Table 2. Algorithm for the diagnosis and treatment of agitated/aggressive persons following psychostimulant use; adapted from (22, 34-36).

Step-by-step procedure	Recommendation	Comment
1. Infrastructure, prevention, preparation	Room planning (optimal lighting, spaciousness, escape routes, quiet working environment) Training measures (de-escalation, communication methods, etc.)
2. Alerting	Define alarm cascade Alarm button/alert Additional staff support for the treatment team Alerting the police or security forces after consultation	Escalation of agitated/aggressive behavior after use of psychostimulants frequently exceeds the resources of the treatment team.
3. De-escalation, calming down	Empathic attitude/approach, patience and interest in helping the agitated person Cooperative approach for managing acutely agitated individuals, ideally without coercive measures Verbal and non-verbal de-escalation (in particular, speaking calmly and soothingly) Staff safety is top priority (e.g., avoiding or removing objects that could be used as weapons; always keeping an escape route clear)	Supporting factors: Uniformed security staff, trained in verbal and non-verbal de-escalation techniques Low-stimulus, dimly lit, calming treatment environment
4. Restrictive measures	Physical restraint and fixation measures (as carefully and gentle as possible) in instances of highly aggressive behavior, for self-protection as well as protection of the agitated person and other persons present	In exceptional situations, restraint measures cannot be avoided. In these cases, a standardized procedure with sufficient staff resources is required (usually 5 persons). Restraint measures constitute deprivation of liberty and can result in health consequences for those affected (asphyxia, stress cardiomyopathy, life-threatening arrhythmias, etc.): These measures must be proportionate and based on a medical indication.
5. Pharmacotherapy for agitation (adapted to the presumed cause)	Benzodiazepines (first-line treatment) Co-medication with antipsychotic drugs, if high doses of benzodiazepines have no effect or in the presence of psychotic symptoms Additional adjunctive therapy in special situations: Hypertensive crisis: Nitroprusside, phentolamine (urapidil, clonidine, nitroglycerin, and clevidipine) significantly lower blood pressure in patients with hypertensive crisis; however, no clinical evaluation is available for persons with substance abuse in acute situations) Hyperthermia: Cooling (convective methods, cooling mats, or neuromuscular blockade in severe cases) Fluid replacement (balanced electrolyte solutions) Considering co-intoxications	Titration (every 10 min IN/IV or every 45 min SL/PO/IM) of (per dose) Diazepam (5-10 mg PO/IV/IM), lorazepam (1-2.5 mg SL/ PO/IV/IM) or midazolam (5-10 mg IN/Sl/IM); high doses of benzodiazepines are typically required! Olanzapine (5-10 mg SL/PO/IM), haloperidol (5-10 mg PO/IM/Iv), droperidol (2.5-5 mg IM/Iv) or ziprasidone (10 mg IM) Antihypertensive drugs: Avoiding beta blockers or antihypertensive drugs with combined alpha-/beta-blocking activity
6. Emergency medicine evaluation	Vital signs (respiratory rate, oxygen saturation, blood pressure, heart rate, body temperature, blood sugar, level of consciousness, etc.) 12-lead electrocardiogram (ECG) Blood gas analysis to evaluate acid-base balance, lactate and electrolyte levels Ethanol levels, possibly salicylates, paracetamol, etc. Drug screening Pregnancy test for women of childbearing potential Optional: creatine kinase, aminotransferases, coagulation	ABCDE for initial evaluation The decision to further escalate treatment (e.g., intubation, anesthesia, use of muscle relaxants) should be made by medical staff experienced in managing such patients. Recent publications favor a conservative approach to intubation (e24).
7. Further diagnostic evaluation, including ruling out somatic causes	Imaging studies (cranial CT or MRI) Spinal tap (encephalitis, meningitis, etc.) Further specific tests related to the indication	Further investigation of possible causes if there is a discrepancy between behavioral abnormalities and laboratory results
8. Disposition	Discharge to outpatient aftercare of patients with mild agitation and improved vital signs Patients with stimulant-related psychosis can also develop symptoms days after discontinuation of substance use. In-patient observation and psychiatric care may be required.	Evidence-based assessment of acute danger to oneself and others (suicidal tendencies in particular) Informing patient about unfitness to drive

ABCDE, Airway, Breathing, Circulation, Disability, Exposure /Environment (Exploration);

CT, computed tomography; etc., et cetera; IM, intramuscular; IN, intranasal; IV, intravenous; min, minutes; MRI, magnetic resonance imaging; PO, oral; SL, sublingual