Applied monitoring for tardive dyskinesia and other extrapyramidal side effects

APPLIED MONITORING FOR TARDIVE DYSKINESIA AND OTHER EXTRAPYRAMIDAL SIDE EFFECTS

In The Caine Mutiny, Herman Wouk, the author, justifies the initial section's devotion to one character, Willie Keith, with, “...the event turned on his personality as the massive door of a vault turns on a small jewel bearing.” This classic analogy can be applied to tardive dyskinesia (TD) and other extrapyramidal system side effects (EPSE) associated with antipsychotic medications since, amongst a plethora of topics over the past 50 years, these side effects have been a small bearing around which a number of contemporary antipsychotic medication issues seem to revolve. These include informed consent; patent compliance; dosing strategies, if possible, such as “start low and go slow” and lower maintenance doses; minimization of long-term anticholinergic medication; objective data to evaluate clinical response; and standardized methods to monitor for side effects. George Paulson, one of the leading figures in the late 1960s working with George Crane in the recognition of TD as a public health issue, recently concluded, “TD represents an amazing historical phenomenon, and one that may yet teach us fundamentals in brain function, just as it has in therapeutic caution.”¹ Table 1 presents some key historical dates in relation to TD.

Table 1. Some Key Historical Dates in Relation to Tardive Dyskinesia While a considerable degree of overlap occurs between phases, the history of TD can be roughly divided into: (1) awakening (1957–1963), (2) awareness (1964–1972), (3) acceptance (1973–1979), (4) adversarial (1980–1984), and (5) approaches (1985-present).

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Despite the advent of atypical or second-generation antipsychotic medications and the general consensus that rates are lower than with typical or first generation antipsychotics, TD and EPSE remain a concern.^2–7 Woods et al. note, “Despite the feeling among some clinicians that TD is much less of a problem now in the atypical era, such a conclusion may be unfortunately premature.⁸ In the 1960s and 1970s, there was some well-intentioned resistance and skepticism about conventional antipsychotics being associated with the risk of TD, and now, during the atypical era, we are perhaps not immune to some of these same forces. Until we are certain we have developed antipsychotics that carry minimal risk, we should continue to inform patients prescribed antipsychotics about TD and continue monitoring for it.” As such, expert consensus guidelines consider monitoring for TD important, with one group of 50 psychiatrists and psychiatric pharmacist specialists considering assessments for TD a standard of care.^9–11 The American Society of Health-System Pharmacists (ASHP) position statement on the use of second generation antipsychotic medications includes EPSE in addition to TD and states, “Despite the lower propensity for causing adverse motor effects, all patients receiving second-generation antipsychotics should be monitored for symptoms of dystonia, parkinsonism, akathisia, and tardive dyskinesia.”¹² Table 2 presents monitoring recommendations from two sources. Please note that a number of variations of these recommendations exist from other groups or for other populations.

Table 2. TD and EPSE Monitoring Recommendations

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Years ago, Gardos and Cole brilliantly borrowed from community psychiatry and conceptualized TD and its minimization in terms of primary, secondary, and tertiary prevention.¹³ With contemporary adjustments to incorporate advances and updates in terms of specific risk factors, differential diagnosis schemas, second generation antipsychotic drug availability, and other treatment options, this remains the working conceptual paradigm.¹⁴ Briefly, primary prevention attempts to minimize causative factors to the degree possible. For example, antipsychotic medications are limited to only clinically appropriate conditions, avoided to the degree possible in high-risk populations such as the elderly, and discontinued in non-responders. Secondary prevention attempts to assess for the condition in order to detect it as early as possible. Tertiary prevention attempts to minimize impact once the condition occurs. For example, antipsychotics medications are tapered and discontinued if psychiatric status allows or, if this is not possible, the lowest dose used; first generation antipsychotic medication use is reviewed within the context of the patient's history and stability to determine if switching to a second generation antipsychotic medication is possible; and the severity of TD and its impact on the patient's functional status is used as a basis for auxiliary pharmacological intervention or change to a second generation or a different second generation antipsychotic medication.^14–15

This model can also be applied to EPSE. The importance of EPSE is relation to TD is that acute onset EPSE is considered a risk factor for TD.¹⁰¹⁴ In and of itself, EPSE is a factor in antipsychotic medication non-adherence and can cause subjective distress, make patients appear odd or peculiar, contribute to lack of energy and slowing of thinking, and interfere with quality of life.¹⁰¹⁶

The purpose of the remainder of this article is to briefly review secondary prevention with emphasis on the use of standardized assessment instruments and the importance of education and training in terms of TD and EPSE monitoring and detection.

RATIONALE FOR THE USE OF STANDARDIZED ASSESSMENT TO DETECT TD AND EPSE

A number of studies have shown that the use of standardized assessment instruments improves the detection of side effects. A study of valproic acid found the frequency of side effects increased from approximately 42% to 81% when a questionnaire was introduced.¹⁷ Another study found when a general inquiry format was compared to a specific inquiry format, the general inquiry format failed to elicit a significant number (about 40%) of mild to moderate troublesome events that would normally have led to change in clinical management.¹⁸ A study of men receiving treatment for benign prostatic hyperplasia compared an open-ended question about side effects, an open-ended defined question, and a checklist of common side effects. The percentage of patients reporting side effects using a checklist was significantly higher at 77% compared to 14% and 13% in the other two groups.¹⁹ A recent well designed study of outpatients receiving pharmacological treatment for depression using the Toronto Side Effects Scale found approximately 90% of patients reported at least one side effect compared to 26% detected and recorded by psychiatrists using open-ended questioning.²⁰ The statistical difference remained present even when analysis was limited to only “frequently occurring side effects” reported on the scale and when analysis was limited to only “troubling side effects” reported on the scale.

The aforementioned pattern for side effects detection and the use of specific assessment scales has also been found specific to the improved detection of EPSE and TD.^21–23

STANDARDIZED ASSESSMENT SCALES FOR TD AND EPSE

It is important to remember that a TD or EPSE scale is not a diagnostic instrument. These scales are assessment instruments. That is, they provide a “snapshot” of what movements are occurring. This snapshot, however, does not explain what may be causing movements observed. The rating scale information must be analyzed within the context of the other variables such as drug history, drug or dose changes, neurological or other causes, duration of movements over time, and rater variability. The generally accepted paradigm for diagnosis of TD is Schooler and Kane's Research Diagnoses for Tardive Dyskinesia (RD-TD).²⁴ Within this paradigm, three criteria are considered: (a) at least 90-days of antipsychotic exposure, (b) two mild scores in different body areas or a moderate or severe score in any one body area using a recognized TD assessment instrument, and (c) elimination of other neurological, medical, or causative conditions in relation to the movements. Assessments are then compared over time to determine if movements continue to be present, dissipate, if medication changes affect movements, or if some other change in severity of movements occurs. Variations of the RD-TD exist in that some schemas use the presence of only one mild movement intensity level or use a shorter antipsychotic exposure period for high-risk populations such as the elderly.

While other TD scales exist, the four major scales to assess TD are the Abnormal Involuntary Movement Scales (AIMS), the Dyskinesia Identification System-Condensed User Scale (DISCUS), the Tardive Dyskinesia Rating Scale (TDRS), and the Texas Research Institute of Mental Sciences Dyskinesia Scale (TRIMS).^25–28 Each of these scales has advantages and disadvantages. The AIMS uses a global body area approach and is the most recognized scale. The DISCUS uses a more specific 15-item approach organized into seven body areas and has a psychometrically developed total score cut-off or “indicator” score, which was validated against the RD-TD scoring intensity criterion using matched groups of physician diagnosed TD cases and non-TD cases. The TRIMS contains items to differentiate Parkinsonism from TD. The TDRS contains a more extensive listing of 44 items and elaborate scoring system.

Similarly, while other scales exist, the major scales to assess EPSE are the Barnes Akathisia Scale, the Hillside Akathisia Scale, the Simpson-Angus Scale, and the Extrapyramidal Rating Scale.^29–32 Gervin and Barnes¹⁶ provide an excellent summary of these scales. One akathisia scale rarely mentioned is the Akathisia Ratings of Movement Scale (ARMS), which contains psychometrics for individuals with intellectual disability and an “indicator” score.³³

THE IMPORTANCE OF TRAINING AND EDUCATION

Owens, in a commentary of Gervin and Barnes, makes two poignantly related statements in relation to standardized TD and EPSE monitoring and the importance of training and education.³⁴¹⁶ The first is, “Drug-related adverse effects would seem ideally suited to standardized monitoring as an outcome or quality-of-care measure, and evaluation and accessible recording of extrapyramidal status could become a required core skill.” The second in regard to the scales reviewed in the article is:

“All are rater subjective – a distinctly different principle. Thus, all biases relevant to patients apply to raters too. These can probably never be eradicated completely, but they can be mitigated by two prerequisites essential to their introduction – teaching and training. The first ensures that all those involved in standardized data recording are aware of, and agree on, what precisely comprises the phenomenology to be rated. The second establishes reliabilities with the chosen instrument. Both are particularly important if multi-disciplinary rating is envisioned. Undertaking this method of data acquisition and recording without them is foolish, and it will produce a veneer of competence on a core of misleading information...Standardized examination has much to commend it and is predicated on the simple principles of structure and practice. Successful standardized recording rests on teaching and training.”

There have been reports of the positive effects of education, training, and establishment of screening systems.^35–40 Two reports compare TD assessment ability before formal training (pretest) and after formal training (posttest). In the first study involving 263 registered nurses, licensed practical nurses, physicians/pharmacists, and others such as psychologists/educators, there was no statistical difference between groups on pretest assessment ability or posttest assessment ability using the DISCUS, and all groups statistically improved from pretest to posttest after training.⁴¹ In the second study of 122 physicians, pharmacists, and psychologists using the DISCUS with three videotaped cases randomized into seven testing sequences, six of the seven sequences showed statistically significant improved assessment ability on the posttest after training compared to the pretest.⁴² The pharmacists, physicians, and psychologists did not statistically differ from each other on pretest assessment ability, posttest assessment ability, and all groups statistically improved from pretest to posttest. The authors concluded that some form of training is critical to assure TD assessment ability, and this applied to any TD scale.

SUMMARY

TD and EPSE remain important considerations despite the advent of second-generation antipsychotic medications. A number of patients are still prescribed first generation antipsychotic medications due to cost or intraclass polypharmacy. Secondary prevention or early detection continues to play an important role in minimizing the effect of TD and EPSE not only in terms of compliance with medication regimens, but also in terms of quality of life. Monitoring for TD and EPSE is recommended by most expert consensus groups and guidelines. The use of standardized assessment instruments is supported by empirical studies and is implied by most consensus groups and guidelines. However, standardized scales do not assure accurate assessment and good care without some form of TD and EPSE education and training. Such education and training may be especially important for students and health-care professionals serving internships because a lull appears to have occurred in the importance of TD and EPSE and monitoring for these conditions several years after the introduction of second-generation antipsychotic medications.