Agitation is a state of heightened psychomotor activity characterized by increased arousal, irritability, restlessness, and, at times, aggressive behavior. It can be triggered by a wide range of physiological, psychological, or pharmacological disturbances. The symptom may present acutely or insidiously, and its duration can range from brief episodes to chronic states.

While agitation is not a diagnosis on its own, it often serves as a red flag for an underlying pathological process that requires thorough investigation.

Pathophysiology of agitation

Agitation results from dysregulation of central nervous system (CNS) neurotransmission, particularly involving the following systems:

1. Dopaminergic Pathways

• Hyperdopaminergic activity, especially in the mesolimbic system, is associated with increased motor activity, paranoia, and hallucinations—commonly observed in schizophrenia, mania, and stimulant intoxication.

• Antipsychotic medications work by blocking dopamine D2 receptors to reduce agitation.

2. Serotonergic Dysfunction

• Decreased serotonin levels are implicated in impulsivity, mood instability, and aggression.

• Serotonin plays a critical modulatory role in emotional regulation and inhibition of excessive responses to stimuli.

3. Noradrenergic Overactivity

• Overactivation of the locus coeruleus and noradrenaline release contributes to autonomic arousal, anxiety, and restlessness.

• This is evident in conditions like alcohol or benzodiazepine withdrawal.

4. GABAergic Deficiency

• Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the CNS.

• A decrease in GABAergic tone, such as during benzodiazepine withdrawal or in hepatic encephalopathy, results in loss of inhibitory control, leading to hyperactivity and agitation.

5. Glutamatergic Excitation

• Excessive activation of glutamate receptors (particularly NMDA receptors) leads to neurotoxicity and over-excitation, contributing to symptoms of delirium, seizures, and agitation.

• Seen in acute brain injury, withdrawal syndromes, and some neurodegenerative conditions.

6. HPA Axis and Stress Response

• Chronic or acute stress leads to activation of the hypothalamic-pituitary-adrenal (HPA) axis, increasing cortisol and catecholamine release.

• This neuroendocrine response heightens vigilance and reactivity, predisposing to agitation in susceptible individuals.

Clinical Assessment

History taking

• Severity and Symptoms: Assess the intensity and nature of symptoms such as restlessness, confusion, emotional instability, hallucinations, memory impairment, and aggression.

• Medical History: Inquire about recent infections, trauma, chronic illnesses, medication usage (prescription, over-the-counter, herbal), and known allergies.

• Substance Use: Ask about alcohol, tobacco, and illicit drug use. Look for signs of intoxication or withdrawal (e.g., needle marks, altered pupils).

• Psychosocial Factors: Assess for recent stressors, sleep disturbances, and any psychiatric history.

• Dietary Intake: Poor nutrition and vitamin deficiencies (e.g., B6) may contribute to agitation.

Physical examination

• Vital Signs: Record baseline temperature, heart rate, respiratory rate, and blood pressure.

• Neurological Status: Assess level of consciousness (LOC), motor function, speech, and pupil response.

• Behavioral Observation: Note signs of emotional distress, inappropriate behavior, or psychomotor agitation.

Medical causes of agitation

Table 1: medical causes of agitation, organized by condition, severity of agitation, and associated findings:

Special Considerations

General Management

• Monitor and document vital signs and neurologic changes frequently.

• Reduce environmental stimuli, provide adequate lighting and sleep, and avoid physical restraints unless necessary.

• Provide hydration, nutrition, and vitamin supplementation as indicated.

• Maintain a calm, supportive, and non-confrontational interaction style.

• Prepare for appropriate diagnostic evaluations (CT scan, MRI, X-rays, blood panels).

Patient counseling

• Reassure and orient the patient regularly.

• Provide emotional support and maintain a calm and structured environment.

• Educate the patient and family about stress management and the importance of adherence to treatment.

Age-specific considerations

Pediatric Patients

In children, agitation may accompany infectious diseases or serious conditions like hyperbilirubinemia, phenylketonuria, or lead poisoning. Always use developmentally appropriate language and watch for nonverbal signs of distress.

Geriatric Patients

Elderly individuals may become agitated due to changes in environment or routine. Underlying causes include dementia, sensory impairment, and polypharmacy. Gentle communication and environmental familiarity are crucial.

Conclusion

Agitation is a critical clinical symptom that necessitates a comprehensive diagnostic approach. Identifying the underlying etiology—whether metabolic, neurologic, infectious, or psychiatric—is essential to effective management and improved patient outcomes.

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