benztropine and Schizophrenia

Topics: Agranulocytosis; Barbiturates; Basal Ganglia Diseases; Benztropine; Biperiden; Delayed-Action Preparations; Depression; Diazepam; Drug Interactions; Eye Manifestations; Fatty Acids; Female; Fluphenazine; Humans; Jaundice; Male; Mental Disorders; Movement Disorders; Parkinson Disease, Secondary; Schizophrenia; Seizures; Skin Manifestations

Blockade of dopamine D2 receptors remains a common feature of all antipsychotics. It has been hypothesized that the extrastriatal (cortical, thalamic) dopamine D2 receptors may be more critical to antipsychotic response than the striatal dopamine D2 receptors. This is the first double-blind controlled study to examine the relationship between striatal and extrastriatal D2 occupancy and clinical effects. Fourteen patients with recent onset psychosis were assigned to low or high doses of risperidone (1 mg vs 4 mg/day) or olanzapine (2.5 mg vs 15 mg/day) in order to achieve a broad range of D2 occupancy levels across subjects. Clinical response, side effects, striatal ([11C]-raclopride-positron emission tomography (PET)), and extrastriatal ([11C]-FLB 457-PET) D2 receptors were evaluated after treatment. The measured D2 occupancies ranged from 50 to 92% in striatal and 4 to 95% in the different extrastriatal (frontal, temporal, thalamic) regions. Striatal and extrastriatal occupancies were correlated with dose, drug plasma levels, and with each other. Striatal D2 occupancy predicted response in positive psychotic symptoms (r=0.62, p=0.01), but not for negative symptoms (r=0.2, p=0.5). Extrastriatal D2 occupancy did not predict response in positive or negative symptoms. The two subjects who experienced motor side effects had the highest striatal occupancies in the cohort. Striatal D2 blockade predicted antipsychotic response better than frontal, temporal, and thalamic occupancy. These results, when combined with the preclinical data implicating the mesolimbic striatum in antipsychotic response, suggest that dopamine D2 blockade within specific regions of the striatum may be most critical for ameliorating psychosis in schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Benztropine; Dopamine Antagonists; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Muscarinic Antagonists; Neostriatum; Positron-Emission Tomography; Prolactin; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Pyrrolidines; Raclopride; Receptors, Dopamine D2; Salicylamides; Schizophrenia; Schizophrenic Psychology

Spatial memory is of interest in schizophrenia because of widespread impairments in adaptive functioning, including independent living skills. Short-term spatial memory is impaired in this disease, whereas spatial reference memory, a longer-term spatial memory, has not been evaluated. Animal studies have demonstrated that anticholinergics impair short-term spatial memory but not spatial reference memory. The effects of haloperidol and risperidone on these two types of spatial memory were evaluated in a double-blind randomized comparison in inpatients with schizophrenia. It was predicted that risperidone would have a greater beneficial effect on spatial working memory than haloperidol. Computerized measures of spatial working memory and spatial reference memory were developed based on animal assessment of these functions. Subjects with schizophrenia were assessed during a medication-free period and again following 4 weeks of fixed-dose treatment. Risperidone, compared to haloperidol, improved spatial working memory performance, an effect that became nonsignificant when benztropine co-treatment was controlled. There were no treatment effects on spatial reference memory performance. Consistent with animal studies, benztropine impaired spatial working memory but not spatial reference memory. The relative benefits of risperidone on spatial working memory performance were largely explained by differential benztropine treatment for the haloperidol-treated subjects.

Topics: Adult; Antipsychotic Agents; Benztropine; Cholinergic Antagonists; Cognition Disorders; Female; Humans; Male; Memory; Memory Disorders; Pattern Recognition, Visual; Psychiatric Status Rating Scales; Psychomotor Performance; Reaction Time; Risperidone; Schizophrenia; Schizophrenic Psychology; Space Perception

Although olanzapine has been widely adopted as a treatment of choice for schizophrenia, its long-term effectiveness and costs have not been evaluated in a controlled trial in comparison with a standard antipsychotic drug.. To evaluate the effectiveness and cost impact of olanzapine compared with haloperidol in the treatment of schizophrenia.. Double-blind, randomized controlled trial with randomization conducted between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical centers.. Three hundred nine patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder, serious symptoms, and serious dysfunction for the previous 2 years. Fifty-nine percent fully completed and 36% partially completed follow-up assessments.. Patients were randomly assigned to receive flexibly dosed olanzapine, 5 to 20 mg/d, with prophylactic benztropine, 1 to 4 mg/d (n = 159); or haloperidol, 5 to 20 mg/d (n = 150), for 12 months.. Standardized measures of symptoms, quality of life, neurocognitive status, and adverse effects of medication. Veterans Affairs administrative data and interviews concerning non-VA service use were used to estimate costs from the perspective of the VA health care system and society as a whole (ie, consumption of all resources on behalf of these patients).. There were no significant differences between groups in study retention; positive, negative, or total symptoms of schizophrenia; quality of life; or extrapyramidal symptoms. Olanzapine was associated with reduced akathisia in the intention-to-treat analysis (P<.001) and with lower symptoms of tardive dyskinesia in a secondary analysis including only observations during blinded treatment with study drug. Small but significant advantages were also observed on measures of memory and motor function. Olanzapine was also associated with more frequent reports of weight gain and significantly greater VA costs, ranging from 3000 dollars to 9000 dollars annually. Differences in societal costs were somewhat smaller and were not significant.. Olanzapine does not demonstrate advantages compared with haloperidol (in combination with prophylactic benztropine) in compliance, symptoms, extrapyramidal symptoms, or overall quality of life, and its benefits in reducing akathisia and improving cognition must be balanced with the problems of weight gain and higher cost.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Benztropine; Double-Blind Method; Female; Haloperidol; Health Care Costs; Health Services; Humans; Male; Middle Aged; Muscarinic Antagonists; Neuropsychological Tests; Olanzapine; Pirenzepine; Quality of Life; Schizophrenia; Treatment Outcome; United States

Effects of fluphenazine on electrodermal activity (EDA) and heart rate (HR) were studied in patients with schizophrenia and normal control subjects during rest periods, presentation of innocuous tones, and a reaction time (RT) task. Two types of analyses were used: (1) between-group analyses-patients taking placebo were compared with patients taking fluphenazine and with control subjects using only data from the first test session; and (2) within-subject analyses-the same patients were tested when taking fluphenazine and when taking placebo. Results showed higher resting EDA and HR and smaller increments to task performance in placebo patients than in control subjects. Fluphenazine attenuated EDA levels but not the tonic response. Fluphenazine attenuated the HR response but did not affect HR level. Placebo patients were electrodermally hyporesponsive to the RT stimuli but not to simple tones. Fluphenazine markedly attenuated responsivity to simple tones but it attenuated responsivity less for RT stimuli. Testing medicated patients may thus produce misleading results with respect to many, but not all, purported autonomic markers of diagnosis in schizophrenia studies.

Topics: Adult; Antiparkinson Agents; Antipsychotic Agents; Benztropine; Electrocardiography; Female; Fluphenazine; Heart Rate; Humans; Male; Parkinsonian Disorders; Reaction Time; Schizophrenia

The aim of the study was to examine effects of haloperidol on the relationships between neuropsychological measures of frontal lobe functioning and the schizophrenia syndromes of psychomotor poverty and disorganization. Twenty-one participants with schizophrenia were initially evaluated when clinically stable and chronically treated with haloperidol, and 19 were evaluated again after a 3-week haloperidol-free period. Participants were evaluated with the Trail Making Test, the Wisconsin Card Sorting Test, the Purdue Pegboard, and psychiatric rating scales at each evaluation. There were significant correlations between schizophrenia syndromes and the tests sensitive to frontal lobe function when participants were medicated but not when drug-free. No significant changes in symptom severity or motor function occurred from the medication to the medication-free evaluation. The results indicate that haloperidol mediates the relationship between tests sensitive to frontal lobe function and the schizophrenia syndromes of psychomotor poverty and disorganization. This mediation effect was not attributable to changes in overall symptom severity or motor function.

Topics: Adult; Antipsychotic Agents; Benztropine; Cross-Over Studies; Double-Blind Method; Frontal Lobe; Haloperidol; Humans; Male; Middle Aged; Muscarinic Antagonists; Neuropsychological Tests; Psychomotor Performance; Recurrence; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome

Sialorrhea is reported by 31% of patients taking clozapine. Anticholinergic agents and adrenergic agonists are used for its treatment based on empirical evidence. In the present study, 10 patients who failed to respond to anticholinergic or adrenergic agents received intranasal ipatropium bromide (IPB) to minimize anticholinergic systemic absorption. Intranasal IPB was given to 10 patients for clozapine-induced sialorrhea who failed to respond to benztropine or clonidine. Pre-, post- and 6 month follow-up values were recorded on a single-item, 5-point Hypersalivation Rating Scale. The sign test was used for statistical comparison (P < 0.05). Eight patient reported initial improvement in sialorrhea values. Two patients reported no change and two patients discontinued IPB. At 6 months, six patients maintained improvement. Side-effects for IPB were minor. A significant trend was observed in the values pre- and post-treatment with IPB (P < 0.004). Improvement was maintained at 6 month follow-up (P < 0.008). This case series demonstrates the possible utility of intranasal IPB for clozapine-induced sialorrhea. Intranasal IPB lacks significant systemic anticholinergic effects when prescribed along with clozapine. This study shows only qualitative differences in salivation values and large controlled-comparative trials are needed.

Topics: Adult; Antipsychotic Agents; Benztropine; Cholinergic Antagonists; Clozapine; Female; Humans; Ipratropium; Male; Middle Aged; Muscarinic Antagonists; Psychiatric Status Rating Scales; Schizophrenia; Sialorrhea

As an expansion of work examining the usefulness of adjunctive imipramine added to fluphenazine decanoate and benztropine in the treatment of post-psychotic depression, a previously successful and informative protocol was extended to a larger and more heterogeneous cohort of clinic and day-treatment patients. Although the benefit of the adjunctive antidepressant strategy was still observable in the total sample, as calculated by the prospectively intended data analysis, the findings were weaker than those obtained for the initial cohort. Owing to the possibility that differences between the later and earlier cohorts might account for the muted nature of the benefit, a post-hoc analysis was undertaken. This revealed that the later cohort was sicker in general and more psychotic in particular. The later cohort was also treated with lower doses of neuroleptic medication while remaining out of hospital longer, consistent with more recent treatment trends. It was also possible that the later cohort was subtly selected for more refractoriness of depression, since treatment of post-psychotic depression with adjunctive antidepressants had become more commonplace, and patients responding to this in general practice would not have gone on to be referred to the study. Thus a benefit from adjunctive antidepressant medication persists, but more remains to be learned about its character and likelihood in specific situations.

Topics: Adult; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benztropine; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Fluphenazine; Humans; Imipramine; Male; Muscarinic Antagonists; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Time Factors

Treatment efficacy in schizophrenia is typically defined in terms of symptom reduction. However, new antipsychotic medications could potentially have an impact on aspects of disability, such as neurocognitive deficits. The authors evaluated the effects of risperidone on verbal working memory, a memory component of theoretical interest because of its link to prefrontal activity and of practical interest because of its link to psychosocial rehabilitation.. Verbal working memory of 59 treatment-resistant schizophrenic patients was assessed as part of a randomized, double-blind comparison of treatment with risperidone and haloperidol. Verbal working memory was measured under both distracting and nondistracting conditions at baseline and after 4 weeks of both fixed- and flexible-dose pharmacotherapy.. Risperidone treatment had a greater beneficial effect on verbal working memory than haloperidol treatment across testing conditions (with and without distraction) and study phases (fixed and flexible dose). The treatment effect remained significant after the effects of benztropine cotreatment, change in psychotic symptoms, and change in negative symptoms were controlled. Neither benztropine status nor symptom changes were significantly related to memory performance.. Treatment with risperidone appears to exert a more favorable effect on verbal working memory than treatment with a conventional neuroleptic. The beneficial effect appears to be due, at least partially, to a direct effect of the drug, possibly through antagonism of the 5-HT2A receptor. Results from this study suggest that pharmacotherapeutic efficacy in schizophrenia treatment could be broadened to include impact on neurocognitive abilities.

Topics: Adult; Benztropine; Double-Blind Method; Female; Haloperidol; Humans; Male; Memory; Neuropsychological Tests; Placebos; Psychiatric Status Rating Scales; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Risperidone; Schizophrenia; Schizophrenic Psychology; Verbal Behavior

The stabilization period that follows the exacerbation of a schizophrenic illness represents a critical point in the course of the illness. Successful stabilization is a prerequisite to long-term tenure in the community and the possibility of improvement in functional outcome. In this paper we present an operational definition of stabilization, developed in the context of a study of long-term maintenance treatment that incorporates time, symptomatic equilibrium and consistency of medication dosage. Patients were identified at the time of hospitalization and followed prospectively to determine whether or not they met stabilization criteria. Characteristics that predicted successful stabilization included measures drawn from the domains of patient personal characteristics and psychiatric history, symptoms of psychopathology and side effects in response to initial treatment and family judgments. These patients were treated primarily with fluphenazine decanoate, and five distinct dosing strategies with this agent were identified retrospectively. The dosing strategies distinguished the length of time to subsequent stabilization. The implications of these findings for clinical management of schizophrenia are discussed.

Topics: Antipsychotic Agents; Benztropine; Fluphenazine; Humans; Prognosis; Schizophrenia

Prominent and persistent anxiety, depression, and/or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal side effects of typical neuroleptic medications often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and their treatment. For patients who remained distressed, controlled trials of supplemental thymoleptics were undertaken.. In trial 1, 92 distressed (depressed and/or anxious) patients and 36 patients in a defect state (patients with negative symptoms) participated in a double-blind, intramuscular challenge that compared centrally acting benztropine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22 patients in a defect state were randomly assigned to a double-blind, neuroleptic medication dose-reduction group. In trial 3, 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were randomly assigned to a supplemental desipramine hydrochloride, lithium carbonate, or placebo group under double-blind conditions for 12 weeks.. For patients who were already maintained on antiparkinsonian medication, impaired affect was not resolved by additional benztropine. Only distressed patients with a family history of severe mental disorder (often affective) showed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose, but negative symptoms persisted. Desipramine improved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improved in women only. Lithium positively affected multiple indexes of anxiety and anxious depression.. Most often, persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits. Thymoleptics improve the nonphasic, chronic types of anxiety and depression in contrast to the acute, episodic forms, for which little support can be found in the literature.

Topics: Adolescent; Adult; Ambulatory Care; Antipsychotic Agents; Anxiety Disorders; Basal Ganglia Diseases; Benztropine; Depressive Disorder; Desipramine; Diagnosis, Differential; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluphenazine; Glycopyrrolate; Humans; Lithium Carbonate; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Sex Factors

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

Although recent studies have documented the benefit of adjunctive antidepressant medication for the short-term treatment of certain patients with operationally defined syndromes of postpsychotic depression, the value of maintenance adjunctive antidepressant treatment in this circumstance has not been properly established.. This study examined 24 schizophrenic or schizoaffective patients with postpsychotic depression or negative symptoms. These patients had all been benefited over the short term by the addition of adjunctive imipramine hydrochloride to their ongoing fluphenazine decanoate/benztropine mesylate regimens, and this adjunctive treatment had been successfully continued for 6 months. In a randomized double-blind protocol, treatment with adjunctive imipramine hydrochloride (mean, 233 +/- 72 mg/d) was then either maintained or tapered to placebo for an ensuing 1-year trial, while treatment with fluphenazine and benztropine continued.. Significantly more patients who received placebo substitution relapsed into depression (P < .001). Patients who received placebo substitution were also more likely to experience relapses into psychosis (P < .02).. These results support the clinical value of maintenance adjunctive imipramine therapy among initially responsive patients with postpsychotic depressions.

Topics: Adult; Antipsychotic Agents; Benztropine; Delayed-Action Preparations; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Fluphenazine; Humans; Imipramine; Male; Middle Aged; Placebos; Psychotic Disorders; Recurrence; Schizophrenia; Schizophrenic Psychology

We challenged five patients suffering from tardive akathisia (TA) with intravenous benztropine (2 mg), propranolol (1 mg) and placebo (saline) using a random, double-blind cross-over design to examine the effects of the drugs on the subjective, objective and global manifestations of neuroleptic-induced akathisia. Benztropine produced a marginally significant, and propranolol a significant improvement in the overall manifestations of the disorder. The patients demonstrated a considerable placebo effect and marked variation in their responses to the drugs. The implications of these findings for the pathophysiology of TA in relation to acute akathisia and tardive dyskinesia are discussed.

Topics: Adult; Akathisia, Drug-Induced; Anxiety; Benztropine; Cross-Over Studies; Double-Blind Method; Dyskinesia, Drug-Induced; Humans; Male; Middle Aged; Propranolol; Schizophrenia

Effects of the dihydropyridine calcium channel inhibitor nifedipine on chronic schizophrenia and tardive dyskinesia were studied in an 8-week double-blind crossover trial. Four of the ten patients had tardive dyskinesia, and three of these were not receiving neuroleptics. No effects on symptoms of chronic schizophrenia were found using Psychiatric Symptom Assessment Scale ratings. In the four patients with tardive dyskinesia, an average improvement in total Abnormal Involuntary Movement Scale scores of 57% was observed. These data suggest that dihydropyridine calcium channel inhibitors may be effective in the treatment of tardive dyskinesia in schizophrenic patients.

Topics: Adult; Antipsychotic Agents; Benztropine; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Male; Nifedipine; Psychiatric Status Rating Scales; Schizophrenia

Serum perphenazine concentrations and early resolution of psychosis were examined to determine if blood level monitoring could be used to maximize drug efficacy while limiting extrapyramidal side effects (EPS). Sixty-six acutely psychotic inpatients were given perphenazine 0.5 mg/kg/day for 10 days, and their response was rated blind to blood level. Although 36 of 66 patients showed resolution of psychosis, neither perphenazine nor N-dealkylated perphenazine levels were related to global response or to Brief Psychiatric Rating Scale (BPRS) totals. Improvement in two individual BPRS items (hallucinations and conceptual disorganization) was related to serum perphenazine levels and suggestive of a lower therapeutic threshold of 0.8 ng/mL. Perphenazine level was not correlated with EPS; but benztropine, given only if required for serious EPS, was more likely to be used when perphenazine levels were elevated. The data suggest that higher perphenazine levels were no more effective than moderate levels but that higher levels may be associated with increased EPS; the data also suggest that individual symptoms rather than global response were associated with a lower therapeutic perphenazine threshold.

Topics: Adult; Akathisia, Drug-Induced; Basal Ganglia Diseases; Benztropine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hospitalization; Humans; Male; Parkinson Disease, Secondary; Perphenazine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology

Twelve DSM-IIIR diagnosed schizophrenics, with neuroleptic-induced akathisia (NIA), were treated with either propranolol or matched placebo for two days, followed by a treatment crossover phase for five more days. Raters and patients were "blind" to treatment. This study shows that 120 mg of propranolol a day is more effective than placebo in reducing akathisia, and that propranolol's antiakathisic effect may require several days of treatment.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Benztropine; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Neurologic Examination; Propranolol; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Benztropine; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Fear; Female; Fluphenazine; Humans; Imipramine; Panic; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology

Fifty-eight actively psychotic inpatients who initially met criteria for long-standing schizophrenia and subsequently met Research Diagnostic Criteria for a current episode of schizoaffective disorder (mainly schizophrenic) with a depressive syndrome, and who scored at least 30 (mean = 55, SEM = 1.6) on the Brief Psychiatric Rating Scale and 17 (mean = 23, SEM = 0.7) on the Hamilton Rating Scale for Depression, were treated for 5 weeks with haloperidol hydrochloride and benztropine. Haloperidol and benztropine treatment was continued, while those patients who consistently scored greater than 17 on the Hamilton Rating Scale for Depression were randomly assigned to the following double-blind treatment groups for 4 weeks: adjunctive amitriptyline hydrochloride, desipramine hydrochloride, or placebo. Adjunctive desipramine or amitriptyline showed no significant therapeutic advantage, when compared with haloperidol and placebo, on the Brief Psychiatric Rating Scale or the Hamilton Rating Scale for Depression. After 4 weeks of combine therapy, patients receiving adjunctive amitriptyline or desipramine, as compared with those receiving adjunctive placebo, tended to score higher on the Brief Psychiatric Rating Scale hallucinatory behavior item and on the thinking disturbance factor than patients receiving placebo. These results suggest that adjunctive antidepressants are not indicated for the treatment of depressive symptoms in actively psychotic schizophrenic inpatients. Adjunctive antidepressants may retard the rate of resolution of psychosis in this population.

Topics: Adolescent; Adult; Amitriptyline; Benztropine; Clinical Trials as Topic; Depressive Disorder; Desipramine; Double-Blind Method; Drug Therapy, Combination; Female; Haloperidol; Hospitalization; Humans; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

The authors studied 46 patients with the operationally defined syndrome of postpsychotic depression following episodes of schizophrenia or schizoaffective disorder. Half of these patients were also found to satisfy criteria for negative symptoms. The patients with negative symptoms were rated as more severely ill on global measures, but there was only limited evidence that they were more depressed. Nevertheless, in a randomized double-blind trial of imipramine versus placebo as an adjunct to the fluphenazine decanoate and benztropine regimens of the patients with negative symptoms, the patients who received imipramine seemed to show more improvement.

Topics: Adolescent; Adult; Aged; Benztropine; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Fluphenazine; Humans; Imipramine; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Random Allocation; Schizophrenia; Schizophrenic Psychology

Adjunctive imipramine has been found to be useful in the treatment of a substantial number of patients with syndromally defined post-psychotic depressions. This paper examines the clinical effects of the combined anticholinergic activity of imipramine, when added to ongoing fluphenazine decanoate/benztropine treatment, in such patients. Little additional anticholinergic impact of the imipramine was observable beyond that already attributable to the benztropine, and no significant relationships were found between a clinical measure of peripheral anticholinergic activity and either global clinical outcome or antidepressive efficacy. This paper also reports on the concentrations of imipramine and its metabolites in plasma under the conditions of this therapeutic trial. The changes in relative concentrations of imipramine and metabolites with time were consistent with the concept that fluphenazine competes with tricyclic metabolism. The relationship of plasma imipramine and desipramine to clinical improvement in this group of secondary depressions did not parallel previously reported relationships of these antidepressant molecules to clinical outcome in primary depressions.

Topics: Adult; Affective Disorders, Psychotic; Benztropine; Clinical Trials as Topic; Drug Interactions; Fluphenazine; Humans; Imipramine; Middle Aged; Schizophrenia; Time Factors; Tropanes

Topics: Adult; Amantadine; Antipsychotic Agents; Benztropine; Drug Interactions; Humans; Male; Memory; Middle Aged; Schizophrenia; Trihexyphenidyl; Tropanes

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

Topics: Benztropine; Depression; Drug Therapy, Combination; Fluphenazine; Humans; Imipramine; Schizophrenia

In this paper we have described early applications of computerized EEG techniques in psychopharmacology. Perhaps our most remarkable finding was there were practically no differences between very chronic drug free schizophrenic patients and normals, which contradicts much of the EEG imaging literature. To us, the most likely explanation is that most of the anterior slowing observed in other studies was due to contamination from orbital artifacts, which we took exceptional pains to remove. Lingering effects of neuroleptic medications may also have contributed. Alternatively, EEG deviations in schizophrenia may recede when the illness reaches a very chronic stage, although this hypothesis is less tenable. There were significant differences between placebo and the three neuroleptics in terms of increased amplitudes in the delta and theta frequency bands in the anterior head regions, which is compatible with data from other studies. These changes were most pronounced with clozapine and least prominent with haloperidol, with chlorpromazine occupying an intermediate position. This order happens to parallel their relative antiserotonergic, antihistaminic and anticholinergic properties. The latter may have been partially obscured by the addition of benztropine. In a subgroup of patients who were recorded under each of the treatment conditions, there were more fast frequencies with clozapine than with the other neuroleptics agreeing with Roubicek and Major. This could be a function of clozapine's increased adrenergic activity as reported by Ackenheil. An unexpected finding was that patients who responded to clozapine had higher amplitudes in the alpha spectrum, most pronounced in the left anterior quadrant, than did the nonresponders. These differences between responders and nonresponders obtained whether patients were on placebo, haloperidol or clozapine. Curiously, Buchsbaum et al. found that anxious patients who responded to benzodiazepines also had higher alpha amplitudes in the same brain regions, which differentiated them from nonresponders. These findings clearly warrant future scientific investigation. In this regard, the generalizability of our data is limited by the extremely chronic, treatment-resistant population studied. However, promising directions for further research in EEG and psychopharmacology have been identified.

Topics: Adolescent; Adult; Alpha Rhythm; Benztropine; Beta Rhythm; Brain Mapping; Chlorpromazine; Clozapine; Delta Rhythm; Dibenzazepines; Double-Blind Method; Electroencephalography; Female; Haloperidol; Humans; Male; Schizophrenia; Signal Processing, Computer-Assisted; Theta Rhythm

Studies on the withdrawal of anticholinergics from patients on antipsychotics have produced conflicting results. This 12-week study employed a double-blind crossover design on 39 adult in-patients selected from a total hospital population of 620. The Colombia Scale was used to determine extrapyramidal side effects (EPS). All patients were stabilised prior to the study on benztropine mesylate 2 mg b.i.d., and gradual withdrawal was employed. Benztropine withdrawal produced a significant increase in overall EPS scores. Ten patients (26%) required reinstatement of benztropine while on placebo. Sialorrhoea, rigidity and postural instability were the most prominent changes. Neither age, sex, nor diagnosis were significantly predictive of EPS. Depot medications and doses greater than 1000 mg/day chlorpromazine-equivalent were related to significant EPS increase. The intrinsic anticholinergic properties of the antipsychotics themselves and concomitant medications, such as antidepressants, appeared protective against development of EPS. Most patients on a combination of antipsychotics and anticholinergics can safely be withdrawn from the latter.

Topics: Adult; Antipsychotic Agents; Benztropine; Clinical Trials as Topic; Double-Blind Method; Dyskinesia, Drug-Induced; Humans; Long-Term Care; Mental Disorders; Middle Aged; Parasympatholytics; Schizophrenia; Substance Withdrawal Syndrome

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

In a 12-week controlled study ethopropazine was compared to benztropine in the treatment of parkinsonism induced by fluphenazine enanthate in 60 schizophrenic outpatients. Ethopropazine and benztropine were found to be equally effective in controlling parkinsonian symptoms and were as efficacious as procyclidine, their previous antiparkinsonian drug. However, benztropine treated patients had a significant increase in tardive dyskinesia compared to their condition during procyclindine treatment, and significantly more anxiety and depression than ethopropazine treated patients. This suggests that benztropine is not the anticholinergic drug of choice in the treatment of neuroleptic-induced parkinsonian symptoms, because of its more toxic central and peripheral atropinic effect.

Topics: Adult; Benztropine; Clinical Trials as Topic; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Fluphenazine; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Phenothiazines; Procyclidine; Schizophrenia; Tropanes

The effectiveness of antiparkinson medication for the prevention of drug induced dystonias has remained a question. Forty patients with acute psychosis who received high potency oral antipsychotic drugs were interviewed to determine the incidence of acute dystonia. An eleven-fold increase in dystonia was found in patients who received no prophylactic medication. Such prophylaxis appears effective in preventing acute dystonia.

Topics: Adult; Aged; Antipsychotic Agents; Benztropine; Clinical Trials as Topic; Dystonia; Female; Haloperidol; Humans; Male; Middle Aged; Phenothiazines; Schizophrenia; Tropanes

Topics: Adolescent; Adult; Basal Ganglia Diseases; Benztropine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluphenazine; Humans; Male; Middle Aged; Schizophrenia

This rater blind project compared the efficacy and safety of using an oral rapid or neuroleptization method (maximum 80 mg./day) versus fixed standard dosage (20 mg./day) fluphenazine, a commonly used neuroleptic. There were 32 hospitalized, acutely decompensated schizophrenic patients in the experiment; the study period for each patient was a maximum of 7 days. The data were collected using the Benjamin Proverb Test and rating scales for psychopathology and adverse effects. Data analysis by means of the analysis of covariance demonstrated few significant differences between the 2 treatment methods: both methods produced a similar reduction in psychopathological symptoms and incidence of adverse effects. The authors conclude that the rapid neuroleptization method is not superior to the fixed standard dosage method in treating acute schizophrenia.

Topics: Acute Disease; Adult; Benztropine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluphenazine; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Psychiatric Status Rating Scales; Psychopathology; Schizophrenia; Schizophrenia, Paranoid

Presently marketed antiparkinsonism drugs are potent anticholinergic agents that, while effective in treating extrapyramidal symptoms (EPS), also are productive of or can exacerbate a number of side effects associated with psychotropic drugs. Some of these include gastrointestinal disturbances, visual difficulties, and tardive dyskinesia. A double-blind study was carried out to assess the efficacy (and adverse effects) of amantadine hydrochloride--an agent without appreciable anticholinergic activity--for the treatment of drug-induced EPS. Amantadine was found to be comparable in effect to benztropine mesylate, but with fewer side effects. The potential role of amantadine may be in the treatment of patients with drug-induced EPS for whom medication with anticholinergic properties is contraindicated.

Topics: Amantadine; Antipsychotic Agents; Basal Ganglia Diseases; Benztropine; Clinical Trials as Topic; Drug Evaluation; Humans; Schizophrenia

This report focuses on two comparisons between oral and depot fluphenazine specifically FPZ decanoate: 1) can equivalent dosages for the two drugs be established and do these equivalencies change over six months of treatment; 2) what are the side effects seen with the two drugs during the early weeks of administration. Patients in the study receive either oral or depot FPZ as the active treatment but in order to preserve double blind conditions, they are also given the other treatment in placebo form. No dosage equivalence is established by the protocol, however, if dosage is adjusted, both forms must be changed and in the same direction. During the first weeks of treatment there is a linear relationship between the two dosage forms but a range of relatively low dosages of the oral compound (5-20 mg) is associated with a single dose (25 mg/q 3 weeks) of FPZ decanoate. At higher dosages of the oral drug the relationship is linear. Side effects of some kind are noted in over 60 percent of patients in both treatment groups after four weeks of treatment, while symptoms of at least moderate severity occur in almost 40 percent. Only symptoms involving the extrapyramidal system and sleep disturbance are observed in more than 20 percent of the patients. Benztropine was prescribed only if needed and was administered to 65% of patients. In general, those receiving benztropine had more side effects than those who did not. These differences reached significance for extrapyramidal symptoms and depression. Based on these data, we conclude that at the dosages used in this study there are no side effect differences between these two forms of fluphenazine in the early weeks of administration. Dosage equivalence between the two drugs can be set within the range of 5-60 mg/day oral and 12.5-100 mg/three weeks depot.

Topics: Administration, Oral; Adolescent; Adult; Benztropine; Clinical Trials as Topic; Delayed-Action Preparations; Female; Fluphenazine; Humans; Male; Middle Aged; Neurologic Manifestations; Schizophrenia

The effect of an anticholinergic antiparkinsonism drug, benztropine, on the therapeutic course of neuroleptic treatment in 18 schizophrenics was investigated in a double blind cross-over study involving haloperidol and chlorpromazine. Significant therapeutic reversal was observed with benztropine in terms of the social, affective,and cognitive dysfunctions chracteristically seen in schizophrenic psychosis. The hallucinatory behavior and disturbed attention were not so affected. The aspects of the clinical picture to show significant nontherapeutic change with benxtropine differed with the stage of treatment and seemed to be determined by the kinetics of the therapeutic process. The effect was one of exacerbation of the disorder and not a toxic confusional state sometimes associated with anticholinergic drugs. The practical and theoretical significance of these findings was discussed. It was suggested that the benztropine reversal of therapeutic changes provided a valuable pharmacological model for understanding the neurobiological basis of schizophrenic decompensation and its restitution with neuroleptics. The reported data were considered as indirect evidence suggesting that cholinergic neuronal mechnisms are involved in both of these processes. It was speculated that these mechanisms may well be the cholinergic suppressor systems, such as the periventricular catecholamine pathways in the limbic organization and bsal ganglia known to be affected by neuroleptics.

Topics: Adult; Affect; Attention; Benztropine; Chlorpromazine; Clinical Trials as Topic; Drug Evaluation; Drug Therapy, Combination; Female; Hallucinations; Haloperidol; Humans; Male; Middle Aged; Schizophrenia; Social Behavior; Thinking; Tropanes

In a double-blind, cross-over study, the comparative therapeutic effects of 6-week courses of two prototypic neuroleptics--haloperidol and chlorpromazine--and the reversal of those effects with benztropine were investigated in a group of 18 schizophrenics. Periodic measurements were made for 32 dimensions of psychopathology, social participation, span of attention, sleeplessness, pulse rate and neurological side effects. The results showed that haloperidol was generally a more effective drug over the period studied. This was particularly apparent in terms of social and emotional responsiveness, communicativeness and cognitive processes. The only superiority of chlorpromazine seemed to be that patients felt less dysphoric on it than they did on haloperidol. Haloperidol also proved to be more rapid in its action. The data failed to support the clinical validity of the distinction often made between "sedative" and "activating" neuroleptics. Consistent with previous reports, benztropine had the effect of diminishing therapeutic response to both neuroleptics. However, haloperidol again proved less susceptible to this effect. The slowness and lesser therapeutic efficiency of chlorpromazine and its greater susceptibility to benztropine reversal were all considered to be due to its built-in anti-cholinergic properties acting in opposition to its antipsychotic activity. The low potency of chlorpromazine-like drugs was attributed to their inherent anticholinergic characteristics. It was suggested that one of the factors determining potency difference among neuroleptics may be the degree of built-in anticholinergic activity.

Topics: Adult; Affect; Anxiety; Basal Ganglia Diseases; Benztropine; Chlorpromazine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Haloperidol; Heart Rate; Humans; Male; Mental Processes; Middle Aged; Parasympatholytics; Schizophrenia; Sleep; Social Behavior; Time Factors; Tropanes

Topics: Administration, Oral; Adult; Behavior; Benztropine; Clinical Trials as Topic; Drug Evaluation; Drug Tolerance; Electrocardiography; Eye; Humans; Hydrocarbons, Halogenated; Middle Aged; Piperidines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Time Factors; Toluene; Tranquilizing Agents

Topics: Administration, Oral; Amantadine; Antiparkinson Agents; Benztropine; Capsules; Chlorpromazine; Clinical Trials as Topic; Humans; Parkinson Disease; Parkinson Disease, Secondary; Placebos; Schizophrenia; Time Factors

Topics: 17-Ketosteroids; Adrenal Cortex Hormones; Adult; Analysis of Variance; Antipsychotic Agents; Benztropine; Body Weight; Butyrophenones; Calcium; Female; Glycine; Humans; Magnesium; Middle Aged; Phenelzine; Phenothiazines; Placebos; Potassium; Psychiatric Status Rating Scales; Schizophrenia; Sodium; Tryptophan

Topics: Adolescent; Adult; Amnesia; Antidepressive Agents; Antiparkinson Agents; Antipsychotic Agents; Anxiety; Benztropine; Female; Hallucinations; Humans; Injections, Intramuscular; Phenothiazines; Physostigmine; Placebos; Psychoses, Substance-Induced; Schizophrenia; 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: Acute Disease; Benztropine; Clinical Trials as Topic; Cognition Disorders; Dose-Response Relationship, Drug; Haloperidol; Humans; Milieu Therapy; Placebos; Psychiatric Status Rating Scales; Research Design; Schizophrenia; Schizophrenic Psychology; Sleep; Time Factors

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

Topics: Antiparkinson Agents; Anxiety; Attitude of Health Personnel; Benztropine; Clinical Trials as Topic; Evaluation Studies as Topic; Haloperidol; Humans; Milieu Therapy; Movement Disorders; Neurotic Disorders; Personality Inventory; Schizophrenia

Topics: Administration, Oral; Adult; Aged; Antiparkinson Agents; Basal Ganglia Diseases; Benztropine; Clinical Trials as Topic; Humans; Middle Aged; Movement Disorders; Neurologic Manifestations; Parasympatholytics; Psychiatric Status Rating Scales; Schizophrenia; Time Factors; Tranquilizing Agents; Tropanes

BACKGROUND Antipsychotic medications are associated with multiple adverse effects, including metabolic syndrome, prolonged QT interval, and extrapyramidal symptoms. Acute laryngeal dystonia (ALD) is a rare and lethal form of extrapyramidal reaction. CASE REPORT A 27-year-old woman with schizophrenia on risperidone presented to our Emergency Department with a sensation of choking and respiratory distress, mimicking a panic attack. She developed a generalized dystonic reaction in the hospital, leading to diagnosis risperidone-associated ALD as a cause of her initial problems. She was discharged with an emphasis on being compliant with anticholinergic medication. However, her persistent respiratory symptoms prompted us to revisit the management plan. Her risperidone dose was tapered down to discontinue and an alternate drug was chosen. CONCLUSIONS ALD must be considered as a differential diagnosis when patients on antipsychotic medications present with respiratory distress. Our case highlights the association of ALD with an atypical antipsychotic agent, risperidone. Prompt recognition of this entity is necessary to prevent complications and guide definitive management.

Topics: Adult; Antipsychotic Agents; Benztropine; Dystonia; Female; Humans; Laryngeal Diseases; Risperidone; Schizophrenia

A 55-year-old female with a diagnosis of schizophrenia currently resides in an assisted living facility in a large metropolitan suburb. For approximately 25 years, the patient was relegated to a life of poor symptom control and social adjustment, largely due to nonadherence, relapse, and rehospitalization. The patient experienced a trial-and-error approach to drug therapy, which resulted in reliance on the older or first generation agents for symptom improvement. This case supports the assertion that the second-generation or atypical antipsychotics used to treat schizophrenia are no better than older drugs in terms of efficacy or tolerability.

Topics: Antipsychotic Agents; Benztropine; Bipolar Disorder; Borderline Personality Disorder; Drug Substitution; Drug Therapy, Combination; Female; Humans; Longitudinal Studies; Middle Aged; Psychotic Disorders; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Thiothixene; Treatment Outcome; Weight Gain

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benztropine; Corpus Striatum; Dose-Response Relationship, Drug; Humans; Male; Piperazines; Prolactin; Quinolones; Receptors, Dopamine D2; Schizophrenia

Performance-based tests of functional capacity are important to utilize in schizophrenia where global measures may underestimate community functioning in the context of impoverished environments and disincentives to return to work. The Test of Adaptive Behavior in Schizophrenia (TABS) is a performance-based measure of adaptive functioning designed to address limitations of other available measures including limited assessment of the ability to initiate and of the ability to identify problems that occur in the course of performing functional activities. The TABS and a variety of symptom, functional outcome, and cognitive measures were administered to 264 outpatients with schizophrenia/schizoaffective disorders at an initial assessment. At 3 months, 110 subjects received a follow-up assessment. Results indicated that the TABS had very good test-retest reliability (0.80) and inter-item consistency (0.84). Moreover, TABS scores were moderately to strongly correlated with other measures of functional outcome, negative symptoms and neuropsychological test scores (convergent validity). Measures of positive symptoms were not found to be related to TABS performance (discriminate validity). The data provide preliminary evidence for the reliability and validity of the TABS. Further studies of the psychometric properties of the TABS including those examining the sensitivity of the TABS to treatments with different pharmacological agents or psychosocial treatments are encouraged.

Topics: Activities of Daily Living; Adaptation, Psychological; Adult; Antipsychotic Agents; Awareness; Benztropine; Clinical Trials as Topic; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Problem Solving; Psychiatric Status Rating Scales; Psychometrics; Rehabilitation, Vocational; Reproducibility of Results; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Statistics as Topic

Dysfunction of inhibitory neurons in the prefrontal cortex (PFC), represented by decreased expression of GABA-related genes such as the 67 kDa isoform of glutamate decarboxylase (GAD67) and parvalbumin (PV), appears to contribute to cognitive deficits in subjects with schizophrenia. We investigated the involvement of signaling mediated by brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase TrkB in producing the altered GABA-related gene expression in schizophrenia. In 15 pairs of subjects with schizophrenia and matched control subjects, both BDNF and TrkB mRNA levels, as assessed by in situ hybridization, were significantly decreased in the PFC of the subjects with schizophrenia, whereas the levels of mRNA encoding the receptor tyrosine kinase for neurotrophin-3, TrkC, were unchanged. In this cohort, within-pair changes in TrkB mRNA levels were significantly correlated with those in both GAD67 and PV mRNA levels. Decreased BDNF, TrkB, and GAD67 mRNA levels were replicated in a second cohort of 12 subject pairs. In the combined cohorts, the correlation between within-pair changes in TrkB and GAD67 mRNA levels was significantly stronger than the correlation between the changes in BDNF and GAD67 mRNA levels. Neither BDNF nor TrkB mRNA levels were changed in the PFC of monkeys after a long-term exposure to haloperidol. Genetically introduced decreases in TrkB expression, but not in BDNF expression, also resulted in decreased GAD67 and PV mRNA levels in the PFC of adult mice; in addition, the cellular pattern of altered GAD67 mRNA expression paralleled that present in schizophrenia. Decreased TrkB signaling appears to underlie the dysfunction of inhibitory neurons in the PFC of subjects with schizophrenia.

Topics: Adult; Aged; Animals; Anti-Dyskinesia Agents; Antipsychotic Agents; Benztropine; Brain-Derived Neurotrophic Factor; Case-Control Studies; Female; gamma-Aminobutyric Acid; Gene Expression Regulation; Haloperidol; Humans; Macaca fascicularis; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Middle Aged; Neural Inhibition; Prefrontal Cortex; Receptor, trkB; RNA, Messenger; Schizophrenia; Signal Transduction

Topics: Akathisia, Drug-Induced; Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Benztropine; Haloperidol; Humans; Olanzapine; Schizophrenia; Selection Bias

Topics: Akathisia, Drug-Induced; Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Benztropine; Haloperidol; Humans; Olanzapine; Schizophrenia

Topics: Akathisia, Drug-Induced; Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Benztropine; Cognition; Haloperidol; Humans; Olanzapine; Receptors, Dopamine D2; Schizophrenia

Topics: Adult; Benztropine; Dopamine; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Interactions; Female; GABA Agents; gamma-Aminobutyric Acid; Haloperidol; Humans; Muscarinic Antagonists; Schizophrenia; Time Factors; Valproic Acid

Markers of inhibitory neurotransmission are altered in the prefrontal cortex (PFC) of subjects with schizophrenia, and several lines of evidence suggest that these alterations may be most prominent in the subset of GABA-containing neurons that express the calcium-binding protein, parvalbumin (PV). To test this hypothesis, we evaluated the expression of mRNAs for PV, another calcium-binding protein, calretinin (CR), and glutamic acid decarboxylase (GAD67) in postmortem brain specimens from 15 pairs of subjects with schizophrenia and matched control subjects using single- and dual-label in situ hybridization. Signal intensity for PV mRNA expression in PFC area 9 was significantly decreased in the subjects with schizophrenia, predominantly in layers III and IV. Analysis at the cellular level revealed that this decrease was attributable principally to a reduction in PV mRNA expression per neuron rather than by a decreased density of PV mRNA-positive neurons. In contrast, the same measures of CR mRNA expression were not altered in schizophrenia. These findings were confirmed by findings from cDNA microarray studies using different probes. Across the subjects with schizophrenia, the decrease in neuronal PV mRNA expression was highly associated (r = 0.84) with the decrease in the density of neurons containing detectable levels of GAD67 mRNA. Furthermore, simultaneous detection of PV and GAD67 mRNAs revealed that in subjects with schizophrenia only 55% of PV mRNA-positive neurons had detectable levels of GAD67 mRNA. Given the critical role that PV-containing GABA neurons appear to play in regulating the cognitive functions mediated by the PFC, the selective alterations in gene expression in these neurons may contribute to the cognitive deficits characteristic of schizophrenia.

Topics: Adult; Aged; Animals; Autoradiography; Benztropine; Calbindin 2; Cell Count; Female; gamma-Aminobutyric Acid; Gene Expression Profiling; Glutamate Decarboxylase; Haloperidol; Humans; In Situ Hybridization; Isoenzymes; Macaca fascicularis; Male; Middle Aged; Neural Inhibition; Neurons; Oligonucleotide Array Sequence Analysis; Parvalbumins; Prefrontal Cortex; RNA, Messenger; S100 Calcium Binding Protein G; Schizophrenia; Substrate Specificity; Synaptic Transmission; Time

Treatment of psychotic symptoms has traditionally involved conventional antipsychotics. While efficacious, their side-effects have been problematic and the approval by the Food and Drug Administration of the newer antipsychotics with improved side-effects profiles heralded important advances in treating psychoses. Prolactin elevation has been associated with all classical and some atypical antipsychotics. We present cases where elevation of prolactin concentrations secondary to antipsychotic treatment was associated with delusions of pregnancy. Risperidone was the antipsychotic employed and elevation of prolactin concentrations were noted each time. The delusions abated and prolactin concentrations decreased when the drug was discontinued. Rechallenge with risperidone resulted in re-elevation of prolactin levels along with recurrent delusions. Substituting risperidone with another antipsychotic (either olanzapine or quetiapine) also led to abatement of the delusions and lowering of prolactin. Although no direct psychotogenic effects of prolactin are known, it is contended that delusions of pregnancy reported during antipsychotic treatment might be associated with rising prolactin concentrations.

Topics: Adult; Antipsychotic Agents; Benztropine; Delusions; Dibenzothiazepines; Female; Humans; Middle Aged; Pregnancy; Prolactin; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology

Aberrant cholinergic inputs and synaptic neurotransmission in the prefrontal cortex induce cognitive impairment, which is a central feature of schizophrenia. Postsynaptic excitatory muscarinic cholinergic M(1) and M(4) receptors are the major cholinoceptive targets in the prefrontal cortex and hence may be involved in the pathology and/or pharmacotherapeutics of schizophrenia.. Using quantitative autoradiography, the authors analyzed the binding of the M(1)/M(4) receptor selective antagonist [(3)H]pirenzepine in prefrontal cortex (Brodmann's areas 8, 9, 10, and 46) from schizophrenia patients who had (N=6) or had not (N=11) been treated with the anticholinergic agent benztropine mesylate and from normal comparison subjects (N=20). Moreover, preliminary studies of [(3)H]pirenzepine binding in rat frontal cortex following administration of antipsychotic drugs or benztropine mesylate were performed.. Relative to those of comparison subjects, the mean levels of [(3)H]pirenzepine binding were significantly lower in Brodmann's areas 9 and 46 of the schizophrenia patients not treated with benztropine mesylate (18% lower in Brodmann's area 9 and 21% lower in Brodmann's area 46) and in all four examined regions of the patients who had received benztropine (51%-64% lower). Antipsychotic or anticholinergic drugs tended to increase or have no effect on the density of [(3)H]pirenzepine-labeled receptors in rat frontal cortex.. Because M(1) and M(4) receptors are critical to the functions of prefrontal cortical acetylcholine, the present findings suggest a functional impairment in cholinergic neurotransmission in schizophrenia and the possibility that muscarinic receptors are involved in the pharmacotherapeutics of the disorder.

Topics: Adolescent; Adult; Aged; Animals; Antipsychotic Agents; Autoradiography; Benztropine; Cause of Death; Female; Humans; Male; Middle Aged; Parasympatholytics; Pirenzepine; Prefrontal Cortex; Rats; Receptors, Muscarinic; Schizophrenia; Tritium

Topics: Anticonvulsants; Antipsychotic Agents; Benztropine; Clonazepam; Humans; Hyponatremia; Inappropriate ADH Syndrome; Loxapine; Male; Middle Aged; Muscarinic Antagonists; Schizophrenia

Topics: Adult; Age Factors; Aged; Benztropine; Delirium; Drug Interactions; Fluoxetine; Humans; Middle Aged; Perphenazine; Schizophrenia; Selective Serotonin Reuptake Inhibitors

This study evaluated the longitudinal course of neuropsychological deficits in a group of patients with new or recent onset schizophrenia. Thirty-five inpatients with DSM-III-R diagnoses of schizophrenia were administered a comprehensive battery of neuropsychological tests during their index hospitalization, and either 1 or 2 years after intake. Cognitive function remained stable in most domains, including motor speed, verbal and nonverbal memory, and verbal learning. Significant improvement in neuropsychological performance was observed on a task of complex attention (Trails B) and a set response shifting task (Stroop). These improvements were correlated with changes in clinical symptoms, but not with changes in medication dose. These findings suggest that most of the neuropsychological functioning in schizophrenia is stable over the first few years of the illness. Moreover, those neuropsychological deficits that remain unchanging appear to be independent of significant change in clinical symptoms, suggesting they may be a trait of the illness. However, a small subset of functions such as complex attention and response inhibition appear to fluctuate with time, and in particular, with clinical symptomatology, and may be considered 'state' dependent.

Topics: Adult; Antipsychotic Agents; Attention; Benztropine; Cognition Disorders; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Mental Recall; Neurocognitive Disorders; Neuropsychological Tests; Patient Admission; Problem Solving; Prospective Studies; Reaction Time; Schizophrenia; Schizophrenic Psychology

Depression is commonly associated with the longitudinal course of schizophrenia. Several etiologies for this problem have been proposed but, to our knowledge, noncompliance with antiparkinsonian medications has not been considered.. Case histories of two patients who were noncompliant and one who threatened noncompliance with antiparkinsonian medications are presented. All three patients were diagnosed with schizophrenia by DSM-III-R criteria and had been clinically stable for long periods.. All three patients became depressed when their adjunctive benztropine was stopped, and their depressions remitted when their benztropine was reinstated.. Noncompliance with antiparkinsonian medications may be associated with a reversible depression in patients receiving maintenance neuroleptics for schizophrenia. Since this is a newly described phenomenon, the scope of the problem is not known; however, it may contribute to the wide prevalence of depressive symptoms in schizophrenia. Clinical measures to facilitate detection of such noncompliance are discussed.

Topics: Adult; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benztropine; Depressive Disorder; Dyskinesia, Drug-Induced; Female; Humans; Male; Parkinson Disease, Secondary; Schizophrenia; Treatment Refusal

This report describes a patient with schizophrenia who developed episodes of ocular dystonia as a delayed side effect of neuroleptic medication. Each episode was preceded and accompanied by marked agitation, stereotypic behaviour and exacerbation of hallucinations. Both the psychotic and dystonic symptoms responded to anticholinergic medication. The theoretical and practical implications of this observation are discussed.

Topics: Adult; Antipsychotic Agents; Benztropine; Chlorpromazine; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Fluphenazine; Haloperidol; Humans; Infusions, Intravenous; Male; Neurologic Examination; Ocular Motility Disorders; Psychoses, Substance-Induced; Schizophrenia; Schizophrenic Psychology

Identification of symptoms that are directly responsive to neuroleptic drugs at progressive phases of treatment is important for monitoring drug response and understanding the relationship between neurochemical mechanisms of drug action and disordered behavior. Using multiple regression analyses that controlled for pretreatment severity, we identified those symptoms that improved in direct relation to serum concentrations of perphenazine after 10 days of treatment. Improvement in two positive symptoms of psychosis--hallucinations and conceptual disorganization--appears to be related to perphenazine level and useful for assessment of early drug response.

Topics: Adult; Benztropine; Bipolar Disorder; Depressive Disorder; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Perphenazine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology

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

Few investigations have assessed the neuropsychological effects of psychotropic medications on schizophrenic patients. In this study, 44 clinically stable schizophrenic inpatients were administered a battery of neuropsychological tests, and their performance was correlated with dosage of neuroleptic medication and benztropine. Neuroleptic dose was correlated with poorer performance on tests of psychomotor speed and attention, and with the number of perserverative errors on the Wisconsin Card Sort. Anticholinergic dose was associated with poorer verbal learning, verbal fluency, and motor speed. Both medication dosages were associated with poorer verbal recognition memory, but this association was strongly influenced by the performance of individuals on the highest medication doses. The findings, which were independent of clinical state and intelligence, indicate that higher doses of neuroleptic and anticholinergic medications are associated with poorer neuropsychological functioning in schizophrenia.

Topics: Adult; Antipsychotic Agents; Benztropine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hospitalization; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Substance-Related Disorders; Trihexyphenidyl

Medicated (n = 17) and unmedicated (n = 17) schizophrenic patients were compared to a normal control group (n = 19) on their performance on auditory and visual versions of the Continuous Performance Test (CPT). Within each stimulus modality, performance was examined on lexical and nonlexical target stimuli. Neuromotor competence was assessed on the basis of motor speed and proficiency. Normal subjects made fewer errors of all types than schizophrenic patients. Unmedicated patients made significantly more errors on nonlexical stimuli than medicated patients, with medication status found not to be associated with stimulus modality effects. Motor proficiency was associated with CPT performance in the medicated patients, but not the unmedicated ones, although this difference in correlations did not account for the group differences between these patients. The authors discuss the implications of these data for the type of cognitive and attentional functions that are affected by medication in schizophrenia.

Topics: Adult; Arousal; Attention; Auditory Perception; Benztropine; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Psychomotor Performance; Schizophrenia; Schizophrenic Psychology; Verbal Learning; Visual Perception

Topics: Adult; Benztropine; Catatonia; Humans; Male; Schizophrenia; Substance-Related Disorders

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benztropine; Humans; Male; Middle Aged; Parasympatholytics; Pilot Projects; Psychomotor Agitation; Schizophrenia; Tryptophan

Topics: Adult; Affect; Benztropine; Female; Humans; Male; Middle Aged; Parasympatholytics; Schizophrenia; Substance-Related Disorders; Trihexyphenidyl

Topics: Administration, Oral; Adult; Benztropine; Enuresis; Humans; Male; Middle Aged; Schizophrenia; Tropanes

Medicated and unmedicated schizophrenic patients and normal subjects (n's = 4) were examined on the extent to which their information-processing performance became automated over time, as reflected by increased competence in dual task performance. The central task was a computerized version of the Continuous Performance Test, and the secondary task was a word-list shadowing task. Normal subjects and medicated schizophrenic patients became much more efficient at performing both tasks simultaneously with practice, with unmedicated patients showing no improvement over time.

Topics: Adult; Attention; Benztropine; Discrimination Learning; Drug Therapy, Combination; Form Perception; Haloperidol; Humans; Male; Pattern Recognition, Visual; Psychiatric Status Rating Scales; Psychomotor Performance; Reaction Time; Schizophrenia; Schizophrenic Psychology; Speech Perception; Tropanes

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

Four of five patients who had had an operationally defined syndrome of postpsychotic depression, which had been responsive to adjunctive imipramine added to an ongoing regimen of fluphenazine decanoate and benztropine, suffered a return of depressive symptomatology following the tapering of the adjunctive imipramine 6 months after the initial response to imipramine therapy. Four comparison patients who were not tapered experienced no such reexacerbations (p = .04). The authors discuss implications of this finding for maintenance adjunctive antidepressant treatment strategies.

Topics: Benztropine; Depressive Disorder; Drug Therapy, Combination; Fluphenazine; Humans; Imipramine; Psychotic Disorders; Recurrence; Schizophrenia; Substance Withdrawal Syndrome

The tendency of antipsychotics to produce extrapyramidal side-effects varies inversely with their antimuscarinic activity. This paper reviews the antipsychotic and antimuscarinic potency of these drugs and compares the total antimuscarinic activity in standard daily doses of antipsychotics, antiparkinson agents and antidepressants. The authors examine factors associated with tolerance of benztropine withdrawal in 39 inpatients. Patients with serious EPS relapse after benztropine withdrawal had an excess of antipsychotic over antimuscarinic activity in their remaining medications. The results suggest an optimal ratio between total antipsychotic and anticholinergic doses, and a simple model for predicting antiparkinson drug requirements.

Topics: Adult; Antiparkinson Agents; Antipsychotic Agents; Benztropine; Brain; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Receptors, Cholinergic; Receptors, Muscarinic; Schizophrenia; Substance Withdrawal Syndrome

The limitations of antiparkinsonian treatment strategy when using anticholinergic drugs are determined by their side effects induced through excessive inhibition of parasympathetic functions. In the present study we have investigated the peripheral effects of antiparkinsonian agents on blood levels of concomitantly administered neuroleptic drugs. We have compared the anticholinergic and a dopamine mimetic antiparkinsonian agent in their effects on serum neuroleptic activity (SNA) and serum anticholinergic activity (SAA). Sixteen schizophrenic patients on chronic neuroleptic therapy with steady state neuroleptic levels were receiving either amantadine, 200 mg/day, or anticholinergic drugs (trihexyphenidyl, 10 mg/day, or benztropine, 6 mg/day) for the first 2 weeks, after which the amantadine group was crossed over to anticholinergic and the anticholinergic group to amantadine for the following 2 weeks. Blood samples were obtained once a week along with clinical testing. The results indicate that SAA was fivefold higher with benztropine than with trihexyphenidyl and that amantadine had no effect on SAA. Moreover, SNA was not altered either by anticholinergics or amantadine coadministration, indicating that the therapeutic blood neuroleptic levels are not compromised by antiparkinsonian administration.

Topics: Adult; Amantadine; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benztropine; Drug Therapy, Combination; Humans; Intestinal Absorption; Male; Middle Aged; Radioligand Assay; Schizophrenia; Trihexyphenidyl

In three studies of comparable design, 47 schizophrenics received anticholinergic anti-Parkinsonism (AP) medications for two to four weeks along the course of neuroleptic treatment. Clinical ratings during the AP phase were contrasted against the preceding and following two-week periods on neuroleptic alone, and these changes were analysed for a total of 27 psychopathology dimensions and for clusters of seven positive and seven negative symptoms. Schizophrenics overall exhibited significant exacerbation of total psychopathology, and positive but not negative symptoms. Only those with a predominantly positive syndrome when drug-free were susceptible to AP therapeutic reversal. However, other subgroup analyses revealed worsening of total psychopathology and positive symptoms among catatonic, schizophreniform, chronic, and good outcome cases, but negative symptoms alone were significantly increased among paranoids. The results were not supportive of a positive-negative dichotomy of schizophrenia, but instead suggested a tripartite model: a distinct paranoid group and a division of the non-paranoids into a positive and a negative type.

Topics: Adolescent; Adult; Benztropine; Chlorpromazine; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychopathology; Schizophrenia; Schizophrenic Psychology; Trihexyphenidyl; Tropanes

Topics: Adult; Benztropine; Dyskinesia, Drug-Induced; Female; Fluphenazine; Humans; Patient Compliance; Schizophrenia

Three cases of akathisia are described in which the manifestations of motor restlessness were subtle enough to be easily missed, but in which the resultant propensities to behavioral "action" nonetheless contributed to significant difficulties for the patients. Appropriate medication adjustments, including adequate treatment with antiparkinsonian agents or suitable lowering of neuroleptic dosage, were beneficial. Subtle manifestations of akathisia of this sort may occur more frequently than is commonly recognized.

Topics: Acting Out; Adolescent; Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benztropine; Female; Humans; Male; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology

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

Topics: Adult; Benztropine; Body Temperature Regulation; Chlorpromazine; Heat Exhaustion; Humans; Male; Psychotropic Drugs; Schizophrenia; Thermosensing

The authors conducted a double-blind, controlled study to test the behavioral, affective, and neurological effects of antiparkinson drug discontinuation. Patients were evaluated at baseline and at 2 and 4 weeks. Of 24 placebo patients 9 left the study early because of adverse effects; none of the 8 patients in the antiparkinsonian group did so. The placebo group had significantly more lower extremity movements, motor agitation, hallucinations, and physical complaints at 2 weeks and scored significantly higher in depression at 4 weeks. A sizable proportion of chronic, drug-treated schizophrenic patients appear to need antiparkinsonians for clinical stability.

Topics: Antiparkinson Agents; Antipsychotic Agents; Benztropine; Biperiden; Double-Blind Method; Drug Therapy, Combination; Humans; Schizophrenia; Substance Withdrawal Syndrome; Trihexyphenidyl

Three patients with low grade tardive dyskinesia developed an acute episode of abnormal involuntary movements after a single injection of fluphenazine decanoate. All three patients had their symptoms relieved after treatment with antiparkinsonian medication. The differential diagnosis of these movements is discussed, and a possible animal model for this phenomenon is described.

Topics: Benztropine; Dyskinesia, Drug-Induced; Female; Fluphenazine; Humans; Male; Middle Aged; Schizophrenia

Topics: Benztropine; Biperiden; Chlorpromazine; Colonic Diseases, Functional; Doxepin; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Obstruction; Male; Pregnancy; Pregnancy Complications; Psychotropic Drugs; Schizophrenia; Thiothixene

Systematic data from three studies suggest that anticholinergic antiparkinsonism agents, when added to ongoing neuroleptic treatment in schizophrenics, have the effect of arresting or reversing therapeutic changes, and when given alone to untreated patients, tend to further worsen their psychosis. The countertherapeutic effects of anticholinergic drugs are reflected particularly in parameters which represent features of schizophrenic psychosis most consistently responsive to neuroleptics. It is proposed that these anticholinergic effects are central in origin and point to the involvement of cholinergic mechanisms in the expression of schizophrenic psychosis and its improvement with neuroleptic medication.

Topics: Antiparkinson Agents; Antipsychotic Agents; Benztropine; Chlorpromazine; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Schizophrenia; Trihexyphenidyl

Topics: Benztropine; Bethanechol Compounds; Drug Therapy, Combination; Fluphenazine; Humans; Male; Middle Aged; Schizophrenia; Tropanes; Visual Acuity; Xerostomia

The case of a 23-year-old patient treated with haloperidol, imipramine, and benztropine mesylate is presented to illustrate an unusually severe reaction to the abrupt cessation of neuroleptic medication. In addition to the description of the withdrawal reaction, a possible explanation of the clinical phenomenon is offered.

Topics: Adult; Benztropine; Depression; Drug Therapy, Combination; Haloperidol; Humans; Imipramine; Male; Schizophrenia; Substance Withdrawal Syndrome; Tropanes; Vomiting

Thrombocytopenia, a fairly uncommon side effect of phenothiazine treatment, usually appears in the presence of a concommitant leukopenia. The authors report 1 patient in whom the illness appeared in the presence of a long known Beta thalassemia but without evidence of alteration in myeloid or lymphoid series. Platelet changes were seen in the presence of a butyrophenone and an aliphatic phenothiazine. A piperazine derivative was used without difficulty.

Topics: Adult; Benztropine; Chlorpromazine; Haloperidol; Humans; Male; Perphenazine; Schizophrenia; Thalassemia; Thrombocytopenia; Trifluoperazine; Trihexyphenidyl; Tropanes

An 18-year-old patient with catatonic schizophrenia developed hypertension when administration of antipsychotic medication was discontinued. Elevated blood pressure was sustained for three days until it was discovered that intramuscular administration of benztropine mesylate immediately reduced it to normal. The fact that the hypertension was not noted earlier while the patient was receiving the antipsychotic drugs suggests that it was a withdrawal phenomenon.

Topics: Adolescent; Benztropine; Fluphenazine; Haloperidol; Humans; Hypertension; Male; Schizophrenia; Substance Withdrawal Syndrome; Trifluoperazine

The frequency of extrapyramidal symptoms (EPS) attributed to chlorpromazine among 86 patients who received benztropine for the prevention of EPS (9.3%) was similar to that of the 568 patients who received chlorpromazine alone (10.6%). The data in this small sample indicated that the prophylactic use of benztropine had no effect in reducing the rate of EPS.

Topics: Adult; Affective Disorders, Psychotic; Basal Ganglia Diseases; Benztropine; Chlorpromazine; Drug Therapy, Combination; Female; Humans; Male; Personality Disorders; Schizophrenia; Tropanes

Topics: Acetylcholine; Basal Ganglia Diseases; Benztropine; Corpus Striatum; Dopamine; Fluphenazine; Haloperidol; Humans; Levodopa; Models, Neurological; Movement Disorders; Parkinson Disease; Reserpine; Schizophrenia; Tranquilizing Agents; Trihexyphenidyl

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

The occurrence of fatal paralytic ileus with peritonitis in a patient receiving phenothiazines and an antiparkinsonian agent is described. Although sporadic reports of this complication have appeared, it has not been emphasized in the literature. Only by being alert to this problem can one hope to achieve earlier diagnosis and begin prompt and appropriate treatment.

Topics: Adult; Antipsychotic Agents; Benztropine; Chlorpromazine; Colon; Female; Humans; Intestinal Mucosa; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Peritonitis; Schizophrenia; Trifluoperazine

The author reports an atypical case of tardive dyskinesia in a 19-year-old male who had been given relatively low dosages of neuroleptic medication for less than 6 months. The symptoms cleared within 3 months after the medication was discontinued. The author reviews the literature regarding similar atypical cases and suggests that increased reporting and careful description of such cases might be useful in furthering our understanding of this syndrome.

Topics: Adult; Age Factors; Benztropine; Haloperidol; Humans; Male; Movement Disorders; Remission, Spontaneous; Schizophrenia; Time Factors; Tropanes

The effects of phenothiazines and social skills training on a severely withdrawn schizophrenic were examined. Regulation of phenothiazine levels had the result that the patient became more receptive to behavioral interventions. Specific application of a token economy program effected a marked improvement in the assertive training was employed to improve the patient's repertoire of ininterpersonal responses. Prior to actual hospital discharge the patient was faded back into his natural environment during a job retraining phase at Goodwill Industries. Specific data on the patient's improved social functioning are presented in a multiple baseline analysis. Follow-up data document the patient's successful adaptation of his natural enviroment.

Topics: Adult; Behavior Therapy; Benztropine; Chlorpromazine; Feedback; Follow-Up Studies; Generalization, Psychological; Humans; Hygiene; Imitative Behavior; Male; Occupational Therapy; Perphenazine; Schizophrenia; Set, Psychology; Social Behavior; Token Economy; Trifluoperazine; Tropanes; Verbal Behavior

Topics: Aged; Benztropine; Cecal Diseases; Constipation; Depression; Diarrhea; Enema; Female; Humans; Intestinal Obstruction; Intestinal Perforation; Male; Megacolon; Schizophrenia; Vomiting

Topics: Adult; Age Factors; Antiparkinson Agents; Basal Ganglia Diseases; Benztropine; Female; Fluphenazine; Humans; Injections; Male; Massachusetts; Mental Disorders; Middle Aged; Residential Treatment; Schizophrenia; Sex Factors; Time Factors; Tropanes

Topics: Administration, Oral; Adult; Antiparkinson Agents; Basal Ganglia Diseases; Benztropine; Community Mental Health Services; Delayed-Action Preparations; Female; Fluphenazine; Hospitalization; Humans; Length of Stay; Male; Schizophrenia; Time Factors; Tranquilizing Agents

Topics: Adult; Basal Ganglia Diseases; Benztropine; Catatonia; Coma; Creatine Kinase; Female; Fever; Fluphenazine; Humans; Movement Disorders; Muscle Rigidity; Phenothiazines; Schizophrenia; Syndrome

Topics: Adult; Antiparkinson Agents; Basal Ganglia Diseases; Benztropine; Drug Antagonism; Female; Haloperidol; Humans; Male; Psychiatric Status Rating Scales; Schizophrenia; Social Behavior; Tranquilizing Agents; Tropanes

Topics: Aged; Anxiety; Basal Ganglia Diseases; Benztropine; Chlorpromazine; Fatigue; Female; Humans; Male; Masticatory Muscles; Middle Aged; Mouth; Movement Disorders; Perphenazine; Procyclidine; Reserpine; Schizophrenia; Syndrome; Tranquilizing Agents; Trifluoperazine; Trihexyphenidyl