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Child Psychiatrist /Adult Psychiatrist

Antipsychotic-Induced Akathisia Treatment: What Medications Are Most Effective?

Mirtazapine, biperiden, and vitamin B6 have the greatest efficacy for antipsychotic-induced akathisia (AIA) treatment, according to a systematic review and network meta-analysis published in JAMA Network Open. Vitamin B6 demonstrated the best efficacy and tolerance profile.



Akathisia Treatment


Antipsychotics are the first-line treatment for patients with schizophrenia spectrum and psychotic disorders. However, some patients taking antipsychotics will experience AIA, a disorder characterized by restlessness and continuous, excessive movement. Patients with AIA are often at increased risk for suicidality and treatment nonadherence. Currently, the primary recommendation for treating AIA is to modify the patient’s current antipsychotic regimen (ie, consider monotherapy, reduce dose, switch to a different antipsychotic), which is not always clinically feasible. Therefore, investigators conducted a systematic review and meta-analysis to determine the efficacy of various drugs for treating AIA.


The investigators searched publication databases for randomized clinical trials (RCTs) that compared adjunctive drugs for AIA relative to placebo, had at least 10 patients, used a validated akathisia score, and had no additional drugs administered during the study period. The primary outcome measured was the reduction in akathisia score, with secondary outcomes including tolerance (number of adverse effects) and acceptability (number of dropouts due to tolerance issues).


The investigators included 15 double-blind RCTs for a pooled sample size of 492 patients. The RCTs consisted of 10 parallel group trials (66.7%), 323 crossover trials (20.0%), and 3 multi-arm studies (20.0%). Across studies, the medications that were analyzed included propranolol, mirtazapine, mianserin, vitamin B6, biperiden, cyproheptadine, clonazepam, and zolmitriptan.


The investigators observed that multiple medications outperformed placebo for the treatment of AIA. These medications include:


  • Mirtazapine (standardized mean difference [SMD], −1.20; 95% CI, −1.83 to −0.58)

  • Biperiden (SMD, −1.01; 95% CI, −1.69 to −0.34)

  • Vitamin B6 (SMD, −0.92; 95% CI, −1.57 to −0.26)

  • Trazodone, (SMD, −0.84; 95% CI, −1.54 to −0.14)

  • Mianserin (SMD, −0.81; 95% CI, −1.44 to −0.19)

  • Propranolol (SMD, −0.78; 95% CI, −1.35 to −0.22)


Conversely, cyproheptadine, clonazepam, zolmitriptan, and valproate had similar efficacy to placebo.


For acceptability and tolerability, some patients reported transient sedation with mianserin, drowsiness and dizziness with trazodone and mirtazapine, hypersalivation and depression with valproate, dry mouth and sedation with biperiden and valproate, and hypotension with propranolol. Additionally, although mirtazapine, biperiden, and vitamin B6 exhibited moderate to large effect sizes with comparable efficacy, mirtazapine may be poorly tolerated due to its sedative effects and potential for weight gain.


This study represents the first network meta-analysis that examines the efficacy

associated with adjunctive drugs for the treatment of AIA. The investigators concluded, “Vitamin B6 may have the most favorable efficacy and tolerability profile, followed by mirtazapine and biperiden, for the treatment of antipsychotic-induced akathisia.”

These findings may be limited by the low statistical power in the subgroup analysis, potential underestimation of the efficacy of propranolol, and variability in the inclusion of benzodiazepines and anticholinergics across studies.


Note: This article originally appeared on Psychiatry Advisor

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