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Akathisia: A Deadly Imposter

— Be on the lookout for it

MedpageToday
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"If you can wait and not be tired of waiting." -- If by Rudyard Kipling

Many diseases have commonly been misdiagnosed, undiagnosed, or hurriedly treated because they mimic many different diseases or present unconventionally. Counted among these have been syphilis and multiple sclerosis with varied and seemingly unrelated symptoms, and the lethal Valentino "ulcer."

Now placed into this relevant and disturbing breach is the data from the Council on Behavioral Health's 2017 Director's Report that over 50% of suicide cases are either misdiagnosed or unrecognized by psychiatrists. Additionally, over 50% of these suicide deaths occurred within hours to 30 days of last clinical contact, and of these, over .

It has been previously reported by the author that ideation requires careful, "waiting" inquiry. This initial and early cortical construct may transform or masquerade along a bidirectional continuum that includes fleeting, transient, impermanent, enduring, permanent, correctible, controllable, reversible, or subcortically hijacked, i.e., unobvious features. These are not distinctions without a difference.

There are differences amid mere description and investigative understanding sandwiched between actual suicide assessment and an optimal evaluation. Indeed, recent research now strongly implicates, and a convincing case can be made that the heretofore unrecognized contribution of psychogenic, as well as infectious, autoimmune, metabolic, and iatrogenic akathisia, represents a final common .

The term akathisia ("inability to sit still") was introduced by L. Haskovec in 1901, clearly predating the psychotropic medication era, a class of assorted medications now considered solely, and mistakenly, . In fact, the mental and motor components were first described by Galen, the 2nd century AD personal physician to the Roman emperor Marcus Aurelius and his ghastly son Commodus, popularized in the movie "Gladiator." In the 17th century, English anatomist, neurologist, and psychiatrist Thomas Willis, who cataloged the anastomotic circle and cranial nerves, described a case consistent with (RLS), now classified as Willis-Ekbom akathisia.

Variously described as , , and , akathisia is appropriately considered a mixed motor and mental disorder. Raskin found that patients were often unable to distinguish or verbalize the differences between .

Indeed, the , pioneered for drug-induced side effects, evaluates both objective and subjective components. What makes the diagnosis difficult is that either one or the other counterparts may predominate, or both, with often unobvious subsyndromal types masquerading as an incompletely treated primary psychiatric diagnosis.

The varied and underappreciated etiologies of or include infectious (Lyme disease, Mycoplasma pneumonia), autoimmune (Group A streptococcal, PANS), metabolic (iron deficiency anemia), iatrogenic (opioids, SSRIs, first- and second-generation antipsychotics, antiemetics, antihistamines), and psychogenic (acute stress, adjustment disorder). Its timestamp can be acute, continuous, or tardive.

There are several types of neuropsychiatric symptoms that range from anxiety to impending doom, stereotypy to automatism, and coarse self-mutilation to suicide without forethought. This overlap in cluster symptoms is considered to parallel activation-like SSRI adverse events in vulnerable persons, such as disinhibition, impulsivity, insomnia, restlessness, hyperactivity, irritability, and suicidality.

The confounding and present one of the most baffling and urgent public health problems encountered by researchers and clinicians. Clearly, saving a life, whether in the emergency department, ICU, or clinic, is hard. If it were easy, everyone would be doing it. Well, in the field of suicidology, everyone, from suicide ideation therapists to mental health first aid proponents to ideation-centric researchers, is doing it, and where are we?

A dismal public health trajectory now represents a in U.S. suicide rates and absolute numbers. Perhaps the words of Louis Pasteur can provide insight into a new direction: "In the field of observation, chance only benefits the prepared mind." In other words, the plural of anecdote is not evidence (multiple candidates). Systematic, scientific evidence is derived from cross-disciplinary observation.

Typically, these diverse suicidal persons belong to that segment of society who wander within a tortured diagnostic landscape. For example, generalizing from the American Psychiatric Association's richly proprietary Diagnostic and Statistical Manual (DSM), the American Foundation for Suicide Prevention deduced that over who commit suicide have a mental illness. Stunningly, to the contrary, the CDC attested in 2018 that over who commit suicide do not have a mental disorder.

On the surface, what a monumental research quagmire.

Yet, perhaps accidentally, though serendipitously, the CDC assisted in addressing the impasse. Enter acute adjustment disorder (AD). Characteristically represented as a DSM step-child, diagnostic wastebasket, a medicalized personal misfortune, and category with deserved poor reimbursement, the CDC showed that AD, as a result of interpersonal conflict or loss, is implicated in over 30% of completed youth suicides, and over 60% of adults older than 24 years. AD carries compared to those without the diagnosis when controlling for depression and other matched factors.

Recall that descriptive AD is one of the few psychiatric disorders attributed to a proximal interpersonal stressor. It is the personal valence, salience, and permeability of the individual to the stressor that is critical. It is not the observer's quantification of the stressful episode that is determinative. Its time course depends on the quality, degree, and duration of symptoms. For example, and in most cases, symptoms may develop in a few hours, consistent with acute gene induction and transcriptional changes. And, in addition to its diagnostic dynamic, longitudinal description, it is possible to delineate neuropsychiatric mental and motor equivalents.

Thus, clinical features may overlap with brief reactive psychosis, or the earlier French adjacent condition termed bouffée délirante. These include derealization, depersonalization, panic, impending dread, motor restlessness, and initial insomnia (diurnal maxima). The acute onset, identifiable stress (physical or psychological), confusion, dysphoria, and absence of schizophrenic relatives not only portend a good prognosis, without recurrence, if quickly recognized, but also strongly suggests treating it as the condition it most closely resembles, AD-induced akathisia.

Beyond the index of suspicion and recognition of patient context, the diagnosis of utilizing an easy-to-perform two-arm test. The examination evaluates mental and motor competency (cortical-subcortical balance) in a short algorithm.

A supplemental diagnostic test, not substitutive but complementary, and a modification of the geste antagoniste, initially described for mental torticollis, is a voluntary sensorimotor technique to suppress some organic akathisia mental and motor signs.

In addition to the thalamocortical projections and basal nuclei pathways implicated in this life-threatening condition are the basolateral amygdala bidirectional communications with the norepinephrine rich locus coeruleus, hence the potential life-saving and early benefit of propranolol confirming a diagnosis ex juvantibus line of reasoning ("from that which helps").

This work is exceedingly difficult. There is an insufferable anguish. Doubters abound. Administrative inertia is substantial. Yet, the requirement to train trainers and trainees is critical.

"If you can keep your head when all about you are losing theirs and blaming it on you. If you can trust yourself when all men doubt you. But make allowance for their doubting too." -- If by Rudyard Kipling.

Russell Copelan, MD (Ret.), lives in Pensacola, Florida. He graduated from Stanford University and UCLA Medical School. He trained in neurosurgery and completed residency and fellowship in emergency department psychiatry. He is a reviewer for Academic Psychiatry and founder of , an originator and distributor of violence assessments. Read more of his posts here.