Positive and negative symptoms in schizophrenia: where are the data?
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Antipsychotic Agents↗
Biomedical subjects
G M Simpson
Publications and source records attributed to G M Simpson.
Neurotoxicity related to lithium and neuroleptic combinations? A retrospective review.
The question of toxic interactions resulting from combinations of lithium and neuroleptic drugs is largely based on anecdotal reports. We replicated the methods of Miller and Menninger (1987) who reported that 27% of manic patients on treatment with lithium and neuroleptics developed toxicity. We found no cases of neurotoxicity as defined in the earlier report. Pharmacologic mechanisms and differences in the clinical findings of the two studies are discussed.
Antipsychotic Agents↗
A rating scale for tardive dyskinesia.
A rating scale for tardive dyskinesia was developed, consisting of nearly all signs seen by two groups of investigators over a 5-year period. Thirty-four items were included in the scale with a possibility of writing in idiosyncratic signs. The scale was shown to have good reliability and validity in studies carried out by both the New York and Boston groups. It is recommended as a suitable instrument for describing the breadth of tardive dyskinesia syndrome and also for quantifying the disorder. A second scale, "the abbreviated dyskinesia scale", contains 13 items which are more global than the items in the original scale. It also has been shown to be both reliable and valid. Its use is suited to situations requiring less extensively detailed assessments.
Dyskinesia, Drug-Induced↗
Effects of loxapine on the sleep of chronic schizophrenics.
The sleep patterns of four male chronic schizophrenic patients were monitored throughout the various phases of a 1-year therapeutic trial with loxapine succinate, a newly developed neuroleptic. Compared with the initial drug-free baseline, the early drug period was characterized by an increase in REM percentage, REM density, and REM activity. During the drug maintenance period, the increase in REM phasic events was accompanied by an increase in total sleep. Severe insomnia was noted during the initial period of drug withdrawal. The absence of time lag between changes in drug administration schedule and the associated alterations in sleep patterns was in contrast with the time latency of the therapeutic response. This neuroleptic on sleep and on psychopathology are mediated by different mechanisms.
Adult↗
Tardive dyskinesia and psychotropic drug history.
The adult population of a large mental hospital was screened for tardive dyskinesia (TD). Approximately 11% of the hospital population showed signs of TD; females and the elderly were over-represented in the TD group. A representative sample of those with TD was selected and a control (non-TD) patient was chosen to match each of the TD subjects in age, sex, length of hospitalization, diagnosis, and race. The charts of these subjects were searched for any indices of brain damage and the complete psychotropic medication history was recorded. There was no difference between the TD and controls in the amount of psychotropics ingested, in the duration of administration, in the kinds of drugs, or in the organicity history. Women as a group, however, tended to have more polypharmacy than men. The role of neuroleptics in TD is discussed as well as other possible etiological factors.
Adult↗
High- and low-potency neuroleptics in elderly psychiatric patients.
The efficacy and side effects of a low-potency neuroleptic, thioridazine hydrochloride, and those of a high-potency neuroleptic, fluphenazine hydrochloride, were compared in 30 elderly chronic schizophrenic patients. Through a crossover design, each patient received both drugs with an intervening washout period. Although both drugs produced a similar degree of improvement, their side effects differed. Fluphenazine caused slightly more extrapyramidal effects than thioridazine, though few occurred with use of either drug. Thioridazine caused weight gain, blood pressure decreases, and ECG changes. High-potency neuroleptic agents appear to be the drugs of choice for elderly schizophrenic patients.
Age Factors↗
Clinical and plasma level characteristics of intramuscular and oral loxapine.
The intramuscular and oral forms of loxapine succinate were compared in their clinical, side effect, and blood level characteristics in ten hospitalized chronic schizophrenic patients. The first phase of the study determined the single dose that produced moderate sedation (i.e., the sedation threshold), and this dose was essentially the same for the two forms. Continuous administration of the two forms using the individualized sedation threshold dosage also failed to indicate any clinical or side effect differences in the two forms. The blood level characteristics, however, did differ between the two forms. The kinetic studies indicated that there was a larger are under the loxapine curve with the intramuscular form than with the oral form, while the 8-OH loxapine area was larger with the oral form. The steady-state studies also showed that the i.m. form had higher loxapine levels than the oral form. The significance of these findings, both clinically and in terms of the relative activity of loxapine and its metabolites, is discussed.
Administration, Oral↗
Clozapine in tardive dyskinesia.
Clozapine, which has had limited clinical testing in the U.S.A., was evaluated in 12 chronic schizophrenic patients with tardive dyskinesia. Its antipsychotic activity was again demonstrated and it suppressed the symptoms of tardive dyskinesia with a marked rebound occurring in these symptoms when it was withdrawn; there was no rigidity or other Parkinsonian symptoms. However, out of a total of 12 patients, neutropenia (800 and 1120) occurred in two patients, convulsion in one patient, marked withdrawal effects in three patients, and a hypotensive collapse with atrial fibrillation in one patient. If these adverse effects are confirmed in a larger sample size, then despite the novel desirable effects of clozapine it would seem unlikely that it will gain widespread or routine use.
Adult↗
Loxapine succinate as a neuroleptic agent: evaluation in two populations of elderly psychiatric patients.
Loxapine succinate, a newly developed neuroleptic drug, was administered to two groups of geropsychiatric patients: (a) 12 with psychosis and organic brain syndrome, and (b) 14 with chronic schizophrenia. After a two-week baseline period, loxapine was given for 12 weeks. The moderate therapeutic effect of loxapine in the "responders" was similar to that of other neuroleptic drugs. The therapeutic dosage range was found to be from 10 to 80 mg daily--about half that used for younger patients. The chief side effects were drowsiness, mild extrapyramidal symptoms, and a slight increase in blood pressure.
Aged↗
Clozapine plasma levels and convulsions.
Two patients receiving clozapine developed grand mal seizures. The plasma levels in one of the patients at the time of the seizure were approximately 100% higher than on 12 previous occasions. This finding led to the conclusion and the patient's admission that she had taken an overdose. Plasma levels in the other patient exceeded the range the authors had noted in previous studies. The authors emphasize the usefulness of plasma level monitoring in relation to safety, drug defaulting, and side effects.
Adult↗
Prediction of individual dosage of nortriptyline.
The authors describe a technique that enables a physician to determine individual patient dosage requirements for nortriptyline from a single 24-hour blood sample. Because the technique reveals immediately those patients at the extremes of dosage ranges, toxicity and the need for time-consuming titration of the dosage regimen can be avoided.
Adult↗
Abnormal gaits in tardive dyskinesia.
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Dyskinesia, Drug-Induced↗
Evaluation of a slow-release lithium carbonate formulation.
A slow-release lithium preparation was compared with a standard formulation in normal volunteers and in patients. Pharmacokinetic parameters of normal volunteers were examined after a single dose of each form and the steady-state levels after a b.i.d. dose of the slow-release form. These initial single-dose data suggested that the two formulations are not bioequivalent. However, the area under the curve of the two forms was similar, and the essentially complete recovery of lithium from urine in steady state indicates equal bioavailability. The patients' steady-state levels for the two formulations essentially confirmed the normal subjects' data: with the slow-release form plasma lithium levels were slightly higher, and the postdose lithium level variability was decreased by as much as 50%.
Biological Availability↗
Baclofen in the treatment of tardive dyskinesia and schizophrenia.
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Adult↗
A long term comparative trial of penfluridol and fluphenazine decanoate in schizophrenic outpatients.
Penfluridol, a diphenylbutylpiperidene derivative, is a new long acting neuroleptic, administered orally, once weekly. It is marketed in several European countries and has been used successfully in the treatment of various acute psychoses, for severely ill chronic schizophrenic patients, and as maintenance therapy for chronic schizophrenic patients. The present study was designed to compare, in a double-blind fashion, the efficacy of penfluridol and fluphenazine decanoate in the maintenance therapy of schizophrenic outpatients.
Adult↗
A paradox in the prognosis of schizophrenia. explanation by a mathematical model.
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Humans↗
Deanol in the treatment of tardive dyskinesia.
Ten hospitalized chronic psychotic patients with symptoms of tardive dyskinesia were given deanol and placebo, each for 8 weeks following a double-bline, crossover design. No psychotropic agents were administered during the trial. Improvement occurred in all patients during the first treatment phase regardless of which drug the patients received; seven patients were on deanol and three on placebo during this time. The possible reasons for this decrease were discussed. It was concluded that deanol may have contributed to the decline but that its effect on the disorder was not dramatic.
Aged↗
Efficacy of loxapine in the treatment of paranoid schizophrenia.
A combined analysis of data from 11 controlled studies of loxapine versus either chlorpromazine or trifluoperazine in acute schizophrenia (5 studies) and chronic schizophrenia (6 studies) showed statistically significant superiority of loxapine on several items and factors of standardized psychiatric rating scales. Upon review of these findings, it was observed that the rating scale symptoms for which loxapine appeared superior to the reference compounds could, in the main, be considered a broad paranoid "cluster". The data were then reanalyzed to detect possible differences in efficacy of loxapine versus the reference compounds in those patients with a clinical diagnosis of schizophrenia, paranoid type and in those patients of any diagnostic subtype other than paranoid. Results of these analyses demonstrated clear superiority of loxapine in paranoid schizophrenic patients; nonparanoid patients responded at least equally as well to loxapine as to the reference compounds. Findings could not be attributed to inadequate dosages of the references compounds or inequality of treatment groups at baseline.
Adult↗