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02. Akathisia: How to Diagnose and Manage?

Published on January 3, 2020 Expired on April 1, 2025

Gregory Pontone, M.D., M.H.S.

Division Chief of Aging, Behavioral, and Cognitive Neurology - University of Florida College of Medicine

Key Points

Akathisia occurs in one-third of chronically treated patients.
Akathisia is associated with side effects and treatment discontinuation.
Address akathisia by reducing the dose of the causal agent or switching to a different one.
Add a medication to treat akathisia.

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Slides and Transcript

Slide 1 of 13

Section 2, akathisia, how to diagnose it and manage it. So first, I’d like to give a definition of akathisia. It comes from the ancient Greek for not to sit.

Akathisia: How to Diagnose and Manage? Slide 1 of 13

Slide 2 of 13

It’s a syndrome that’s often characterized by the inner feeling that one has to move or fidget and people will often shuffle their feet or shift in their chair or get up and pace. The incidence is between 21% and 75% onset after exposure to the drug per year. The prevalence is somewhere between 1 in 5 and maybe as high as 35% or more of patients will develop akathisia when exposed to the medications that cause it.

References:

Weiden, P. J., Manning, R., Wolfgang, C. D., Ryan, J. M., Mancione, L., Han, G., … & Mayo, M. G. (2016). A randomized trial of iloperidone for prevention of relapse in schizophrenia: the REPRIEVE study. CNS drugs, 30(8), 735-747.

Akathisia: How to Diagnose and Manage? Slide 2 of 13

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Slide 3 of 13

We know that akathisia is associated with a lower quality of life and as I mentioned earlier discontinuation of treatment. There’s also a literature that suggests that in extreme cases it’s been associated with an increased risk of suicide or even aggressive behavior. And in some geriatric populations, it’s been associated with falls due to the pacing and constant movement.

References:

Kane, J. M., Fleischhacker, W. W., Hansen, L., Perlis, R., Pikalov III, A., & Assuncao-Talbott, S. (2009). Akathisia: an updated review focusing on second-generation antipsychotics. Journal of Clinical Psychiatry, 70(5), 627.

Akathisia: How to Diagnose and Manage? Slide 3 of 13

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The differential diagnosis of akathisia includes anxiety. So anxious patients often wring their hands, fidget or move around as well. Restless legs syndrome is something that should be excluded from the differential diagnoses. Levodopa-induced dyskinesia in patients who might be taking levodopa. Peripheral neuropathy. So if there’s a sensation other than restlessness or the need to move associated like a pain or tingling, be suspicious of peripheral neuropathy.

References:

Salem, H., Nagpal, C., Pigott, T., & Lucio Teixeira, A. (2017). Revisiting antipsychotic-induced akathisia: current issues and prospective challenges. Current neuropharmacology, 15(5), 789-798.

Akathisia: How to Diagnose and Manage? Slide 4 of 13

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Slide 5 of 13

Low iron is another condition that can masquerade sometimes as akathisia. Hyperthyroidism. Alcohol or opiate withdrawal is another common one that produces a similar sense of restlessness. And then, stimulant intoxication is something to be evaluated as well.

References:

Sachdev, P. (1995). The epidemiology of drug-induced akathisia: Part I. Acute akathisia. Schizophrenia bulletin, 21(3), 431-449.

Akathisia: How to Diagnose and Manage? Slide 5 of 13

Slide 6 of 13

Now, there are different types of akathisia and these have to do with the timeframe within which they manifest or endure. And so acute akathisia is a duration of six months or less. Chronic is when it persists for six months or more after any dose is changed, up or down. Tardive akathisia is a delayed onset that’s not related to dose change. So for instance, you start the medication at whatever dose and you reach a steady dosing amount. And then within a few months, you see this restlessness emerge. That would be a tardive akathisia. And then withdrawal akathisia is not uncommon. And often, you’ll see this when switching from one antipsychotic to another or after withdrawing anticholinergic medications. So for instance, if you’re using benztropine or trihexyphenidyl to work against drug-induced side effects and let’s say you decrease or withdraw those, sometimes you’ll see akathisia emerge as those medications are reduced.

References:

Sachdev, P. (1995). The epidemiology of drug-induced akathisia: Part II. Chronic, tardive, and withdrawal akathisias. Schizophrenia bulletin, 21(3), 451-461.

Akathisia: How to Diagnose and Manage? Slide 6 of 13

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Slide 7 of 13

There’s also this concept that’s been reported in a few case series called pseudoakathisia. And it’s controversial. But essentially, it’s many of the symptoms that go along with akathisia but without the patient’s awareness of that inner restlessness. Again, some people think that it might be just a manifestation of psychomotor agitation or actually tardive dyskinesia and it’s being miscalled akathisia. But essentially, patients are pacing and doing all the things that make them look as if they have akathisia but if you ask them, they don’t have that inner sense of restlessness.

References:

Sachdev, P. (1995). The epidemiology of drug-induced akathisia: Part II. Chronic, tardive, and withdrawal akathisias. Schizophrenia bulletin, 21(3), 451-461.

Akathisia: How to Diagnose and Manage? Slide 7 of 13

Slide 8 of 13

The medications that are most often associated with akathisia are your first- and second-generation antipsychotics. Antidepressants especially at high doses can be associated with akathisia. Dopamine-blocking antiemetics or your metoclopramides are often a cause of the akathisia. Antihypertensives especially things like reserpine or alpha-methyldopa have been associated with akathisia. Lithium. Calcium channel blockers are associated. And tetrabenazine and the VMAT2 inhibitors can cause akathisia. But the highest risk by far and the ones that you’ll see the most reports about are the antipsychotics.

References:

Salem, H., Nagpal, C., Pigott, T., & Lucio Teixeira, A. (2017). Revisiting antipsychotic-induced akathisia: current issues and prospective challenges. Current neuropharmacology, 15(5), 789-798.

Akathisia: How to Diagnose and Manage? Slide 8 of 13

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Slide 9 of 13

Now, despite the adverse impact of akathisia, you know, we mentioned that it causes subjective distress in patients and in extreme cases maybe agitation or even increased suicide risk, prophylactic treatment is not generally recommended due to the risk of polypharmacy. And that’s because these other outcomes are less prevalent on average. And so really until you see the symptom of akathisia, it’s better to not start medications prophylactically. So what medications would treat akathisia? We’ll talk about those. But before you introduce a medication, again because we’re really worried about unnecessary polypharmacy, you’re going to want to try to do a few things to mitigate the akathisia before introducing new medications. And so one common thing is to try to lower the medication dose of the causal agent. Another thing that’s commonly tried is to switch antipsychotics. So oftentimes, switching from a first generation or a typical antipsychotic which might have a higher affinity for the D2 receptor to a second-generation antipsychotic might be helpful. The other reason that it also helps is not just the reduced affinity for D2 but also the fact that many of the second-generation antipsychotics have an anticholinergic property that can also work against the akathisia. Again, check for an iron deficiency because remember that’s in the differential diagnoses for akathisia.

References:

Salem, H., Nagpal, C., Pigott, T., & Lucio Teixeira, A. (2017). Revisiting antipsychotic-induced akathisia: current issues and prospective challenges. Current neuropharmacology, 15(5), 789-798.

Akathisia: How to Diagnose and Manage? Slide 9 of 13

Slide 10 of 13

Beta-blockers especially propranolol have shown efficacy in reducing akathisia. Benzodiazepines may be helpful. Typically, we like to go with the longer acting benzodiazepines like clonazepam or lorazepam rather than the shorter acting ones like is alprazolam. Anticholinergic medications, so your benztropine or trihexyphenidyl. However, remember anticholinergics have a range of side effects. They were recently named in a JAMA Internal Medicine article as agents that can increase the risk of dementia later in life. And so use those very judiciously but they certainly can be helpful. Clonidine and amantadine have shown some benefit. And then others that maybe have less evidence from case reports or case series are mirtazapine which is an antidepressant or serotonin antagonists like cyproheptadine and mianserin. So depending on the acuity of the clinical illness that you’re treating, treatment of akathisia should begin with a determination of whether the suspected causal agent can be reduced to eliminate the akathisia. Obviously, if someone is acutely psychotic and agitated, it’s going to be difficult to lower the dose. So you want to be cautious. But in situations where reduction of the causal agent either doesn’t help or isn’t clinically indicated, you want to then at that point go ahead and start looking at some of these options I just mentioned, the beta-blockers, benzodiazepines, anticholinergics, clonidine and amantadine, possibly in that order because that’s aligned pretty much in the order of evidence to treat the akathisia.

References:

Kane, J. M., Fleischhacker, W. W., Hansen, L., Perlis, R., Pikalov III, A., & Assuncao-Talbott, S. (2009). Akathisia: an updated review focusing on second-generation antipsychotics. Journal of Clinical Psychiatry, 70(5), 627.

Akathisia: How to Diagnose and Manage? Slide 10 of 13

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Slide 11 of 13

So the key points are that akathisia occurs in about 1/3 of patients treated chronically for mental illness. Akathisia is associated with side effects and treatment discontinuation. So once it’s recognized, you should aggressively manage it.

Akathisia: How to Diagnose and Manage? Slide 11 of 13

Slide 12 of 13

And then treating akathisia may include reducing the dose of the causal agent or switching treatment for ones that have a lower liability for causing the akathisia. And then finally, if these things don’t work or not clinically tenable, add a medication to treat akathisia.

Akathisia: How to Diagnose and Manage? Slide 12 of 13

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Slide 13 of 13

Akathisia: How to Diagnose and Manage? Slide 13 of 13

Next Section

03. How to Spot Extrapyramidal Symptoms in Clinical Practice?

Learning Objectives:

After completing this activity, the learner will be able to:

Recognize drug-induced movement disorders and recommend the appropriate treatment.
Differentiate between medication-induced and Parkinson's disease tremors to be able to treat accordingly.

Original Release Date: January 3, 2020

Review and Re-release Date: March 1, 2024

Expiration Date: April 1, 2025

Expert: Gregory Pontone, M.D.

Medical Editor: Jessica Diaz, M.D

Relevant Financial Disclosures:

The following planners, faculty, and reviewers have the following relevant financial relationships with commercial interests to disclose:

Dr. Pontone has disclosed the following relationships:

Acadia Pharmaceuticals Inc: Consulting

All of the relevant financial relationships listed for these individuals have been mitigated.

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