Correlation between extrapyramidal and therapeutic effects of neuroleptics

The ability to elicit extrapyramidal side effects appears to be a necessary (although not a sufficient) characteristic of the major tranquilizers. The relations between these effects and therapeutic action is not well established. During the first weeks of treatment in a homogenous (for age, sex and chronicity) group of schizophrenics, a fixed dose incremental schedule of trifluoperazine was followed. Extrapyramidal effects were measured through quantitative analysis of digital tremor. Treatment response was measured after four weeks of medication. Evidence developed suggests that patients who show a better treatment response are less vulnerable to extrapyramidal effects. A number of methodological issues, placing restraints on the generalization of the data, are discussed.     

Increased extrapyramidal symptoms with addition of lithium to neuroleptics

To explore whether lithium exacerbates neuroleptic-induced extrapyramidal symptoms (EPS), the authors prospectively rated 10 patients on neuroleptics before and after the addition of lithium. EPS ratings increased steadily after the initiation of lithium and were significantly elevated compared with baseline. Individual items that increased significantly were: gait, shoulder shaking, elbow rigidity, and tremor. These findings indicate that usual therapeutic levels of lithium may significantly worsen neuroleptic-induced EPS. Potential mechanisms for this interaction are discussed.     

Two cases of neuroleptic-induced prolonged extrapyramidal symptoms

Neuroleptic-induced extrapyramidal symptoms (EPS) are generally categorized as acute, withdrawal and tardive EPS. Here, we report two cases of a unique late-onset, long-lasting EPS (e.g., prolonged EPS); in those cases, EPS appeared a few months following initiation of haloperidol and lasted for a few months after significant reduction or complete withdrawal of neuroleptics. Case 1, a 41-year-old female, began to exhibit EPS such as bradykinesia, rigidity and parkinsonian gait 4 months after the haloperidol treatment. Her rigidity was ameliorated by a reduction of haloperidol; however, reduction of neuroleptics made it difficult for her to maintain a seated posture because of an imbalance of muscle tonus. Her EPS continued for 9 months even after haloperidol was switched to very low doses of thioridazine (10?mg/day). Case 2 is a 42-year-old female. She exhibited EPS including dysphagia and a difficulty in opening her mouth 3 months after the haloperidol treatment began. Her EPS lasted for 45 days, even after complete withdrawal of neuroleptics. The EPS observed in these two cases occurred even after prolactin levels became normal. “Prolonged EPS” is a unique subclass of neuroleptic-induced reversible EPS that might involve the coexistence of hypo- and hyper-dopaminergic transmission, especially in patients who show very low tolerance to neuroleptics.     

硫酸亚铁对抗精神病药物所致锥体外系副反应预防作用的探讨

目的探讨硫酸亚铁对精神药物所致锥体外系副反应(EPS)的预防作用，评价其临床实用性。方法采取双盲随机研究，对80例符合入组条件的精神分裂症患者，进行氯丙嗪合并硫酸亚铁治疗(研究组)与氯丙嗪合并安慰剂治疗(对照组)对照，时间6周，应用修订Sampson锥体外系副反应量表(ESRS)对EPS进行评定。结果研究组EPS发生率低于对照组，研究组首次出现EPS的时间较对照组延迟，ESRS评分在2～5周末均较对照组低，在首次出现EPS反应及试验结束时，研究组氯丙嗪用量均较对照组高，而两组副反应无统计学差异。结论硫酸亚铁对．EPS具有良好的预防作用，且副反应小，可应用于临床。     

Chronology of the extrapyramidal effects of neuroleptics, and the nigrostriatal dopaminergic system]

Authors after analysis of the data in literature describe the chronologic appearance of the extrapyramidal effects of neuroleptics. In order to restore a neurophysiological coherence to dissimilar or even contradictory clinical emergences this sequence is analysed in function of the actual data, relative to the mechanism and to the modalities of adaptation of the dopaminergic synapse of the nigro striatal system.     

Biochemical markers in the study of clinical effects and extrapyramidal side effects of neuroleptics

Neuroleptic treatment was instituted in 20 female schizophrenic patients, who had not received neuroleptics for at least the preceding 3 months. Both the therapeutic response to neuroleptics and the development of parkinsonian side effects were monitored in these patients. In addition, plasma dopamine-beta-hydroxylase (DBH) and platelet monoamine oxidase (MAO) activities were measured. None of the neuroleptic responders developed parkinsonian symptoms. During the course of the 28-day treatment, there was a significant decrease in platelet MAO activity. There was a tendency for responders without parkinsonian symptoms to have lower plasma DBH activity than did nonresponders with parkinsonian symptoms.     

Clinical use of the radioreceptor assay for neuroleptics

The potential clinical utility of the radioreceptor assay for neuroleptics (NRRA) was examined. The NRRA was able to detect neuroleptic activity in blood specimens from patients receiving a variety of neuroleptic medications. For each medication, mean plasma neuroleptic activity was lower in patients showing a poor response to treatment than in those showing a good response. Because the range of plasma neuroleptic activities found was quite different from drug to drug, it appears that results obtained by the NRRA must be standarized for each drug.     

Gender and the use of neuroleptics in schizophrenia

INTRODUCTION: The oestrogen hypothesis proposes that the lower need for neuroleptic drugs in female schizophrenia patients is caused by the antidopaminergic effect of oestrogens, and that when oestrogen production decreases at menopause, the need for neuroleptic drugs increases in female schizophrenia patients. SUBJECTS AND METHOD: The oestrogen hypothesis was tested in a sample of 4338 schizophrenia patients (DSM III R), who were discharged from hospital and followed up for 3 years. Prescribed daily doses of neuroleptics (DDN) were recorded and converted to chlorpromazine equivalents. RESULTS: Males had higher DDN than females. When the age at first admission (AFA) was controlled, DDNs were higher in males than in females in all age groups. In addition to AFA, DDNs were associated with duration of illness (DUI), education, smoking and clinical status as well as with concurrently prescribed antidepressants, anti-manics, sedatives and hypnotics, but these factors did not explain the gender differences in DDN. CONCLUSIONS: The results did not support the original oestrogen hypothesis. It is proposed that testosterone secretion may explain why male schizophrenia patients are prescribed higher DDNs than female patients. Ageing processes in the central nervous system (CNS) may explain why DDNs decrease after middle age in both genders.