Akathisia and Restless Legs

Akathisia and Restless Legs

P Sachdev

New York: Cambridge University Press; 1995. 425 p

This book provides the most comprehensive review to date on akathisia, restless legs, and neuroleptic-induced dysphoria. The volume is divided into 4 distinct parts. Part 1 provides a historical review of akathisia and restlessness as well as a concise and excellent review of neuroleptic-induced dysphoria. Part 2 focuses extensively on drug-induced akathisia. The definition, epidemiology, differential diagnosis, and clinical characteristics of both acute and tardive akathisia are well presented. Assessment procedures are discussed, as are the etiology, pathogenesis, and treatment of the disorder. Part 3 reviews the clinical features, pathophysiology, and treatment of restless legs syndrome. Part 4 offers the reader a summary and recommendations for future research followed by appendices of 4 akathisia clinical rating scales.

In part 1, the book offers a detailed introduction to the development of the concept of akathisia, which was 1st reported by Thomas Willis (1621-1675). The term “akathisia” translated from its Greek root, however, means “not to sit” and was 1st used by Lad Haskovec in 1902. Ekbom introduced the term “restless legs syndrome (RLS)” in 1945 and described the most characteristic symptom of this disorder as “creeping or crawling sensations most frequently localized to the lower leg.” By the 1960s, RLS was firmly established as a neurological disorder, albeit of unknown etiology. After antipsychotic drugs became widely available, a number of reports of akathisia appeared in the literature, with descriptions of patients being restless, being unable to sit, or marching like soldiers. In spite of the few interesting papers examining the psychological and psychodynamic meaning of the akathisic reaction, consensus emerged in the early 1960s that akathisia was an extrapyramidal side effect (EPS) of neuroleptic medication.

Acute akathisia (AA) refers to akathisia that develops soon after the introduction of neuroleptic drugs; by contrast, tardive akathisia develops as a delayed side effect of long-term neuroleptic medication.

Akathisia is often used synonymously with neuroleptic-induced restlessness, yet the term was introduced well before neuroleptic drugs became available. In the clinical setting, restlessness can be caused by psychological factors, organic disorders (drug-induced disorders, drug withdrawal reactions, delirium, dementia, head injury, hypoglycemia, and RLS), and nonorganic psychiatric disorders (affective disorders, psychotic disorders, anxiety disorders, and childhood disorders like attention-deficit hyperactivity disorder).

The author distinguishes 2 aspects of restlessness — a motor (objective) component and a mental (subjective) component — and suggests a comprehensive operational definition.

The motor component of restlessness is typically considered to be under voluntary control; there is, however, a compelling need to move, and suppression of movement results in mounting distress. Sachdev reminds us that the functional neuroanatomy and the neurochemical basis of restlessness remain poorly understood. In many cases, restlessness must be treated because of its negative impact on the patient and caregivers. It is important, however, to identify and, if possible, to rectify the various psychological, social, and environmental determinants of restlessness. Drug therapy may be required to reduce motor activity and subjective distress. The choice of a particular drug is guided by the setting and the possible etiology. Neuroleptics are probably the drugs most commonly used for the management of agitation in dementia and delirium. Benzodiazepines are used quite extensively in the treatment of agitation, and a number of studies attest to their efficacy in some patients.

Neuroleptic drugs induce unpleasant subjective effects among healthy controls and in many psychiatric patients. A dysphoric response is often a predictor of neuroleptic non-compliance. The manifestations of neuroleptic-induced dysphoria (NID) are varied and range from complaints like “the drug disagrees with me” and “I feel emotionally unresponsive” to neuroleptic noncompliance, anxiety and dere-alization, school and work avoidance, painful sensory symptoms, and even depression. The question of whether or not NID can also manifest as a cause of or contributor to depression is a controversial issue that remains to be resolved.

NID may result in a poor outcome, but while many NID patients become noncompliant, others benefit from dysphoria by negotiating with their psychiatrists for lower yet effective doses of neuroleptics, resulting in less severe EPS. The neurobiological basis of NID remains poorly understood.

While the importance of akathisia is now well recognized, there is no consensus on its essential characteristics and hence its diagnostic criteria. The essential features of drug-induced akathisia (DIA) are: 1) exposure to neuroleptic drugs; 2) subjective component: feelings of restlessness, constant urge to move the legs, difficulty or inability to maintain a posture for several minutes; 3) objective component: movements while sitting, standing, or lying. The assessment scale Sachdev uses is the Prince Henry Hospital Akathisia Scale, which includes 3 subjective items, 7 objective items, and a global akathisia score. Sachdev also proposes detailed criteria to diagnose akathisia. It is appropriate to consider onset of symptoms after 3 mo of continuous use of the drug without change in dose or type as tardive akathisia. Onset within 6 weeks of stopping or significantly reducing the dosage of a neuroleptic drug should be considered a withdrawal akathisia, and if the diagnosis of akathisia persists beyond 3 mo after drug cessation or reduction, tardive akathisia should be diagnosed. Akathisia that continues for 3 mo or longer is considered to be chronic.

The published rates of AA with conventional neuroleptics vary from 8% to 76%. A conservative estimate of the incidence of akathisia with classical neuroleptics at clinical dosage levels is about 20% to 30%, but this rate is significantly affected by treatment-related and other variables (parenteral administration and drug potency, for example). Akathisia can also be induced by novel or atypical neuroleptic drugs. Current evidence suggests a reduced rate of AA with these novel agents, and further systematic work is necessary. Nonneuroleptic drugs that can also induce AA include serotonin reuptake inhibitors, serotonin antagonists, heterocyclic antidepressants, anticonvulsants, calcium channel antagonists, and lithium carbonate.

There are no accurate estimates available as to the prevalence or incidence of tardive akathisia, and data on the epidemiology of withdrawal akathisia are extremely limited. In children and adolescents, drug-induced movement disorders have been poorly documented, and akathisia has been relatively neglected. In individuals with developmental disabilities on long-term neuroleptic medication, akathisia appears to be common, but the overall data are too few to make comparisons with nondisabled populations. In the geriatric population, reports of akathisia have been few.

The main feature of AA is subjective distress. In its milder form, it is experienced as a vague feeling of apprehension, irritability, dysphoria, impatience, or general unease. While the restlessness of akathisia may be felt in the mind or body or both, the characteristic that distinguishes it from restlessness of other etiology is its reference to the lower limbs. The movements are described as a response to an irresistible urge to move, but the movement alleviates the urge and the distress only temporarily. Akathisia has been associated with psychotic exacerbation, violence, and suicide. Fidgetiness is perhaps the most common motor sign of akathisia and is usually manifest as semipurposive or purposeless movements of legs, feet, and toes. While the emphasis is on leg and postural movements, semipurposeful or purposeless arm and hand movements may occur. Upper limb movements are less prominent and virtually never occur in isolation. Activating maneuvers in the case of akathisia tend to diminish or suppress movements.

Tardive akathisia has not been universally accepted as a distinct syndrome. The phenomenological examination of patients on long-term neuroleptic medication suggests that tardive akathisia is distinct from tardive dyskinesia, with overlap between the 2. “Chronic,” in terms of describing akathisia, refers to the duration of the disorder, irrespective of the nature of onset, whereas “tardive” denotes a delayed onset.

The most popular method of measuring akathisia is with the multiitem rating scales such as the Barnes Akathisia Rating Scale, the Hillside Akathisia Scale, and the Prince Henry Hospital Akathisia Scale. The measurement of akathisia presents a number of difficulties owing to the complex manifestations of the disorder, the lack of a well-accepted definition, and its variability. No instrumental method is totally satisfactory, but a combination of strain-gauge measurements and actigraphy can provide an accurate measurement of the motor component of akathisia.

The etiology of akathisia must be understood in terms of the drugs that are directly causative and in view of a number of background variables that are likely to increase the risk of its development. Its pathogenesis is incompletely understood, and many competing hypotheses exist. tardive akathisia and withdrawal akathisia have not been reported with nonneuroleptic drugs, suggesting that, unlike AA, they may be purely neuroleptic-related syndromes.

Treatments for AA include modification of the offending drug (cessation, dosage reduction, change to another type, reduction in rate of increment); modification of risk factors; and introduction of benzodiazepines, anticholinergic, antiadrenergic (β-antagonists, α2-agonists), or other agents (ristanserin, amantadine, piracetam, tricyclic antidepressants, and sodium valproate). The treatment of tardive akathisia is, in general, unsatisfactory and the main emphasis should be on its prevention.

There is still no consensus on the incidence and prevalence of RLS. Like akathisia, it is characterized by sensory and motor features. The restlessness in RLS is different from the movements seen in DIA. The other main motor feature in RLS is myoclonic jerks. RLS often leads to sleep disruption. The course of idiopathic RLS is variable — starting in childhood, adulthood, or old age, being progressive or staying the same or even getting better. Table 12.5 (p 317-318) contrasts the DIA and RLS disorders clearly. In RLS treatment, clonazepam remains the drug of 1st choice. Although evidence supports the use of 1-dopa, problems with the long-term use of this drug make clonazepam a better initial agent. If 1-dopa is not tolerated, bromocriptine can be used.

In summary, this is a timely, well-written, and well-researched volume. Dr Sachdev is to be congratulated for offering readers the 1st book-length review of akathisia and related syndromes. Undoubtedly, this book will be a welcome reference for psychiatrists and neurologists.