benztropine and fluphenazine-depot

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

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

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

Patients receiving fluphenazine decanoate who were switched from adjunctive benztropine to imipramine in a double-blind trial experienced marked exacerbations of extrapyramidal side effects. No substantial increase in anticholinergic side effects occurred, however, when imipramine was added to fluphenazine decanoate and benztropine.

Topics: Adult; Benztropine; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Fluphenazine; Humans; Imipramine; Male; Middle Aged; Tropanes

4 racehorses were examined because of markedly abnormal behavior following administration of fluphenazine decanoate.. Clinical signs included restlessness, agitation, profuse sweating, hypermetria, aimless circling, intense pawing and striking with the thoracic limbs, and rhythmic swinging of the head and neck alternating with episodes of severe stupor. Fluphenazine was detected in serum or plasma from all 4 horses. The dose of fluphenazine decanoate administered to 3 of the 4 horses was within the range (25 to 50 mg) routinely administered to adult humans.. In 2 horses, there was no response to IV administration of diphenhydramine hydrochloride, but the abnormal behavior in these 2 horses appeared to resolve following administration of benztropine mesylate, and both horses returned to racing. The other 2 horses responded to diphenhydramine administration. One returned to racing. The other was euthanized because of severe neurologic signs, respiratory failure, and acute renal failure.. Findings indicate that adverse extrapyramidal effects may occur in horses given fluphenazine decanoate. These effects appear to be unpredictable and may be severe and life threatening. Use of fluphenazine decanoate as an anxiolytic in performance horses is not permitted in many racing and horse show jurisdictions, and analytic procedures are now available to detect the presence of fluphenazine in serum or plasma.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Benztropine; Diphenhydramine; Extrapyramidal Tracts; Fatal Outcome; Female; Fluphenazine; Horse Diseases; Horses; Male; Nervous System Diseases; Treatment Outcome

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

"Rubral" tremor is a rare movement disorder that occurs typically with midbrain damage. It is defined by its presence at rest, with sustained posture, and with movement. Whether it is a single-tremor disorder or a combination of two distinct tremors is debated. This report chronicles a severe neuroleptic induced "rubral" tremor in a patient who had had a stable posttraumatic ataxia. The dramatic response to benztropine and bromocriptine is illustrated in the videotape.

Topics: Adult; Benztropine; Bromocriptine; Corpus Striatum; Fluphenazine; Humans; Male; Neural Pathways; Red Nucleus; Substantia Nigra; Tremor

Ten patients with histories of postpsychotic depression responsive to adjunctive imipramine added to fluphenazine decanoate and benztropine underwent a double-blind trial of imipramine discontinuation 6 months after responding to the adjunctive imipramine. Discontinuation of imipramine was associated with depressive relapse.

Topics: Adult; Benztropine; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Fluphenazine; Humans; Imipramine; Middle Aged; Psychotic Disorders; Tranquilizing Agents

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

A 27-year-old man was admitted to the emergency department with a fluphenazine decanoate-induced dystonia. He was treated with 125 mg diphenhydramine IV in four doses and 2 mg benztropine IM. A fluctuating response was observed before continued remission of the dystonia. Possible reasons for variable patient responses to diphenhydramine are discussed.

Topics: Adult; Benztropine; Delayed-Action Preparations; Diphenhydramine; Dystonia; Fluphenazine; Humans; Male; Mental Disorders

Two different studies were performed in subhuman primates in an attempt to induce symptoms of tardive dyskinesia. The first study lasted for over 5 years. This involved elderly Macaca speciosa. The animals were given first 25 mg of fluphenazine decanoate and later the enanthate IM (3.2 mg/kg) every 2 weeks and on 5 days a week, haloperidol, first IM and later PO. Haloperidol was given first in doses of 1.0 mg/kg and ultimately after years of therapy, in doses of 6.4 mg/kg per day. Those animals who survived gained weight to over 10 kg. After neuroleptic withdrawal, tardive dyskinesia became evident in 1 month. The symptoms of tardive dyskinesia following cessation of medication lasted a maximum of 1 year. This animal model produced very impressive symptoms in one of the three animals treated who survived. This is not a very practical animal model from the aspects of economics (costly), time (5 years), and animal availability (rare and endangered species). However, the symptoms of tardive dyskinesia are very striking and identical with human tardive dyskinesia in a susceptible animal. A more practical experimental animal model involved Cebus apella. Depot fluphenazine (0.1 to 3.2 mg/kg) was given continuously every 2 weeks for 1 year. In this species the symptoms of tardive dyskinesia became progressively prolonged and intense with each course of fluphenazine therapy and withdrawal, suggesting that reversible tardive dyskinesia may turn into irreversible tardive dyskinesia. With each succeeding course of fluphenazine therapy (1 month) and withdrawal (1-3 months), the animals appeared to be sensitized to both the acute extrapyramidal and the tardive dyskinesia symptoms. These animals were also given various experimental drug treatments including biperiden lactate, benztropine mesylate, and d-amphetamine after they developed signs of tardive dyskinesia.

Topics: Animals; Antipsychotic Agents; Benztropine; Cebus; Death, Sudden; Disease Models, Animal; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Fluphenazine; Haloperidol; Humans; Macaca; Male; Motor Activity; Stereotyped Behavior; Substance Withdrawal Syndrome

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

A case is reported in which catatonia and autonomic abnormalities occurred in a patient on long-term fluphenazine decanoate following overdose with an oral anorectic agent containing phenylpropanolamine and caffeine. The catatonic symptoms showed a rapid and complete resolution following intramuscular benztropine. A possible mechanism to explain the catatonic symptoms is discussed.

Topics: Benztropine; Caffeine; Catatonia; Fluphenazine; Humans; Male; Middle Aged; Phenylpropanolamine; Receptors, Dopamine