What medications are used to treat aggressive behaviors?

Medications for Aggressive Behaviors

For acute agitation in adults, use benzodiazepines (lorazepam 2-4 mg) combined with antipsychotics (haloperidol 5 mg or ziprasidone 20 mg IM), as combination therapy shows superior improvement rates with lower extrapyramidal side effects compared to either agent alone. 1, 2

Acute Agitation Management (Emergency Settings)

First-Line Approach: Combination Therapy

• Offer oral medication first before proceeding to intramuscular administration to build therapeutic alliance and suggest internal locus of control 2
• Lorazepam 2-4 mg plus haloperidol 5 mg is the most studied combination, demonstrating higher improvement rates than either agent alone 1
• Ziprasidone 20 mg IM is highly effective with notably absent movement disorders (no extrapyramidal symptoms, dystonia, or hypertonia) and decreases restraint time compared to conventional therapy 1

Alternative Acute Agents

• Droperidol (weight-based IV dosing) produces significantly better sedation than lorazepam starting at 5 minutes post-administration, though it requires continuous monitoring 1
• Olanzapine IM is FDA-approved for agitation associated with schizophrenia and bipolar I mania 3

Critical Caution

• 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 before pharmacologic intervention 1

Chronic Aggression in Children and Adolescents

ADHD-Related Aggression Algorithm

Step 1: Optimize stimulant medication (methylphenidate or amphetamine) as first-line therapy, as stimulants reduce both core ADHD symptoms and aggressive behaviors in most children 4, 5

Step 2: Add divalproex sodium if aggression persists after optimizing stimulants, as it demonstrates 70% reduction in aggression scores after 6 weeks and is particularly effective for explosive temper 4, 5

• Dose: 20-30 mg/kg/day divided BID-TID, titrated to therapeutic blood levels of 40-90 mcg/mL 4
• Monitor liver enzymes regularly 4, 5
• Allow 6-8 weeks at therapeutic levels before declaring treatment failure 4, 5

Step 3: Add risperidone if divalproex fails, as it has the strongest controlled trial evidence for reducing aggression when added to stimulants 4, 5

• Target dose: 0.5-2 mg/day 4, 5
• Monitor for metabolic syndrome, weight gain, movement disorders, and prolactin elevation 4, 5

Alternative Options for Specific Comorbidities

• Alpha-2 agonists (clonidine, guanfacine) can be considered as first-line alternatives when comorbid sleep disorders, substance use disorders, disruptive behavior disorders, or tic/Tourette's disorder are present 4

Chemical Restraint in Pediatric Institutions

For emergency chemical restraint in children:

• Haloperidol (high-potency neuroleptic) or chlorpromazine (low-potency neuroleptic) have been used, though both carry risk of extrapyramidal symptoms and dystonic reactions 1
• Lorazepam (short-acting anxiolytic) or hydroxyzine/diphenhydramine (antihistamines) can be used individually or combined with neuroleptics 1
• Critical warning: Paradoxical rage reactions can occur with anxiolytics and antihistamines, which cannot be predicted unless previously documented 1
• Droperidol is concerning due to its amnestic effect and obligatory intramuscular administration, which raises trauma potential 1

Pediatric Chemical Restraint Requirements

• Must be administered on stat/emergency basis with continuous monitoring by trained nursing personnel 1
• Offer oral medication before intramuscular injection whenever possible 1
• Monitor continuously for allergic reactions, paradoxical reactions, dystonias, extrapyramidal side effects, and neuroleptic malignant syndrome until patient is awake and ambulatory 1
• PRN use of chemical restraints is prohibited 1

Chronic Aggression in Adults with Intellectual Disability

Most Commonly Used Medications

• Risperidone is the most commonly prescribed antipsychotic, followed by chlorpromazine, haloperidol, olanzapine, zuclopenthixol, and quetiapine 1, 6
• Multiple RCTs demonstrate risperidone improves irritability and aggression in youth with intellectual disability, with positive findings starting within 2 weeks 1
• Common side effects include headache, somnolence, weight gain, and asymptomatic prolactin increases, though extrapyramidal symptoms are comparable to placebo 1

SSRI Antidepressants and Mood Stabilizers

• Citalopram, paroxetine, and fluoxetine are commonly used SSRIs 6
• Carbamazepine and sodium valproate are frequently prescribed, though often for epilepsy treatment rather than aggression per se 6

Polypharmacy Warning

• 45% of patients receive polypharmacy (more than one psychotropic medication), with 10% receiving multiple antipsychotics simultaneously 6
• Higher antipsychotic doses correlate with more severe aggressive behavior, not better control 6

Chronic Aggression in Dementia

Risperidone for Dementia-Related Agitation

• Modal optimal dose is 0.5 mg/day for elderly patients with dementia and agitation 7
• Agitation remits in most patients, with aggressive behaviors improving early in treatment 7
• Extrapyramidal symptoms develop in over 50% of patients, and cognitive decline occurs in 20%, even with low doses 7

Alternative Chronic Agents (General Populations)

• Lithium appears effective for aggression in nonepileptic prison inmates, mentally retarded patients, and conduct-disordered children with explosive behavior 8, 9
• Beta-blockers (propranolol) are effective in dementia, brain injury, schizophrenia, mental retardation, and organic brain syndrome, though limited by hypotension and bradycardia at higher doses 8, 9
• Carbamazepine and valproate show efficacy in dementia, organic brain syndrome, psychosis, and personality disorders 8
• Minimum trial period of 6-8 weeks at maximum tolerated dosages should be used to assess drug efficacy 9

Critical Pitfalls to Avoid

• Never use benzodiazepines for chronic aggression due to risk of paradoxical rage reactions and dependence 4, 5
• Avoid lamotrigine off-label for aggression, as it lacks antimanic and anti-aggressive properties 5
• Traditional antipsychotics have little evidence beyond sedative effects in non-psychotic aggression, and may actually increase aggressiveness in mentally retarded subjects 8
• Avoid polypharmacy: trial one medication class thoroughly (6-8 weeks at therapeutic doses) before switching 4, 5
• Reassess diagnosis if aggression persists, as it may indicate unmasking of comorbid conduct disorder, oppositional defiant disorder, or mood dysregulation requiring separate treatment 4