Akathisia is a constant internal urge to move, pathological restlessness. The subjective component of the phenomenon is a painful desire to move, uncomfortable sensations, a feeling of increasing anxiety in the absence of movement. Objective symptoms are expressed in fussiness, restlessness, trampling on the spot, aimless movement. Diagnosis is carried out clinically, instrumental studies are used to exclude organic brain damage. Treatment depends on the etiology of the condition, it is possible to use magnesium, cholinolytics, adrenoblockers, 5-HT2-receptor blockers, GABA potentiating and adrenoblocking drugs.
G25.8 Other specified extrapyramidal and motor disorders
The term “akathisia” was introduced in 1901 by the Czech psychiatrist L. Gaskovets to denote the constant need for movement that occurs in a number of patients with mental disorders. In 1923, French psychiatrists described akathisia in patients with secondary Parkinsonism, which developed after suffering encephalitis. Soon there were descriptions of pathological restlessness in Parkinson’s disease, as well as drug addiction, alcoholism, post-acute awakening. After the introduction of typical antipsychotics into medical practice (in the middle of the 20th century), it turned out that they, along with other side extrapyramidal effects, quite often cause an akathisive syndrome. According to modern data, akathisia occurs in 8-75% of cases when treated with typical antipsychotics. A significant spread of this indicator is due to the variability of the therapeutic methods used (dosages, duration of treatment, drugs used) and diagnostic approaches to the establishment of akathisia.
In modern neurology and psychiatry, the syndrome of pathological restlessness has become almost synonymous with the side effect of a number of psychotropic pharmaceuticals. However, in some cases there are other causes of this phenomenon. The main etiofactors, under the influence of which akathisia occurs, can be divided into the following groups:
- Psychotropic drugs. Most often, pathology is a side effect of the use of typical neuroleptics (haloperidol, pimozide, droperidol), less often — atypical antipsychotics (aripiprazole, olanzapine), antidepressants (mirtazapine), sedative pharmaceuticals (chlorpromazine). In the literature there are indications of the occurrence of this syndrome with abstinence against the background of abuse of certain groups of sleeping pills (for example, barbiturates).
- Taking drugs. Akathisia is observed against the background of cocaine intoxication, opium addiction, abuse of other psychostimulants (amphetamines, methylphenidate). The development of the akathisive syndrome is caused by the effect of these chemicals on the main neurotransmitter systems of the brain.
- Chronic alcoholism. The toxic effect of alcohol on brain neurons eventually leads to degenerative changes in subcortical ganglia. The latter are directly involved in the synthesis of neurotransmitters, their metabolism and interaction with the corresponding receptors. Violation of these transmitter systems provokes akathisia.
- Parkinsonism. The disorder occurs in a number of cases of primary and secondary Parkinsonism. It has not been reliably established whether it is a consequence of the disease or occurs as a result of the use of dopaminomimetics – levodopa drugs, D2-agonists.
There are predisposing factors that increase the likelihood of pathological restlessness. Thus, patients with anxiety disorders and affective states are more susceptible to the occurrence of extrapyramidal disorders than patients with schizophrenia. The risk of the disease is increased in patients with organic damage to the central nervous system, a history of TBI, dementia. A number of studies have shown the existence of a genetically determined predisposition associated with the DRD2 gene of the 1st chromosome.
Recent studies indicate that akathisia has a more complex mechanism of development than isolated dopaminergic dysfunction. Disorders of the noradrenergic, serotonin, GABA-mediated, cholinergic systems play a certain role. In 2011, a theory was put forward according to which a decrease in dopaminergic activity in parkinsonism or treatment with antipsychotics sometimes involves compensatory mechanisms. The latter include activation of noradrenergic axons of the bluish nucleus, stimulating the nucleus accumbens, which causes the occurrence of motor anxiety, anxiety sensations.
In parallel, under the influence of noradrenergic stimuli, the secretion of adrenaline by the adrenal glands increases, which supports the feeling of anxiety and excitement. It is also assumed that there is an indirect increase in the concentration of glutamate in the central nervous system, which accelerates the transmission of signals in various neurotransmitter systems and, with excessive accumulation, leads to overstrain of neurons. Excess glutamate is accompanied by a decrease in the concentration of GABA synthesized from glutamic acid — an inhibitory mediator that provides a calm state, composure, balance.
There are several clinically significant classifications of akathisive syndrome. According to the etiological principle, pathology is divided into iatrogenic, parkinsonian, arising from the use of psychoactive substances, withdrawal, spontaneous (due to mental disorders), post-stroke. According to the prevailing clinical manifestations , there are three forms:
- Motor — characterized mainly by motor manifestations. The tendency to constant movement prevails: walking, trampling on the spot. Patients do not feel significant psychological discomfort, anxiety.
- Sensory-mental (subjective) — characterized by the presence of subjective complaints in the absence of an objective motor component. Patients are subject to constant discomfort, anxiety, various unpleasant sensations in the legs. There is no visible hyperkinesia.
- Classical — is a combination of subjective sensations and objective motor hyperactivity. Patients complain of internal discomfort that makes them constantly move. Pathological restlessness is confirmed when observing the patient.
In the case of iatrogenic etiology, an important point in the choice of therapeutic tactics is to determine the time of occurrence of the syndrome in relation to the beginning of the therapy that provoked its development. According to the time factor , there are four types of akathisia:
- Spicy. Develops in the first days or weeks of antipsychotic therapy, less often in the first hours. It may be triggered by an increase in dosage. Regresses after the replacement of the drug. Against the background of continued administration without increasing the dose, the symptoms may decrease, sometimes persist.
- Chronic. Symptoms appear with the duration of treatment for a month or more. It is noted in 25-30% of cases of therapy with neuroleptics. The cancellation of the provoking pharmaceutical leads to a gradual regression of manifestations.
- Late. It is detected after many months (several years) of treatment. The cancellation of therapy is accompanied by an increase in manifestations, an increase in dosages may cause a temporary improvement in the condition, followed by an increase in symptoms. After the withdrawal of the drug-provocateur, the symptoms slowly decrease, sometimes remaining until the end of life.
- Akathisia of cancellation. Occurs in the first two weeks after discontinuation of medication, persists for 1-1.5 months. A longer course indicates the probable presence of a late form.
Classical akathisive syndrome includes subjective and objective (motor) components. Initially, motor manifestations are localized mainly in the lower extremities. The patient cannot lie down, sit or stand still. He constantly walks, often aimlessly along one trajectory, does not stand, but tramples on the spot. Lying in bed, the patient often changes his position, turns over, tirelessly moves his legs while sitting on a chair — fidgets, twists, swings his legs. As the pathology progresses, the movements become more stereotypical, akathisia spreads from the bottom up, covers the trunk, upper limbs, and head. With a pronounced degree of violations, the patient turns, swings, wriggles with his whole body, can move by jumping, grimacing, running, his eyes are constantly moving, his gaze is moving.
The subjective component of the syndrome is painfully tolerated by patients, the sensations experienced are difficult to describe and formulate. Sensory akathisia includes a variety of extremely uncomfortable sensations (burning, tingling, twisting, itching) localized in the depths of muscles and joints. The mental component is expressed in an unclear need for movement, strong anxiety, constant tension, inability to relax, dysphoria. Patients indicate that movement brings them some relief, while staying at rest, internal anxiety and tension increase rapidly.
In most cases, pathology provokes sleep disorders, difficulties falling asleep are caused by twisting in bed, night awakenings are associated with an irresistible need to walk. Prolonged akathisia is accompanied by the gradual formation of pathological character changes. Patients become annoying, suspicious, anxious, ingratiatingly sweet, irritable. Untreated disorder aggravates the course of the underlying mental illness, leads to the development of complications.
Akathisia can become a reason for the patient’s negative attitude to the therapy, up to the complete rejection of it. Pathological restlessness makes it difficult for the patient to fully participate in psychotherapeutic and social rehabilitation classes. Unbearable dysphoria is complicated by depression, the occurrence of suicidal thoughts, suicide attempts. Pronounced akathisia can provoke impulsive actions, aggressive behavior of the patient with autoaggression, danger to others. In the absence of adequate treatment of the akathisive syndrome, it is possible to develop complete intolerance to psychopharmacological agents. Attempts by patients to alleviate symptoms by smoking, taking alcohol, and various psychoactive substances cause the development of addictions.
It is extremely difficult to suspect the presence of an akathisive syndrome at an early stage. Patients can restrain motor manifestations by willpower, tend to hide subjective feelings, are unable to express them in words, sometimes do not understand what is happening to them due to the characteristics of the underlying mental illness, dementia. In some cases, the only clinical symptom is a sudden negative attitude of the patient to treatment. Modern neurophysiological (EEG, REG) and neuroimaging (MRI, CT brain) studies are informative only in terms of differential diagnosis.
The diagnostic search is carried out by a psychiatrist as part of a survey and clinical observation. Considering that the patient is able to restrain motor activity with an effort of will, a survey of relatives is practiced, observation of the patient’s behavior without his knowledge. The identification of the akathisive syndrome, the determination of its severity is facilitated by the use of the Burns scale, which includes:
- Objective assessment of motor anxiety. 0 — motor sphere without features. 1 — motor restlessness is noted less than half of the observation time. 2 — manifestations of motor restlessness cover more than half of the examination time. 3 — motor akathisia is so pronounced that the patient is unable to stay in place during the examination.
- Determination of the severity of subjective feelings. 0 — there is no concern. 1 — vague uncomfortable sensations. 2 — inability to keep the lower limbs motionless, increased anxiety at rest. 3 — a strong desire to move, a feeling of compulsion of motor activity. Separately, the degree of experiencing restlessness is assessed: zero, weak, medium, pronounced.
- General conclusion about the degree of akathisia. If only a subjective component is present, the disorder is considered doubtful (pseudoacathisia). The presence of nonspecific complaints and objective increased fussiness indicates a weakly expressed syndrome. Moderate severity corresponds to a combination of nonspecific subjective sensations with an obvious motor component. Distinct akathisia is diagnosed in the presence of internal anxiety and a motor component, pronounced — in combination with insomnia.
Pathology requires differential diagnosis of anxiety, psychomotor agitation, Tourette’s syndrome, hyperkinesis. Anxiety states are characterized by a lower need to move, the presence of vegetative symptoms, the predominance of excessive movements in the upper extremities (twisting buttons, fingering rosaries). Psychomotor agitation is characterized by a diffuse increase in motor skills, has no specific subjective coloring, movements do not bring mental relief. Tourette’s syndrome is accompanied by vocal, facial tics, patients note an “itchy” desire to make a certain movement only when trying to restrain the tic. Hyperkinesis has a typical motor pattern, can only be partially restrained.
Adequate therapy is based on the exact establishment of the etiology of the akathisive syndrome. Since the vast majority of cases have an iatrogenic nature, the existing treatment regimen is being reviewed for the presence of pharmaceuticals – a potential cause of the phenomenon that has arisen. Doses are reduced or these medications are replaced with drugs with less extrapyramidal potential. Almost all patients are recommended to take magnesium preparations, with severe symptoms — its parenteral administration. Further treatment is carried out with the combined use of the following main groups of pharmaceuticals:
- Central cholinolytics. They are prescribed if akathisia is combined with extrapyramidal symptoms (tremor, drug parkinsonism). A combination with medications of other groups is recommended, since cholinolytics are not effective enough against pronounced akathisive manifestations.
- Beta-blockers. Lipophilic agents capable of penetrating the blood-brain barrier are used. They are first-line drugs in the treatment of patients without extrapyramidal disorders.
- GABAergic agents. By potentiating GABA, they reduce anxiety, arousal, and improve sleep. They have a weak effect on the motor component, therefore they are prescribed in combination with drugs of the previous two groups.
- 5-HT2-blockers. The theoretical basis for the use of medicines of this group was the observation that akathisia occurs less often when antipsychotics with a 5-HT2-blocking effect are prescribed. Subsequent clinical trials have proven their therapeutic effectiveness.
- Antiadrenergetics. The positive effect of these pharmaceuticals confirms the pathogenetic role of the noradrenergic system. Along with the anti-physical effect, they reduce the severity of nightmares.
- Dopaminergic drugs. They are used for persistent symptoms. Additionally, depressive, dysphoric disorders are corrected.
Prognosis and prevention
The success of therapy depends on the timeliness of its initiation, etiology, form and severity of the akathisive syndrome. In most patients, adequate therapy makes it possible to improve the condition and avoid complications. Since akathisia is mainly a complication of drug therapy, the measures of its prevention are the rational use of antipsychotic pharmaceuticals and antidepressants, careful dose selection, the preparation of combined treatment regimens taking into account drug-drug interaction. The use of atypical antipsychotics with the lowest potential for extrapyramidal symptoms is recommended. If it is necessary to use drugs with a high risk of akathisia, cholinolytics, beta-blockers or gabaergic agents should be prescribed prophylactically.