Can Seroquel (quetiapine) cause restlessness, particularly in the form of akathisia, in patients?

Can Seroquel Cause Restlessness (Akathisia)?

Yes, Seroquel (quetiapine) can definitely cause restlessness in the form of akathisia, though it occurs less frequently compared to typical antipsychotics. 1

Evidence from FDA Drug Label

The FDA-approved labeling for quetiapine explicitly lists akathisia as a documented adverse reaction across multiple patient populations:

• In bipolar depression trials: 4% of quetiapine-treated patients experienced akathisia versus 1% on placebo 1
• In pediatric bipolar mania trials: The aggregated incidence of extrapyramidal symptoms (including akathisia) was 3.6% for quetiapine versus 1.1% for placebo 1
• In adolescent schizophrenia trials: 4.8% of quetiapine-treated patients experienced akathisia compared to 4.0% on placebo 1

The FDA label specifically warns patients and prescribers to monitor for "akathisia (psychomotor restlessness)" as part of suicidal risk assessment, noting it can emerge during treatment and may be "severe, abrupt in onset" 1

Clinical Context from Guidelines

Quetiapine is actually considered a lower-risk antipsychotic for akathisia, which is why it's recommended as a switch option when akathisia occurs with other agents 2, 3. The American College of Psychiatry recommends "switching to an antipsychotic with lower akathisia risk, such as quetiapine or olanzapine" when akathisia develops 2

However, this does not mean quetiapine cannot cause akathisia—research confirms that "even drugs which induce no other extrapyramidal side effects (such as clozapine, quetiapine, aripiprazole and cariprazine) may induce akathisia" 4

Key Clinical Pitfalls

The most dangerous mistake is misinterpreting akathisia as worsening psychiatric symptoms. The American Academy of Pediatrics explicitly warns that "akathisia can be misinterpreted as psychotic agitation or anxiety, leading to inappropriate increases in antipsychotic dosage that worsen the condition" 2, 5

Patients experiencing quetiapine-induced akathisia may present with:

• Subjective inner restlessness and urge to move 4
• Purposeless movements that relieve subjective tension 4
• Severe distress that limits treatment adherence 4

Management Algorithm

If akathisia occurs on quetiapine, follow this sequence:

1. First-line: Lower the quetiapine dose if clinically feasible 2, 5

2. If dose reduction insufficient: Add propranolol 10-30 mg two to three times daily, which is "the most consistently effective treatment for akathisia" 2, 3, 6

3. If propranolol fails: Consider benzodiazepines such as clonazepam for symptomatic relief, especially for subjective distress 2, 6

4. Alternative options: Gabapentin has shown efficacy in case reports specifically for quetiapine-induced akathisia at doses of 1200 mg daily 7

5. If all fail: Switch to a different antipsychotic entirely, though quetiapine is already among the lowest-risk options 2

Important Monitoring Considerations

The American Academy of Child and Adolescent Psychiatry recommends using standardized scales like the Barnes Akathisia Rating Scale to objectively track symptoms rather than relying solely on subjective reports 5

Anticholinergic agents (like benztropine) are notably less effective for akathisia compared to other extrapyramidal side effects, despite being commonly prescribed 2. Beta-blockers remain the evidence-based first-line pharmacological intervention 2, 3, 6