How should I manage drug-induced akathisia in a patient whose haloperidol was increased from 20 mg to 25 mg, valproic acid from 500 mg to 750 mg, and who is taking nightly trazodone 100 mg, presenting with lip tremor, hand-rubbing and restless feet?

Management of Drug-Induced Akathisia

Immediately reduce the haloperidol dose back to 20 mg (or lower if clinically feasible) and add propranolol 10-30 mg two to three times daily as first-line treatment for this clear case of drug-induced akathisia. 1, 2

Clinical Recognition

The presentation of lip quivering (tremor), hand-rubbing, and constant foot movement following a haloperidol dose increase from 20 mg to 25 mg is classic akathisia—a severe restlessness manifesting as pacing or physical agitation that is one of the most distressing extrapyramidal side effects. 1

Key Distinguishing Features

• Akathisia involves semi-voluntary movements (hand-rubbing, inability to sit still, marching in place, crossing/uncrossing legs, trunk rocking) driven by an inner sense of restlessness and compulsion to move. 1
• The subjective component of severe tension and restlessness is what differentiates this from tardive dyskinesia, which presents with involuntary rhythmic orofacial movements (blinking, grimacing, chewing). 1
• Location matters: predominantly leg/trunk movements with pacing suggests akathisia, while orofacial movements suggest tardive dyskinesia. 1

Critical Pitfall to Avoid

Akathisia is frequently misinterpreted as psychotic agitation or anxiety, leading clinicians to inappropriately increase antipsychotic doses, which worsens the condition. 2, 3 This patient's symptoms appeared immediately after the haloperidol dose was increased—do not make the mistake of increasing it further.

First-Line Treatment Algorithm

Step 1: Reduce the Offending Agent

• Lower the haloperidol dose back to 20 mg or below if clinically feasible while remaining within therapeutic range. 1, 2
• Haloperidol is a high-potency typical antipsychotic with the highest risk for extrapyramidal symptoms including akathisia. 1, 3

Step 2: Add Beta-Blocker Therapy

• Propranolol 10-30 mg two to three times daily is the most consistently effective treatment for akathisia with the strongest evidence base. 2, 4
• Propranolol is endorsed as first-line therapy by the American Academy of Psychiatry and the Law. 2
• Response is typically seen within days of initiation. 4

Second-Line Options if Beta-Blockers Fail or Are Contraindicated

Step 3: Consider Benzodiazepines

• Clonazepam or lorazepam can provide symptomatic relief and address the anxiety component of akathisia. 2, 4
• Benzodiazepines are particularly useful if subjective distress persists despite beta-blocker therapy. 4

Step 4: Alternative Agents

• Anticholinergic agents (benztropine 1-4 mg once or twice daily) are notably less effective for akathisia compared to other extrapyramidal side effects, despite being commonly prescribed. 2, 3
• Monitor carefully for anticholinergic side effects if this route is chosen. 2

Novel Approach: Serotonin 5-HT2a Antagonists

Interestingly, the patient is already on trazodone 100 mg, which has serotonin 5-HT2a antagonist properties and has shown efficacy for akathisia in open-label studies. 5, 6

• Trazodone at 100 mg/day has demonstrated marked improvement in akathisia symptoms in patients receiving stable antipsychotic doses. 6
• The trazodone may be providing some benefit, but is clearly insufficient at the current haloperidol dose. 5, 6
• Do not discontinue the trazodone—it may be partially mitigating what would otherwise be even more severe akathisia. 5, 6

Consideration of Valproic Acid Contribution

While less common, valproic acid itself can rarely cause akathisia, and the dose was increased from 500 mg to 750 mg concurrently with the haloperidol increase. 7

• However, given the temporal relationship with haloperidol dose escalation and the well-established high risk of akathisia with high-potency typical antipsychotics, haloperidol is the most likely culprit. 1, 3, 8
• If symptoms persist despite haloperidol dose reduction and propranolol addition, consider whether the valproic acid increase is contributing. 7

Long-Term Considerations

Switch to Atypical Antipsychotic

• If continued antipsychotic treatment at therapeutic doses is necessary and akathisia persists, switch to an atypical antipsychotic with lower akathisia risk such as quetiapine or olanzapine. 1, 2
• Atypical antipsychotics have significantly lower rates of extrapyramidal symptoms compared to typical antipsychotics like haloperidol. 1
• Among newer atypical agents, iloperidone and asenapine have the lowest akathisia incidence rates (3.9% and 6.8% respectively), while cariprazine has the highest (17.2%). 8

Monitoring

• Avoid antipsychotic polypharmacy, which increases side effect burden. 2
• Young age and male gender are risk factors for akathisia, though this applies across all demographics. 1, 3

Special Warning About Suicidality

SSRI-induced akathisia is associated with increased suicidality, and clinicians should systematically inquire about suicidal ideation when akathisia is present, particularly if any SSRIs are added in the future. 2