What is the recommended treatment for managing aggression in adults?

Management of Aggression in Adults

For acute aggression in adults, use combination therapy with lorazepam 2-4 mg plus either haloperidol 5 mg or ziprasidone 20 mg IM, as this combination demonstrates superior improvement rates compared to monotherapy. 1

Acute Agitation Management

First-Line Pharmacologic Approach

• Combination therapy is superior to monotherapy for acute agitation, with lorazepam 2-4 mg plus haloperidol 5 mg showing the strongest evidence base and higher improvement rates than either agent alone 1
• Ziprasidone 20 mg IM is an alternative antipsychotic option that demonstrates highly effective sedation with notably absent movement disorders and decreased restraint time compared to conventional therapy 1
• Droperidol (weight-based IV dosing) produces significantly better sedation than lorazepam starting at 5 minutes post-administration, though requires continuous monitoring 1

Critical Pre-Treatment Assessment

• Rule out anticholinergic or sympathomimetic drug ingestions first, as antipsychotics can paradoxically worsen agitation in these scenarios due to their anticholinergic properties 1
• Identify and treat reversible medical causes (hypoglycemia, hypoxia, infection, metabolic derangements) before initiating pharmacologic intervention 1

Non-Pharmacologic De-Escalation

• Verbal de-escalation should be attempted before chemical or physical restraint whenever safety permits 2
• Create a calming physical environment with decreased sensory stimulation and safety-proofed rooms (removal of potential weapons) 2
• Modify or eliminate triggers of agitation (argumentative individuals, long wait times) 2

Chronic Aggression Management

When ADHD is Present or Suspected

• Stimulants (methylphenidate or amphetamine) are first-line therapy, as they reduce both core ADHD symptoms and aggressive behaviors in most adults 3, 4, 1
• Optimize stimulant dosing before adding adjunctive agents 4, 1

Adjunctive Therapy for Persistent Aggression

If aggression persists despite optimized stimulant therapy:

1. Add divalproex sodium as first-line adjunctive agent, which demonstrates a 70% reduction in aggression scores after 6 weeks and is particularly effective for explosive temper and mood lability 3, 4, 1

   • Target dose: 20-30 mg/kg/day divided BID-TID 3
   • Allow 6-8 weeks at therapeutic levels before declaring treatment failure 3, 1

2. Add risperidone if divalproex fails or is not tolerated, as it has the strongest controlled trial evidence for reducing aggression 3, 4, 1

   • FDA-approved for irritability in autism spectrum disorder with aggression symptoms 5
   • Target dose: 0.5-2 mg/day in adults 3
   • Monitor for metabolic syndrome risk, movement disorders, and prolactin elevation 3

3. Alpha-2 agonists (clonidine, guanfacine) are alternative adjunctive options when comorbid sleep disorders, substance use disorders, or tic disorders are present 3, 1

Aggression Without ADHD

For adults with chronic aggression unrelated to ADHD:

• Lithium or propranolol should be considered first-line agents based on extensive clinical experience 6
• Lithium appears effective in treating aggression among prison inmates and patients with explosive behavior 7
• Beta-blockers (propranolol) appear effective in reducing violent and assaultive behavior in patients with dementia, brain injury, schizophrenia, and organic brain syndrome 7, 8
• Carbamazepine and valproate have evidence for treating pathologic aggression in patients with dementia, organic brain syndrome, psychosis, and personality disorders 7

Autism Spectrum Disorder with Aggression

• Risperidone has the strongest controlled trial evidence for treating aggression in adults with ASD 8
• Propranolol, fluvoxamine, and vigorous aerobic exercise also have controlled trial evidence supporting efficacy 8
• Consider functional assessment-informed behavioral interventions along with regular vigorous aerobic exercise before or concurrent with pharmacotherapy 8

Critical Pitfalls to Avoid

• Never use benzodiazepines for chronic aggression due to risk of paradoxical rage reactions, behavioral disinhibition, and dependence 1, 7, 6
• Avoid polypharmacy—trial one medication class thoroughly (6-8 weeks at therapeutic doses) before switching to another 3, 1
• Do not use lamotrigine off-label for aggression, as it lacks antimanic and anti-aggressive properties 1
• Traditional antipsychotics have little evidence for effectiveness beyond sedative effects in agitated patients or treating aggression related to active psychosis 7
• Reassess the underlying diagnosis if aggression persists, as it may indicate unmasking of comorbid conduct disorder, mood dysregulation, or other psychiatric conditions requiring separate treatment 3, 4, 1

Treatment Algorithm Summary

Acute aggression: Lorazepam 2-4 mg + haloperidol 5 mg (or ziprasidone 20 mg) IM 1

Chronic aggression with ADHD:

1. Optimize stimulant medication 4, 1
2. Add divalproex sodium if inadequate response 3, 1
3. Add risperidone if divalproex fails 3, 1

Chronic aggression without ADHD:

1. Lithium or propranolol as first-line 6
2. Valproate or carbamazepine as alternatives 7
3. Atypical antipsychotics (risperidone) if other options fail 7, 8