Сlinical and Psychopathological Phenomenology of Mild Acute Drug-Induced Akathisia

Abstract

The study is devoted to the clinical and psychopathological phenomenology of mild acute drug-induced akathisia that occurs in the treatment of schizophrenia. The relationship between clinical symptoms and features of neurocognitive status with acute drug-induced akathisia resulting from the appointment of standardized antipsychotic therapy to patients was studied. It was found that patients with paranoid schizophrenia with mild acute drug-induced akathisia have more pronounced general psychopathological symptoms, such as anxiety, tension, depression, refusal to cooperate, weakening of impulsivity control, and congestion of mental experiences. According to the assessment of the risk profile of aggression, additional symptoms are more pronounced, such as anger, difficulties in delaying gratification (delayed reward), and affective lability. According to the results of the study of the neurocognitive status, markers of mild acute drug-induced akathisia were identified: impaired stability of active attention, impaired working memory, decreased automation of thinking, and impaired executive functions.

1. Introduction

Schizophrenia is a disease that exerts a significant economic cost in terms of loss of the patient’s ability to work, destruction of social ties, and critically reducing the quality of life [1]. Medical care for paranoid schizophrenia is not devoid of controversial and problematic issues that require careful consideration and comprehensive analysis [2]. One of them is the issue of timely diagnosis of acute drug-induced akathisia. The American Psychiatric Association’s Diagnostic and statistical manual of mental disorders (DSM-5) describes medication-induced acute akathisia as subjective complaints of restlessness, often accompanied by observed excessive movements (e.g., fidgety movements of the legs, rocking from foot to foot, pacing, and inability to sit or stand still), developing within a few weeks of starting or raising the dosage of a medication (such as neuroleptic), or after reducing the dosage of a medication used to treat extrapyramidal symptoms. Rocking, pacing, shifting weight while standing, and an inability to remain seated are commonly observed clinically [3].

There are no clear recent data on the prevalence of akathisia. Akathisia may appear as a side effect of prolonged use of antipsychotic drugs. From 15–45% of people taking antipsychotic drugs experience akathisia [4, 5].

Since it is known that this occurs as a result of the treatment of a mental disorder, the timely recognition of akathisia is of key importance [6]. Correction and treatment of drug-induced extrapyramidal disorders (EPR), which include akathisia, begin with a statement of their pronounced nature, the main sign of which is their obvious motor component. However, after reaching the degree of severity, acute drug-induced akathisia tends to become chronic, despite the recommended methods of correction [7]. Pronounced acute drug-induced akathisia often leads the patient to the decision to abandon the recommended treatment regimens [8], aggravates the psychotic and affective symptoms of the underlying disease [9, 10], and almost always worsens the quality of life of patients [11, 12]. The appearance of signs of akathisia in the patient negatively affects labor and social activity [13] and leads to additional social stigmatization [11].

The main problem with timely detection of acute drug-induced akathisia is that before the stage of development of pronounced motor manifestations, it is manifested by psychopathological symptoms that have an external similarity with some symptoms of schizophrenia, often taken by doctors as symptoms of the disease and regarded as a worsening of the underlying disease [14]. Acute drug-induced akathisia is often manifested only by a subjective feeling of unexplained anxiety and internal anxiety, which can be regarded by a doctor as an exacerbation of the underlying disease and lead to an erroneous decision to increase the dose of the prescribed antipsychotic, which in turn enhances akathisia [8].

The relevance of the study lies in the absence of reliable clinical and psychopathological markers for the diagnosis of mild acute drug-induced akathisia, which manifests itself in the actual provision of assistance after the occurrence of its pronounced motor manifestations when their correction itself counter-productively leads to additional adverse reactions from corrective medications [15, 16].

The aim of this study is to identify the clinical features and neurocognitive profile of patients with paranoid schizophrenia and mild acute drug-induced akathisia.

2. Materials and methods

Study design: open, observational, and cross-sectional study with directed formation of comparison groups. The comparison groups were congruent by gender (χ2 = 0.899; p = 0.638), age (F = 2.773; p = 0.064), family (χ2 = 4.782; p = 0.572), social (χ2 = 13.789; p = 0.063) status, and level of education (χ2 = 9.330; p = 0.501).

The object of the study was 333 patients (171 men, 162 women; average age 36.8 ± 11.71) with paranoid schizophrenia (F20.09, F20.01, F20.00, F20.02, F20.03 according to ICD10) undergoing inpatient treatment at the state institution “Republican Research and Practice Center for Mental Health” (Minsk, Belarus). All patients at the time of the study were taking antipsychotic drug therapy in accordance with the protocol for the diagnosis and treatment of mental and behavioral disorders [17]. Informed consent to participate in the study was signed by all participants of the study.

Diagnosis of clinical symptoms of schizophrenia was carried out using the PANSS scale [18].

To assess the severity of early drug-induced extrapyramidal symptoms, the extrapyramidal symptoms rating scale (ESRSA) was used [19].

The main group included patients with schizophrenia who, at the time of the study, had only mild acute drug-induced akathisia (group A), which, according to the guidelines for the use of the ESRS-A scale [19], is characterized by subjective complaints of the patient about a feeling of anxiety or a desire to move, with which, it is possible to cope that do not affect the patient’s daily activity and manifest themselves less than 50% of the time, as well as objective little-expressed restless movements when the patient feels the need to move at least one limb, which manifests themselves less than 50% of the patient’s observation time. Scores on the subscales of the ESRS scale N (parkinsonism) = 0, A (akathisia) = 1–2, D (dystonia) = 0, DK (dyskinesia) = 0. The comparison group consisted of patients with neuroleptic parkinsonism (NP) (group B), which is characterized by resistance to passive movements in the upper extremities, lower extremities or neck; low amplitude tremor of the face, jaws, lips, head, upper limbs or hands, lower limbs or feet during movement or postural tremor (observed periodically less than 50% of the time, absent at rest); slight decrease in facial expression, hypomimia; slight decrease in friendly hand movements, slight stoop posture; latero-, antero- or retropulsion in which the patient regains balance without assistance; moderately slow movements, weak impoverishment of movements. Estimates by subscales of the ESRS scale N = 1–2, A = 0, D = 0, and DC = 0. The control group consisted of patients with paranoid schizophrenia without extrapyramidal disorders: scores on the subscales of the ESRS scale N = 0, A = 0, D = 0, and DC = 0.

Inclusion criteria: The main group (n = 127) included patients with schizophrenia who had acute drug-induced akathisia at the time of the study; (group A): scores on the ESRS scale subscales N (parkinsonism) = 0, A (akathisia) = 1–2, D (dystonia) = 0, DK (dyskinesia) = 0, and total ESRS score = 1–2. The comparison group (n = 115) consisted of patients with neuroleptic parkinsonism (group B): scores on the subscales of the ESRS scale N = 1–2, A = 0, D = 0, DC = 0, and total ESRS score = 1–2. The control group (n = 91) consisted of patients with paranoid schizophrenia without extrapyramidal disorders: scores on the subscales of the ESRS scale N = 0, A = 0, D = 0, DK = 0, and total ESRS score = 0.

The criteria for excluding patients from the sample were: the presence of acute psychotic symptoms in the patient (on the PANSS scale and the sum of positive symptoms >30 points), pronounced manifestations of a personality defect (on the PANSS scale and the sum of negative symptoms >35 points), scores on the subscales of the ESRS scale N > 2, A > 2,D > 0, DK > 0, total ESRS score > 2.

The comparison groups were congruent by gender (χ2 = 0.899; p = 0.638), age (F = 2.773; p = 0.064), family (χ2 = 4.782; p = 0.572), social (χ2 = 13.789; p = 0.063) status, level of education (χ2 = 9.330; p = 0.501).

The cognitive sphere of the patients under study was assessed using the following techniques: Schulte tables; Luria test for auditory memorization of 10 and unrelated words; visual memorization test for 10 and unrelated words; trail-making test (TMT); Stroop color-word interference test; and Wisconsin card sorting test (WCST).

The data were processed on a personal computer using the SPSS 20.0 statistical package.

3. Results and discussion

When conducting a one-factor analysis of variance, it was found that there were no differences in any of the clusters of positive symptoms in the comparison groups (ANOVA, p > 0.05).

It was found that there were significant differences in the severity of negative symptoms in the comparison groups (total score of negative symptoms, ANOVA, F = 26.09; p = 0.001). These differences occurred due to clusters H1 blunted affect (ANOVA, F = 29.14; p = 0.001) and H2 emotional detachment (ANOVA, F = 22.09; p = 0.006). For other negative symptoms, no differences were found in the groups during comparison (ANOVA, F < 3.0; p > 0). (Table 1).

Negative symptoms on the PANSS scale	Statistical significance of differences
H1 - blunted effect	F = 29,14	p = 0,001
H2 - emotional detachment	F = 22,09	p = 0,006
H3 - difficulties in communication	F = 2,19	p = 0,09
H4 - passive-apathetic social withdrawal	F = 2,85	p = 0,07
Н5 – violation of abstract thinking	F = 1,94	p = 0,12
Н6 – violation of spontaneity and smooth thinking	F = 2,90	p = 0,06
H7 - stereotypical thinking	F = 2,1	p = 0,1

Table 1.

Intergroup differences in negative symptoms (ANOVA and p-significance level).

In a pairwise comparison, it was found that the negative symptoms in group A patients did not differ from those in the control group (post hoc analysis, LSD, and p > 0.05). Blunted affect and emotional detachment were statistically more pronounced in group B patients compared to group A and control group patients (post hoc analysis, LSD, and p < 0.05) (Table 2).

Comparison groups	H1 - blunted affect				H2 - emotional detachment				H3 - communication difficulties
	Group А, М = 1,75	Group B, М = 5,01		Control group, М = 1,20	Group А, М = 2,09	Group B, М = 5,08	Control group, М = 2,20		Group А, М = 3,71	Group B, М = 3,12	Control group, М = 3,75
Group А		0,01		0,12		0,04	0,41			0,14	0,14
Group B	0,01			0,04	0,04		<0,001		0,14		0,75
Control group	0,12	0,04			0,41	<0,001			0,14	0,75
Comparison groups	H4 - passive-apathetic social isolation			H5 - violation of abstract thinking			H6 - violation of spontaneity and smooth thinking			H7 – stereotypical thinking
	Group А, М = 3,75	Group B, М = 4,01	Control group, М = 3,20	Group А, М = 3,09	Group B, М = 3,08	Control group, М = 3,36	Group А, М = 2,71	Group B, М = 2,12	Control group, М = 2,75	Group А, М = 2,71	Group B, М = 3,12	Control group, М = 2,75
Group А		0,49	0,10		0,25	0,16		0,24	0,24		0,16	0,16
Group B	0,49		0,34	0,25		0,17	0,24		0,75	0,16		0,75
Control group	0,10	0,34		0,16	0,17		0,24	0,75		0,16	0,75

Table 2.

Intergroup differences in negative symptoms (post hoc analysis, LSD, and p-significance level).

It was found that there were significant differences in the severity of general psychopathological symptoms in the comparison groups (total score of general psychopathological symptoms, ANOVA, F = 25.92; p = 0.001).

These differences occurred due to clusters O2 anxiety (ANOVA, F = 31.09; p < 0.001) and O4 tension (ANOVA, F = 12.82; p = 0.04), O6 - depression (ANOVA, F = 28.78; p < 0.001), O8 - refusal to cooperate (ANOVA, F = 9.34; p = 0.001), O14 - weakening of impulsivity control (ANOVA, F = 27.23; p = 0.001), O15 - congestion of mental experiences (ANOVA, F = 19.26; p = 0.004). For other common psychopathological symptoms, no differences were found in the comparison groups (ANOVA, F = 2.8; p > 0.05) (Table 3).

General psychopathological symptoms on the PANSS scale	Statistical significance of differences
О1 - somatic concern	F = 2,17	p = 0,09
О2 - anxiety	F = 31,09	P < 0,001
О3 - feeling guilty	F = 2,01	p = 0,11
О4 - tension	F = 12,82	p = 0,04
О5 - mannerism and posture	F = 1,94	p = 0,12
О6 - depression	F = 28,78	p < 0,001
О7 - motor retardation	F = 2,11	p = 0,1
О8 - refusal to cooperate	F = 9,34	p = 0,01
О9 - unusual content of thoughts	F = 2,23	p = 0,1
О10 - disorientation	F = 1,79	p = 0,15
О11 - attention disorder	F = 2,85	p = 0,07
О12 - reduced criticality and awareness of the disease	F = 1,98	p = 0,12
О13 - violations of the will	F = 1,75	p = 0,17
О14 - weakening of impulsivity control	F = 27,23	p = 0,001
О15 - preoccupation with mental experiences	F = 19,26	p = 0,004
О16 - active social exclusion	F = 2,55	p = 0,07

Table 3.

Intergroup differences in general psychopathological symptoms (ANOVA and p-significance level).

In a pairwise comparison, it was found that the group of patients with acute drug-induced akathisia (group A) differs from patients with neuroleptic parkinsonism (group B) and groups without extrapyramidal disorders (control group) with statistically more pronounced following signs: anxiety (O2), tension (O3), depression (O4), refusal to cooperation (O8), weakening of impulsivity control (O14), and workload with mental experiences (O15) (post hoc analysis, LSD, and p < 0.05). For other common psychopathological symptoms, no differences were found in the comparison groups (post hoc analysis, LSD, and p > 0.05) (Table 4).

Comparison groups	О1 - somatic concern			O2 - anxiety			О3 - feeling guilty
	Group А; М = 3,79	Group B; М = 2,01	Control group; М = 1,21	Group А; М = 5,25	Group B; М = 2,01	Control group; М = 1,20	Group А; М = 2,70	Group B; М = 3,11	Control group; М = 2,73
Group А		0,48	0,11		<0,001	<0,001		0,17	0,16
Group B	0,48		0,52	<0,001		0,08	0,17		0,75
Control group	0,11	0,52		<0,001	0,08		0,16	0,75
Группы сравнения	О4 ˗ tension			О5 ˗ mannerism and posture			О6 ˗ depression
	Group А, М = 5,09	Group B, М = 2,38	Control group, М = 2,21	Group А, М = 2,72	Group B, М = 3,13	Control group, М = 2,11	Group А, М = 5,01	Group B, М = 2,68	Control group, М = 1,67
Group А		0,04	<0,001		0,16	0,11		0,001	<0,001
Group B	0,04		0,42	0,16		0,06	0,001		0,06
Control group	<0,001	0,42		0,11	0,06		<0,001	0,06
Comparison groups	О7 ˗ motor retardation			О8 ˗ refusal to cooperate			О9 ˗ unusual content of thoughts
	Group А; М = 2,75	Group B; М = 4,01	Control group; М = 3,20	Group А; М = 4,91	Group B; М = 2,28	Control group; М = 1,90	Group А; М = 3,71	Group B; М = 2,12	Control group; М = 2,05
Group А		0,29	0,34		0,04	<0,001		0,15	0,11
Group B	0,29		0,09	0,04		0,43	0,15		0,79
Control group	0,34	0,09		<0,001	0,43		0,11	0,79
Comparison groups	О10 - disorientation			О11 ˗ attention disorders			О12 ˗ reduced criticality and awareness of the disease
	Group А; М = 3,62	Group B; М = 2,25	Control group; М = 2,01	Group А; М = 3,62	Group B; М = 3,55	Control group; М = 2,41	Group А; М = 3,65	Group B; М = 1,50	Control group; М = 2,48
Group А		0,17	0,11		0,87	0,15		0,11	0,53
Group B	0,17		0,78	0,87		0,16	0,11		0,36
Control group	0,11	0,78		0,15	0,16		0,53	0,36
Comparison groups	О13˗ violations of the will				О14 ˗ weakening of impulsivity control
	Group А; М = 2,81	Group B; М = 3,34		Control group; М = 2,17	Group А; М = 5,19		Group B; М = 1,38	Control group; М = 2,20
Group А		0,45		0,30			<0,001	0,007
Group B	0,45			0,21	<0,001			0,22
Control group	0,30	0,21			0,007		0,22
Comparison groups	О15˗ preoccupation with mental experiences				О16 ˗ active social exclusion
	Group А; М = 5,10		Group B М = 2,28	Control group М = 2,01	Group А; М = 3,10		Group B М = 2,91	Control group; М = 2,13
Group А			<0,001	0,008			0,67	0,16
Group B	<0,001			0,72	0,67			0,25
Control group	0,008		0,72		0,16		0,25

Table 4.

Intergroup differences in common psychopathological symptoms (post hoc analysis, LSD, and p-significance level).

It was found that there were significant differences in the severity of additional symptoms in the three compared groups (F = 29.25; p = 0.001).

These differences occurred due to all three clusters of additional symptoms: D1 anger (ANOVA, F = 27.34; p < 0.001), aD2 difficulty in delaying gratification (delayed gratification) (ANOVA, F = 22.15; p = 0.001), and D3 affective lability (ANOVA, F = 29.19; p < 0.001) (Table 5).

Additional symptoms on a scale; PANSS	Statistical significance of differences
D1 - anger	F = 27,34	P < 0,001
D2 - difficulties in delaying gratification	F = 22,15	P = 0,001
D3 - affective lability	F = 29,19	P < 0,001

Table 5.

Intergroup differences of additional symptoms (ANOVA and p-significance level).

In a pairwise comparison, it was found that the group of patients with acute drug-induced akathisia (group A) differs from patients with neuroleptic parkinsonism (group B) and the group without extrapyramidal disorders (control group) by the following more pronounced signs: “anger” (D1), “difficulty in delaying ratification (delayed reward)” (D2) and “affective lability” (D3) (post hoc analysis, LSD, and p < 0.05) (Table 6).

Comparison groups	D1 - anger			D2 - difficulties in delaying gratification			D3 - affective lability
	Group A; М = 5,10	Group B; М = 1,78	Control group; М = 2,03	Group А; М = 5,01	Group B; М = 1,86	Control group; М = 1,98	Group А; М = 5,89	Group B; М = 1,61	Control group; М = 2,15
Group А		<0,001	0,007		<0,001	0,006		<0,001	<0,001
Group B	<0,001		0,31	<0,001		0,52	<0,001		0,12
Control group	0,007	0,31		0,006	0,52		<0,001	0,12

Table 6.

Intergroup differences of additional features for assessing the risk profile of aggression (post hoc analysis, LSD, and p-significance level).

Analysis of the data obtained during clinical examination and subsequent statistical processing reliably demonstrates mild acute drug-induced akathisia in patients with paranoid schizophrenia has its own clinico-psychopathological phenomenology comparable to the disease itself.

In patients with paranoid schizophrenia and mild acute drug-induced akathisia, general psychopathological symptoms are most pronounced: anxiety, tension, depression, refusal to cooperate, weakening of impulsivity control, and congestion with mental experiences (post hoc analysis, LSD, p < 0.05).

In patients with paranoid schizophrenia with mild acute drug-induced akathisia, additional symptoms are more pronounced according to the assessment of the risk profile of aggression: anger, difficulties in delaying gratification (delayed gratification), and affective lability (post hoc analysis, LSD, p < 0.05).

The study of neurocognitive functions also revealed the characteristic features of drug-induced akathisia.

When passing the Luria test for visual memorization of 10 unrelated words, it was revealed that there were significant differences in the volume of short-term visual memory in comparison groups (ANOVA, F = 11.27; p = 0.01).

When performing the Luria test for auditory memorization of 10 unrelated words, differences in performance indicators of auditory short-term memory was not detected in the comparison groups (ANOVA, F = 2.03; p = 0.13).

When performing the “Schulte table” technique in comparison groups, significant differences were revealed in such characteristics of attention as work efficiency (ANOVA, F = 21.72; p = 0.001), workability (ANOVA, F = 22.09; p = 0.001), and mental stability (ANOVA, F = 24.01; p < 0.001) (Table 1).

In a pairwise comparison it was found that the group of patients with acute drug-induced akathisia (group A) differs from patients with neuroleptic parkinsonism (group B) and differs from the group without extrapyramidal disorders (control group) by a more pronounced violation of mental stability (NP) (post hoc analysis, LSD, p < 0.05). In turn, the group of patients with neuroleptic parkinsonism (group B) differs from the group with acute drug-induced akathisia (group A), and the group without extrapyramidal disorders (control group) by pronounced violations of visual short-term memory and attention characteristics, such as work efficiency (WE) and workability (WA) (post hoc analysis, LSD, and p < 0.05). There were no differences in the performance of auditory short-term memory in the comparison groups (post hoc analysis, LSD, and p > 0.05) (Table 7).

Neurocognitive functions	Statistical significance of differences
OE - operational efficiency	F = 21,72	p = 0,001
WA - Workability	F = 22,09	P = 0,001
MT - mental toughness	F = 24,01	р < 0,001
WSTM - verbal short-term memory	F = 2,03	p = 0,13
STVM - short-term visual memory	F = 11,27	p = 0,01
WM(e) - working memory (test execution time)	F = 18,38	P = 0,003
WM(e) - working memory (number of errors)	F = 19,12	p = 0,002
CF - Cognitive flexibility (number of errors in part 2 of the Stroop test)	F = 21,34	p = 0,001
AS - automation style (time to complete part 2 of the Stroop test)	F = 22,32	p = 0,001

Table 7.

Intergroup differences in the characteristics of attention, short-term and working memory, cognitive flexibility, and automation (ANOVA and p-significance level).

When performing the trail-making test (TMT), significant differences were revealed in the comparison groups both in terms of test execution time (ANOVA, F = 18.38; p = 0.003) and in the number of errors made (ANOVA, F = 19.12; p = 0.002) (Table 7).

In a pairwise comparison, it was found that the group of patients with acute drug-induced akathisia (group A) differs from patients with neuroleptic parkinsonism (group B) and the group without extrapyramidal disorders (control group) by a large number of errors made when performing the working memory test (RP(t) (post hoc analysis, LSD, p < 0.05). In turn, the group of patients with neuroleptic parkinsonism (group B) differs from the group of patients with acute drug-induced akathisia (group A) and the group without extrapyramidal disorders (control group) by a greater time spent on the working memory test (RP (e) (post hoc analysis, LSD, and p < 0.05) (Table 8).

Patient groups	P ˗ performance (efficiency factor)			WP ˗ work-in-progress (work-in-progress coefficient)			MT ˗ mental toughness (resilience coefficient)
	Group A М = 52,26	Group B М = 60,13	Control group; М = 46,29	Group A; М = 1,33	Group B М = 1,48	Control group; М = 1,23	Group A; М = 1,89	GroupB; М = 1,39		Control group; М = 1,27
Group A		0,001	0,09		0,04	0,12		0,04		<0,001
Group B	0,001		<0,001	0,04		<0,001	0,04			0,06
Control group	0,09	<0,001		0,12	<0,001		<0,001	0,06
Patient groups	VShM ˗ verbal short-term memory (number of words) group			VSM ˗ visual short-term memory (number of words)				WM(s) ˗ working memory (time in seconds)
	Group A, М = 5,34	Group B, М = 5,72	Control group, М = 5,49	Group, AМ = 5,97	Group B, М = 5,57	Control group, М = 6,38		Group A, М = 202,90	Group B, М = 234,73	Control group, М = 193,98
Group A		0,07	0,10		0,08	0,11			0,03	0,12
Group B	0,07		0,33	0,08		0,003		0,03		<0,001
Control group	0,10	0,33		0,11	0,003			0,12	<0,001
Patient groups	WM(e) ˗ working memory (number of errors)			CF ˗ cognitive flexibility (number of errors)				AS ˗ automation style (time in seconds)
	Group A М = 6,98	Group B М = 6,04	Control group; М = 5,73	Group A М = 6,50	Group B М = 5,25	Control group; М = 4,61		Group A М = 106,31	Group B М = 134,05	Control group; М = 95,94
Group A		0,01	<0,001		0,01	<0,001			0,001	0,06
Group B	0,01		0,06	0,01		0,09		0,001		<0,001
Control group	<0,001	0,06		<0,001	0,09			0,06	<0,001

Table 8.

Intergroup differences in the characteristics of attention, short-term and working memory, cognitive flexibility, and automation (post hoc analysis, LSD, and p-significance level).

Note: Group A is a group with mild acute drug-induced akathisia, group B is a group with mild early neuroleptic parkinsonism, and control group is a group without extrapyramidal disorders.

When performing the Stroop test in the comparison groups, there are significant differences both in terms of the execution time of the 2nd part of the test (ANOVA, F = 21.34; p = 0.001) and in the number of errors made when performing the 2nd part of the test (ANOVA, F = 22.32; p = 0.001).

In a pairwise comparison, it was found that the group of patients with acute drug-induced akathisia (group A) differs from patients with neuroleptic parkinsonism (group B) and groups without extrapyramidal disorders (control group) in the automation style (AS), which is manifested by a large number of mistakes made when performing the 2nd part of the Stroop test (post hoc-analysis, LSD, p < 0.05). In turn, the group of patients with neuroleptic parkinsonism (group B) differs from the group of patients with acute drug-induced akathisia (group A) and the group without extrapyramidal disorders (control group) with impaired cognitive flexibility (CF), which is revealed by the greater time spent on the 2nd part of the Stroop test (post hoc analysis, LSD, and p < 0.05) (Table 8).

In the study of performance functions based on the Wisconsin card sorting test (WTSC) in comparison groups, differences were revealed in such indicators as the number of perseverative (ANOVA, F = 19.71; p = 0.003) and non-perseverative errors (ANOVA, F = 21.92; p = 0.001), the number of cards for passing the first category (ANOVA, F = 22.01;p = 0.001), and the number of district errors (ANOVA, F = 24.81; p < 0.001) (Table 9).

Test performance characteristics WTSC	Statistical significance of differences
FС - number of cards to pass the 1st category	F = 19,71	p = 0,003
РЕ - perseverative errors	F = 21,92	P = 0,001
NE - non-perseverative errors	F = 22,01	p = 0,001
DE - distributive errors	F = 24,81	P < 0,001

Table 9.

Intergroup differences in performing functions (ANOVA and p-significance level).

In a pairwise comparison it was found that the group of patients with acute drug-induced akathisia (group A) differs from patients with neuroleptic parkinsonism (group B) and the group without extrapyramidal disorders (control group) by a large number of non-superseverative (NS) and distributive errors (DE) when performing WTSC (post hoc analysis, LSD, p < 0.05). In turn, the group of patients with neuroleptic parkinsonism (group B) differs from the group of patients with acute drug-induced akathisia (group A) and the group without extrapyramidal disorders (control group) by a large number of cards for passing the first category of WTSC (FC) and a large number of perseverative errors when performing WTSC (PE) (post hoc analysis, LSD, and p < 0.05) (Table 10).

Patient groups	СN ˗ number of cards to pass the 1st category			РЕ ˗ perseverative errors (errors caused by fixation on a previous task)
	Group A М = 10,79	Group B М = 12,62	Control group; М = 9,91	Group A; М = 21,92	Group B; М = 26,65	Control group; М = 20,26
Group A		0,01	0,12		0,04	0,07
Group B	0,01		<0,001	0,04		<0,001
Control group	0,12	<0,001		0,07	<0,001
Patient groups	NE ˗ non-perseverative errors (other errors)			DE ˗ distributive errors (card sorting errors without rules)
	Group A М = 21,22	Group B М = 18,26	М = 16,50	Group A М = 16,25	Group B М = 13,24	Control group; М = 13,20
Group A		0,01	<0,001		<0,001	<0,001
Group B	0,01		0,07	<0,001		0,41
Control group	<0,001	0,07		<0,001	0,41

Table 10.

Intergroup differences in performance functions in comparison groups (post hoc analysis, LSD, and p-significance level).

Note: Group A is a group with mild acute drug-induced akathisia, group B is a group with mild early neuroleptic parkinsonism, and control group is a group without extrapyramidal disorders.

Summing up the results of this study, we can say that patients with schizophrenia who have developed mild acute drug-induced akathisia have statistically proven neurocognitive disorders that differ in their structure. Markers of mild acute drug-induced akathisia are impaired stability of active attention, impaired working memory, decreased automation of thinking, and impaired executive functions due to high distractibility (post hoc analysis, LSD, p < 0.05). Significant differences in neurocognitive profiles in patients with neuroleptic parkinsonism and acute drug-induced akathisia indicate a different pathoplastic basis for these disorders. This is important not only in the differential diagnosis of these types of extrapyramidal disorders among themselves but also in the specifics of their treatment. The participation of various neurocognitive blocks in the brain supports this phenomenon and is clinically significant for the development of further research in terms of treatment and rehabilitation of patients with acute drug-induced akathisia. Also, based on the data obtained, in the absence of expressed manifestations of acute drug-induced akathisia, the study of neurocognitive functions can be an important additional diagnostic tool for these disorders.

4. Conclusions

In patients with schizophrenia and mild acute drug-induced akathisia, the clinical picture is dominated by tension, depression, refusal to cooperate, weakening of impulsivity control, workload with mental experiences, anger, difficulties in delaying gratification, and affective lability (post hoc analysis, LSD, p < 0.05). The neurocognitive sphere suffers the stability of active attention, working memory, automation of thinking, and performing functions (post hoc analysis, LSD, p < 0.05). Timely diagnosis of acute drug-induced akathisia by clinical and neuropsychological signs will improve the quality and effectiveness of treatment.

Acknowledgments

The authors would like to thank the patients who agreed to the publication of this article, as well as the staff of the psychiatric department who supported the management of cases in ^the state institution «Republican Research and Practice Center for Mental Health», Minsk, Belarus. The study was funded by the Ministry of Health of Belarus.

Conflict of interest

The authors declare no conflict of interest.