| Meeting conclusions |
There is no doubt that EPS are a distressing aspect of antipsychotic therapies. EPS span a broad spectrum of symptomatology; they may be acute, tardive, or mixed; may or may not be recognized by the patient and the physician; and may be reversible or irreversible.
Features such as decreased emotional expressiveness, physical inactivity and dulled social responsiveness often leave the patient feeling ‘zombie-like’ or in a ‘chemical strait jacket’, and impact adversely on his/her quality of life. The aberrant movements of akathisia, TD, and related serious EPS may furthermore stigmatize patients and are major causes of non-compliance.
In addition to motor side-effects, there is increasing awareness that similar problems may arise from the subjective effects of antipsychotics, something largely ignored in the literature. These subjective symptoms are difficult to evaluate and it is not unusual in clinical practice for them to be mis-attributed to features of the mental state. However, such complaints ought not be dismissed, as they likewise have an adverse impact on patient compliance, social functioning, and quality of life.
EPS and
medication compliance
Non-compliance with
antipsychotic drugs in schizophrenia is a major public health problem.
Approximately 74% of responsive schizophrenic out-patients become non-compliant
with their antipsychotic regimes within two years of discharge. Thus EPS
and their relationship to antipsychotic medication are an issue of great
practical importance to all involved in the management of major psychiatric
disorders.
Non-compliance is very costly, not only for society, but also for individuals. Non-compliance has also been associated with increased rates of suicide, assault and homicide. For all of these reasons, EPS should be aggressively managed.
The most common current treatments for symptomatology at the acute end of the EPS spectrum are anticholinergics, which unfortunately have their own profile of adverse effects. These include dry mouth, blurred vision, constipation, and CNS impairment, including short-term memory and even on occasion confusion and frank delirium.
Pathophysiology
Although models of
pathophysiology have been proposed, we still have little clear understanding
of the mechanisms underlying these disorders. Current models remain predicated
on disruption to central dopamine systems, but how this translates into
symptomatology, and especially how this interacts with individual susceptibility,
is unknown. There is a pressing need for further research in the field,
including the role of genetic and individual factors.
Identifying
and managing EPS
Despite the importance
of EPS, this area is frequently overlooked. Syndromes are often not
recognized by the physician or the patient, and may come to be seen as
an unavoidable element of treatment. Professional under-estimation of the
frequency and impact of such adverse effects is likely to become less acceptable
to an increasingly litigious society, and to health-care purchasers who
in many countries are now setting more stringent quality-of-care indicators.
Education of professionals must clearly play a major role in improving the current situation, and should include more training for doctors and other medical staff in all matters relating to recognition and evaluation of EPS.
Future
medications
Perhaps the most promising
feature of some of the new antipsychotic medications currently being developed
is their reported low propensity to cause EPS. However, the new antipsychotics
are as different from each other, as they are from the traditional drugs,
and not all new antipsychotics currently under development appear to have
a desirable EPS profile, i.e. one similar to that of clozapine. The potential
to cause EPS must form an important part of the assessment of any new antipsychotic
treatment.
The discrimination between ‘typical’ and ‘atypical’ antipsychotics in terms of EPS liability should be based on activity in a broad range of preclinical models incorporating cross-species comparisons, as well as on clinical experience.
It is hoped that newer atypical antipsychotic agents will not be associated with the subjective and objective unwanted side-effects of standard compounds. In doing so, new drugs should increase the patient’s ability and motivation to participate in treatment and rehabilitation and thus improve the overall quality of life.