Introduction

Tardive Dyskinesia is a drug-induced hyperkinetic movement disorder that is precipitated due to prolonged exposure to dopamine receptor-blocking agents, usually antipsychotics, which persists for minimum 30 days after stopping the drug (1). This condition can be non-reversible and might last a whole lifetime. The condition can be stigmatizing and disabling, with detrimental effects on mental and physical health and quality of life.

The term "tardive," or late, differentiates tardive dyskinesia from various drug-induced extrapyramidal symptoms that usually appear either acutely or very soon after exposure to dopamine receptor-blocking agents and that resolve after the drug is discontinued.

Tardive dyskinesia (TD) is characterized by choreiform, athetoid, and rhythmic abnormal involuntary movements.

The estimated annual incidence of TD with first-generation antipsychotics is 5% to 6% overall (2,3) and 10% to 25% in adults(4,5). The risk is similar among various first-generation antipsychotics when used as dose equivalents.

The estimated annual risk of tardive dyskinesia with exposure to second-generation antipsychotics is approximately 4% in the population(6) and 5% to 7% in older adults(7).

Tardive dyskinesia is an important marker for patients at risk of adverse healthcare outcomes and diminished quality of life.

With a rise access to psychiatric services and use of antipsychotics, the need to study tardive dyskinesia becomes important. The current global prevalence is believed to be between 15-50% but the true prevalence is not well studied, especially in the Indian context.(8)

This study will help in knowing the extent of tardive dyskinesia among persons with chronic mental illness in a Psychiatry Rehabilitation setting in India and will also give us insights to the factors involved to help prevent the same.

Materials and Methods:

The present study was carried out between January 1st, 2021 and April 2022 in the following rehabilitation centres in Dakshina Kannada district, after obtaining the clearance from Institution’s Ethics Committee (YEC2/658).

1. Swadhara women’s home Jeppu, Mangalore.
2. Snehalaya asharam, Manjeshwara.

Study Design: Descriptive type of observational study, cross-sectional study

Assessment Tools:

Abnormal Involuntary Movement Scale (AIMS)

The AIMS(9) is a 12 items clinician-rated scale to assess the severity of dyskinesia in patients taking antipsychotic medications. Additional items are present to assess the overall severity, incapacitation, and the subject’s level of awareness of the movements, and distress associated with them.

The AIMS has been used extensively to assess Tardive Dyskinesia in clinical trials of antipsychotic medications. Due to its simple design and low assessment time, the AIMS can be done regularly and effectively by all clinicians.

Items are scored on a 0 (none) to 4 (severe) basis. The scale provides a total score or item 8 can be used in isolation as an indication of the overall severity of symptoms.

Kane Schooler Criteria

It is a diagnostic criterion(10) for tardive dyskinesia that has three components and makes use of the AIMS scale to do so. The components of this criteria are-

1. At least 3 months of cumulative exposure to neuroleptics (antipsychotics).
2. Absence of other conditions that might cause involuntary movements
3. At least moderate dyskinetic movements in one body area (≥ 3 on AIMS) or mild dyskinetic movements in two body areas (≥ 2 on AIMS)

Sources of Data/ Sampling Method: Inhabitants of Swadhara women’s home Jeppu and Snehalaya asharam who fulfilled the inclusion criteria were recruited for this study. Written permission was sought from the Rehabilitation center incharge and the treating team. Informed consent was then obtained from all the participants.

Type of sampling: Convenience sampling

Sample Size

From the published article, “Prevalence and risk factors associated with tardive dyskinesia among Indian patients with schizophrenia” by Rashmin M. Achalia(11) at 5% level of significance and anticipated prevalence was 26.4% (from related article) and estimation error (absolute precision) of 6%

Sample size calculation was done using the formula, n= [Z²Xp(1-p)]/d² where, n= sample size d=absolute precision p=prevalence. Total sample size was found to be 207.

Inclusion Criteria:

1. Patients of ages 18 or above
2. Males/ females
3. Patients with chronic mental illness currently on antipsychotics for a minimum period of 3 months duration

Exclusion Criteria:

1. Patients unfit for a formal examination
2. Patients with active symptoms of present mental illness
3. Subnormal intelligence clinically

The authors were not directly involved in the treatment of all these patients; as they were managed by their primary physicians and psychiatrists.

Statistical Analysis:

The data was entered into a MS-Excel worksheet and cleaned for any corrections and errors. Further analysis of data was done using statistical package IBM SPSS Statistics 26.0.

The nominal and ordinal variables were presented using frequency and percentages. The ratio scale variables were presented using descriptive statistics such as Mean and SD. Further analysis was done using Chi-square test and unpaired t-test. The level of significance was set at 5%. All p-values less than 0.05 were treated as significant.

Results:

Table 1 describes the sociodemographic variables.

The average age of study subjects was 45.39 years (SD=12.6336), and the median age was 47.0 years and modal age was 55.0. The minimum and maximum age was 18 and 74 respectively.

Out of 207 study subjects, the 139 (67.10%) had psychosis unspecified/ schizophrenia and 68 (32.90%) had bipolar disorder. Out of 207 study subjects, 45 (21.73%) had used anticholinergics.

Figure 1 indicates that 67% participants were diagnosed with schizophrenia and 33% were diagnosed with bipolar disorder.

Fig. 1: Diagnosis among participants (N=207)

Table 2 indicates distribution of study subjects according to the medicines used.

Fig. 2: Duration of treatment

Figure 2 depicts the distribution of subjects according to the duration of treatment.

Table 3 indicates distribution of study subjects according to the CPZ equivalent doses/day for current ongoing antipsychotics.

Figure 3 indicates distribution of study subjects according to the AIMS- facial and oral score. Out of 207 study subjects, 18 (8.69%) had mild Tardive Dyskinesia and 30 (14.49%) had moderate Tardive Dyskinesia.

Fig. 3: AIMS - facial and oral (N=207)

Overall prevalence of Tardive Dyskinesia according to AIMS (facial and oral) was 23.2%.

According to AIMS (extremity) and AIMS (trunk) scores, none of the 207 subjects had TD.

Table 4 indicates distribution of study subjects according to the AIMS- global score and distribution of study subjects according to the Schooler Kane criteria. Out of 207 study subjects, 13 (6.28%) had mild Tardive Dyskinesia and 20 (9.66%) had moderate Tardive Dyskinesia.

Overall prevalence of Tardive Dyskinesia according to AIMS (global) score was 16%

Out of 207 study subjects, 31 (14.5%) had mild Tardive Dyskinesia. Overall prevalence of Tardive Dyskinesia according to Schooler Kane criteria was 14.5%.

Figure 4 depicts comparison of CPZ equivalent doses/day for current ongoing antipsychotics according to Schooler Kane criteria. The average CPZ equivalents among study subjects who satisfied the Schooler Kane criteria was 345.83 (±101.73) and the average CPZ equivalents among study subjects who did not satisfy the Schooler Kane criteria was 242.51 (± 96.88). The difference was statistically significant (p<.001).

Fig. 4: Comparison of duration of Chlorpromazine equivalents according to the Schooler Kane criteria

Discussion:

Tardive dyskinesia is a movement disorder which can occur due to the use of antipsychotics. The oral, buccal, and lingual regions of the face are often afflicted by TD; while the trunk and limbs may also be affected, they are typically less severely affected. Athetoid or choreiform movements are common terms used to characterise involuntary movements. (8)

Women are more likely than men to develop tardive dyskinesia, particularly in patients who are middle-aged to elderly. Patients who are elderly may be more susceptible to tardive dyskinesia because of age-related changes in the body and brain. (12)

Tardive dyskinesia (TD) gets its name from the slow or tardive onset of involuntary movements of the face, lips, tongue, trunk, and extremities. A number of theories have been put forth regarding the mechanism, including the following: oxidative stress, gamma-aminobutyric acid (GABA) depletion, cholinergic deficiency, prolonged blockade of postsynaptic dopamine receptors resulting in dopamine receptor hypersensitivity; altered synaptic plasticity; neurotoxicity; and impaired neuroadaptive signalling. (13)

In this study, the majority of patients were in the 51–60 age range, with an average age of 45.39 years (SD=12.6336) (Table 1). This almost exactly matches the findings of the study by Sahel Hemmati et al (14), which revealed that the study's youngest and oldest participants were, respectively, 19 and 60 years old. Half of the sample group had an average age of 44 or less, according to the average, mean, and standard deviation. This is consistent with the research done by Daniel SJ et al (15), where the sample's average age was 43.75 years (SD 10.5). This is consistent with the study by Bhatia T et al (16), in which the mean age was 47.6±11.09 years.

Out of 207 participants in this study, 139 (67.1%) had schizophrenia or an unexplained psychosis, and 68 (32.9%) had bipolar (Figure 1). This is consistent with a research by Abdeta T et al (17), in which a maximum of 79.5% of participants were diagnosed with schizophrenia. This is almost in line with a research by N Gatere et al(18), in which 48 people (28.8%) had bipolar and 91 people (45%) had schizophrenia or an unexplained psychosis. This nearly matches the findings of the study by Bakker PR et al,(19) which found that schizophrenia and psychosis, as defined by DSM-IV Axis I, accounted for 69.6% and 5.3%, respectively, of diagnoses.

Out of 207 study participants, 116 utilized the drug Risperidone in this study (Table 2). This almost matches the findings of Bhatia T's(16) study. Among 96 patients with TD, Risperidone was the only antipsychotic medication used in 39.6% of cases and in 47.9% of cases. This is consistent with research by Achalia RM et al(11), in which Risperidone was the most often prescribed antipsychotic (n = 50) for 90 individuals using SGAs. This is consistent with the Santhanakrishna et al study(20), in which 45.71% of patients received Risperidone as their most frequent prescription.

According to Bhatia T et al,(16) atypical antipsychotic medications are known to elicit extra- pyramidal symptoms less frequently (only 1% of the time) and to be related with milder TD than older, traditional antipsychotic medications (5%). In a high-risk group of elderly patients, Jeste DV et al(21) came to the conclusion that Risperidone was considerably less likely to cause TD than the traditional neuroleptic medicines, at least over a nine-month period.

A maximum of 32 study participants received treatment for 5 years in this trial (Figure 2). According to a study by Abdeta T et al,(17) 49% of participants took their prescribed medications for more than five years. This is consistent with the study of Assefa Kumsa et al(22), in which 246 (60.0%) of the patients had received treatment for an average of 4.8 years, with an SD of 3.9 years, ranging from 1 to 5 years.

Of the 207 participants in this study, 99 are urban dwellers, and 111 are rural (Table 1).

This contradicts  research by Assefa Kumsa et al (22), in which 206 study participants lived in urban regions and 204 in rural areas. Out of 207 study participants, 71.5% were illiterate in this study (Table 1). This contradicts a research by Abdeta T et al (17), in which 42.4% of respondents had educational status in grades 1-6.

In this study, 79 study participants received a cumulative equivalent dose of 200 mg of Chlorpromazine (Table 5). According to a study by Abdeta T et al (17), 74.2% of the study individuals had a cumulative equivalent dose of 100–<400 mg of Chlorpromazine. This is almost in line with the findings of the study by N Gatere et al (18), in which 133 of the study individuals received less than 500 mg of Chlorpromazine cumulative equivalent dose each day. The average Chlorpromazine-equivalent dose used in this population in the past was 336.95, according to a study by Woniak K et al.(23)

Hyperkinetic choreiform involuntary motions that frequently change in severity are referred to as dyskinesia. TD was evaluated using the Abnormal Involuntary Movement Scale (AIMS)(9) and the Schooler and Kane criteria(10) were used to define the case. These criteria required (i) the presence of moderate dyskinesia in at least one body area or mild dyskinesia in at least two body parts, and (ii) the absence of other conditions that cause abnormal involuntary movements.

Of the 207 participants in this study 18 (8.7%) had mild Tardive Dyskinesia, and 30 (14.5%) had significant Tardive Dyskinesia (Figure 3). Tardive Dyskinesia affected 23.2% of people overall, according to AIMS (facial and oral) score. This is consistent with a study by Bakker PR et al,(19) which found that the overall prevalence of tardive dyskinesia for orofacial TD ranged from 21.7 to 32.5%. According to the study done by O Gureje et al,(24) the prevalence of orofacial involuntary movements was 26% and was determined by an AIMS rating of 2 on any one orofacial area. According to the research done by Anusa A,(25) mild Tardive Dyskinesia affected 24 people (21.1%), whereas moderate Tardive Dyskinesia affected 28 people (24.5%). According to AIMS (extremity) score, none of the study participants had TD of extremities. This is approximately in line with the research done by Anusa A et al, (25) where the maximum percentage of subjects that met the study's goals (extremity) was 68.4%.

According to AIMS – trunk scores, none of the study participants had truncal TD. This is almost in line with a study by Bakker PR, (19) where the majority of individuals were normal for limb truncal TD goals (extremity).The average AIMS total score, according to Bhatia T et al,(16) was 2.29±3.25 (6.29±3.48 for TD positive cases), whereas the average orofacial score, average extremities score, and average trunk score were each 0.53±1.29 (1.72±1.90 for TD positive cases) and 0.09±0.29 (0.32±0.47 for TD positive).

This is in contrast to a study by Santhanakrishna et al (20), which found that among extrapyramidal symptoms, involvement of the extremities was most common in 42.5% of cases, followed by involvement of the trunk in 35.7% of cases and of the face and mouth in 21.42% of cases. In 45% of the patients, the severity of the extrapyramidal symptoms was moderate, while in 25.71% of the patients, it was mild.

This study shows how the study volunteers were distributed based on the overall study goal score. 13 (6.3%) and 20 (9.7%) of the 207 study participants had mild and significant Tardive Dyskinesia, respectively (Table 4). According to AIMS (global), 16% of people worldwide had Tardive Dyskinesia. This is in line with the research done by Abdeta T et al (17), who found that 14.6% of participants in the current study had TD, with a range of 10.76% to 18.4%. This almost matches the findings of the study by Taye H et al.,(26) which found that 11.9% of patients experienced TD and that the prevalence of TD among psychiatric patients taking first-generation antipsychotics is similar to that. This is consistent with the research done by Achalia RM et al.,(11) which found that 26.4% of the sample overall had probable TD.

This study shows how the study subjects were distributed using the Schooler-Kane criteria (Table 4). 31 (14.5%) of the 207 participants in the research exhibited mild Tardive Dyskinesia. According to Schooler Kane criterion, Tardive Dyskinesia by Woerner MG et al(4), was present in 14.5% of people nationwide. According to a research by Gatere et al(18), 12% of participants had TD (as defined by the Schooler Kane criteria). This is in contrast to a research by Munshi T et al(27), where 29% of participants met the Schooler Kane criteria for TD.

In this study, Chlorpromazine equivalents are compared using Schooler-Kane criteria (Figure 4). According to study subjects who met the Schooler Kane requirements, the average Chlorpromazine equivalents were 345.83 (±101.73), whereas those who did not met the criterion had Chlorpromazine equivalents of 242.51 (±96.88). There was a statistically significant difference (p<.001). This is consistent with the research done by Wozniak K et al(23) in which the average chlorpromazine-equivalent dose used in this population in the past who met the Schooler Kane requirements were 336.95.

Future studies could include a bigger sample size. Studies could also be done with patients who are followed up longitudinally.

Strengths:

The strengths of this study are that standard diagnostic criteria and rating scales were used. A good sample size was taken, involving both males and females. Also, patients with chronic mental illness from two rehabilitation centres were considered. A single examiner has conducted the examination process, eliminating inter-observer variability.

Limitations:

The limitation of this study is that it is necessary to conduct studies with sizable samples that are tracked over long periods of time to confirm the results of the current study.

Conclusion:

Many patients with psychotic diseases experienced movement difficulties brought on by conventional antipsychotics, which were viewed as burdensome and stigmatizing events. It was also discovered that chlorpromazine comparable dosages were significantly higher among participants with TD. Orofacial TD had the highest overall prevalence. Designing treatment guidelines, expanding the availability of medications with minimum adverse effects, and providing psychoeducation on related aspects are crucial.

Funding: Nil

Conflict of Interest: Nil

Disclosure: This paper has been presented at KANCIPS and IPSOCON conferences 2023. It has received the HS Subramanyam award for the best PG oral paper.

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