Extrapyramidal
symptoms (EPS) and their implications for antipsychotic medication are
issues of great practical importance to all involved in the management
of major psychiatric disorders. Despite its importance, this area
is frequently overlooked.
| The why and wherefore of EPS |
Extrapyramidal
symptoms (EPS) and their implications for antipsychotic medication are
issues of great practical importance to all involved in the management
of major psychiatric disorders. Despite its importance, this area
is frequently overlooked.
This subject is far from new. Drug-induced parkinsonism was first reported in psychiatric patients in India by De2 in 1944. He was commenting on the effects of rauwolfia alkaloids, and described parkinsonism as ‘common’ and as occurring ‘even with therapeutic doses’ – but made little of the issue. At the first symposium on chlorpromazine, held in Basel in 1953, Staehelin2 said:
“This parkinsonoid syndrome occurs more or less developed depending on dosage but also on predisposition or previous brain stem disease. Usually the syndrome quickly recedes if dosage is reduced; so far we have never seen persistent parkinsonism after discontinuation of [chlorpromazine].”
This idea of reversibility upon discontinuation appears to have played a crucial role in developing the perception of drug-induced parkinsonism as a fairly trivial clinical issue. This was perhaps an understandable view for psychiatrists emerging from an era of therapeutic impotence. However, not everyone was so confident. In a comment that would be the best part of 25 years in the heeding, Baruk2 stated in 1956 :
“High doses do not give better results, but add to the mental disease a neurologic disorder undoubtedly in general transitory, but if the intoxication has been intense and prolonged it may result in a lesional syndrome.....”
By 1955, extrapyramidal symptomatology was being discussed as a necessary rather than an adverse effect, and was transformed from the inconsequential to the essential. This perception was enshrined in the term ‘antipsychotic’, coined in the same year by Delay2 for this new class of drugs.
It is interesting that the term ‘antipsychotic’ persisted for so long after the neurological effects had been well and truly returned to the ranks of the adverse, and were no longer perceived as essential. There were of course alternatives. In 1955, the neurologist Howard Fabing and the classicist Alistair Cameron2 coined the term ‘ataraxy’ to describe the mental state phenomenon of ‘detachment’ that was so consistently described in the early literature. The concept never caught on in English language psychiatry, though one still comes across the idea of ‘specific sedation’ in the European literature. What ‘ataraxy’ was, or is, has never been resolved. Recently, the idea of neuroleptic-induced deficit syndrome (NIDS)3 has emerged from the literature. It is not clear whether NIDS is related to ataraxy or to the subjective effects of parkinsonism.
With the return of neurological effects to the ‘adverse’ category, the old lack of concern appeared to creep back. It was only after almost 30 years of widespread use that researchers began to take the issues seriously. Today, the problem remains under-recognized by clinicians in routine practice.
Vigilance
and awareness
Many psychiatrists
are poorly trained to recognize or acknowledge the impact of movement disorders.
Weiden and colleagues1
at the Bronx Psychiatric Hospital compared assessments of EPS by clinicians
in routine practice with those of researchers trained in detection. Comparison
of the findings of the two groups demonstrated
clinicians as a percentage of the number of cases identified by researchers. |
considerable under-recognition in routine practice (Table 1). Although this study was carried out in the USA, its findings are likely to be equally relevant elsewhere. Sadly, if the same study were performed today, many of the same findings would probably emerge.
Another revealing study
was performed by Hoge et al4.
They asked patients and the clinicians treating them why they did not want
to take their drugs. While 35% of patients cited side-effects as
the cause, only 7% of the clinicians gave the same reason (Table 2).
|
These data clearly illustrate the fact that psychiatrists underestimate the impact of the adverse effects of antipsychotics. This is becoming increasingly unacceptable, not least because of the medico-legal implications which, in the UK at least, remain unclear.
A further issue relates to organizational changes within the UK National Health Service (NHS), which have separated the functions of purchasing and providing health care. Purchasers are now laying down clear standards of care in contracts with providers, with increasing emphasis on outcome parameters. This reflects a fairly widespread development in health care around the world.
For necessary treatments with a defined adverse-effect profile, tolerability is obviously an important outcome parameter. In discussing such issues with purchasers, it has become clear that rating scales are an extremely popular way of assessing tolerability. The standardized assessment of extrapyramidal status may soon become a quality-of-care issue.
Assessment
of antipsychotic agents
Any antipsychotic,
new or established, should be evaluated systematically according to a number
of criteria:
Efficacy :
How much confidence can we place in ratings of ‘negativity’ recorded in the presence of EPS? Many clinicians feel able to draw the distinction between core negative symptomatology and the subtle and especially subjective manifestations of parkinsonism. The literature on treatment of negative states raises legitimate doubts with respect to this distinction. Even if it can be made by ‘experts’, in a research setting, can it be made routinely by clinicians in outpatient clinics? When it comes to issues of awareness, the ‘experts’ need to be careful of criticizing clinicians, whose error may only be one of degree or emphasis.
Unresolved
questions
We need to consider
how the whole area of EPS can be made a practical issue for clinicians.
Expert gatherings, such as this, can help by bringing together information
to maintain awareness.
New drugs for schizophrenia offer advantages, but carry with them the seeds of a problem. The clozapine data are salutary, for they demonstrate a diminished, but not necessarily absent, EPS liability. There is a risk that, as the demand for competent assessment skills increases as a result of increasing quality-of-care and medico-legal demands, a sense of complacency may be engendered, with clinicians becoming less motivated and less skilled in seeking out these problems.
Methods
of assessment
The assessment and
recording of movement disorders remains problematic in psychiatry.
The lack of standardization means that we are still unable to make valid cross-compound comparisons, and there is a pressing need for some consensus on recording instruments. This is also true of general adverse effects, for which clinicians have no consistent methodology, and thus no data from which to construct the profile of side-effects necessary to make detailed comparisons. With new drugs in the pipeline, it will prove increasingly necessary, and valuable, to provide such comparisons.
It is hoped that some agreement can be reached, even if initially this only extends to a consensus on those methods that are not adequate. This raises the question as to who determines the recording methodology for evaluating both efficacy and tolerability in treatment response studies. The newer combined scales are certainly a major improvement, but who determines which ones are to be used? It would seem inappropriate for such decisions to be left to regulatory authorities. It is those who conduct, appraise and sponsor these studies who should be determining the agendum. It would seem important for these groups to discuss and agree guidelines, so that valid and clinically meaningful comparisons of specific antipsychotic efficacy and tolerability become realities.