In a patient taking lurasidone (Latuda) 20 mg, naltrexone 50 mg, sertraline 100 mg, and trazodone 150 mg daily who develops akathisia, should the other medications also be discontinued?

Management of Akathisia in a Patient on Multiple Medications

No, the patient should not stop the other medications—only lurasidone (Latuda) needs to be discontinued immediately, as it is the clear culprit for akathisia. Sertraline, naltrexone, and trazodone do not cause akathisia and should be continued without interruption. 1

Why Lurasidone is the Sole Offender

Lurasidone carries a high akathisia risk (12.7% incidence rate), making it the obvious cause of this patient's symptoms. 2 Among the newer atypical antipsychotics, lurasidone ranks among the highest for akathisia risk, with an odds ratio of 3.74 compared to placebo—meaning patients on lurasidone are nearly four times more likely to develop akathisia than those on placebo. 2

Lurasidone can also cause irreversible tardive akathisia and tardive dystonia, underscoring the importance of immediate discontinuation when akathisia emerges. 3

Why the Other Medications Are Not Responsible

Sertraline (SSRI)

• SSRIs like sertraline can rarely cause akathisia, but this is uncommon and typically occurs early in treatment or with dose increases. 1 If the patient has been stable on sertraline 100 mg without prior akathisia, it is not the cause. 1
• SSRI-induced akathisia is associated with increased suicidality, so clinicians should systematically inquire about suicidal ideation if sertraline were suspected—but in this case, the temporal relationship clearly implicates lurasidone. 1

Naltrexone

• Naltrexone does not cause akathisia. It is an opioid antagonist used for alcohol use disorder or opioid use disorder and has no dopaminergic or serotonergic effects that would trigger extrapyramidal symptoms.

Trazodone

• Trazodone does not cause akathisia—in fact, it may actually treat it. 4, 5 Trazodone is a serotonin antagonist (particularly at 5-HT2A receptors) and has been studied as a treatment for neuroleptic-induced akathisia, with evidence showing significant improvement in both subjective and objective akathisia symptoms. 4, 5
• A placebo-controlled trial demonstrated that trazodone 50 mg daily significantly improved akathisia symptoms by day 5, with particular benefit for subjective restlessness and global clinical assessment. 5

Immediate Next Steps After Stopping Lurasidone

After discontinuing lurasidone, initiate propranolol 10–30 mg two to three times daily as first-line pharmacological treatment for residual akathisia symptoms. 1, 6, 7 Propranolol is the most consistently effective treatment for acute akathisia across all guidelines and research. 1, 6, 7

Alternative First-Line Options

• If propranolol is contraindicated (e.g., asthma, bradycardia, hypotension), consider switching to another antipsychotic with lower akathisia risk, such as quetiapine or olanzapine. 6 However, since you have already instructed the patient to stop lurasidone, this may not be necessary unless the underlying psychiatric condition requires antipsychotic continuation. 6

Second-Line Options if Propranolol Fails

• Add clonazepam for symptomatic relief and to address the anxiety component of akathisia, providing moderate-strength evidence for benefit when first-line treatments are insufficient. 1, 6 However, benzodiazepines should be used cautiously due to sedation and fall risk. 6
• If both propranolol and benzodiazepines fail, consider amantadine or clonidine as third-line options. 7

Critical Monitoring Considerations

Systematically assess for suicidal ideation before and after stopping lurasidone, as akathisia is strongly associated with acute suicidality, particularly with antipsychotics and SSRIs. 1, 6 Akathisia is frequently misdiagnosed as worsening psychosis, anxiety, or agitation, which can lead to inappropriate dose increases that worsen the condition. 1

Re-evaluate the need for propranolol after the acute phase (typically 2–4 weeks), as many patients no longer require adjunctive medications during long-term therapy once the offending agent is removed. 1, 6

Common Pitfalls to Avoid

• Do not increase lurasidone dose or add another antipsychotic thinking the patient is "worsening"—this will exacerbate akathisia. 1
• Do not stop sertraline, naltrexone, or trazodone, as none of these medications cause akathisia and discontinuing them may destabilize the patient's underlying psychiatric conditions. 1, 4, 5
• Do not use anticholinergic agents (e.g., benztropine) as first-line treatment for akathisia—they are notably less effective for akathisia compared to other extrapyramidal side effects, despite being commonly prescribed. 1