The role of antipsychotics
Pharmacologic intervention for violent behavior targets the underlying disorder, such as schizophrenia or bipolar disorder. Usual regimens used to treat patients with these disorders may need to be modified, however, for persistently violent patients (Table 2).
Second-generation antipsychotics (SGAs)—particularly clozapine—have superior antiaggressive properties beyond their antipsychotic or sedative effects, compared with first-generation antipsychotics. Retrospective studies have shown clozapine can significantly decrease the number of violent incidents and episodes of seclusion and restraint.15,16 Evidence for efficacy of other SGAs in reducing physical assaults is more limited:
- Risperidone had a greater effect than haloperidol on hostility in a large, multicenter comparison trial.17
- Clozapine was more effective than haloperidol or risperidone in reducing hostility in a double-blind study of schizophrenia patients.18 This finding was independent of clozapine’s antipsychotic effect.
Clozapine also was more effective than haloperidol in reducing the number and severity of aggressive incidents.19 The patients in this study, however, were not selected on the basis of aggressive behavior.
One large federally funded, double-blind, randomized trial compared clozapine, olanzapine, and haloperidol in 110 assaultive patients with schizophrenia or schizoaffective disorder. Patients had documented episodes of recent physical assaults and persistent aggressive behaviors during a 2-week period. Clozapine showed greater efficacy than olanzapine—and olanzapine greater efficacy than haloperidol—in reducing aggressive behavior.20 This effect was independent of the drugs’ antipsychotic and sedative actions.
Table 2
Medications used to treat persistent violence
| Drug | Initial dosage | Target dosage |
|---|---|---|
| Second-generation antipsychotics | ||
| Clozapine | 12.5 to 50 mg/d | 300 to 450 mg/d* |
| Olanzapine | 5 to 10 mg/d | 15 to 30 mg/d |
| Quetiapine | 50 to 100 mg/d | 400 to 700 mg/d |
| Risperidone | 1 to 3 mg/d | 4 to 6 mg/d |
| First-generation antipsychotic | ||
| Haloperidol | 5 to 10 mg/d | 10 to 20 mg/d |
| Mood stabilizers | ||
| Carbamazepine | 200 to 400 mg/d | 1,000 to 1,400 mg/d* |
| Lithium | 300 mg bid | 300 mg tid* |
| Valproate | 500 to 1,000 mg/d | 1,000 to 1,500 mg/d* |
| Beta blockers† | ||
| Nadolol | 40 mg/d | 80 to 140 mg/d |
| Propranolol | 20 mg tid | 200 mg to 600 (delayed onset of action) |
| * Serum levels should be obtained. | ||
| † Contraindicated for patients with cardiovascular disease, asthma, or diabetes. | ||
Dual-diagnosis patients. Clozapine may be beneficial for patients with concurrent substance abuse because in addition to reducing aggression, it also may prevent relapse to substance abuse. In addition to intoxication, drug and alcohol abuse has disruptive effects on prefrontal function. These impairments play an important role in substance use-related aggression.
Substance abuse also can exacerbate psychotic symptoms, both directly and indirectly through poor treatment compliance. Patients with psychopathy are much more likely to abuse drugs. The association between drug abuse and violence can then be due in part to the higher percentage of psychopaths in the group of drug abusers.
Fortunately, patients with dual diagnosis who receive extensive substance abuse treatment show greater clinical improvement and better outcomes.21 Several studies found that clozapine was associated with decreased substance use. In one trial, schizophrenic patients with a history of drug abuse who received clozapine were much less likely to use substances over the next year than patients taking other antipsychotic medications.22
Thus, clozapine has clear antiaggressive effects, but its use as a first-choice treatment for aggression is limited by the risk of side effects, in particular agranulocytosis. With careful blood monitoring, this complication is very rare, but persistently violent patients might not cooperate fully with the required monitoring.
Other medications
Other agents used to treat violent patients with mental disorders include mood stabilizers, beta blockers, and antidepressants.23
Mood stabilizers such as lithium, carbamazepine, or valproate might be useful as adjuncts to antipsychotic medications in managing assaultive patients with schizophrenia or other major psychiatric disorders. These medications might decrease violence by enhancing serotonergic activity.
Most evidence for mood stabilizers’ anti-aggressive effect comes from studies of patients with personality disorders. Divalproex, for example, was more effective than placebo in reducing impulsive aggression in patients with Cluster B personality disorders.24
Lithium reduces aggression and irritability in bipolar mania, while stabilizing the underlying disorder. Lithium can decrease aggression in other populations as well, including:
- the developmentally disabled
- prisoners with no apparent psychiatric diagnoses
- aggressive children and adolescents with conduct disorder
- adults with borderline personality disorder.
Beta blockers such as nadolol, pindolol, and propranolol have been reported to reduce aggression. Their usefulness is limited, however, because they are contraindicated in patients with cardiovascular disease, asthma, or diabetes.
Antidepressants. Selective serotonin reuptake inhibitors may reduce impulsive aggression in nondepressed patients with personality disorders.25
Nonpharmacologic treatments
To provide proper treatment, the clinician must understand the patient as a whole person, including his perception of his aggressive behavior. Nonpharmacologic interventions should be implemented with this in mind.
Compared with standard care, for example, intensive case management reduces the incidence of violence.26