Efficacy of maintenance use of anticholinergic agents. [Postoperative routine use of physostigmine on vigilance, cardiovascular parameters and need of analgesics]. Effect of switching to atypical antipsychotics on memory in patients with chronic schizophrenia.
Twenty-seven long-term psychiatric inpatients maintained on neuroleptics with concomitant antiparkinsonian medication were entered into a study in which anticholinergic medication was gradually withdrawn in a randomized double-blind within-subjects design. The extrapyramidal symptoms of each patient were compared when taking their usual anticholinergic medication, when taking placebo and when taking no antiparkinsonian drug. The relapse rate on no medication was 14%, and if patients relapsed on no medication they also relapsed on placebo. The relapse rate was not significantly different on active medication. Nor were there significant differences in ratings of parkinsonism or dyskinesia. The lack of difference between double-blind and overt withdrawal does not mean that studies that find a much higher relapse rate are necessarily unaffected by nonspecific factors, as significant unblinding may occur in clinical trials. A central anticholinergic syndrome (CAS) can be related to the majority of anesthetic agents, but is often not recognized as such. Thus, most anesthesiologists seem to miss the occurrence of an anticholinergic syndrome especially when agitation and/or restlessness are the major symptoms. Therefore, the following study was undertaken to test the hypothesis that routine administration of the anticholinergic agent physostigmin is of benefit for patients in regard to vigilance, the cardiovascular system and the need of analgesics easing the time in the post anesthesia care unit (PACU).
                After approval by the local ethics committee and written informed consent, 100 patients undergoing a cholecystectomy or a struma resection, were given either physostigmin (n = 51) or saline 0.9 % (n = 49) in a randomized fashion. The study was conceived to block a possible isoflurane-N2O/O2 (opioid-based plus relaxant) induced central anticholinergic syndrome and to evaluate the effects on the cardiovascular system on vigilance and on postoperative analgesic demand. Following parameters were measured: systolic and diastolic blood pressure, heart rate, respiratory rate, and arterial blood gases. In addition, vigilance was determined and typical anticholinergic symptoms (disorientation, slurred speech, agitation, nausea, emesis, cardiac arrhythmia and muscle shivering) were determined 10, 20, 40 and 60 minutes following the intravenous injection of physostigmin. Also, the need for the postoperative analgesic pethidine was evaluated among the two groups.
                Except for a significant reduction in the need of analgesics, a reduced diastolic pressure and heart rate and a lower incidence of muscle shivering there was no difference among the two groups. One major side effect following the use of physostigmin was the higher incidence of nausea in the im mediate minutes following injection. This effect may be due to the rapid injection of the anticholinergic compound. Otherwise there were no detrimental effects of physostigmin in patients.
                From the results it can be concluded that routine administration of an anticholinergic agent results in a short term beneficial effect in regard to vigilance, a lesser incidence of muscle shivering and a lesser demand for analgesics. However, because of the low incidence of a classical central anticholinergic syndrome, routine physostigmine is only indicated when agitation is diagnosed. While the usefulness of atypical antipsychotics for improving cognitive function has been proven, the specific effects of these drugs are still unknown. The objective of this study was to investigate changes of the immediate memory and verbal working memory in patients with chronic schizophrenia after switching to one of four atypical antipsychotic agents and cessation of anticholinergic therapy. The subjects included 77 schizophrenic patients who were treated primarily with typical antipsychotics. Treatment was randomly switched to one of four atypical antipsychotics (olanzapine, perospirone, quetiapine, or risperidone) over a 4-week period, and then the drug was continued for another 4 weeks while the patient was taken off anticholinergics. The immediate memory, verbal working memory, and symptoms were evaluated. Significant improvement of immediate memory was only seen with olanzapine and risperidone. Improvement was also seen after switching to perospirone, but immediate memory worsened after treatment with this anticholinergic drug was discontinued. Deterioration was seen after switching to quetiapine, but immediate memory improved and reached the previous level after treatment with anticholinergic drugs was discontinued. Significant improvement of the verbal working memory was only seen during risperidone administration. The findings suggested that switching chronic schizophrenic patients to atypical antipsychotics can improve both the immediate memory and the verbal working memory when risperidone is used, while improvement of immediate memory can be expected with olanzapine. From the viewpoint of improving the memory, quetiapine should not be administered concomitantly with anticholinergic drugs, and caution should be exercised when discontinuing anticholinergic drugs during treatment with perospirone.
From the available evidence we cannot advocate the use of anticholinergics in MS.