What Drugs are Used for PSH? A Guide to Pharmacological Management

October 14, 2025 •

4 min read

Affecting up to one-third of severe traumatic brain injury survivors, paroxysmal sympathetic hyperactivity (PSH) is a serious neurological syndrome requiring swift intervention. PSH, also known as neurostorming or autonomic storming, is characterized by episodes of heightened sympathetic nervous system activity, necessitating a multi-modal pharmacological approach to manage and mitigate its effects. The drugs used for PSH target different aspects of the condition to stabilize the patient and prevent further complications.

Quick Summary

Pharmacological management of PSH involves a combination of drugs to control symptoms like tachycardia, hypertension, and hyperthermia. Medications are categorized into abortive therapies for acute episodes and preventative therapies for long-term control. Key drug classes include beta-blockers, alpha-2 agonists, opioids, and GABAergic agents.

Key Points

Diverse Drug Classes: PSH is managed using multiple drug classes, including beta-blockers, alpha-2 agonists, opioids, and GABAergic agents, to control various symptoms.
Preventative vs. Abortive Therapy: Medications serve distinct roles, with some used for continuous, preventative management (e.g., propranolol) and others for immediate, abortive treatment of acute episodes (e.g., morphine).
Propranolol for Prevention: The lipophilic beta-blocker propranolol is a first-line preventative agent due to its ability to act on the central nervous system to control heart rate and blood pressure.
Morphine for Acute Episodes: For severe, acute sympathetic storms, intravenous morphine is often the most effective abortive therapy.
Gabapentin for Long-Term Control: Gabapentin is a well-tolerated long-term preventative option that helps modulate excitatory neurotransmission and address pain-related triggers.
Baclofen for Spasticity: A GABA-B receptor agonist, baclofen, is used for muscle spasticity, with intrathecal delivery offering superior results for refractory cases.
Individualized, Multimodal Approach: Successful PSH management requires a personalized, combination therapy approach, as no single drug is effective for all patients or symptoms.

Understanding Paroxysmal Sympathetic Hyperactivity

Paroxysmal sympathetic hyperactivity (PSH) is a debilitating condition that can occur after a severe acquired brain injury, including traumatic brain injury (TBI), anoxic brain injury, or stroke. It is characterized by episodes of uncontrolled sympathetic nervous system discharge, leading to a constellation of symptoms that can increase patient morbidity and prolong recovery. These symptoms include tachycardia, hypertension, tachypnea, hyperthermia, and diaphoresis, often accompanied by motor phenomena like posturing or dystonia. Treatment is crucial for managing these severe symptoms and reducing the risk of adverse events like cardiac hypertrophy, muscle wasting, and prolonged hospitalization. The cornerstone of management is a multimodal pharmacological strategy tailored to the individual patient.

Categories of Pharmacological Treatment for PSH

Medications for PSH fall into several categories, each targeting a specific component of the sympathetic overactivity. A combination of agents is often required, addressing different aspects of the sympathetic surge and associated motor symptoms.

Beta-Blockers

Beta-blockers are a cornerstone of preventative therapy for PSH, primarily used to control tachycardia and hypertension.

Propranolol: A non-selective, lipophilic beta-blocker that can cross the blood-brain barrier, allowing it to exert central effects. It helps blunt the sympathetic response and is considered a front-line preventative agent.
Labetalol: This agent has both alpha and beta-blocking properties, making it effective for relieving both hypertension and tachycardia.

Alpha-2 Agonists

These agents act centrally to reduce sympathetic outflow from the brain, helping to control cardiovascular symptoms.

Dexmedetomidine: A potent intravenous alpha-2 agonist commonly used in the intensive care unit (ICU) setting. It provides sedation and anxiolysis with limited respiratory depression, making it valuable for managing severe PSH episodes.
Clonidine: An oral alpha-2 agonist that can be used for long-term management. Patients who respond well to dexmedetomidine may be transitioned to clonidine.

Opioids

Opioids are particularly effective as abortive therapy for severe, acute PSH episodes, especially those triggered by noxious stimuli or associated with pain.

Morphine: Often the most effective and preferred abortive agent, given intravenously during acute episodes.
Fentanyl: Offers a faster onset than morphine and is also used for acute episode control.

GABAergic Agents

This class includes several drugs that enhance inhibitory neurotransmission in the central nervous system.

Gabapentin: A GABA analog used for prevention, often for long-term use. It modulates excitatory neurotransmission and helps control the allodynic responses that can trigger PSH.
Baclofen: A GABAB receptor agonist that is effective for managing muscle spasticity and dystonia. While oral baclofen is an option, intrathecal baclofen, delivered directly to the spinal cord, can be more effective for severe, refractory cases.
Benzodiazepines: Short-acting agents like midazolam or diazepam can be used for acute episodes, while longer-acting options like clonazepam are sometimes used for preventative effects. However, long-term use can lead to tolerance and delirium.

Dopamine D2 Agonists

Bromocriptine: This agent acts on dopamine receptors in the hypothalamus and is primarily used for refractory hyperthermia. It is typically reserved as a third-line agent due to potential side effects like confusion and dyskinesia.

Muscle Relaxants

Dantrolene: This drug can be used to treat muscle rigidity and spasticity. Its use is limited by potential hepatotoxicity.

Comparison of Key Medications for PSH


Drug Class	Example Drugs	Primary Use	Key Considerations
Beta-Blockers	Propranolol, Labetalol	Prevention (Tachycardia, Hypertension)	Propranolol's lipophilic nature allows central action. Avoid in patients with bradycardia or hypotension.
Alpha-2 Agonists	Dexmedetomidine, Clonidine	Prevention/Treatment (Tachycardia, Hypertension, Agitation)	Dexmedetomidine for ICU. Clonidine for long-term oral use. Can cause bradycardia and hypotension.
Opioids	Morphine, Fentanyl	Abortive (Severe Episodes, Pain)	Highly effective for acute crises. Responsiveness can support diagnosis. Use with caution due to dependence risk.
GABAergic Agents	Gabapentin, Baclofen, Benzodiazepines	Prevention & Symptom Management (Allodynia, Spasticity, Agitation)	Gabapentin for long-term use, low side effect profile. Intrathecal baclofen for refractory spasticity. Long-term benzodiazepine use can cause tolerance.
Dopamine Agonists	Bromocriptine	Refractory Hyperthermia	Third-line agent with potential for neurological side effects.

Multimodal Strategy and Individualized Care

The most effective approach to PSH management is a multimodal strategy, combining medications from different classes to address the broad spectrum of symptoms. Treatment should be individualized based on the patient's specific presentation, severity, and response to therapy. Patients often require scheduled preventative medications, with abortive therapies available for breakthrough episodes. For instance, a patient might be on scheduled oral propranolol and gabapentin for prevention, with intravenous morphine reserved for severe, acute episodes. Management is a dynamic process, with medications and dosages constantly adjusted as the patient’s condition evolves.

Non-pharmacological interventions are also critical. Minimizing environmental stimuli, such as loud noises or excessive handling, can help reduce triggers for sympathetic paroxysms. Adequate nutrition and hydration are also vital, as the hypermetabolic state associated with PSH can lead to muscle wasting and dehydration.

Conclusion: The Path to Symptom Management

While the pathophysiology of PSH is still being fully elucidated, targeted pharmacological management with a diverse toolkit of medications is critical for patient stabilization and improved outcomes. A combination of preventative agents like beta-blockers, alpha-2 agonists, and gabapentin, alongside abortive therapies such as opioids and benzodiazepines, is the current standard of care. There is no one-size-fits-all solution, and successful treatment hinges on a careful, individualized strategy that balances symptom control with potential side effects. As research continues to advance, our understanding of PSH and the optimal use of these medications will undoubtedly improve.

For more detailed clinical practice information, consult the EMCrit Project's Paroxysmal sympathetic hyperactivity (PSH) resource.

Frequently Asked Questions

A combination of drugs is often necessary because PSH presents with a wide range of symptoms, including cardiovascular instability, hyperthermia, and motor symptoms. Medications from different classes are used to target these various symptoms simultaneously and create a more comprehensive and effective management strategy.

Abortive therapy, using fast-acting drugs like intravenous morphine or benzodiazepines, is used to stop an acute, severe episode of PSH. Preventative therapy, involving scheduled, long-acting medications like propranolol or gabapentin, aims to reduce the frequency and severity of future episodes.

While benzodiazepines like clonazepam are sometimes used for preventative effects, their long-term use is limited by the potential for tolerance, withdrawal symptoms, and increased rates of delirium. They are more frequently used for acute symptom control.

Propranolol is a non-selective beta-blocker that, due to its lipophilic properties, can cross the blood-brain barrier. It helps treat PSH by directly antagonizing central sympathetic overactivity, effectively controlling heart rate and blood pressure.

Intrathecal baclofen is a GABAB receptor agonist delivered directly to the spinal fluid. It is used to manage severe spasticity and dystonia, particularly in patients with refractory PSH who have not responded well to oral medications.

Morphine is highly effective for aborting severe PSH episodes, likely by modulating autonomic reflex pathways and inhibiting central sympathetic output via opioid receptors. It can help blunt the disproportionate 'fight or flight' response often seen in PSH, which is especially useful when pain is a trigger.

Yes, PSH is a diagnosis of exclusion and can be misdiagnosed due to overlapping symptoms with other conditions. The paroxysmal nature of PSH symptoms, which include fever and autonomic changes, can mimic conditions like sepsis, drug withdrawal, neuroleptic malignant syndrome, or pulmonary embolism.