In the 1950s, the development of
antipsychotic drugs called neuroleptics(抑制精神病药物 )radically changed the clinical
outlook for patients in mental institutions who had previously been considered
hopelessly psychotic. Daily medication controlled delusions and made
psychotherapy possible. Many who otherwise might never have left institutions
returned to society. Now physicians have learned that there is a price to be
paid for these benefits. Approximately 10 to 15 percent of patients who undergo
long-term treatment with antipsychotic drugs develop a cluster of symptoms
called tardive dyskinesia (迟发性运动障碍), the most common symptoms of which are
involuntary repetitive movement of the tongue, mouth, and face, and sometimes
the limbs and trunk.
Neuroleptic drugs interfere with the action
of dopamine (多巴胺) , an important neurotransmitter in the brain, by binding to
the dopamine receptors of nerve cells, and dopamine is a prime suspect in the
pathophysiology of schizophrenia. Large doses of drugs such as
amphetamines(苯丙胺), which stimulate secretion of dopamine, produce a psychosis
resembling schizophrenia. Reducing the activity of this neurotransmitter
alleviates the delusions that cause psychotic behavior. Although the inhibition
of dopamine activity can control psychotic behavior, researchers now believe
that the central nervous system of some patients adapts to long-term therapy by
increasing the number of specific dopamine binding sites. The net result is
dopamine hypersensitivity which is correlated with the subsequent appearance of
tardive dyskinesia.
The risk of developing tardive dyskinesia is
not so great that doctors have considered abandoning the use of antipsychotic
drugs. Patients generally are bothered only slightly by the physical side
effects, though the abnormal movements are troubling and may hinder social
adjustment. Additionally, early diagnosis and prompt discontinuation of the
neuroleptics might decrease the incidence of the movement disorders.
Unfortunately, without neuroleptic drugs, psychotic behavior returns. So
researchers have tried to achieve a satisfactory balance between the two
effects, lowering dosage to a level that minimizes movement disorders yet
control psychosis. In a five-year study of twenty-seven psychiatric patients
treated with neuroleptics representing all classes of antipsychotic drugs,
researchers attempted to decrease drug doses to their lowest effective levels.
Patient responses suggested that low to moderate doses of antipsychotic drugs
could control psychoses just as well as high doses, and tardive dyskinesia
symptoms stabilized and gradually diminished or completely
disappeared.
The fact that psychoses can be controlled at the
same time that tardive dyskensia symptoms are reduced suggests that a drug more
specifically affecting the mechanism of psychoses might not cause movement
disorders. Sulpiride, a drug not available in the United States but widely used
in Europe, where it was developed, may be one such alternative. The drug
selectively blocks D-2 dopamine receptors, perhaps especially those in the
limbic area of the brain, which is involved in emotion and behavior. It does not
adversely affect the adenylate (腺苷酸) cyclase (环化酶) -linked D-1 dopamine
receptors. Sulpiride has proven effective in the short term, but whether it
suppresses tardive dyskenesia over a long period of treatment is not yet
known. |
