This page contains extensive excerpts from peer-reviewed literature as well as vital information that cannot be found in medical journals. This includes tips for diagnosing akathisia, the reasons it is often misdiagnosed as a functional neurological disorder, and about its dangerous subjective symptoms that can only be understood by those who have experienced it.

Thank you for your interest in learning more about akathisia from the Akathisia Alliance for Education and Research nonprofit organization. We have 500+ members, including physicians, scientists, nurses, college professors, and others from all walks of life who have experienced akathisia and are working together to help prevent others from suffering as we did.

Table of Contents

What is Akathisia? - In Brief

Akathisia is an extremely distressing neurological disorder most often characterized by severe agitation, an inability to remain still, and an overwhelming sense of terror. The symptoms are so torturous that it can lead to impulsive suicide, violence, and homicide.

Although akathisia can occur in Parkinson’s disease, traumatic brain injury, and other neurological disorders, it is primarily medication induced and most often occurs when starting, stopping, adjusting dosages, or changing medications. The most frequent offenders are antipsychotics, antidepressants, antibiotics, and anti-nausea medications; however, it has been associated with many others. Akathisia is very common in benzodiazepine withdrawal, especially with rapid cessation after long-term use. It can also result from the withdrawal of opioids and drugs such as cocaine and amphetamines.

The "Serious Problem"

“Akathisia is generally underdiagnosed or misdiagnosed, which is a serious problem because it can lead to such adverse outcomes as exacerbation of psychiatric symptoms, aggression, violence, and suicide” (Lohr, et al., 2015).1

Akathisia is a Suicide- and Homicide-Prevention Emergency

Akathisia was linked to homicide in 1978 and suicide in 1983, yet it remains “commonly overlooked or misdiagnosed by clinicians” today.2 Click on the titles below to read full-text PDFs.

Evidence that suggests unrecognized akathisia played a role in several high-profile suicides, homicides, and mass shootings can be found in “The Missing Link to Causation” report and video here.

Signs and Symptoms of Akathisia

“There are two sides to akathisia. One is outer restlessness that you can observe, but the other, much more important one, is an extraordinary state of terror inside a person” (Glenmullen, Akathisia Alliance, 2006).8

Based upon observation in the support groups, a symptom survey was designed and completed by 107 registered members of the Akathisia Alliance who experienced the sudden onset of akathisia with the first dose of a medication, primarily metoclopramide (Reglan). Each symptom listed below was experienced by 48-98% of those surveyed:

• constant and intense physical restlessness (pacing, rocking, fidgeting, etc.)

• an overwhelming sense of terror (see video below)

• extreme agitation, impatience, and irritability

• racing thoughts with pressured speech

• suicidal and/or violent impulses

• monophobia

• agoraphobia

• subjective neurosensory symptoms such as electrical zaps or bugs crawling under the skin

• depersonalization-derealization

• insomnia

• hypersensitivity to light and sound

Please watch this 1.5-minute video to better understand the crucial difference between anxiety and the terror of akathisia.

Diagnosing Akathisia

Why is akathisia "generally underdiagnosed"?

As evident among the 500+ registered members of the Akathisia Alliance, akathisia is often incorrectly ruled out for the following reasons.

The patient does not exhibit excessive movements.

As noted below, patients with akathisia can present without signs of a movement disorder:

•  “Akathisia is usually grouped with movement disorders. Yet, it can present as a purely subjective clinical complaint without overt movement abnormalities” (Lohr, et al., 2015).9

•  “The syndrome of akathisia is perhaps the least understood and appreciated side effect of neuroleptic therapy. Because it is primarily an internal sensation, which may not present with any externally visible manifestation, the clinician must be certain to question the patient before ruling out its presence” (Schulte, 1985).10

• “In the milder cases, only the subjective report may be present, at least on a brief examination, and only prolonged observation will reveal any motor disorder” (Sachdev, 2004).11

The patient has not taken a medication "known to cause akathisia."

Given that akathisia has been under-diagnosed and under-reported for decades, the current medical literature cannot be a reliable reference. It is, therefore, very possible that there are cases of akathisia due to many medications, supplements, chemicals, and medical conditions that have not been published.

The medication is "out of your system."

Drug-induced akathisia can persist for many years following discontinuation of the medication that caused it, as noted in this excerpt from a study published in 1989 (Burke, et al.):12

In recent years, there has been increasing recognition that akathisia occurs not only as an acute, self-limited complication of dopamine (DA) antagonist treatment, but also as a persistent form called tardive akathisia…. In the 26 patients who were able to discontinue DA antagonists, akathisia persisted for years (mean = 2.7 years, range of 0.3-7 years) until abatement of symptoms or last follow-up.

Why is akathisia so often misdiagnosed as a functional neurological disorder?

It is well-known in the support groups that, at least in the milder cases, akathisia is most often misdiagnosed by Neurology as a functional neurological /functional movement disorder (FND/FMD). This is causing significant harm, including increased hopelessness and suicidality.

Please note that the following “rule-in” signs of FND/FMD on clinical assessment are also positive features of akathisia.

The movements of akathisia decrease with distraction.

Motor symptoms appear to be in response to sensory symptoms and decrease with distraction (Factor, 2017).13

The movements of akathisia are suppressible.

Except for the most severe cases, patients are able to voluntarily suppress the movements at least for short periods (Sachdev, 2004).14

The movements of akathisia are variable.

Another feature of the movements is their marked variability over time (Sachdev, 2004).15

Akathisia and the “whack-a-mole” sign

In 2015, Park et al., introduced an FMD assessment technique they refer to as a “whack-a-mole” sign.16

They state:

In this phenomenon, movement suppression of one body part is followed by immediate reemergence of movement in another. We propose that this phenomenon be referred to as the “whack‐a‐mole” sign. This name is derived from the arcade game whack‐a‐mole, in which a mole, when hit into its original hole, re‐emerges elsewhere.

The whack-a-mole sign will be positive in patients with akathisia as the movements are variable, but the compulsion to move remains constant. Therefore, suppression of movement in one body part will necessitate movement of another.

Akathisia and the functional gait assessment

A “rule-in” sign of a functional gait disorder was reported by Nonnekes, et al. (2020)17:

A commonly observed inconsistency in patients with functional gait disorders resembling ataxia is balance control that is actually much better than what is perceived by the patient. During straight walking, patients may seek support of chairs, doorposts, or walls, but do not actually fall even when such support is absent.

As demonstrated in this video, akathisia should not be ruled out based upon the gait disorder assessment described above. A specific difficulty with tandem gait was reported by 24 out of 28 patients (85%) with akathisia that was not present when supported, as demonstrated in the video below (1.54 minutes). None of the patients reported falling, though they were instructed to abort the test if a fall was imminent.

Akathisia vs. Health Anxiety, Functional Neurological, and Factitious Disorders

Patients with symptoms severe enough to cause suicidality may easily meet diagnostic criteria for health anxiety, functional neurological and factitious disorders until they find a doctor who recognizes their akathisia. They will appear to have disproportionate and persistent thoughts about the seriousness of their symptoms, have a persistently high level of anxiety about their symptoms, and spend excessive time devoted to these symptoms. They will do their own research, know the correct medical terms, be eager to have numerous tests performed, and have a history of visiting many doctors and hospitals while searching for an accurate diagnosis.

Akathisia and Drug-Induced Parkinsonism

A strong link between akathisia and parkinsonism has been established. Van Putten reported that 59% of people with drug-induced akathisia have concomitant drug-induced parkinsonism (DIP) (1975),18 and a study published in 1987 indicated that 68% of people with idiopathic Parkinson’s disease also experience akathisia at some point during the course of their disease (Lang & Johnson).19 Therefore, assessing for drug-induced parkinsonism could aid in diagnosing akathisia.

Given that akathisia is often misdiagnosed as FND, and DIP commonly accompanies akathisia, it is possible that many cases of DIP are misdiagnosed as FND as well. According to Shin and Chung (2012)20:

Drug-induced parkinsonism is likely the most common drug-induced movement disorder…. Any medication that interferes with dopamine transmission may cause [it]…. The exact prevalence of drug-induced parkinsonism is unclear because the symptoms are often under-recognized and misdiagnosed, even by neurologists.

Clinical Assessment

From “Acute and Tardive Drug-Induced Akathisia” by Perminder Sachdev, MD, PhD, FRANZCP (2004):21

There is no consensus regarding which movements, if any, are characteristic of akathisia. In our study, the features that best discriminated akathisia from non-akathisia were: i) shifting weight from foot to foot, or walking on the spot, ii) inability to keep legs still (subjectively), iii) feelings of inner restlessness, and iv) shifting of body position in the chair. However, these features are not present in every patient, and in the milder cases, only the subjective report may be present, at least on a brief examination, and only prolonged observation will reveal any motor disorder. Voluntary movements and effortful tasks tend to reduce the movements of akathisia. The majority of the patients report that akathisic movements are voluntary and in response to subjective distress. Except for the most severe cases, patients are able to voluntarily suppress the movements at least for short periods. A few patients manifest myoclonic jerks of the legs and toes, but these are not prominent features. Tremor of the extremities is not uncommonly associated, and this may be regarded as the co-occurrence of drug-induced parkinsonism. Another feature of the movements is their marked variability over time, and their usual disappearance during sleep.

"The Clinical Challenges of Akathisia"

Additional information about akathisia such as the history, pathophysiology, and treatment, can be found in "The Clinical Challenges of Akathisia" by Lohr, et al. (2015). See references at the end of this page for additional recommended reading.

Medications that can cause or worsen akathisia

The list below should not be used as a means of ruling out akathisia on the basis that a patient is not taking, or has not recently taken, these medications. There are published and anecdotal reports of akathisia due to many other pharmacological and non-pharmacological agents, and akathisia can persist for many years after an offending medication is discontinued.
 
The medications that most commonly cause or exacerbate akathisia are listed below, including all antipsychotics and antiemetics that deplete dopamine as well as most classes of antidepressants as they can indirectly do this as well.22,23 Although low-dose mirtazapine is often listed as a potential treatment for akathisia, it is included because there are several published cases of mirtazapine-induced akathisia.24 As there are published cases of akathisia induced by calcium channel blockers,25 certain antibiotics (fluoroquinolones,26 macrolides,27 and tetracyclines28), lithium,29 gabapentin,30 and pregabalin,31 they are also included.

References

1. Lohr, J. B., Eidt, C.A., Abdulrazzaq Alfaraj, A., Soliman, M.A. The clinical challenges of akathisia. CNS Spectr. 2015 Dec;20 Suppl 1:1-14; quiz 15-6. doi: 10.1017/S1092852915000838. PMID: 26683525.

2. Demir, B., Sancaktar, M., & Altindag, A. (2021). Lithium-Induced Treatment-Resistant Akathisia: A Case Report and Literature Overview. Clinical neuropharmacology, 44(3), 112–113. https://doi.org/10.1097/WNF.0000000000000453

3. Keckich, W. A. (1978). Neuroleptics. Violence as a manifestation of akathisia. JAMA, 240(20), 2185. https://doi.org/10.1001/jama.240.20.2185

4. Shear, M. K., Frances, A., Weiden, P. (1983). Suicide associated with akathisia and depot fluphenazine treatment. Journal of clinical psychopharmacology, 3(4), 235–236. https://doi.org/10.1097/00004714-198308000-00006

5. Schulte, J. L. (1985). Homicide and suicide associated with akathisia and haloperidol. American Journal of Forensic Psychiatry, 6(2), 3–7. https://jamanetwork.com/journals/jama/article-abstract/362208

6. Azhar, M., Varma, S. (1992). Akathisia-induced suicidal behaviour. European Psychiatry, 7(5), 239-241. https://doi.org/10.1017/s0924933800003497

7. Lucire, Y., Crotty, C. (2011). Antidepressant-induced akathisia-related homicides associated with diminishing mutations in metabolizing genes of the CYP450 family. Pharmacogenomics and personalized medicine, 4, 65–81. https://doi.org/10.2147/PGPM.S17445

8. Akathisia Alliance for Education and Research. (2019, August 26). Akathisia is Torture [Video]. YouTube. https://www.youtube.com/watch?v=_6eix3cdwoU

9. Lohr, J. B., Eidt, C.A., Abdulrazzaq Alfaraj, A., Soliman, M.A. The clinical challenges of akathisia. CNS Spectr. 2015 Dec;20 Suppl 1:1-14; quiz 15-6. doi: 10.1017/S1092852915000838. PMID: 26683525.

10. Schulte, J. L. (1985). Homicide and suicide associated with akathisia and haloperidol. American Journal of Forensic Psychiatry, 6(2), 3–7. https://jamanetwork.com/journals/jama/article-abstract/362208

11. Sachdev, P. Acute and tardive drug-induced akathisia. In: Sethi KD (Ed) Drug induced movement disorders. Neurological Disease and Therapy Series. Macel Dekker, New York, USA. 2004;129-164

12. Burke, R. E., Kang, U. J., Jankovic, J., Miller, L. G., & Fahn, S. (1989). Tardive akathisia: an analysis of clinical features and response to open therapeutic trials. Movement disorders : official journal of the Movement Disorder Society, 4(2), 157–175. https://doi.org/10.1002/mds.870040208

13. Factor, S. Akathisia. (2023, March 15). MedLink Neurology. https://www.medlink.com/articles/akathisia

14. Sachdev, P. Acute and tardive drug-induced akathisia. In: Sethi KD (Ed) Drug induced movement disorders. Neurological Disease and Therapy Series. Macel Dekker, New York, USA. 2004;129-164

15. Sachdev, P. Acute and tardive drug-induced akathisia. In: Sethi KD (Ed) Drug induced movement disorders. Neurological Disease and Therapy Series. Macel Dekker, New York, USA. 2004;129-164

16. Park, J. E., Maurer, C. W., & Hallett, M. (2015). The “Whack-a-Mole” Sign in Functional Movement Disorders. Movement disorders clinical practice, 2(3), 286–288. https://doi.org/10.1002/mdc3.12177

17. Nonnekes, J., Růžička, E., Serranová, T., Reich, S. G., Bloem, B. R., & Hallett, M. (2020). Functional gait disorders: A sign-based approach. Neurology, 94(24), 1093–1099. https://doi.org/10.1212/WNL.0000000000009649

18. Van Putten, T. (1975). The many faces of akathisia. Comprehensive psychiatry, 16(1), 43-47. https://doi.org/10.1016/0010-44x(75)90019-x

19. Lang, A. E., Johnson, K. (1987). Akathisia in idiopathic Parkinson’s disease. Neurology, 37(3), 477-481. https://doi.org/10.1212/wnl.37.3.477

20. Shin, H. W., & Chung, S. J. (2012). Drug-induced parkinsonism. Journal of clinical neurology (Seoul, Korea), 8(1), 15–21. https://doi.org/10.3988/jcn.2012.8.1.15

21. Sachdev, P. Acute and tardive drug-induced akathisia. In: Sethi KD (Ed) Drug induced movement disorders. Neurological Disease and Therapy Series. Macel Dekker, New York, USA. 2004;129-164

22. Zubenko, G.S., Cohen,  B. M., Lipinski, J. F., Jr., Antidepressant-related akathisia. J Clin Psychopharmacol. 1987 Aug;7(4):254-7. PMID: 3624508.

23. Ak, S., Anıl Yağcıoğlu, A. E. (2014). Escitalopram-induced Parkinsonism. General hospital psychiatry, 36(1), 126.e1–126.e1262. https://doi.org/10.1016/j.genhosppsych.2013.09.010

24. Rissardo, J.P., Caprara A. L. F. Mirtazapine-associated movement disorders: A literature review. Tzu Chi Med J. 2020 Jul 13;32(4):318-330. doi: 10.4103/tcmj.tcmj_13_20. PMID: 33163376; PMCID: PMC7605300

25. Jacobs, M. B. Diltiazem and akathisia. Ann Intern Med. 1983 Dec;99(6):794-5. doi: 10.7326/0003-4819-99-6-794. PMID: 6651024.

26. Owusu Aboagye, G., Ankrah, D. Drug-Drug-Induced Akathisia: Two Case Reports. Case Rep Psychiatry. 2020 Apr 23;2020:9649483. doi: 10.1155/2020/9649483. PMID: 32373382; PMCID: PMC7196143.

27. Riesselman, A., El-Mallakh, R. S. Akathisia with azithromycin. Ann Pharmacother. 2015 May;49(5):609. doi: 10.1177/1060028015570728. PMID: 25870444.

28. Healy, D. (2021, November 22). Mentally Hijacked by Doxycycline RxISK. https://rxisk.org/mentally-hijacked-by-doxycyline/

29. Demir, B., Sancaktar, M., Altindag A. Lithium-Induced Treatment-Resistant Akathisia: A Case Report and Literature Overview. Clin Neuropharmacol. 2021 May-Jun 01;44(3):112-113. doi: 10.1097/WNF.0000000000000453. PMID: 33811193.

30. Tuccori, M., Lombardo, G., Lapi, F., Vannacci, A., Blandizzi, C., Del Tacca, M. Gabapentin-induced severe myopathy. Ann Pharmacother. 2007 Jul;41(7):1301-5. doi: 10.1345/aph.1K077. Epub 2007 Jun 12. PMID: 17565043.

31. Rissardo, J.P., Caprara, A. L. F. Pregabalin-associated movement disorders: A literature review. Brain Circ. 2020 Jun 26;6(2):96-106. doi: 10.4103/bc.bc_57_19. PMID: 33033779; PMCID: PMC7511912