benztropine and Chronic-Disease

The use of opioid analgesics for chronic non-cancer pain is controversial. Some surveys report good pain relief and improvement in performance while others suggest a poor outcome with a propensity to psychological dependence or addiction.. We undertook a randomised double-blind crossover study to test the hypothesis that oral morphine relieves pain and improves the quality of life in patients with chronic regional pain of soft tissue or musculoskeletal origin who have not responded to codeine, anti-inflammatory agents, and antidepressants. Morphine was administered as a sustained-release preparation in doses up to 60 mg twice daily and compared with benztropine (active placebo) in doses up to 1 mg twice daily over three-week titration, six-week evaluation, and two-week washout phases. Pain intensity, pain relief, and drug liking were rated weekly and psychological features, functional status, and cognition were assessed at baseline and at the end of each evaluation phase.. After dose titration in the 46 patients who completed the study, the mean daily doses of drugs were morphine 83.5 mg and benztropine 1.7 mg. On visual analogue scales, the morphine group showed a reduction in pain intensity relative to placebo in period I (p = 0.01) and this group also fared better in a crossover analysis of the sum of pain intensity differences from baseline (p = 0.02). No other significant differences were detected.. In patients with treatment-resistant chronic regional pain of soft-tissue or musculoskeletal origin, nine weeks of oral morphine in doses up to 120 mg daily may confer analgesic benefit with a low risk of addiction but is unlikely to yield psychological or functional improvement.

Topics: Administration, Oral; Adolescent; Adult; Aged; Analgesics, Opioid; Benztropine; Chronic Disease; Cognition; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphine; Musculoskeletal Diseases; Pain; Pain Measurement; Patient Satisfaction; Placebos; Quality of Life; Treatment Outcome

Four patients with chronic schizophrenia were treated with a combination of fluvoxamine, haloperidol, and benztropine. The combination significantly impaired performance on tests of delayed recall memory and attentional function. Haloperidol concentrations in serum were monitored in three patients and were robustly elevated by fluvoxamine.

Topics: Adult; Benztropine; Chronic Disease; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fluvoxamine; Haloperidol; Humans; Male; Middle Aged; Neurologic Examination; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

A patient with tardive neuroleptic-induced akathisia was investigated with multiple pharmacological challenges. It was noted that the patient responded positively to benztropine, bromocriptine, and propranolol, and negatively to physostigmine, and showed little or no response to discontinuation of neuroleptics and challenges with metoclopramide, metoprolol, atenolol, and clonidine. The implications of this pharmacological characterization for the understanding of the pathophysiology of tardive akathisia in relation to acute akathisia and tardive dyskinesia are discussed.

Topics: Administration, Oral; Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Arousal; Atenolol; Benztropine; Brain; Bromocriptine; Chronic Disease; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Humans; Infusions, Intravenous; Male; Metoclopramide; Metoprolol; Physostigmine; Propranolol; Psychomotor Agitation; Schizophrenia, Paranoid

Anticholinergic drugs have been shown to impair new memory acquisition. In a double-blind study, 22 chronically schizophrenic patients had the anticholinergic drugs that they had been taking to control the extrapyramidal side effects (EPSE) of neuroleptic drugs discontinued and were randomly assigned to treatment either with benztropine (an anticholinergic) or with amantadine (which has little or no anticholinergic effect). The EPSE of five of the ten patients assigned to amantadine could not be adequately controlled with that drug alone, and these patients were withdrawn from the study prematurely. The five patients who completed the six-week trial on amantadine showed improved performance on tests of memory acquisition in comparison with patients treated with benztropine. Global inspection of the results showed that only 36% of the patients taking benztropine showed improvement in memory acquisition at the four- and six-week assessments, whereas 80% of the amantadine users showed improvement at the four-week assessment. Analysis of covariance, however, revealed that the performance of the latter group decreased almost to baseline at six weeks, as an additional two of the remaining patients developed distressing EPSE.

Topics: Adult; Amantadine; Antipsychotic Agents; Benztropine; Chronic Disease; Dyskinesia, Drug-Induced; Female; Humans; Male; Memory; Mental Recall; Middle Aged; Schizophrenia; Schizophrenic Psychology; Tropanes; Verbal Learning

Benztropine mesylate (intravenous [IV] and oral) challenge was compared with brief neuroleptic withdrawal on dyskinesia ratings and symptom measures. Thirty-six neuroleptic-treated patients underwent a placebo-controlled acute IV challenge with 2 mg benztropine and a placebo-controlled two-week trial of oral benztropine mesylate (2 mg three times a day), followed by a double-blind placebo-controlled neuroleptic withdrawal involving four weeks of dose tapering and six weeks of placebo treatment. Benztropine given IV had no significant effect. Orally administered benztropine, however, led to statistically significant increases in dyskinesia and dysphoric mood. The brief neuroleptic withdrawal significantly increased dyskinesia scores and dysphoria and resulted in early termination of therapy in 12 of 36 patients (33%) due to symptom exacerbation. There was a striking absence of correlation between dyskinesia change measures brought about by benztropine and changes following neuroleptic withdrawal. Therefore anticholinergic challenge does not appear to be a fruitful procedure for identifying patients with covert dyskinesia.

Topics: Administration, Oral; Adult; Aged; Antipsychotic Agents; Benztropine; Chronic Disease; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Injections, Intravenous; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome; Tropanes

In this double-blind, four-week study, 28 chronic schizophrenic patients receiving neuroleptic medication plus the antiparkinsonian drug, benztropine mesylate, were either switched to placebo or maintained on benztropine. Patients withdrawn from benztropine reliably increased their overall scores on the Wechsler Memory Scale in comparison with the drug group. Sub-test scores suggest that deficits in attention and concentration were induced by treatment with benztropine. Psychotic decompensation appeared to develop simultaneously with extrapyramidal symptoms (EPS) in some patients, but only 14.2 per cent of the placebo group experienced extrapyramidal symptoms severe enough to require resumption of benztropine therapy. It is suggested that antiparkinsonian agents should be prescribed only if and when EPS occur.

Topics: Adolescent; Adult; Attention; Basal Ganglia Diseases; Benztropine; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Memory; Middle Aged; Orientation; Psychological Tests; Psychoses, Substance-Induced; Schizophrenia; Substance Withdrawal Syndrome; Tropanes

Topics: Acute Disease; Adult; Antiparkinson Agents; Arousal; Benztropine; Chronic Disease; Clinical Trials as Topic; Female; Hallucinations; Haloperidol; Humans; Male; Placebos; Psychopathology; Schizophrenia; Sleep Initiation and Maintenance Disorders; Trihexyphenidyl; Tropanes

Topics: 1-Propanol; Adult; Antiparkinson Agents; Basal Ganglia Diseases; Benztropine; Biperiden; Chronic Disease; Clinical Trials as Topic; Drug Combinations; Evaluation Studies as Topic; Humans; Male; Middle Aged; Movement Disorders; Parasympatholytics; Piperidines; Procyclidine; Pyrrolidines; Schizophrenia; Tranquilizing Agents; Trihexyphenidyl; Tropanes

Memory for temporal order information was examined in patients with chronic schizophrenia using the recency discrimination task. In this task, subjects were shown a pair of previously studied words and were asked to choose which one of the two words they had seen more recently. In addition, subjects performed the Wisconsin Card Sorting Test (WCST). The results showed that schizophrenic patients differed from normal control subjects in their performance on the recency discrimination task. In addition, for schizophrenic patients, performance on the recency discrimination task was inversely related to the number of perseverative errors on the WCST. These results provide further evidence of prefrontal-type cognitive deficits in schizophrenia.

Topics: Adult; Antipsychotic Agents; Benztropine; Chronic Disease; Discrimination Learning; Female; Humans; Male; Mental Recall; Middle Aged; Neuropsychological Tests; Parasympatholytics; Schizophrenia; Schizophrenic Psychology; Serial Learning

Marching-in-place (MIP) was observed in 12 out of 133 (9%) chronically hospitalized psychiatric patients and in none of 60 hospital staff controls. The prevalence was similar in both sexes. MIP was associated with tardive dyskinesia or parkinsonism or both but did not occur alone. Counting the number of steps per minute provides a reliable method to quantify MIP and may permit a simple objective method for investigating the neuropharmacology of this phenomenon. Preliminary observations suggest that anticholinergic agents may improve MIP in some patients but worsen it in others.

Topics: Adult; Antipsychotic Agents; Benztropine; Chronic Disease; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Motor Activity; Propranolol; Schizophrenia; Stereotyped Behavior

In an open-label study, glycine was administered orally (10.8 g/day in three divided doses) to six chronically psychotic patients, as an adjunct to conventional neuroleptic therapy, for periods extending from 4 days to 8 weeks. Glycine was administered in an effort to facilitate endogenous glutamatergic transmission at the level of the N-methyl-D-aspartate (NMDA) receptor complex, since a glutamatergic deficiency in the pathophysiology of schizophrenia has been postulated. Therapeutic efficacy was assessed with standardized psychiatric rating scales. Beneficial effects on behavioral symptomatology were observed in two patients, whereas two others worsened. In one of the two responders, clinical deterioration occurred after glycine withdrawal consistent with a positive adjuvant effect in this patient. However, glycine rechallenge in this patient was not associated with the clinical improvement seen during the initial glycine period. Clinical worsening was not observed after glycine discontinuation in the second responder. Glycine administration reduced neuroleptic-induced muscle stiffness and extrapyramidal dysfunction in three of the six patients. All patients tolerated the clinical trial. The limited penetrability of glycine across the blood-brain barrier is a major limitation of this approach to facilitating glutamatergic transmission at the level of the NMDA receptor complex.

Topics: Adjuvants, Pharmaceutic; Adult; Aged; Basal Ganglia Diseases; Benztropine; Chronic Disease; Cognition; Drug Therapy, Combination; Glycine; Haloperidol; Humans; Loxapine; Male; Pilot Projects; Schizophrenia; Thiothixene; Vitamin E

A fatal case of heatstroke occurred in a chronic schizophrenic patient treated with high-potency neuroleptics. The author differentiates heatstroke from other hyperthermic syndromes related to treatment with major tranquilizers and suggests that an awareness of factors that predispose psychiatric patients to the development of heatstroke may aid in its prevention.

Topics: Antipsychotic Agents; Benztropine; Chronic Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fluphenazine; Haloperidol; Heat Exhaustion; Humans; Male; Middle Aged; Schizophrenia

Polydipsia and polyuria have a long association with schizophrenia. To assess the prevalence of polydipsia and polyuria in schizophrenia, urine volume was examined in medication-free chronic schizophrenic patients, normal controls, and nonschizophrenic patients. Mean urine volume was significantly higher in the schizophrenic patients (2319 +/- SD 2052 ml/24 hours) than in the other two groups (1054 +/- SD 471 ml/24 hours for nonschizophrenic patients and 1265 +/- SD 613 ml/24 hours for normals). Seven of 35 patients with schizophrenia but 0/7 nonschizophrenics had urine volumes greater than any normal control. Polyuria was associated with a good premorbid history and a positive neuroleptic response. Among polyuric patients, those with hyponatremia may represent a different, distinct subgroup. Neuroleptic treatment was associated with a further, significant increase in urine volume. Hence, polydipsia and polyuria appear to be relatively common in schizophrenia.

Topics: Adult; Benztropine; Chronic Disease; Drinking; Female; Haloperidol; Humans; Hyponatremia; Male; Polyuria; Psychiatric Status Rating Scales; Schizophrenia

The authors found higher serotonin concentrations in the blood of unmedicated chronic schizophrenic patients than in the blood of medicated schizophrenic patients or normal control subjects. This finding is consistent with the previous observation that the level of monoamine oxidase activity is low in the platelets of chronic schizophrenics.

Topics: Adolescent; Adult; Amitriptyline; Antipsychotic Agents; Benztropine; Blood Cell Count; Blood Platelets; Chronic Disease; Fasting; Female; Humans; Male; Monoamine Oxidase; Phenothiazines; Schizophrenia; Serotonin; Trihexyphenidyl