What is the treatment for a mephedrone overdose?

Treatment of Mephedrone Overdose

Mephedrone overdose should be managed with supportive care focused on controlling sympathomimetic toxicity—there is no specific antidote, and treatment centers on managing agitation, hypertension, tachycardia, and hyperthermia using benzodiazepines as first-line therapy.

Initial Stabilization and Assessment

Immediately assess airway, breathing, and circulation with continuous cardiorespiratory monitoring. 1, 2 The priority is securing the airway and providing assisted ventilation if respiratory depression occurs, though this is less common with pure sympathomimetic toxicity. 1

• Obtain IV access and perform bedside glucose testing to rule out hypoglycemia as a cause of altered mental status 2, 3
• Establish continuous cardiac monitoring with serial ECGs to detect arrhythmias 2, 3
• Monitor vital signs continuously, watching specifically for tachycardia (heart rate >140 bpm), severe hypertension (systolic BP ≥160 mmHg), and hyperthermia 4, 5

Understanding Mephedrone Toxicity

Mephedrone produces a sympathomimetic toxidrome clinically indistinguishable from MDMA or cocaine overdose. 4 The most common presentations include:

• Cardiovascular effects: Tachycardia (mean heart rate 109 bpm, range 80-140), hypertension (mean systolic BP 153 mmHg, range 110-210), palpitations, and chest pain 4, 6
• Neuropsychiatric effects: Agitation (most common), anxiety, paranoid delusions, visual and kinesthetic hallucinations, and potential for seizures 7, 4, 5
• Increased cardiac contractility: Elevated cardiac output, ejection fraction, and stroke volume similar to methamphetamine 6

Specific Management Strategies

Control Agitation and Seizures

Benzodiazepines are the first-line treatment for agitation, anxiety, and seizures associated with sympathomimetic overdose. 1, 3 Titrate doses to achieve adequate sedation and control of sympathomimetic symptoms.

• Agitation was the most common presenting symptom in confirmed mephedrone toxicity cases 4
• Benzodiazepines also help reduce tachycardia and hypertension indirectly by decreasing sympathetic outflow 1

Manage Cardiovascular Complications

For persistent severe hypertension or tachycardia despite benzodiazepines:

• Consider short-acting beta-blockers or calcium channel blockers cautiously 1
• Avoid pure beta-blockers in isolation due to risk of unopposed alpha-adrenergic stimulation 1
• The cardiovascular effects persist even after reserpine pretreatment, suggesting direct sympathomimetic action 6

Temperature Control

Monitor for hyperthermia, which can occur with sympathomimetic toxicity and requires aggressive cooling measures if present. 4, 5

Laboratory and Diagnostic Workup

• Comprehensive metabolic panel including electrolytes, renal function, and hepatic function 3
• Complete blood count 3
• Urine drug screen to identify co-ingestants, particularly other stimulants, opioids, or alcohol 3, 5
• Cardiac biomarkers if chest pain is present 4
• Arterial or venous blood gas if respiratory compromise exists 3

Note that 30 patients in one case series used mephedrone in isolation, while 27 used it with alcohol, highlighting the importance of screening for co-ingestants. 5

Critical Pitfalls to Avoid

Do not assume naloxone will be helpful—mephedrone is not an opioid and naloxone has no role in pure mephedrone toxicity. 1 However, polysubstance use is common, so if respiratory depression is prominent, consider co-ingestion of opioids. 5

Do not use flumazenil if benzodiazepines were administered therapeutically or if co-ingestion with other substances is suspected, as this can precipitate seizures. 1, 3

Do not discharge patients prematurely—psychiatric complications including paranoid psychosis and intense craving have been reported, requiring extended observation. 7, 5

Observation and Disposition

Patients should be observed in a healthcare setting until vital signs normalize and psychiatric symptoms resolve. 1, 2, 8

• Minimum observation period should extend until sympathomimetic symptoms completely resolve 2, 3
• ICU admission criteria include severe hypertension, significant arrhythmias, seizures, or severe agitation requiring continuous sedation 3
• Mandatory psychiatric evaluation before discharge to assess for substance use disorder and suicide risk, as compulsive use patterns and addiction have been documented 2, 7, 5

Long-term Considerations

Mephedrone produces intense craving and compulsive drug use patterns, with high rates of bingeing and addiction reported. 7, 5 Patients require substance abuse treatment referral and psychiatric follow-up, as there is no approved pharmacological treatment for mephedrone dependence. 9