erythrocyte sedimentation rate), which helps identify systemic inflammatory processes, and antinuclear antibodies (ANA), used to rule out autoimmune diseases that may present with neuropsychiatric symptoms. Screening for infectious diseases is crucial, particularly for conditions like HIV, hepatitis B and C, and neurosyphilis, which are known to affect the central nervous system and contribute to psychosis.

For suspected metabolic or genetic causes, ceruloplasmin levels may be assessed to rule out Wilson’s disease, a rare disorder that can lead to neuropsychiatric symptoms. CT scans are considered in specific circumstances, such as cases of late-onset psychosis, to identify structural brain abnormalities or other intracranial pathologies [9].

These investigations provide a systematic approach to diagnosing psychosis by addressing potential medical, infectious, metabolic, and autoimmune causes, ensuring comprehensive and accurate patient evaluation.

Management

The management of psychosis, particularly in acute cases, requires a holistic approach grounded in the biopsychosocial model, addressing biological, social, and psychological factors to ensure comprehensive care. The primary goals are to recognize the issue early, intervene before behavior escalates, stabilize life-threatening conditions, and ensure the safety of both the individual and others [6]. A systematic approach combining non-pharmacological and pharmacological interventions is critical for achieving these objectives while addressing the underlying causes of agitation or psychosis [10].

A thorough risk assessment is an essential first step for patients presenting with acute psychosis or agitation in the emergency department. Tools such as the unstructured interview, HCR-20, and DASSA scales can help determine the appropriate level of observation and the patient’s disposition [11]. When verbal de-escalation or medication fails to control aggression, physical or mechanical restraints may be necessary. Before applying restraints, the physician should clearly explain the rationale to the patient, and staff should remain nearby to provide reassurance, alleviate fear, and release the patient as soon as they are calm. This integrated approach ensures patient safety while promoting stabilization and recovery.

The first step in managing an acutely agitated or psychotic patient is to assess and ensure that the patient’s airway, breathing, and circulation (ABCs) are intact. If the patient poses an immediate threat to themselves or medical staff, factors such as age, psychiatric history, substance use, and severity of agitation should guide the intervention. Patients should be placed on monitors, and a complete set of vital signs, including temperature, should be obtained. A primary survey using the ABCDE mnemonic is critical (details are given in the physical examination section):

A: Assess airway patency.
B: Evaluate respiratory effort and adequacy.
C: Ensure adequate circulation, ruling out hypotension or arrhythmias.
D: Assess consciousness, check pupils, and measure blood glucose.
E: Fully expose the patient to identify signs of trauma or concealed weapons.

The management of psychosis is best approached through a biopsychosocial model, which addresses biological, social, and psychological factors across three stages: immediate, intermediate, and long-term management. This structured approach combines non-pharmacological and pharmacological strategies, creating a comprehensive framework to ensure patient safety, stabilization, and recovery while preventing future episodes [6].

Biological management focuses on medication to address the symptoms of psychosis. In the immediate phase, oral antipsychotics should be offered, with injectable options used if the patient refuses. Pharmacological interventions typically involve the use of antipsychotics and benzodiazepines [6], administered intramuscularly or intravenously for rapid tranquilization. Haloperidol, an antipsychotic, is effective for patients with a known history or high suspicion of psychosis [6]. Lorazepam, a benzodiazepine, is preferred for undifferentiated agitation or psychosis due to its anxiolytic properties and efficacy in cases of substance-related psychosis, such as PCP intoxication or alcohol withdrawal [6]. During the intermediate phase, medication dosages should be adjusted, and side effects closely monitored. In the long-term phase, maintaining a stable medication regimen helps prevent relapse and ensures sustained symptom control.

Social management emphasizes the importance of stabilizing the patient’s environment and facilitating reintegration. Immediate interventions may include hospital admission to relieve family burdens and ensure patient safety. In the intermediate phase, a social study can identify stressors contributing to the psychosis, while long-term support focuses on helping the patient return to work or prior activities to promote social reintegration.

Psychological management addresses both the patient’s and family’s understanding and adaptation to the condition. In the immediate phase, family education provides insight into the condition and support mechanisms. Non-pharmacological strategies are essential for creating a safe and calming environment [6]. These include environmental modifications such as screening for weapons, minimizing noise, and dimming lights to reduce sensory overstimulation. De-escalation techniques, such as establishing rapport, addressing basic needs (e.g., safety, hunger, and comfort), and maintaining a calm, respectful demeanor, can effectively reduce agitation [6]. Acknowledging the patient’s feelings, respecting personal space, and avoiding confrontational behavior further enhance the effectiveness of these strategies. When non-pharmacological approaches fail, mechanical restraints or seclusion may be used as a last resort, though these measures carry risks and should be applied cautiously. During the intermediate phase, psychometric tools like the Positive and Negative Syndrome Scale (PANSS) can assess symptom severity and progression. The long-term phase emphasizes ongoing psychological support to prevent relapse, enhance insight, and promote well-being.

Medications

The pharmacological management of agitated patients involves the use of various drug categories, each tailored to the severity of agitation and underlying clinical conditions. Below is an overview of the commonly used pharmacological agents, their dosages, onset times, and important considerations [1].

First-Generation Antipsychotics

Haloperidol (Haldol)
Haloperidol is commonly used for agitation across mild, moderate, and severe cases. The dosage varies depending on the severity: 2.5 mg orally for mild cases, 5 mg orally for moderate agitation, and 5 mg intramuscularly for severe agitation. The time of onset is approximately 30 minutes for all routes. However, haloperidol carries a high risk of extrapyramidal symptoms (EPS). Co-administration with agents such as benztropine, diphenhydramine, lorazepam, or promethazine can help reduce this risk. Care should be taken to avoid combining three of these medications simultaneously. Intravenous use is associated with an increased risk of QTc prolongation, and the medication may lower the seizure threshold. The maximum daily dose is 30 mg, and repeat dosing is allowed every 0.5–4 hours as needed.
Droperidol (Inapsine)
Droperidol is primarily used in severe agitation, with a dose of 5 mg administered intramuscularly or intravenously. The onset of action is faster than haloperidol, typically around 15 minutes. It shares a similar risk profile for EPS and QTc prolongation. Combining droperidol with midazolam (5 mg) is recommended to optimize efficacy. The maximum daily dose ranges between 10–20 mg.

Second-Generation Antipsychotics

Olanzapine (Zyprexa)
Olanzapine is effective for agitation and can be administered as 5 mg orally disintegrating tablets (ODT) for mild cases, 5–10 mg ODT for moderate cases, and 10 mg intramuscularly for severe agitation. The onset of action is approximately 15–60 minutes depending on the route of administration. Concomitant use with benzodiazepines should be avoided within one hour. The maximum daily dose is 20 mg.
Risperidone (Risperdal)
Risperidone is used at 1 mg ODT for mild agitation and 2 mg ODT for moderate agitation, with an onset time of approximately 60 minutes. It is particularly effective for undifferentiated or substance-related agitation but should not be used in cases of CNS depressant intoxication. Risperidone carries the highest risk of EPS among second-generation antipsychotics and may cause orthostatic hypotension. Repeat dosing is allowed every 4–6 hours, but caution is advised for doses exceeding 10 mg per day.
Ziprasidone (Geodon)
Ziprasidone is typically reserved for severe agitation, with doses of 10–20 mg intramuscularly and an onset time of 15–30 minutes. It has a high risk of QTc prolongation, exceeding even that of haloperidol, making it unsuitable for patients with cardiac disease or pre-existing QTc prolongation. The medication requires reconstitution before administration, and the maximum daily dose is 40 mg.

Benzodiazepines

Lorazepam (Ativan)
Lorazepam is a versatile benzodiazepine used for mild agitation (2 mg orally), moderate agitation (5 mg intramuscularly or 2.5 mg intravenously), and severe agitation (10 mg intramuscularly or 5 mg intravenously). The onset of action is 20–30 minutes for oral administration and faster for intramuscular or intravenous routes. While effective for undifferentiated agitation, caution is required in patients with CNS depression (e.g., ethanol intoxication).
Midazolam (Versed)
Midazolam, administered as 5 mg intramuscularly or intravenously, has a faster onset time of 5–15 minutes depending on the route. It is often used in combination with haloperidol or droperidol for severe agitation. Care must be taken due to its sedative effects.

Dissociative Anesthetic

Ketamine (Ketalar)
Ketamine is a dissociative anesthetic used for severely agitated patients, such as those experiencing excited delirium. Doses range from 1–2 mg/kg intravenously or up to 5 mg/kg intramuscularly, with an onset time of 1–2 minutes (IV) or 3 minutes (IM). Ketamine can cause emergence reactions, bronchorrhea, and, rarely, laryngospasm, and may increase the need for intubation. It is known to elevate heart rate, cardiac output, and blood pressure, making it suitable for patients requiring rapid sedation.

When To Admit This Patient

Disposition decisions for acutely agitated or psychotic patients should be guided by the underlying cause of the agitation, once the patient has been stabilized [6]. For cases involving organic causes, such as sepsis, acute intracranial hemorrhage, or severe metabolic disturbances, hospitalization is necessary until the underlying condition is adequately treated and stabilized. Patients with substance-induced psychosis may be eligible for discharge if they are no longer clinically intoxicated and have returned to their baseline mental status. However, if a thorough medical evaluation reveals no medical cause for the agitation or psychosis, the patient should undergo a psychiatric assessment [6]. Psychiatric admission is typically indicated for patients with acute psychosis due to an underlying psychiatric disorder if they pose a high risk of harm to themselves or others. Additionally, admission is strongly recommended for first episodes of psychosis attributed to psychiatric causes to ensure appropriate evaluation and management [6].

Clinical Pearls

Patients with a brief psychotic disorder experience psychotic symptoms that last at least one day but not more than one month, with gradual recovery. If symptoms persist beyond one month but less than six months, the condition is termed schizophreniform disorder. If symptoms extend beyond six months, it is classified as schizophrenia [12].
Children and elderly patients should generally be dosed at the lower end of the dosing spectrum to account for their increased sensitivity to medications.
Neuroleptic malignant syndrome can develop at any time during treatment. Physicians should remain vigilant for clinical symptoms, which include hyperthermia, muscle rigidity, altered mental status, and autonomic dysregulation.

Revisiting Your Patient

This patient presented with prominent symptoms of grossly disorganized behavior, auditory hallucinations, and paranoid delusions, followed by a rapid return to baseline mental state, consistent with a diagnosis of Brief Psychotic Disorder (BPD) [12]. This diagnosis includes two specifiers: with marked stressors or without marked stressors, previously classified under the term Brief Reactive Psychosis.

When a patient is admitted with an unclear duration of psychotic symptoms, they are often initially diagnosed with Unspecified Psychotic Disorder. However, if symptoms resolve within one month, the diagnosis is revised to Brief Psychotic Disorder. Antipsychotic treatment has been shown to reduce the duration of symptoms in BPD, facilitating quicker recovery. If symptoms persist beyond one month, the diagnosis transitions to Schizophreniform Disorder; persistence beyond six months supports a diagnosis of Schizophrenia.

Positive symptoms, such as hallucinations and delusions, are generally associated with a better prognosis than negative symptoms due to their typically acute onset and favorable response to treatment. It is critical to exclude organic etiologies, medication side effects, or substance-induced psychosis through a comprehensive physical examination and targeted investigations based on clinical findings. In this case, all relevant investigations were unremarkable, supporting a primary psychotic diagnosis.

Author

Mazin A Mukhtar

Dr. Mazin Mukhtar is a psychiatrist with over 15 years of experience, currently practicing at Amal Hospital in Dubai. Before moving to Dubai, Dr. Mukhtar served as an Assistant Professor of Psychiatry at the University of Bahri, where he was appointed as Head of the Department in 2015. In addition to his qualifications in psychiatry, Dr. Mukhtar has a strong interest in leadership and holds a Professional Diploma in Clinical Leadership from the Royal College of Surgeons of Ireland. He also possesses a Clinical Diploma in Cognitive Behavioural Therapy (CBT) from Notting Hill College.

Listen to the chapter

References

Roppolo LP, Morris DW, Khan F, et al. Improving the management of acutely agitated patients in the emergency department through implementation of Project BETA (Best Practices in the Evaluation and Treatment of Agitation). J Am Coll Emerg Physicians Open. 2020;1(5):898-907. doi:10.1002/emp2.12138.
Psych Central. What Are the Symptoms of Psychosis? Updated May 28, 2021. Accessed January 10, 2025. https://psychcentral.com/lib/symptoms-of-psychosis#signs-and-symptoms.
National Institute of Mental Health. Understanding Psychosis. Updated 2023. Accessed January 10, 2025. https://www.nimh.nih.gov/health/publications/understanding-psychosis.
Harrison PJ, Cowen P, Burns T, Fazel M. Shorter Oxford Textbook of Psychiatry. 7th ed. Oxford University Press; 2018.
Sadock BJ, Sadock VA, Ruiz P. Kaplan & Sadock’s Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. 11th ed. Wolters Kluwer; 2015.
Chan M, Moukaddam N, Tucci V. Stabilization and Management of the Acutely Agitated or Psychotic Patient. International Emergency Medicine Education Project. Accessed January 10, 2025. https://iem-student.org/stabilization-and-management-of-the-acutely-agitated-or-psychotic-patient/.
Vyas CM, Petriceks AH, Paudel S, Donovan AL, Stern TA. Acute Psychosis. Prim Care Companion CNS Disord. 2023;25(2). doi:10.4088/pcc.22f03338.
Reidy L, Junquera P, Van Dijck K, Steele BW, Nemeroff CB. Underestimation of substance abuse in psychiatric patients by conventional hospital screening. J Psychiatr Res. 2014;59:206-212. doi:10.1016/j.jpsychires.2014.08.020.
Khandanpour N, Hoggard N, Connolly DJA. The role of MRI and CT of the brain in first episodes of psychosis. Clin Radiol. 2013;68(3):245-250. doi:10.1016/j.crad.2012.07.010.
Schleifer JJ. Management of acute agitation in psychosis: an evidence-based approach in the USA. Adv Psychiatr Treat. 2011;17(2):91-100. doi:10.1192/apt.bp.109.007310.
Frick PJ, Barry CT, Kamphaus RW. Structured Diagnostic Interviews. In: Clinical Assessment of Child and Adolescent Personality and Behavior. 3rd ed. Springer; 2010:253-270. doi:10.1007/978-1-4419-0641-0_11.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 5th ed. American Psychiatric Publishing; 2013.

Reviewed and Edited By

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.