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Psychiatry Research Feb 2023This large-scale pharmacoepidemiologic study was conducted to confirm a previous signal for decreased risk of suicide attempt following prescription fills for... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This large-scale pharmacoepidemiologic study was conducted to confirm a previous signal for decreased risk of suicide attempt following prescription fills for benztropine.
METHODS
We used a within-person exposure-only cohort design to study the dynamic association between benztropine prescription fills over a 12-month period and suicidal events (suicide attempts and intentional self-harm) in 62,493 patients with private health insurance (MarketScan - MS) who filled a new benztropine prescription between 2011 and 2019. A discrete-time survival analysis was used to analyze the data, adjusting for age, sex, diagnoses related to suicidal behavior, Parkinson's disease, medical comorbidities, history of suicide attempts, concomitant CNS medications, and time-varying antipsychotic use.
RESULTS
Overall, there were 486 suicidal events (0.8%) following the index end-date of the one-year baseline period. Benztropine use was associated with fewer suicidal events (HR=0.63, 95% CI = 0.50, 0.80). Patients treated with antipsychotics and benztropine had a similar reduction in suicidal events as patients treated with benztropine alone in both within-subject and between-subject analyses. Similar associations were found for patients with bipolar disorder or schizophrenia, and those treated with newer versus older generation antipsychotics. Dose-response and duration response relationships were found, with an overall 6% reduction in suicidal events per 1 mg equivalent dosage per month, that was similar in those treated and those not treated with antipsychotics.
INTERPRETATIONS
Benztropine was found to lower suicidal event rates, comparably in those receiving or not receiving antipsychotic medications, regardless of the presence of major psychiatric disorders. This observation warrants testing in a randomized clinical trial.
FUNDING
No funding sources were utilized for this manuscript.
Topics: Humans; Suicide, Attempted; Benztropine; Antipsychotic Agents; Self-Injurious Behavior; Suicidal Ideation; Risk Factors
PubMed: 36638693
DOI: 10.1016/j.psychres.2023.115054 -
Adverse Drug Reactions and... Jun 1997The abuse and overdose of anti-cholinergic agents such as benztropine is well reported in the psychiatric and emergency medicine journals. However, despite almost 40... (Review)
Review
The abuse and overdose of anti-cholinergic agents such as benztropine is well reported in the psychiatric and emergency medicine journals. However, despite almost 40 years since the first modern report, physicians in general remain poorly aware of anti-cholinergic abuse. A case report of recreational overdose of benztropine in a 19 year old schizophrenic patient is presented. Delirium and anti-cholinergic manifestations persisted for five days necessitating prolonged hospitalization. The literature on benztropine abuse and overdose is reviewed.
Topics: Adult; Benztropine; Drug Overdose; Humans; Male; Muscarinic Antagonists; Substance-Related Disorders
PubMed: 9359932
DOI: No ID Found -
Canadian Psychiatric Association Journal Oct 1973
Topics: Adult; Antiparkinson Agents; Basal Ganglia Diseases; Benztropine; Consciousness; Female; Humans; Male; Middle Aged; Psychoses, Substance-Induced; Tropanes
PubMed: 4746144
DOI: 10.1177/070674377301800511 -
Biochemical Pharmacology Jan 2008The discovery and development of medications to treat addiction and notably, cocaine addiction, have been frustrated by both the complexity of the disorder and the lack... (Review)
Review
The discovery and development of medications to treat addiction and notably, cocaine addiction, have been frustrated by both the complexity of the disorder and the lack of target validation in human subjects. The dopamine transporter has historically been a primary target for cocaine abuse medication development, but addictive liability and other confounds of such inhibitors of dopamine uptake have limited clinical evaluation and validation. Herein we describe efforts to develop analogues of the dopamine uptake inhibitors GBR 12909 and benztropine that show promising profiles in animal models of cocaine abuse that contrast to that of cocaine. Their unique pharmacological profiles have provided important insights into the reinforcing actions of cocaine and we propose that clinical investigation of novel dopamine uptake inhibitors will facilitate the discovery of cocaine-abuse medications.
Topics: Animals; Behavior, Animal; Benztropine; Cocaine-Related Disorders; Conditioning, Psychological; Disease Models, Animal; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Humans; Piperazines; Structure-Activity Relationship
PubMed: 17897630
DOI: 10.1016/j.bcp.2007.08.007 -
WMJ : Official Publication of the State... May 2023Benztropine is an anticholinergic drug used as a therapy for Parkinson's disease and treatment for extrapyramidal side effects. While tardive dyskinesia is an...
INTRODUCTION
Benztropine is an anticholinergic drug used as a therapy for Parkinson's disease and treatment for extrapyramidal side effects. While tardive dyskinesia is an involuntary movement disorder that often occurs gradually after long-term use of medications, it does not commonly present acutely.
CASE PRESENTATION
A 31-year-old White woman experiencing psychosis presented with spontaneous, acute-onset dyskinesia induced with the withdrawal of benztropine. She had been followed in our academic outpatient clinic for medication management and intermittent psychotherapy.
DISCUSSION
The pathophysiology of tardive dyskinesia is not fully understood, but several hypotheses exist, including the involvement of changes in basal ganglia neuronal systems. To our knowledge, this is the first case report to document acute-onset dyskinesia associated with the withdrawal of benztropine.
CONCLUSION
his case report, which describes an atypical response to discontinuing benztropine, might offer the scientific community potential clues to better understand the pathophysiology of tardive dyskinesia.
Topics: Female; Humans; Adult; Benztropine; Tardive Dyskinesia; Dyskinesia, Drug-Induced; Antipsychotic Agents
PubMed: 37141483
DOI: No ID Found -
Journal of Forensic Sciences Nov 2014A woman was found unresponsive with an empty bottle of Cogentin(®) prescribed to another. Admitted to an area hospital, her condition steadily declined until death...
A woman was found unresponsive with an empty bottle of Cogentin(®) prescribed to another. Admitted to an area hospital, her condition steadily declined until death 29 h after admission. Following toxicological screening on hospital (admission) whole blood, the only significant compound detected was benztropine. Benztropine was confirmed at 0.28 mg/L - the highest antemortem blood concentration recorded in a case of toxicity or fatality uniquely associated with benztropine. A second serum antemortem specimen showed a benztropine concentration of 0.19 mg/L. Despite over 24 h in the hospital, benztropine was also found in the postmortem specimens collected at autopsy. Peripheral blood, central blood, liver, and gastric concentrations were 0.47 mg/L, 0.36 mg/L, 9.6 mg/kg, and 44 mg, respectively. These results indicate that benztropine exhibited a potential difference between whole-blood and serum (plasma) concentrations. Additionally, in consideration of literature data, benztropine was found indicative of a compound prone to at least some postmortem redistribution.
Topics: Benztropine; Cholinergic Antagonists; Female; Gastrointestinal Contents; Humans; Liver; Middle Aged; Suicide
PubMed: 24697166
DOI: 10.1111/1556-4029.12489 -
Psychopharmacology Dec 2020Methylphenidate and d-amphetamine, medications used for treatment of attention deficit hyperactivity disorder (ADHD), are used recreationally and self-administered by...
RATIONALE
Methylphenidate and d-amphetamine, medications used for treatment of attention deficit hyperactivity disorder (ADHD), are used recreationally and self-administered by laboratory animals. Benztropine (BZT) analogs, like those medications, increase synaptic dopamine levels but are less effective in maintaining self-administration, suggesting clinical utility with less abuse liability.
OBJECTIVES
The current study was designed to evaluate potential therapeutic effects of BZT analogs related to ADHD.
METHODS
Rats responded under a delay-discounting procedure in which responses on one lever produced immediate delivery of a single food pellet and alternative responses produced four food pellets either immediately or with various temporal delays, with those delays arranged in ascending or random orders in different groups of rats. Selection of the smaller more immediate reinforcer has been suggested as an aspect of "impulsivity," a trait with suggested involvement in ADHD. Other rats were studied under fixed-interval (FI) 300-s schedules to assess drug effects on behavior under temporal control.
RESULTS
d-Amphetamine, methylphenidate, and the BZT analog AHN 1-055, but not AHN 2-005 or JHW 007, increased selection of the large, delayed reinforcer with either arrangement of delays. All drugs changed the temporal distribution of responses within the FI from one with responses concentrated at the end to a more uniform distribution. Changes in the temporal distribution of FI responding occurred with drugs that did not affect discounting suggesting that discounting does not arise directly from the same temporal control processes controlling FI responding.
CONCLUSIONS
AHN 1-055 may be of clinical utility in the treatment of ADHD.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Benztropine; Conditioning, Operant; Delay Discounting; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Impulsive Behavior; Male; Rats; Rats, Sprague-Dawley; Self Administration
PubMed: 32964243
DOI: 10.1007/s00213-020-05655-0 -
The Primary Care Companion For CNS... Aug 2023To evaluate real-world treatment patterns for patients initiating benztropine and to understand treatment approaches in patients with drug-induced movement disorders...
To evaluate real-world treatment patterns for patients initiating benztropine and to understand treatment approaches in patients with drug-induced movement disorders from a health care provider perspective. A retrospective claims analysis was conducted among patients with evidence of benztropine initiation from January 2017 through March 2020 to assess treatment patterns and patient health care resource utilization. Subsequently, a 30-minute, United States-based online survey fielded from December 2021 to January 2022 was sent to physicians, nurse practitioners, and physician assistants who reported a primary care or psychiatry specialty currently treating drug-induced movement disorders and prescribed benztropine. The health care claims analysis included 112,542 patients. Polypharmacy and multiple comorbidities were frequent characteristics in this population; 54.1% of patients had ≥ 2 comorbidities at baseline, and 59.1% had claims for > 10 medications. Benztropine was used for > 3 months in > 50% of the population. Health care costs and resource utilization were high, with mean all-cause pharmacy and outpatient costs totaling $11,755. Survey results from 349 primary care or psychiatry health care providers indicated that benztropine is often used in non-tardive dyskinesia drug-induced movement disorders but frequently continued for > 3 months or used in tardive dyskinesia. In this study, psychiatry providers prescribed benztropine in line with guideline recommendations more often than primary care providers; however, < 40% indicated familiarity with 2020 American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia. These complementary analyses suggest that benztropine is used long-term in non-tardive dyskinesia drug-induced movement disorders and in tardive dyskinesia despite risks of worsening tardive dyskinesia or adverse effects. .
Topics: Humans; Benztropine; Insurance Claim Review; Retrospective Studies; Movement Disorders; Tardive Dyskinesia; Health Personnel
PubMed: 37671827
DOI: 10.4088/PCC.22m03472 -
Medicine, Science, and the Law Apr 2001Benztropine is an anticholinergic agent used in the treatment of Parkinson's disease and drug induced extrapyramidal disorders. We report a case of fatal benztropine...
Benztropine is an anticholinergic agent used in the treatment of Parkinson's disease and drug induced extrapyramidal disorders. We report a case of fatal benztropine toxicity. This drug is regarded as relatively safe and reports of isolated toxicity are scarce. In ascribing a particular death to fatal drug toxicity the forensic pathologist must take into account the circumstances surrounding the death, the presence and significance of any co-existent natural disease and the potential contribution of any other detected therapeutic or illicit agents. This interpretation will occur in the knowledge that certain drugs will not be detected and that with respect to quantification of postmortem drug levels, the notion of postmortem redistribution should always be considered.
Topics: Antiparkinson Agents; Autopsy; Benztropine; Drug Overdose; Female; Humans; Middle Aged; Muscarinic Antagonists
PubMed: 11368397
DOI: 10.1177/002580240104100212 -
Journal of Neuro-ophthalmology : the... Dec 2007
Topics: Adolescent; Benztropine; Dopamine Uptake Inhibitors; Esotropia; Female; Humans; Mental Disorders; Mydriasis; Pseudohypoaldosteronism
PubMed: 18090571
DOI: 10.1097/WNO.0b013e31815bfb04