Concomitant Use Of Anticholinergics Research Articles

Association of silodosin, tamsulosin, and naftopidil with delirium: analysis of the pharmacovigilance database in Japan.

An association between adrenergic alpha-1 receptor antagonists and delirium has been suggested, but the details are unclear. This study investigated the association between adrenergic alpha-1 receptor antagonists and delirium in patients with benign prostatic hyperplasia using the Japanese Adverse Drug Event Report database. First, disproportionality analysis compared the frequency of delirium in the adrenergic alpha-1 receptor antagonists silodosin, tamsulosin, and naftopidil. Next, multivariate logistic analysis was performed to examine the association between delirium and adrenergic alpha-1 receptor antagonists where disproportionality was detected. A disproportionality in delirium was observed in patients receiving tamsulosin (reporting odds ratio [ROR] 1.85, 95% confidence interval [CI] 1.38-2.44, P < 0.01) compared with those who did not, and also in patients receiving naftopidil (ROR 2.23, 95% CI 1.45-3.28, P < 0.01) compared with those who did not. Multivariate logistic analysis revealed that in addition to previously reported risk factors for delirium, delirium in patients receiving tamsulosin was significantly increased with concomitant use of anticholinergics (odds ratio 2.73, 95% CI 1.41-5.29, P < 0.01) and delirium in patients receiving naftopidil was significantly increased with concomitant use of beta3-adrenergic receptor agonists (odds ratio 4.19, 95% CI 1.66-10.6, P < 0.01). Anticholinergics or beta3-adrenergic receptor agonists to treat overactive bladder in patients receiving tamsulosin and naftopidil was strongly associated with delirium. Confirming the medical history and concomitant medications of patients receiving tamsulosin or naftopidil may contribute to preventing delirium in patients with benign prostatic hyperplasia and to improving their outcomes.

Prescribing Trends for the Same Patients with Schizophrenia Over 20 Years.

Recent pharmacoepidemiology data show an increase in the proportion of patients receiving second-generation antipsychotic (SGA) monotherapy, but no studies have analyzed the same patients over a long period of time. Therefore, in this study, we retrospectively evaluated schizophrenia patients with available data for 20 years to determine whether the drug treatments in the same patients have changed in the past 20 years. The study began in April 2021 and was conducted in 15 psychiatric hospitals in Japan. Schizophrenia patients treated in the same hospital for 20 years were retrospectively examined for all prescriptions in 2016, 2011, 2006, and 2001 (ie, every 5 years). The mean age of the 716 patients surveyed in 2021 was 61.7 years, with 49.0% being female. The rate of antipsychotic monotherapy use showed a slight increasing trend over the past 20 years; the rate of SGA use showed a marked increasing trend from 28.9% to 70.3% over the past 20 years, while the rate of SGA monotherapy use showed a gradual increasing trend over the past 20 years. The rates of concomitant use of anticholinergics, antidepressants, anxiolytics/sleep medications, and mood stabilizers showed decreasing, flat, flat, and flat trends over the past 20 years, respectively. The results of this study showed a slow but steady substitution of SGAs for first-generation antipsychotics (FGAs) over time, even in the same patients.

Factors affecting the effect of naldemedine for opioid-induced constipation: a single-institution, retrospective analysis.

Naldemedine is the newest orally available, peripherally selective μ-opioid receptor antagonist blocker approved for opioid-induced constipation (OIC) treatment in adult patients. On the other hand, some patients have insufficient OIC control even with naldemedine. Thus, this retrospective study was conducted to identify factors affecting the effect of naldemedine. The participants were 210 patients who had received naldemedine at our institute between June 2017 and August 2019. Variables associated with alleviation of OIC were extracted from clinical records and used for regression analysis. The effect of naldemedine was determined according to the degree of constipation. The degree of constipation was categorized as grade 0 - 2 with reference to the CTCAE version 5.0. Multivariate ordered logistic regression analysis was conducted to identify factors affecting the effect of naldemedine. Use of naldemedine within 2 days of opioid initiation [odds ratio (OR) =0.346, 95% confidence interval (CI) =0.173-0.693; P = 0.003], concomitant use of anticholinergics (OR = 2.033, 95% CI = 1.150-3.594; P = 0.015), tramadol (OR = 0.488, 95% CI = 0.250-0.953; P =0.036), and chronic non-cancer pain (OR = 0.429, 95% CI = 0.197-0.937; P = 0.034) were identified as significant factors related to the effect of naldemedine.

Erratum to: OnabotulinumtoxinA is Effective in Patients with Urinary Incontinence due to Neurogenic Detrusor Overactivity Regardless of Concomitant Anticholinergic Use or Neurologic Etiology

Erratum to: OnabotulinumtoxinA is Effective in Patients with Urinary Incontinence due to Neurogenic Detrusor Overactivity Regardless of Concomitant Anticholinergic Use or Neurologic Etiology

OnabotulinumtoxinA is Effective in Patients with Urinary Incontinence due to Neurogenic Detrusor Activity Regardless of Concomitant Anticholinergic Use or Neurologic Etiology

IntroductionTo evaluate the efficacy and safety of onabotulinumtoxinA for the treatment of neurogenic detrusor overactivity (NDO) in subpopulations of etiology (multiple sclerosis [MS] or spinal cord injury [SCI]) and concomitant anticholinergics (use/non-use).MethodsData were pooled from two double-blind, placebo-controlled, pivotal, phase 3 studies including a total of 691 patients with ≥14 urinary incontinence (UI) episodes/week due to MS (n = 381) or SCI (n = 310). Patients received intradetrusor injections of onabotulinumtoxinA 200U (n = 227), 300U (n = 223), or placebo (n = 241). Change from baseline at week 6 in UI episodes/week (primary endpoint), urodynamics, quality of life (QOL), and adverse events (AEs) were assessed.ResultsSignificant and similar reductions in UI episodes were observed regardless of etiology or anticholinergic use: at week 6, mean weekly decreases of −22.6 and −19.6 were seen in MS and SCI patients, respectively, and −20.3 and −22.5 in anticholinergic users and non-users, respectively, treated with onabotulinumtoxinA 200U. The 300U dose did not add to the clinical efficacy in any subpopulation. Similar proportions of patients achieved ≥50% or 100% reductions in UI episodes in all subgroups. Improvements in maximum cystometric capacity, maximum detrusor pressure during first involuntary detrusor contraction, and QOL were significant in both etiologies and were independent of anticholinergic use. The most common AEs in all groups were urinary tract infection and urinary retention.ConclusionRegardless of concomitant anticholinergic use or etiology, onabotulinumtoxinA significantly improved UI symptoms, urodynamics, and QOL in patients with UI due to NDO. OnabotulinumtoxinA was well tolerated in all groups.

461 Efficacy of onabotulinumtoxinA in neurogenic detrusor overactivity is independent of concomitant anticholinergic use

461 Efficacy of onabotulinumtoxinA in neurogenic detrusor overactivity is independent of concomitant anticholinergic use

Phase IIb/III Dose Ranging Study of Tamsulosin as Treatment for Children With Neuropathic Bladder

We evaluated the efficacy and safety of tamsulosin hydrochloride in children with increased detrusor leak point pressure associated with neuropathic bladder. In a double-blind, randomized, placebo controlled trial patients with detrusor leak point pressure 40 cm H(2)O or greater were stratified by age (2 to less than 5 years, 5 to less than 10 years, 10 to 16 years) and concomitant anticholinergic use, and were randomized to receive various doses of tamsulosin or placebo. A 2-week titration was followed by a 12-week maintenance treatment period. Primary end point was response, ie detrusor leak point pressure less than 40 cm H(2)O from 2 evaluations on the same day at week 14. Secondary end points included detrusor leak point pressure change from baseline, hydronephrosis and hydroureter responses, change in catheterization volumes and adverse events. A total of 161 patients received 1 or more treatment doses between January 2008 and February 2009, and 135 were evaluable for the primary end point. A total of 51 patients (37.8%) were detrusor leak point pressure responders, with no statistically significant difference in response rates between each tamsulosin dose and placebo. Adjusting for stratification variables, mean detrusor leak point pressure changes from baseline to week 14 for placebo and low, medium and high dose groups were -11.4, -17.6, -4.6 and -14.3 cm H(2)O, respectively. In 141 evaluable patients hydroureter/hydronephrosis improvement rates were 7.1% and 5.7% in left and right kidneys (hydroureter), respectively, and 14.9% and 14.2% in left and right kidneys (hydronephrosis), respectively. No group experienced decreases in median post-void residual volume at week 14. Drug related adverse event incidences were 4.9% (placebo) and 5.8% (tamsulosin). Tamsulosin was well tolerated but not efficacious in this pediatric population with neuropathic bladder.

Efficacy and Tolerability of Botulinum Toxin Type A in Patients with Neurogenic Detrusor Overactivity and Without Concomitant Anticholinergic Therapy: Comparison of Two Doses

BackgroundBotulinum toxin type A (BoNTA) has been reported to be effective for treatment of patients with neurogenic detrusor overactivity (NDO) refractory to anticholinergic agents. However, in most of the studies, the efficacy was associated with concomitant use of anticholinergics. ObjectiveTo evaluate the efficacy and tolerability of BoNTA and compare two different doses in patients with NDO without concomitant anticholinergics. Design, setting, and participantsBetween 2004 and 2006, adults with NDO refractory to anticholinergics or discontinued anticholinergics due to adverse events or contraindications from four different French clinical centres were included in a prospective, randomised, double-blind, comparative trial. Inclusion criteria were urinary incontinence (UI) resulting from NDO that could not be managed with anticholinergics. Patients with bladder cancer, lithiasis, or urinary infection were excluded. InterventionPatients were randomised to receive an intradetrusor injection of 500 U or 750 U of BoNTA. MeasurementsThe initial evaluation (ie, clinical and urodynamic variables and quality of life [QoL]) was repeated at days 30, 90, 180, and 360. Primary outcome was complete continence rate at day 30. Secondary outcomes were cumulative incontinence rate, reappearance of leakages, pad usage, urodynamics, and QoL. Results and limitationsSeventy-seven patients received 500 U (n=39) or 750 U (n=38) of BoNTA and were included in the full analysis set for efficacy analysis. Complete continence at day 30 was observed in 22 patients (56.4%) and 28 patients (73.7%) receiving 500 U or 750 U of BoNTA, respectively (p=0.056; one-sided χ2 test to compare to α=0.025). The median delay in the reappearance of leakages was 168 d. Monotherapy of BoNTA significantly improved UI in patients with NDO. Although there was a trend towards a greater improvement with 750 U of BoNTA, no statistically significant differences in terms of clinical and urodynamic variables and QoL were found between the treatment groups. Tolerability was excellent and equivalent for both doses. ConclusionsMonotherapy of BoNTA at Dysport (Ipsen, Brisbane, CA, USA) doses of 500 U or 750 U seems to be effective and well tolerated in patients with NDO.

Prescription persistence and safety of antipsychotic medication: a national registry-based 3-year follow-up

Long-term persistence of use, lack of co-prescribed anticholinergic antiparkinson drugs and low mortality may indicate effectiveness and safety of antipsychotic drugs. We aimed to assess 3-year prescription persistence, concomitant use of anticholinergics and mortality related to the use of all antipsychotic agents available in Norway. Data were drawn from the Norwegian Prescription Database on the sales of antipsychotic and anticholinergic antiparkinson agents in 2004 to a total of 52,427 patients. The primary study group was a subgroup of 34,494 patients who were prescribed only one antipsychotic agent in 2004. The patients were re-investigated in 2007. For each of the 13 antipsychotic agents studied, assumed prescription persistence was assessed in light of use of anticholinergic antiparkinson agents in 2004, and casualty rates were noted. The highest persistence was demonstrated for zuclopenthixol (69.8%) and clozapine (88.4%). Zuclopenthixol was often co-prescribed with anticholinergics (22.2%), in contrast to clozapine (3.6%). Ziprasidone was associated with a low mortality (OR = 0.08), while chlorprotixene and haloperidol were associated with a high mortality (OR = 1.34 and 3.97, respectively) compared to levomepromazine. Clozapine demonstrated a high degree of continuity of prescription and a low level of concomitant use of anticholinergics. Zuclopenthixol also demonstrated a high degree of continuity of prescription, despite a considerable degree of co-prescribed anticholinergics. We did not find that any antipsychotic other than ziprasidone was associated with a low mortality. The use of haloperidol seemed to confer a mortality risk three times that of any of the other antipsychotic agents included.

Association between the use of anticholinergic antiparkinson drugs and safety and receptor drug-binding profiles of antipsychotic agents

The use of anticholinergic antiparkinson drugs is almost exclusively confined to treating antipsychotic-induced extrapyramidal side effects (EPS). We investigated the prevalence of concomitant prescription of anticholinergics as a proxy for antipsychotic-induced EPS and compared variance in prevalence with differences in the assumed mechanisms of action of antipsychotics on central nervous system (CNS) transmitter systems (i.e., receptor drug-binding profiles). We paid special attention to potential differences between typical and atypical antipsychotics. Data were drawn from the Norwegian Prescription Database on sales of antipsychotic and anticholinergic antiparkinson drugs to a total of 57,130 outpatients in 2004. We assessed concomitant dispensations of antipsychotic and anticholinergic drugs and correlated the prevalence of concomitantly prescribed anticholinergics to previously assessed receptor-binding profiles of antipsychotics. The concurrent use of anticholinergics varied between 0.4% and 26.0% for patients using a single antipsychotic agent. The prevalence of anticholinergic comedication was more than twice as high in patients using two or more antipsychotic drugs. Four typical antipsychotics (fluphenazine, zuclopenthixol, haloperidol, and perphenazine) were associated with higher concomitant use of anticholinergics than the rest. For the remaining 14 antipsychotic agents, the difference between typical and atypical antipsychotics was neither pronounced nor systematic. A high degree of D2-receptor antagonism and a high 5-HT2A/D2-receptor-affinity ratio coincided with the use of anticholinergics. The liability of antipsychotic drugs to cause EPS seemed to vary considerably and largely independently of the distinction between typical and atypical antipsychotics.

Concomitant Use of Anticholinergics with Acetylcholinesterase Inhibitors in Medicaid Recipients with Dementia and Residing in Nursing Homes

To evaluate the extent of concomitant use of anticholinergic and cholinesterase inhibitor medications in Medicaid recipients with dementia residing in nursing homes. Cross-sectional survey of medical claims data. Indiana Medicaid claims for 2004. Indiana Medicaid recipients continuously eligible for Medicaid in 2004 aged 65 and older with dementia who were residing in nursing homes and taking cholinesterase inhibitors. Rates of concomitant anticholinergic and cholinesterase inhibitor use, number of days residents experienced concomitant use, and concomitant use according to therapeutic class and level of anticholinergic activity were determined. A large proportion (46.7%) of 3,251 Medicaid beneficiaries living in nursing homes and taking cholinesterase inhibitors received anticholinergics concomitantly. Anticholinergics designated as Level 3, or having markedly anticholinergic adverse effects, accounted for most of the concomitant anticholinergic use. More than half (58.1%) of the individuals with concomitant anticholinergic use had 100 or more days of such use. Nearly half of Indiana Medicaid recipients with dementia residing in nursing homes who were taking cholinesterase inhibitors in 2004 were using anticholinergics concomitantly. Patterns of concomitant use in the population examined may assist practitioners in reviewing their prescribing decisions for this vulnerable population.

Effect of warnings in a medical journal on the use of orphenadrine

This thesis is based on two fundamental questions: Which patients are currently using anticholinergic antiparkinson drugs? Does it matter which anticholinergic antiparkinson drug they are using? These questions were further investigated, using a variety of methods, as follows: Are anticholinergic antiparkinson agents predominantly used to treat Parkinson’s disease or antipsychotic induced extrapyramidal side-effects (EPS)? Is there a high risk of abuse of anticholinergic antiparkinson agents? Can alleged differences in receptor binding profiles of typical first- (FGA) and atypical second (SGA) -generation antipsychotic agents predict concomitant use of anticholinergic agents? Can long-term co-prescription of anticholinergic antiparkinson agents shed some light on the efficacy of antipsychotic agents? Does the literature indicate differences in toxicity and fatality rates of anticholinergic antiparkinson agents? Does an autopsy material indicate differences between anticholinergic agents regarding toxicity and fatality risk? Are warnings in a medical journal against the use of the most toxic anticholinergic agent enough to reduce its use? Can patients stop using anticholinergic agents without further remedies? The thesis has the following conclusions: The overwhelming majority of anticholinergic users were patients concomitantly using antipsychotic agents, presumably for the alleviation of antipsychotic induced EPS. The use of anticholinergics was not particularly skewed and we could not find any other indication of abuse, indicating that concomitant use of anticholinergics can be a proxy for the liability of specific antipsychotic agents to cause EPS. For patients using only one antipsychotic agent, the concurrent use of anticholinergics varied between 0.4% and 26.0%, but largely independently of the distinction between typical and atypical antipsychotics. High D2-receptor antagonism and a high 5-HT2A/D 2- receptor-affinity ratio coincided with the use of anticholinergics. Clozapine and zuclopentixol demonstrated the highest level of prescription persistence in a three-year period. The high prevalence of concomitant use of anticholinergics and zuclopentixol may indicate that the latter was considered efficacious enough to outweigh its probable side-effects. Haloperidol was associated with a mortality three times that of any other antipsychotic agent in the study. Orphenadrine is by far the most toxic anticholinergic antiparkinson agent with a high mortality risk. Warnings in a medical journal against the use of a toxic drug can have an impact on prescription patterns. At least one-third of the patients using anticholinergic antiparkinson agents do not need them.

Life-Threatening Clozapine-Induced Gastrointestinal Hypomotility

To raise awareness of potentially lethal clozapine-induced gastrointestinal hypomotility (CIGH) by reviewing cases from the literature and unpublished pharmacovigilance data and to offer strategies aimed at prevention and early treatment. Databases (PsycINFO, 1967-2007; MEDLINE, 1950-2007; and EMBASE, 1988-2007) were searched using the term clozapine together with each of the following: gastrointestinal, dysmotility, constipation, obstipation, fecal impaction, fecaloma, paralytic ileus, adynamic ileus, subileus, ischemic colitis, colon ischemia, bowel ischemia, gastrointestinal ischemia, gut ischemia, obstruction, necrosis, gangrene, bowel perforation, micro-perforation, megacolon, toxic megacolon, acquired megacolon, pseudo-obstruction, Ogilvie, and Ogilvie's syndrome. We analyzed the electronic database entries held by the Adverse Drug Reactions Advisory Committee and the New Zealand Intensive Medicines Monitoring Program, which cited suspected clozapine-related gastrointestinal side effects, as well as all relevant published case reports. We reviewed the literature on the treatment of gastrointestinal hypomotility and constipation. We compiled a database of 102 cases of suspected life-threatening CIGH. There was a mortality rate of 27.5% and considerable morbidity, largely due to bowel resection. Within Australasia, at least 15 patients have died of CIGH. Probable risk factors are identified as recent instigation of clozapine, high clozapine dose or serum level, concomitant anticholinergic use, or intercurrent illness. The paucity of literature on CIGH suggests that the significance of this uncommon but important and frequently fatal side effect has not been recognized. Clozapine can affect the entire gastrointestinal system, from esophagus to rectum, and may cause bowel obstruction, ischemia, perforation, and aspiration. The mechanism is likely to be anticholinergic and antiserotonergic. Clozapine prescribing should be accompanied by regular physical monitoring, appropriate and timely use of laxatives, and early referral of constipated patients--before life-threatening pathologic processes develop.

PMH34 LONG-TERM TREATMENT OF SCHIZOPHRENIA FOR RELAPSE PREVENTION (LASER): 6-MONTH OUTCOMES IN PATIENTS STARTED ON RISPERIDONE LONG-ACTING INJECTABLE IN GERMANY—DATA FROM THE E-STAR DATABASE

• Previous treatment for the majority of patients was an atypical antipsychotic (61.7%), while 32.8% of the patients received a conventional depot and 22.4% were treated with a conventional oral neuroleptic. More than one medication per patient was possible. For 12.5% of the patients, no antipsychotic treatment was recorded. • Of the 991 patients, 862 (87%) were still on LAIR at 6 months. The most common reasons for discontinuation were family choice (3.5%) and insufficient response (2.5%). (Table 2) • Considering all patients enrolled in the German cohort (n=2740), 79.2% of ABSTRACT Objectives: To evaluate 6-month clinical and economic outcomes following initiation of long-acting injectable risperidone (LAIR) in patients with schizophrenia/schizoaffective disorder. Methods: Data are collected via a secured web-based system, retrospectively for 12 months and prospectively for 2 years. Patient demographics, treatment and hospitalisation history, reason for initiating new treatment, Clinical Global Impression - Severity (CGI-S), Global Assessment of Functioning (GAF) and adverse event data are collected. This interim analysis includes the first 991 patients in Germany with at least 6 months follow-up or who discontinued treatment during this 6 month period. Results: Of the 991 patients, 56% were male. Mean age was 43 (±14) years, mean duration of illness at initiation of LAIR was 10 (±10) years. 79% were diagnosed with schizophrenia whilst 17% had schizoaffective disorder. After 6 months, 75% of patients still received their original starting dose. Compared with the preceding 6-month period, fewer patients required full hospitalisations (34% vs 20%; p<0.001). Decreases from baseline were seen in the concomitant use of anticholinergics (13.3% to 6.1%), antidepressants (18.1% to 11.8%), mood stabilisers (9.8% to 7.1%), benzodiazepines (17.3% to 8.4%), and somatic medication (14.7% to 8.5%; all comparisons p<0.001). Compared to baseline, CGI-S ratings improved from 4.7 to 3.8, and patient functioning (GAF) increased from 46.7 to 58.0 at 6 months (both p<0.001). 13% of patients discontinued treatment with LAIR. Most frequent reason (3.5%) was patient/family choice; 1.2% discontinued due to adverse event. Conclusions: The 6-month interim data show that the majority of patients initiated on LAIR remained on stable doses. Discontinuation rates were low. Need for inpatient care was reduced, as was use of psychotropic and somatic concomitant medication. There was significant and clinically relevant improvement in illness and functioning. Longer term data with larger sample size are being accrued to further explore these outcomes over time. Age in years (mean ±SD) 42.7 ±13.7

Pharmacobezoar: an evolving new entity.

Pharmacobezoars, bezoars comprised of medications, are unusual entities. Medications reported to cause bezoars include aluminum hydroxide gel, enteric-coated aspirin, sucralfate, guar gum, cholestyramine, enteral feeding formulas, psyllium preparations, nifedipine XL, and meprobamate. They most often occur, as do bezoars of any type, in a background of altered motility or anatomy of the gastrointestinal tract. Bowel hypoactivity, dehydration, and concomitant use of anticholinergics and narcotis appear to contribute to the propensity for bezoar formation by aluminum hydroxide gel and Isocal. The hygroscopic properties of psyllium and guar gum appear to contribute to their propensity to form bezoars. Insolubility of the carrying vehicle of enteric-coated aspirin and nifedipine is the setting in which these medications form bezoars. In contrast to nonmedication bezoars, pharmacobezoars may produce additional symptoms, those related to the release of their active ingredients. In patients with suspected gastrointestinal tract emptying problems, whether esophageal, gastric, small bowel, or colonic, the astute clinician should consider pharmacobezoar in the differential diagnosis.

Problems in therapeutic blood monitoring of chlorpromazine.

Chlorpromazine (CPZ) therapeutic drug monitoring is beset by inconclusive and controversial evidence on the positive correlation of plasma CPZ concentration and psychiatric improvement. Failure to establish meaningful correlation between plasma concentration and clinical benefit may be explained by chemical assay problems; differences in the pharmacokinetic plasma CPZ and metabolite profile due to age, acuteness or chronicity of the disease; drug interactions; and duration of neuroleptic treatment. At the other end, measurement of clinical effects in psychiatry suffers such drawbacks as less distinct and specific clinical end points, the patient's subjectiveness of symptoms and the investigator's subjectiveness on clinical scoring, and the ethical consideration of placebo use. Our data showed the following:L (1) Plasma levels of CPZ parent compound correlated better with improvement in thought disorders and paranoid delusion than with total Brief Psychiatric Rating Scale; there were no correlations with depression and withdrawal retardation. (2) Chronically treated patients achieved significantly lower plasma CPZ compared to acutely treated patients on oral CPZ dose but not those treated with an intramuscular dose. (3) Children, in comparison to adults, require higher doses to achieve similar plasma CPZ levels and have a lower response threshold, both for clinical improvement and toxicity. (4) The plasma concentration of CPZ can be diminished by concomitant use of anticholinergics. (5) A drug "holiday" increases peak plasma concentration of CPZ and may benefit the nonresponders.