Can benzodiazepines (benzos) cause akathisia?

Can Benzodiazepines Cause Akathisia?

Yes, benzodiazepines can cause akathisia, though this is considered a paradoxical or atypical reaction that occurs less commonly than with antipsychotic medications. 1

Understanding Akathisia

Akathisia is characterized by:

• A sense of severe inner restlessness and the urge to move, often accompanied by objective symptoms such as rocking while standing or sitting, lifting feet as if marching on the spot, and crossing/uncrossing legs 2
• Significant subjective distress that can lead to medication non-compliance 3
• Most commonly associated with antipsychotic medications that block dopamine D2 receptors, but can occur with other medication classes 3

Benzodiazepines and Akathisia: The Evidence

Paradoxical Reactions

• Benzodiazepines can paradoxically cause akathisia in some patients, particularly those with traumatic brain injury and seizure disorders 1
• This reaction has been documented with specific benzodiazepines including clonazepam, clorazepate, and lorazepam 1
• The FDA label for alprazolam specifically lists akathisia as a reported adverse event, with an incidence of 1.6% in patients treated for anxiety disorders and 3.0% in patients treated for panic disorders 4

Mechanism of Benzodiazepine-Induced Akathisia

• May differ from the mechanism of antipsychotic-induced akathisia 1
• Could potentially involve serotonergic systems or the "forced normalization phenomenon" 1
• May represent a subtype of benzodiazepine-induced disinhibition in certain patients 1

Risk Factors for Benzodiazepine-Induced Akathisia

• History of traumatic brain injury 1
• Seizure disorders 1
• Concurrent use with other medications that may cause akathisia (e.g., antipsychotics, SSRIs) 3
• Advanced age or frailty may increase sensitivity to benzodiazepine effects in general 5

Clinical Implications

Diagnostic Challenges

• Akathisia may be misinterpreted as psychotic agitation, anxiety, or restless legs syndrome 6
• The subjective distress of akathisia is a common reason for medication non-compliance 2

Treatment Considerations

• When benzodiazepines cause akathisia, the primary intervention should be discontinuation or dose reduction of the causative agent 3
• Ironically, benzodiazepines are sometimes used to treat antipsychotic-induced akathisia 2
• For akathisia caused by other medications, propranolol or other lipophilic beta-blockers are considered first-line treatment 2
• Low-dose mirtazapine (7.5-15mg daily) has shown promising evidence for treating akathisia 7

Monitoring and Prevention

• Clinicians should maintain a high index of suspicion for akathisia in patients taking benzodiazepines, especially those with risk factors 3
• When prescribing benzodiazepines:
  • Use lower doses in older or frail patients 5
  • Be aware that benzodiazepines themselves can cause increased patient agitation and delirium 5
  • Monitor for paradoxical reactions, especially during the initial phases of treatment 5

Clinical Pitfalls to Avoid

• Misdiagnosing akathisia as worsening anxiety or agitation, which could lead to inappropriate dose increases 2
• Failing to recognize the connection between newly emerged restlessness and benzodiazepine therapy 3
• Overlooking the possibility of akathisia in patients on multiple medications that might contribute to this adverse effect 3

While benzodiazepines are more commonly used to treat akathisia caused by other medications, clinicians should be aware of their potential to paradoxically cause this distressing condition in some patients.