Prolonged Antimuscarinic Delirium in a Child Due to Benztropine Exposure Treated With Multiple Doses of Physostigmine.

An 11-year-old boy presented with an antimuscarinic toxidrome due to benztropine and risperidone ingestion. His delirium was prolonged and difficult to treat with benzodiazepines. Multiple doses of physostigmine successfully treated it. Benztropine is a potent antimuscarinic agent, whereas risperidone has not been reported to cause antimuscarinic toxicity. The use of physostigmine to treat benztropine intoxication in a pediatric patient has not previously been described. In this case, multiple doses were used and were well tolerated.

The effect of anticholinergic drugs on cognition of patients with Parkinson's disease: a cohort study from the Egyptian population.

BACKGROUND: Cognitive dysfunction is a non-motor manifestation of Parkinson's disease (PD). We aimed to determine the frequency and patterns of cognitive dysfunction in treated patients with PD and their predictors. RESEARCH DESIGN AND METHODS: This study included 80 patients (male = 48; female = 32) and 30 healthy individuals. They underwent neuropsychiatric evaluations. Measurements included Beck's depression inventory - II (BDI-II), mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA). RESULTS: Patients had mean age of 55.56 ± 9.06 yrs, duration of PD of 4.86 ± 2.71 yrs and Hoehn and Yahr Scoring of 2.19 ± 0.89. They were on levodopa/carbidopa therapy and adjuvant therapy with benztropine mesylate, an anticholinergic drug, (n = 51) or amantadine sulfate, a dopaminergic drug, (n = 29). Sixteen (20%) had moderate depressive symptoms. Mild and moderate cognitive impairments were reported in 38.8% and 28.8% (by MMSE) and 46.3% and 31.3% (by MoCA). Patients had lower global cognitive scoring (p = 0.0001) and scorings of different cognitive functions (naming, attention, language, abstraction, memory and orientation) than controls. Patients treated with benztropine had lower cognition than with amantadine. Correlation analyses showed that lower cognition was only associated with chronic PD and its treatment (p = 0.0001). CONCLUSIONS: Cognitive dysfunction is common with PD (77.5%) particularly with anticholinergic drugs. De-prescription of anticholinergics is recommended for patients with PD.

Withdrawal-Emergent Dyskinesia Related to Benztropine: A Case Report.

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.

Olanzapine and benztropine as a cause of ischemic colitis in a 27-year-old man.

Ischemic colitis is a rare adverse effect of antipsychotic medications and is most commonly associated with the phenothiazine class of antipsychotics and atypical antipsychotics such as clozapine and olanzapine. The risk is further increased when antipsychotics are taken in conjunction with anticholinergics. A 27-year-old man with a history of bipolar disorder and depression presented to the emergency department with 6 days of constipation, abdominal pain, nausea, and nonbloody vomiting. He later developed multiple episodes of hematochezia and fever. Within the preceding 2 weeks, his medication regimen of divalproex sodium, aripiprazole, and trihexyphenidyl, had been changed to olanzapine, benztropine, and bupropion. The patient's physical examination showed diffuse abdominal tenderness, guarding, and distension and laboratory tests revealed a leukocytosis. A computed tomographic scan of the abdomen/pelvis showed colitis extending from the splenic flexure to the sigmoid colon, without evidence of perforation. A colonoscopy revealed severe ischemic colitis involving the descending and sigmoid colon, which was confirmed on biopsy. Given the temporal association between the new medications and onset of symptoms, the patient's ischemic colitis was likely caused by olanzapine or the combination of olanzapine and benztropine, likely secondary to their anticholinergic properties. Thus, providers should take a thorough history and counsel patients regarding the risks of constipation when starting antipsychotic medications, particularly those with anticholinergic activity. Despite the fact that ischemic colitis is such a rare adverse effect of antipsychotic medications, it is important to consider because of its potentially fatal outcomes.

Full circle-old drugs prove more beneficial than newer agents for schizophrenia: a case report.

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.

Incidence of delirium in older adults newly prescribed lithium or valproate: a population-based cohort study.

BACKGROUND: The use of lithium carbonate for the treatment of mood disorders in old age has decreased at a dramatic rate in favor of valproate. Because of lithium's narrow therapeutic range, neurotoxicity can be an important complication in lithium therapy and potentially influence prescription patterns. Therefore, we compared the incidence of delirium in older adults with mood disorders who were newly dispensed either lithium or valproate. METHOD: Using 4 population-based administrative databases from the province of Ontario, Canada (the Ontario Drug Benefit program, the Canadian Institute for Health Information, the Ontario Health Insurance Plan, and the Registered Persons Data Base), we were able to identify a cohort of mood disorder patients 66 years and older who were newly dispensed lithium or valproate over an 8-year period (1993-2001). Measures were taken to ensure that the sample was composed of mood disorder patients. As a comparator, we included a known deliriogenic drug, benztropine. The main outcome measure was a new diagnosis of delirium on a hospitalization record during 1 year of follow-up. RESULTS: Our study cohort consisted of 2422 new users of lithium and 2918 new users of valproate over an 8-year period. There was no statistically significant difference in the incidence of delirium between lithium (2.8 per 100 person-years) and valproate (4.1 per 100 person-years). Compared with patients who received lithium, patients who received benztropine had a significantly higher risk of delirium (p < .001). CONCLUSION: The incidence of hospitalizations with delirium was similar in patients treated with lithium and valproate. These findings add to the evidence suggesting that the shift away from the use of lithium carbonate to manage mood disorders in older adults is not justified on the basis of concerns of neurotoxicity.

A controlled trial of amantadine in drug-induced extrapyramidal disorders.

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.

Physostigmine. Its use in acute anticholinergic syndrome with antidepressant and antiparkinson drugs.

We reviewed the use of physostigmine in the diagnosis and management of acute toxic psychosis due to drugs with anticholinergic properties. The syndrome of agitation and toxic confusional psychosis associated with peripheral signs of cholinergic blockade is produced by several plant toxins, antispasmodics, ophthalmic preparations, and certain proprietary sedatives, as well as antiparkinson medications, antidepressants, and some antipsychotic drugs. Physostigmine, uniquely among the available reversible anticholinesterase agents, can pass the blood-brain barrier to exert central as well as peripheral cholinomimetic actions to reverse this syndrome. Psychiatrists should make more use of this safe, specific, rapid, and effective treatment for anticholinergic drug toxicity, and should particularly be alert to reversible anticholinergic brain syndromes associated with antidepressants and antiparkinson medications, and even with antipsychotic medications.

Prevention of acute dystonic reactions in patients beginning high-potency neuroleptics.

The authors performed a prospective double-blind study of 39 inpatients beginning high-potency neuroleptics. Patients were randomly assigned to a 7-day course of benztropine or placebo in addition to a neuroleptic. Of 17 patients receiving placebo, eight (47%) suffered an acute dystonic reaction; of 22 patients receiving benztropine, none suffered this reaction--a highly significant difference. The authors also found minimal anticholinergic toxicity attributable to the addition of benztropine to the neuroleptic regimen. These results suggest that an initial 7-day prophylaxis with benztropine is a high-benefit, low-risk adjunctive treatment to neuroleptic therapy.

Comparative side effects of imipramine, benztropine, or their combination in patients receiving fluphenazine decanoate.

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.

Atypical tardive dyskinesia.

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.

Cogwheel rigidity related to lithium maintenance.

Neurological examinations of 27 outpatients receiving lithium carbonate maintenance therapy for recurrent affective illness revealed that most of the patients receiving lithium for more than 8 months had cogwheel rigidity. The data suggest a positive correlation between the duration of lithium maintenance and the severity of cogwheeling. Intravenous administration of benztropine, an antiparkinsonian drug, did not abolish or significantly ameliorate this symptom.

Adverse effects of antiparkinson drug withdrawal.

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.

Benztropine versus clozapine for the treatment of tremor in Parkinson's disease.

Four open-label studies have reported beneficial effects of clozapine on the tremor of idiopathic Parkinson's disease (PD). We performed a double-blind crossover trial with a 2-week washout, comparing low-dose clozapine to benztropine for the treatment of tremor in PD. Twenty-two subjects enrolled and 19 completed the study. Benztropine and clozapine were equally effective in improving tremor and the motor score of the United Parkinson's Disease Rating Scale at mean doses of 3.0 and 39 mg/day, respectively. Significant adverse events were experienced with each drug, but leukopenia was not encountered. We conclude that the atypical antipsychotic drug clozapine is helpful in the treatment of tremor in PD and should be considered when all other drug therapies fail.

Pharmacology of blepharospasm-oromandibular dystonia syndrome.

Blepharospasm and oromandibular dystonia are clinically similar to other hyperkinetic movement disorders. Dopaminergic antagonist (neuroleptic) and purported cholinergic agonist (deanol) treatment improved symptoms, whereas dopaminergic agonist (carbidopa/levodopa) and cholinergic antagonist (benztropine) drugs worsened symptoms in two patients. This suggested that the syndrome is also pharmacologically related to the hyperkinetic dyskinesias. Symptoms worsened substantially during carbidopa/levodopa but temporarily resolved in one patient and improved in another when the drug was discontinued. This suggests that the pathophysiology of these symptoms involves an idiopathic form of receptor hypersensitivity that can be modified by agonist treatment. The effect of cholinergic agents was less than the effect of dopaminergic drugs, implying that dopamine plays a predominant role in the pathophysiology.

Medication-induced somnambulism in a patient with schizoaffective disorder.

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.

Thrombocytopenia in the absence of leukopenia associated with the use of neuroleptics.

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.

Delirium associated with the combination of a neuroleptic, an SSRI, and benztropine.

BACKGROUND: On the basis of recent findings, the increased use of serotonin selective reuptake inhibitors (SSRIs) in combination with antipsychotics and concomitant benztropine is likely. METHOD: Five patients who developed delirium while receiving a neuroleptic, an SSRI, and benztropine are described. RESULTS: The timing of the delirium in relation to drug administration suggests the delirium was the result of an interaction of the SSRI and benztropine. CONCLUSION: Possible mechanisms are explored. Clinicians should be aware that patients receiving this combination may be at increased risk for delirium.

Ethopropazine and benztropine in neuroleptic-induced parkinsonism.

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.

Effects of anticholinergic medication on memory in schizophrenia.

Verbal memory and reaction time of ten schizophrenic patients were compared at two different serum anticholinergic levels. Verbal recall was worse at higher drug levels, while reaction time tended to be improved by anticholinergic treatment. Implications for studies of memory in schizophrenia are considered.