Can Buspirone Cause Erratic Behavior?
Yes, buspirone can cause erratic behavior, though this is uncommon; the FDA label specifically warns about a syndrome of restlessness and agitation appearing shortly after treatment initiation, and rare cases of worsening psychosis have been documented, particularly in patients with pre-existing psychiatric conditions. 1, 2
Key Safety Concerns from FDA Labeling
The FDA-approved prescribing information identifies several behavioral concerns related to buspirone's dopaminergic effects 1:
Restlessness syndrome: A syndrome of restlessness appearing shortly after initiation of treatment has been reported in a small fraction of buspirone-treated patients, potentially explained by increased central noradrenergic activity or dopaminergic effects (akathisia) 1
Withdrawal-related agitation: The syndrome of withdrawal from prior sedative/hypnotic/anxiolytic drugs can manifest as irritability, anxiety, agitation, insomnia, and tremor when transitioning to buspirone 1
Dopamine receptor concerns: Because buspirone binds to central dopamine receptors, there is potential for acute and chronic changes in dopamine-mediated neurological function, though clinical trials have not identified significant neuroleptic-like activity 1
Evidence in Psychiatric Populations
Patients with psychotic disorders are at particular risk 2:
A 2023 case report documented buspirone worsening psychosis in a patient with schizoaffective disorder, with increased aggression, odd behaviors, and paranoia occurring on two separate administration trials 2
Buspirone acts as an antagonist at presynaptic dopamine D2, D3, and D4 receptors, and contrary to expected outcomes, resulted in substantial increases in dopaminergic metabolites rather than antipsychotic effects 2
The route of administration matters: intranasal administration leads to faster drug absorption and increased bioavailability (compared to ~4% oral bioavailability after first-pass metabolism), potentially enhancing adverse effects 2
Clinical Context from Guidelines
Guidelines for managing agitation note important distinctions 3:
Buspirone is described as "useful only in patients with mild to moderate agitation" and "may take 2 to 4 weeks to become effective" 3
In contrast, benzodiazepines carry a warning that "paradoxic agitation occurs in about 10% of patients" 3
For acute behavioral emergencies, buspirone is not recommended due to its delayed onset of action 3
Positive Evidence for Behavioral Disorders
Paradoxically, buspirone may reduce certain types of erratic behavior 4, 5:
In patients with mental retardation and severe challenging behavior (aggressive outbursts, self-injurious behavior, impulsivity), buspirone 20-50 mg daily was effective in reducing behavioral disturbances and improving sociability 4
This may result from a de-arousing phenomenon mediated via corticosteroid-dependent stress homeostatic mechanisms 4
Clinical Recommendations
Monitor closely for behavioral changes, especially in the following scenarios:
First 1-2 weeks of treatment: Watch for restlessness syndrome or paradoxical agitation 1
Patients with psychotic disorders: Exercise extreme caution or avoid buspirone entirely, as worsening psychosis with increased aggression and paranoia has been documented 2
Patients transitioning from benzodiazepines: Gradual withdrawal from prior CNS depressants is essential, as buspirone will not block withdrawal symptoms that can include agitation and irritability 1
Patients demanding immediate relief: Buspirone's 1-2 week lag time to anxiolytic effect may lead to frustration and non-compliance 6, 7
Important Caveats
The overall side effect profile of buspirone is favorable compared to benzodiazepines, with sedation occurring much less frequently 6
Clinical trials have demonstrated buspirone does not impair psychomotor or cognitive function and has limited potential for abuse and dependence 6, 7
Most patients tolerate buspirone well, but unpredictable CNS effects in individual patients necessitate caution with activities requiring alertness until response is established 1