Akathisia Diagnosis: Recognizing and Managing Psychomotor Restlessness

Introduction

Akathisia, derived from the Greek words “a” (without) and “kathisia” (sitting), is a neuropsychiatric syndrome characterized by an inability to remain still, manifesting as psychomotor restlessness. Individuals experiencing akathisia report an overwhelming sense of inner unease or restlessness, predominantly affecting the lower extremities, leading to an irresistible urge to move. This compulsion often results in repetitive movements such as pacing, rocking, shifting weight from one foot to another, or crossing and uncrossing legs. To an observer, these actions might simply appear as persistent fidgeting.

Initially recognized as a significant side effect of antipsychotic medications, particularly first-generation antipsychotics, akathisia is now understood to be associated with a broader range of pharmacological agents. These include calcium channel blockers, antiemetics, anti-vertigo drugs, sedatives used in anesthesia, and even cocaine abuse. The onset of akathisia can be acute, appearing shortly after initiating medication or increasing the dosage, or it can become chronic, with symptoms persisting for months or even years, significantly impacting the patient’s quality of life. Accurate Akathisia Diagnosis is crucial for effective management and to differentiate it from other conditions with overlapping symptoms.

Etiology of Akathisia

The precise cause of akathisia remains elusive, but the prevailing theory centers on the disruption of dopamine neurotransmission in the brain, particularly the blockade of dopamine D2 receptors. This dopamine blockade is a well-established mechanism of action for antipsychotic medications, which are frequently implicated in drug-induced akathisia.

It is hypothesized that an imbalance within the intricate neurotransmitter systems of the brain, specifically between cholinergic/dopaminergic or serotonergic/dopaminergic pathways, plays a pivotal role. The nucleus accumbens, a brain region crucial for motor control and motivation, is strongly suspected as the primary site where this neurochemical imbalance precipitates akathisia. Further research is needed to fully elucidate the complex neurobiological mechanisms underlying this distressing condition.

Epidemiology of Akathisia

The reported incidence of akathisia exhibits considerable variability, influenced by factors such as the type of antipsychotic medication used, dosage, and patient population. Notably, first-generation, or typical, antipsychotics, especially high-potency agents like haloperidol, carry a higher risk of inducing akathisia compared to second-generation, or atypical, antipsychotics. Studies suggest that akathisia can affect a significant proportion of individuals treated with antipsychotics, with estimates ranging widely depending on diagnostic criteria and study methodology.

Understanding the epidemiology of akathisia is essential for risk stratification and preventive strategies, particularly in vulnerable populations initiating antipsychotic treatment. Further epidemiological research is warranted to refine incidence estimates and identify specific risk factors contributing to the development of akathisia.

Pathophysiology of Akathisia

The pathophysiology of akathisia is not completely understood, although it is thought to involve disruptions in dopamine pathways within the brain. Extrapyramidal symptoms (EPS), such as acute dystonia and pseudoparkinsonism, are known side effects of antipsychotic drugs and are attributed to an imbalance between dopamine and acetylcholine in the nigrostriatal pathway, resulting from the blockade of dopamine D2 receptors. These EPS are often managed with anticholinergic agents like benztropine.

While akathisia also arises from dopamine D2 receptor blockade, suggesting a link to reduced dopamine transmission, it typically does not respond to anticholinergic medications. This lack of response implies a different underlying mechanism compared to other EPS. Current research explores the involvement of other neurotransmitter systems, such as serotonin and GABA, and brain regions beyond the nigrostriatal pathway, in the complex pathophysiology of akathisia.

History and Physical Examination in Akathisia Diagnosis

A thorough history and physical examination are paramount in the akathisia diagnosis process. Clinicians should be vigilant for patients presenting with restlessness, particularly those who have recently commenced antipsychotic medication or had their dosage increased. Akathisia typically manifests within the first few weeks of starting antipsychotic therapy.

The clinical presentation of akathisia encompasses both subjective and objective components. Subjectively, patients describe an intense inner restlessness, an overwhelming urge to move, and a profound sense of discomfort and unease. Objectively, this restlessness is observable through behaviors such as pacing, rocking back and forth, constant shifting of posture, and fidgeting movements. Patients often express significant distress and anxiety related to these symptoms.

To quantify the severity of akathisia, standardized rating scales like the Barnes Akathisia Rating Scale (BARS) are valuable tools. The BARS assesses both subjective feelings of restlessness and objective motor manifestations, providing a comprehensive evaluation of akathisia severity. It is crucial for healthcare providers to recognize the profound dysphoria and anxiety that often accompany inner restlessness in akathisia, as chronic cases have been linked to an elevated risk of self-harm and suicidal ideation. Therefore, assessing for a history of depression, anxiety, and suicidal thoughts is an integral part of the evaluation.

Evaluation and Akathisia Diagnosis

The cornerstone of akathisia diagnosis is clinical evaluation, primarily relying on careful observation of the patient’s symptoms and behaviors, coupled with a detailed history, particularly regarding medication use. While the Barnes Akathisia Rating Scale (BARS) is a validated instrument for assessing akathisia severity, clinical judgment remains central to diagnosis.

Currently, there are no specific laboratory tests or radiographic imaging techniques to definitively diagnose akathisia. The diagnosis is mainly clinical, based on the characteristic symptoms of restlessness and the temporal association with medication exposure, especially antipsychotics. Differential diagnosis is crucial to rule out other conditions that may mimic akathisia, such as anxiety disorders, agitation secondary to psychosis, or restless legs syndrome.

Treatment and Management Strategies for Akathisia

Managing antipsychotic-induced akathisia often involves a multi-faceted approach. The initial step may include reducing the dosage of the offending antipsychotic agent, if clinically feasible, or switching to an alternative antipsychotic with a lower propensity for inducing akathisia, such as certain second-generation antipsychotics.

Pharmacological interventions historically used to treat akathisia include beta-blockers like propranolol and benzodiazepines. While these agents are commonly used in clinical practice, the evidence base supporting their efficacy, particularly from high-quality randomized controlled trials, is somewhat limited. Beta-blockers are thought to alleviate the subjective feelings of restlessness, while benzodiazepines may provide a calming effect and reduce motor activity.

Anticholinergic agents like benztropine, typically used for pseudoparkinsonism, are generally not effective for akathisia and are not recommended as primary treatment. However, in cases where pseudoparkinsonism coexists with akathisia, anticholinergics may be considered for managing parkinsonian symptoms.

Mirtazapine, an antidepressant with noradrenergic and serotonergic activity, has emerged as a potentially effective agent for akathisia management. Low doses of mirtazapine have shown promise and may be considered as a first-line treatment option. However, caution is advised, as paradoxical worsening of akathisia has been reported with higher doses of mirtazapine in some individuals.

When utilizing beta-blockers, clinicians must be mindful of potential side effects such as bradycardia and hypotension, particularly in vulnerable patients. Numerous other agents, including vitamin B6, have been explored for akathisia treatment, but robust evidence from randomized controlled trials supporting their efficacy is currently lacking. Further research is needed to identify and validate novel and effective treatments for akathisia.

Differential Diagnosis of Akathisia

Akathisia is frequently underdiagnosed due to the overlap of its symptoms with other psychiatric conditions. It is crucial to differentiate akathisia from:

• Psychosis: Agitation in psychosis may mimic akathisia, but psychotic agitation is typically associated with thought disorder and hallucinations, which are not primary features of akathisia.
• Mania: The psychomotor agitation in mania can resemble akathisia; however, mania is characterized by elevated mood, grandiosity, and racing thoughts, distinct from the dysphoria and inner restlessness of akathisia.
• Attention-Deficit/Hyperactivity Disorder (ADHD): Restlessness and fidgeting in ADHD may superficially resemble akathisia, but ADHD is a developmental disorder with onset in childhood and lacks the specific subjective experience of inner restlessness seen in akathisia.
• Agitated Depression: While restlessness can be a symptom of agitated depression, depression is characterized by persistent low mood, anhedonia, and other depressive symptoms, which are not the core features of akathisia.
• Anxiety Disorders: Anxiety can present with restlessness and agitation. However, in akathisia, the restlessness is more specifically motoric and driven by an inner compulsion to move, rather than generalized anxiety-related agitation.
• Restless Legs Syndrome (RLS): RLS is characterized by an urge to move the legs, often accompanied by uncomfortable sensations, typically occurring at rest and relieved by movement. While there’s overlap, akathisia is more generalized restlessness and directly linked to medication use.

A comprehensive medical history, including medication review, and a careful psychiatric evaluation are essential to accurately differentiate akathisia from these conditions and establish the correct diagnosis.

Prognosis of Akathisia

The prognosis for akathisia is generally favorable if the condition is promptly recognized and the causative agent, particularly medication, is discontinued or adjusted. Early intervention is key to alleviating symptoms and preventing chronicity. However, if left untreated or misdiagnosed, akathisia can become a chronic and debilitating condition, significantly impairing quality of life and potentially leading to severe complications.

Complications of Untreated Akathisia

Untreated akathisia can have significant adverse consequences. The persistent and distressing restlessness can be profoundly disabling, interfering with daily activities, social functioning, and overall well-being. Many individuals with chronic akathisia experience severe anxiety and dysphoria due to the unrelenting inner turmoil and motor restlessness. Alarmingly, akathisia has been associated with an increased risk of suicidal ideation and self-harm behaviors in some individuals, underscoring the importance of timely diagnosis and effective management.

Consultations for Akathisia

Upon establishing an akathisia diagnosis, it is prudent to involve specialists in the patient’s care. Consultation with a neurologist is beneficial to rule out other movement disorders and to further characterize the akathisia. Psychiatric consultation is essential for managing the underlying psychiatric condition, adjusting psychotropic medications, and addressing the psychological distress associated with akathisia. Collaborative care between neurology and psychiatry is often optimal for comprehensive akathisia management.

Deterrence and Patient Education Regarding Akathisia

Preventive strategies and patient education are crucial in mitigating the risk of akathisia, particularly in individuals initiating medications known to potentially induce this syndrome. When prescribing antipsychotics or other implicated drugs, clinicians should:

• Carefully assess individual patient risk factors for akathisia.
• Initiate treatment at the lowest effective dose and titrate gradually.
• Educate patients about the signs and symptoms of akathisia, emphasizing the importance of reporting any restlessness or urge to move.
• Closely monitor patients, especially during the initial weeks of treatment or after dosage adjustments, for the emergence of akathisia.

Patient education empowers individuals to recognize early symptoms and seek prompt medical attention, facilitating timely intervention and preventing the progression of akathisia.

Pearls and Key Considerations in Akathisia Diagnosis and Management

• Akathisia is defined by an inability to stay still, characterized by psychomotor restlessness and an inner sense of unease.
• It is primarily associated with dopamine-blocking agents, particularly antipsychotic medications, but can be induced by other drugs as well.
• Distinguishing akathisia from anxiety, agitation, or underlying psychiatric symptoms is critical for accurate diagnosis.
• Early identification and management are paramount to minimize patient distress and prevent potential complications, including treatment nonadherence and suicidality.
• Management strategies include dose reduction or medication switch, and pharmacological treatments like beta-blockers, benzodiazepines, and low-dose mirtazapine.
• Interprofessional collaboration between physicians, pharmacists, and nurses is essential for optimal patient care.

Enhancing Healthcare Team Outcomes in Akathisia Management

Effective management of akathisia necessitates a collaborative, interprofessional healthcare team approach. Mental health nurses, pharmacists, and primary care physicians play a crucial role in recognizing early signs of akathisia and promptly referring patients to psychiatrists for specialized care. Given the potential chronicity and associated risks of akathisia, including suicidality, ongoing monitoring and close follow-up are essential. Educating family members about akathisia and the importance of treatment adherence and suicide risk awareness is also a vital component of comprehensive care. Open communication and coordinated efforts among all team members are crucial to optimize outcomes for patients experiencing akathisia.

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