benztropine and Psychotic-Disorders

Patients who present with acute neuropsychiatric syndromes pose difficult diagnostic and treatment challenges. A history of psychiatric illness and treatment with psychotropic medication may be valuable clues to diagnosis and management of such patients. However, this information may also tempt a clinician to focus on a premature diagnosis, excluding other important possibilities. A case of a 42-year-old male with recurrent psychotic illness who developed an abrupt deterioration in mental and physical status is presented. Despite an initial good response to physostigmine, he was diagnosed with neuroleptic malignant syndrome and did not receive subsequent treatment with cholinesterase inhibitors. The patient expired within hours of arriving in the emergency room. The postmortem benztropine level was elevated, leading to the attribution of death to anticholinergic toxicity. This case serves to illustrate the difficulties in distinguishing features of anticholinergic toxicity and neuroleptic malignant syndrome.

Topics: Adult; Antipsychotic Agents; Benztropine; Catatonia; Cholinergic Antagonists; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fatal Outcome; Humans; Male; Neuroleptic Malignant Syndrome; Psychotic Disorders

The neuroleptic malignant syndrome (NMS) is a rare but potentially lethal disorder associated with the administration of neuroleptic agents. This syndrome may be underdiagnosed because it is poorly understood and often unrecognized. It affects all age groups and has a 20% mortality. Presenting features include extrapyramidal symptoms, altered mental consciousness, autonomic dysfunction, and hyperthermia. The underlying explanation for these manifestations is a disturbance of the dopaminergic system within the basal ganglia and hypothalamus. Dantrolene (Dantrium), amantadine (Symmetrel), and bromocriptine mesylate (Parlodel) have been efficacious in conjunction with supportive therapy. I report three cases successfully treated with bromocriptine and supportive therapy.

Topics: Adolescent; Adult; Benztropine; Bromocriptine; Catatonia; Child; Child, Preschool; Diagnosis, Differential; Female; Fluphenazine; Haloperidol; Heat Exhaustion; Humans; Male; Malignant Hyperthermia; Middle Aged; Neuroleptic Malignant Syndrome; Psychotic Disorders; Schizophrenia, Paranoid; Time Factors

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

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

Twenty-nine inpatients with major psychotic disorders were treated for 14 days with a clinician-determined dose of haloperidol and with either benztropine or placebo given by double-blind random assignment on days 1 through 7. No differences were noted in haloperidol mean dose, haloperidol blood levels, or BPRS scores during the first seven days between benztropine (N = 14) and placebo (N = 15) groups. Benztropine-treated patients demonstrated increased dry mouth and diminished sweat and a non-significantly lower rate of dystonia compared to placebo (14% vs. 33%). Dystonic patients were significantly younger than nondystonic patients, but did not differ in haloperidol mean dose or plasma concentration. The effect of benztropine on the incidence of dystonia was consistent with other studies, which, when analyzed together, demonstrate the efficacy of anticholinergic prophylaxis. The relatively low incidence of anticholinergic side effects, coupled with the lack of effect on haloperidol blood levels or antipsychotic efficacy, suggest that moderate doses of benztropine in conjunction with haloperidol are a rational approach for the treatment of acute psychosis in young patients.

Topics: Adult; Benztropine; Double-Blind Method; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Haloperidol; Humans; Male; Neurologic Examination; Parasympatholytics; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders

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

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

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; Adult; Antiparkinson Agents; Basal Ganglia Diseases; Benztropine; Benzyl Compounds; Clinical Trials as Topic; Delayed-Action Preparations; Evaluation Studies as Topic; Haloperidol; Humans; Injections, Intramuscular; Intraocular Pressure; Male; Middle Aged; Movement Disorders; Parasympatholytics; Piperidines; Piperidones; Placebos; Psychotic Disorders; Tropanes

Akathisia tends to develop as an early complication of antipsychotic treatment in a dose-dependent manner. Although withdrawal akathisia has been reported after the discontinuation or dose reduction of typical antipsychotic drugs, akathisia following atypical antipsychotic drug withdrawal remains a rare phenomenon.. A 24-year-old woman with an acute psychotic episode was admitted and initially treated with aripiprazole. The aripiprazole dose was titrated up to 30 mg/day over 9 days and maintained for the next 3 days; however, her psychotic symptoms persisted without change. She was switched to amisulpride, with the dose increased over 2 weeks to 1000 mg/day. Subsequently, although the patient's psychotic episode subsided, her serum prolactin levels increased markedly. After discharge, the amisulpride dose was increased to 1200 mg/day owing to auditory hallucinations and was maintained with quetiapine (100-200 mg/day) and benztropine (1 mg/day) for 13 weeks. Given the potential for hyperprolactinemia as a side effect, the amisulpride dose was reduced to 800 mg/day concurrently with the discontinuation of benztropine; however, these changes resulted in severe restlessness without other extrapyramidal symptoms. The withdrawal akathisia disappeared over 2 weeks after switching to aripiprazole (10 mg/day) with propranolol (40 mg/day) and the patient's prolactin levels had normalized after 6 months of aripiprazole monotherapy.. The present case highlights the potential for the development of withdrawal akathisia when the dose of amisulpride is tapered abruptly. Thus, a slow tapering and careful monitoring are recommended when switching from amisulpride to other antipsychotic drugs. Furthermore, this case suggests that changing the regimen to aripiprazole with propranolol may be a potential option for amisulpride withdrawal akathisia superimposed on pre-existing hyperprolactinemia.

Topics: Adult; Amisulpride; Antipsychotic Agents; Aripiprazole; Benztropine; Female; Humans; Hyperprolactinemia; Prolactin; Propranolol; Psychomotor Agitation; Psychotic Disorders; Young Adult

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: Acute Disease; Adult; Antipsychotic Agents; Benztropine; Consciousness Disorders; Diagnosis, Differential; Female; Haloperidol; Humans; Parasympatholytics; Psychotic Disorders

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Benztropine; Dementia; Drug Resistance; Humans; Muscarinic Antagonists; Olanzapine; Psychotic Disorders; Risperidone

We studied whether movements associated with tardive dyskinesia (TD) served operant functions in 2 men with developmental disabilities. We found that TD-related movements occurred more frequently in the alone and attention conditions and less frequently in control and demand conditions. Our findings suggest that TD-related movements may not be maintained by social reinforcers and that decreases in TD movements are possibly a result of engagement in activities that are incompatible with TD movements.

Topics: Antipsychotic Agents; Benztropine; Clozapine; Dyskinesia, Drug-Induced; Humans; Male; Middle Aged; Observer Variation; Psychotic Disorders; Severity of Illness Index; Videotape Recording

A broad range of neuropsychological function was compared in samples of young adult unipolar depressed inpatients with and without psychotic features. Consistent with expectations, the psychotic depressive group demonstrated a broad range of deficit and had more impaired performances than the nonpsychotic group. Relevance of these data for hypotheses concerning psychotic depression as a unique diagnostic entity is discussed. In the context of previous research, the current findings suggest that accounting for individual differences in depression may clarify discrepancies between earlier studies of neuropsychological function in depression, and our understanding of the mechanisms by which depression influences cognition may be refined.

Topics: Adult; Attention; Benztropine; Cognition Disorders; Depressive Disorder; Dopamine; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Female; Humans; Male; Memory Disorders; Neuropsychological Tests; Psychotic Disorders; Severity of Illness Index; Verbal Behavior; Verbal Learning

Topics: Adolescent; Antipsychotic Agents; Benztropine; Haloperidol; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Neurologic Examination; Parasympatholytics; Psychotic Disorders; Torticollis

Topics: Benztropine; Colonic Pseudo-Obstruction; Drug Therapy, Combination; Esophageal Achalasia; Esophageal Motility Disorders; Humans; Male; Middle Aged; Psychotic Disorders; Radiography; Thiothixene; Urinary Retention

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

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

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

We describe a group of psychotic patients who became worse early in the course of neuroleptic treatment. Characteristics of this group were: predominantly female sex, relatively brief onset, family history of affective disorder, hypomotoric presentation, and severe neuroleptic side effects. We propose that some patients with affective psychoses are uniquely susceptible to profound blockade of the nigrostriatal dopaminergic system by neuroleptics.

Topics: Adolescent; Adult; Antipsychotic Agents; Benztropine; Chlorpromazine; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Psychoses, Substance-Induced; Psychotic Disorders; Thiothixene

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

Seventeen hospitalized psychotic patients were treated with a fixed oral dose of haloperidol, 5 mg twice daily for 28 days. Most were chronic schizophrenics with an acute exacerbation of their illness. All patients also received benztropine 3 mg twice daily during the last 11 days of the study, regardless of the presence or absence of extrapyramidal side effects. No significant linear or curvilinear relationship was found between steady state plasma levels of haloperidol and clinical response measured by total Brief Psychiatric Rating Scale score. At 28 days, the correlations between plasma levels and percent improvement were rs = 0.187 (not significant) for haloperidol and rs = 0.582 (p = 0.04) for the hydroxymetabolite, reduced haloperidol. The correlation for the sum was rs = 0.511 (p = 0.078). Metabolite levels were substantially higher than plasma haloperidol, on the average 2.7 times greater. Eleven days of benztropine treatment had no significant effect on haloperidol or metabolite plasma levels or on clinical status. At the end of the study, nine of 17 patients (53%) had recovered as judged by discharge readiness. Within the limitations implied by the small number of patients, these data suggest that reduced haloperidol is an important component of plasma antipsychotic activity and cannot be neglected in correlative studies, and that a substantial proportion of patients--about half--can be successfully treated with only 10 mg of haloperidol. The routine use of large doses is thus not necessary for many patients.

Topics: Adult; Basal Ganglia Diseases; Benztropine; Female; Haloperidol; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders

Young adults treated with a high potency neuroleptic such as haloperidol are at high risk of developing dystonic reactions. In this retrospective study, 15 of 16 young adult patients treated only with haloperidol had such reactions within 60 hours of beginning the drug, while none of the seven patients treated with haloperidol plus prophylactic benztropine mesylate developed dystonia. Although methodologic considerations limit the generalization of these results, they are consistent with other reports and suggest that initial anticholinergic prophylaxis is warranted in young patients treated with high potency antipsychotics. All dystonic reactions in these patients occurred within 2 1/2 days, justifying the consideration of discontinuing prophylaxis (which also causes side effects) after 1 week.

Topics: Acute Disease; Adult; Benztropine; Drug Therapy, Combination; Dystonia; Female; Haloperidol; Humans; Male; Parasympatholytics; Psychotic Disorders; Retrospective Studies; Tropanes

A 39-year-old man with schizoaffective disorder experienced somnambulism only when taking a combination of lithium carbonate, chlorpromazine, triazolam, and benztropine. This was confirmed in the sleep laboratory. The sleepwalking occurred during Stage 2 sleep; the sleep record showed a marked paucity of REM sleep. The patient's brother had had one episode of somnambulism, also following exposure to a substance affecting the CNS. A role for CNS-active medications in triggering some pathologic sleep phenomena in predisposed individuals is hypothesized. Medications with central anticholinergic activity may be particularly important.

Topics: Adult; Benztropine; Chlorpromazine; Humans; Lithium; Lithium Carbonate; Male; Psychotic Disorders; Psychotropic Drugs; Somnambulism; Triazolam

Twenty-two acutely psychotic patients were rigorously assessed for psychopathology at baseline and after 14 days of neuroleptic treatment. The neuroleptic radioreceptor assay (NRRA) was used to determine serum neuroleptic concentrations. Serum neuroleptic concentration was significantly, nonlinearly related to changes in BPRS Total Score, and BPRS Factor Scores for Thought Disturbance and Anxiety-Depression. Clinical improvement was associated with intermediate (11-50, 51-126 ng/ml haloperidol equivalents) while poor clinical outcome was related to both low (less than or equal to 10 ng/ml) or high (greater than 125 ng/ml) serum levels. The results are discussed in terms of a possible "therapeutic window" for the neuroleptics and the implications this might have for clinical practice.

Topics: Adolescent; Adult; Antipsychotic Agents; Benztropine; Female; Fluphenazine; Haloperidol; Humans; Male; Middle Aged; Psychotic Disorders; Radioligand Assay; Thiothixene

This report describes a male college student who experienced akinesia lasting almost 3 weeks following withdrawal from relatively brief, low-dose neuroleptic treatment. The literature is reviewed and the case is discussed with special focus upon the duration of extrapyramidal side effects. These syndromes are often undiagnosed or misdiagnosed and lead to unnecessary morbidity and noncompliance with recommended pharmacotherapy.

Topics: Adult; Antipsychotic Agents; Benztropine; Dyskinesia, Drug-Induced; Humans; Male; Psychotic Disorders; Substance Withdrawal Syndrome

The hypothesis that neuroleptic drugs exert their therapeutic effects by blocking dopaminergic transmission has been investigated by examining the effects of 3 neuroleptic drugs on dopamine turnover in 2 dopaminergically innervated regions of brain--the neostriatum and nucleus accumbens. The drugs chlorpromazine, thioridazine and fluphenazine, known to be therapeutically active in the treatment of schizophrenia, but to have differing incidences of extrapyramidal side effects, were administered to rats in dose ratios approximating to those effective in man. All 3 drugs induced a similar rise in the content of the dopamine metabolite homovanillic acid (HVA) in the nucleus accumbens, whilst the changes in HVA observed in the neostriatum were in the rank order in which these drugs produce extrapyramidal side effects. While the concentrations of dopamine metabolites in the frontal cortex were too low to assess the possibility that neuroleptic drugs have actions at this level, our results are consistent with the hypothesis that these drugs exert their therapeutic effects by dopamine receptor blockade in the nucleus accumbens.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Benztropine; Chlorpromazine; Corpus Striatum; Dopamine; Dose-Response Relationship, Drug; Fluphenazine; Homovanillic Acid; Humans; Male; Psychotic Disorders; Rats; Receptors, Dopamine; Scopolamine; Tegmentum Mesencephali; Thioridazine; Tranquilizing Agents

Topics: Benztropine; Dementia; France; Geriatrics; Mental Disorders; Parasympatholytics; Parkinsonian Disorders; Psychotic Disorders; Toxicology; Tranquilizing Agents