clozapine and Delirium

The development of delirium in patients with idiopathic Parkinson's disease (IPD) is a feared complication, which is often associated with sustained worsening of motor symptoms and psychopathological sequelae. Little is known regarding the prevalence and incidence rates, course and prognosis. Clinical studies from which recommendations for evidence-based management of delirium in IPD can be derived are lacking.. To summarize the state of the art regarding epidemiological and clinical features of delirium in IPD. Discussion of prevention strategies and non-pharmacological and pharmacological treatment options.. A literature search was carried out in PubMed.. The IPD is an independent risk factor for the development of delirium. Patients with IPD show poorer clinical outcome frequently with cognitive worsening and motor complications following development of delirium.. So far no validated rating scales for recognition and course evaluation of delirium in IPD are available. Preventive strategies and non-pharmacological measures should be consistently implemented to improve management. There are insufficient data concerning pharmacotherapy with quetiapine and clozapine, whereas other neuroleptics are contraindicated for delirium in IPD due to antidopaminergic side effects.

Topics: Antipsychotic Agents; Clozapine; Delirium; Humans; Parkinson Disease; Risk Factors

To review the literature on efficacy and risks of combining antipsychotics (atypical with atypical or conventional) and suggest a rationale and strategies for future clinical trials.. A computerized Medline search supplemented by an examination of cross-references and reviews was performed.. Empirical evidence for the efficacy of combining antipsychotics is too limited to draw firm conclusions. The practice of augmenting clozapine with more 'tightly bound' D2 receptor antagonists as exemplified by risperidone augmentation of clozapine has some empirical and theoretical support. The risks of augmentation strategies have not been studied systematically. No study has examined the economic impact of combination treatment.. Further trials of antipsychotic combination therapies are needed before this currently unsupported practice can be recommended. Rationales for combination treatment include a broadening of the range of receptor activity or an increase in D2 receptor occupancy with certain atypical agents. Trial methodology needs to take into account subject characteristics, duration of treatment, optimization of monotherapy comparators, and appropriate outcome measures.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Clozapine; Delirium; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Risk; Risperidone; Schizophrenia; Schizophrenic Psychology; Sialorrhea; Treatment Outcome

The authors emphasize the need for careful differential diagnosis when symptoms of psychosis arise in patients over the age of 65 years. Prevalence of psychotic disorders in the elderly ranges from 0.2%-4.7% in community-based samples to 10% in a nursing home population and as high as 63% in a study of Alzheimer's patients. Risk factors associated with the development of psychotic symptoms and common causes of delirium are reviewed. Because age-related changes affect the pharmacokinetics of neuroleptics, the authors' treatment recommendations, which include the use of traditional and novel antipsychotics, take into account the higher risk of side effects in the elderly.

Topics: Age Factors; Aged; Antipsychotic Agents; Clozapine; Decision Trees; Delirium; Diagnosis, Differential; Drug Administration Schedule; Female; Half-Life; Humans; Male; Middle Aged; Nursing Homes; Psychotic Disorders; Risk Factors; Risperidone; United States

Withdrawal symptoms for typical antipsychotics are generally mild, self-limited and do not include development of psychotic symptoms. In contrast, withdrawal symptoms for clozapine can be severe with rapid onset of agitation, abnormal movements, and psychotic symptoms. Different pathophysiologic etiologies have been suggested for these severe symptoms, including dopaminergic supersensitivity and rebound.. Three case reports of clozapine withdrawal symptoms are presented. A review of previous case reports and discussion of the etiology of withdrawal symptoms of typical antipsychotics and clozapine are provided.. These three patients developed delirium with psychotic symptoms that resolved rapidly and completely upon resumption of low doses of clozapine.. The severe agitation and psychotic symptoms after clozapine withdrawal in these three patients were due to delirium, perhaps the result of central cholinergic rebound. The withdrawal symptoms and delirium resolved rapidly with resumption of low doses of clozapine. Severe withdrawal symptoms can probably be avoided by slowly tapering clozapine and/or simultaneously substituting another psychotropic with high anticholinergic activity, such as thioridazine.

Topics: Adult; Clozapine; Delirium; Dopamine; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Middle Aged; Psychoses, Substance-Induced; Psychotic Disorders; Receptors, Dopamine; Recurrence; Schizophrenia; Schizophrenia, Paranoid; Substance Withdrawal Syndrome; Thioridazine

Topics: Antipsychotic Agents; Clozapine; Combined Modality Therapy; Delirium; Electroconvulsive Therapy; Humans

Successful treatment of delirium depends on the detection of the reversible contributors. Drugs with delirogenic properties are the most prevalent reversible cause of delirium.. This observational study is based on data from Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries recording severe adverse drug reactions (ADRs) in psychiatric inpatients. The present study analyzes drug-induced delirium (DID) during treatment with antidepressants and antipsychotics.. A total of 436 565 psychiatric inpatients were treated with antidepressants and/or antipsychotics during the observation period from 1993 to 2016 in the participating 110 hospitals. Overall, 254 cases (0.06% of all patients treated with antidepressants and/or antipsychotics) of DID were detected. Implicated either in combination or alone (multiple drugs were implicated in 70.1% of DID), clomipramine (0.24%), amitriptyline (0.21%), and clozapine (0.18%) showed the highest incidence rates of DID. When implicated alone (98 cases overall), clozapine (0.11%) followed by amitriptyline (0.05%) were most likely causally associated with the occurrence of DID. Drugs with strong antimuscarinic properties generally exhibited higher risk of DID.. With an incidence rate of <0.1%, the use of antidepressants and antipsychotics was rarely associated with DID within the Arzneimittelsicherheit in der Psychiatrie program. Tricyclic antidepressants and clozapine were the most commonly implicated psychotropic drugs. These data support the specific role of antimuscarinic properties in DID.

Topics: Adverse Drug Reaction Reporting Systems; Amitriptyline; Antidepressive Agents; Antipsychotic Agents; Clozapine; Delirium; Humans; Incidence; Muscarinic Antagonists; Psychoses, Substance-Induced

Delirium superimposed on dementia (DSD) is difficult to diagnose because symptoms of delirium might be interpreted as symptoms of dementia. To improve diagnostic accuracy, we investigated the potential of a brief point-of-care EEG measurement.. Thirty older patients were included, all with Major Neurocognitive Disorder (i.e. dementia) according to DSM-5 criteria. EEG was registered at right prefrontal and right temporal site, with eyes either open or closed for three minutes, simultaneously with the Discomfort Scale for Dementia of Alzheimer Type. The Confusion Assessment Method for the Intensive Care Unit was administered to determine the presence of symptoms of a delirium at the time of EEG administration. Video registrations were reviewed independently by two delirium experts.. Higher activities of delta and theta1, and lower activities of theta2, alpha, and beta activity, were found in DSD when compared to dementia only. The ratio of delta and theta power during eyes-open conditions had the highest accuracy (AUC = 0.80 [0.63-0.94]; p <.001) to distinguish DSD from dementia alone. All subjects were on benzodiazepines and half on clozapine, thus the effects of psychotropics on EEG cannot be fully excluded.. A brief point-of-care EEG at two sites of the head has the potential to aid in the detection of DSD.. The diagnostic accuracy of EEG in recognizing or excluding delirium in patients who already have dementia is of large potential given the lack of proper diagnostic tools.

Topics: Benzodiazepines; Clozapine; Delirium; Dementia; Electroencephalography; Feasibility Studies; Humans

Treatment resistant schizophrenia (TRS) is often encountered in clinical practice. Clozapine remains the drug of choice in the management of TRS. Several studies have shown that clozapine is the most effective antipsychotic medication to date for TRS. But it is also well known that it has multiple side effects. Some side effects are transient and relatively benign, while other adverse effects are menacing, serious and life-threatening. Delirium may occur with clozapine and is a therapeutic challenge as there is always a risk of precipitating delirium on clozapine rechallenge. Limited management strategies are available as alternatives for the management of psychiatric illness stabilized on clozapine. In this case report, we describe an older adult patient who developed delirium on clozapine. The aims of this case report are to discuss the mechanism by which clozapine leads to delirium, revisit various factors which could possibly lead to delirium, and discuss the different management strategies available for management of psychiatric illness for a patient previously stabilized on clozapine.

Topics: Aged; Antipsychotic Agents; Clozapine; Delirium; Friends; Humans; Schizophrenia; Schizophrenia, Treatment-Resistant

Topics: Antipsychotic Agents; Clozapine; Delirium; Dysarthria; Humans; Male; Middle Aged

Clozapine intoxications have a varied clinical presentation and may have severe complications. Management and treatment guidelines rarely highlight the risks of delayed clinical presentations. We present the case of a 50-year-old man showing severe complications 15 hours after intoxication with 4200 mg clozapine. Treatment consisted of strict monitoring, including vital support and regular clozapine blood levels. Clinical presentations may be delayed up to 5 days after intoxication, for which strict monitoring of clinical symptoms and vital functions during this period is of major importance. We discuss the clinical course of clozapine intoxication, the value of sampling clozapine blood levels and provide an overview of the current treatment guidelines, which we suggest to update to include the management of delayed complications.

Topics: Antipsychotic Agents; Clozapine; Delirium; Humans; Male; Middle Aged

Topics: Adult; Antipsychotic Agents; Clozapine; Colitis; Delirium; Female; Humans; Syndrome; Treatment Outcome

To examine clinical characteristics and treatment responses of patients presenting with delirium and mania to a psychiatric inpatient unit.. Chart review of 16 cases admitted to McLean Hospital with delirium and mania was conducted. We examined the demographics, psychiatric symptoms, clinical course, and response to treatment with medications and electroconvulsive therapy (ECT).. Patients with delirium and mania had negative medical and neurological work-ups and were more likely to be younger, female and with a prior diagnosis of bipolar disorder. Sudden onset of symptoms, incontinence/inappropriate toiletting, and denudativeness are distinctive features of the syndrome. Consistent and significant benefit was seen with ECT. In many cases, high dose benzodiazepines were helpful. In a small number of cases, clozapine was also beneficial but this effect took an average of four weeks to be seen, while atypical antipsychotics, lithium and valproate produced variable results and took an average of three and a half weeks to work, if at all. Typical antipsychotics and anticholinergic drugs led to clinical worsening.. Most patients were on more than one medication and hence treatment responses cannot be definitively ascribed to a specific intervention. Studies of larger groups of such patients in different clinical settings need to be done to confirm our observations.. Delirious mania is a severe psychiatric syndrome which can be accurately recognized and effectively treated. The definitive treatment for this condition is ECT. In cases where ECT is not available, high dose benzodiazepines should be used. Clozapine, quetiapine, lithium and valproate cannot be considered first-line treatments and these medications take an unacceptably long time to work even when helpful; typical antipsychotics and anticholinergic drugs should be avoided.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Combined Modality Therapy; Delirium; Electroconvulsive Therapy; Humans; Middle Aged; Retrospective Studies; Severity of Illness Index

Topics: Adult; Antipsychotic Agents; Clozapine; Delirium; Humans; Magnetic Resonance Imaging; Male; Schizophrenia

Extra care must be taken in treating patients with clozapine because of the serious side-effects. A 44-year-old man with schizophrenia developed delirium on two occasions immediately after restarting clozapine at the dosage he had previously tolerated well; the clozapine-free periods had lasted 2 and 10 days respectively. Because of this 're-challenge' it seems very likely that there is a causal relation between the direct resumption of treatment with clozapine and delirium. Even if clozapine treatment is interrupted for only a short time it is important that the 'new' course begins with a low dosage and is increased very cautiously until it reaches the former, tolerated level.

Topics: Adult; Antipsychotic Agents; Clozapine; Delirium; Drug Tolerance; Humans; Male; Schizophrenia

Postictal delirium is an acute confusional state occurring during the immediate postictal phase in patients receiving electroconvulsive therapy that is characterized by motor agitation, disorientation, clouded consciousness, repetitive stereotyped movements, and poor response to commands. A schizophrenic patient with severe and recurrent postictal delirium is described. The possible role of the clozapine-electroconvulsive therapy combination in the occurrence of postictal delirium is discussed. Several management strategies were tried, with various degrees of success. Propofol proved to be effective in preventing agitation when used as induction agent or when administered at seizure end. However, propofol could not prevent a delirious state when only administered after the first signs of motor restlessness had emerged.

Topics: Adult; Anesthetics, Intravenous; Antipsychotic Agents; Clozapine; Combined Modality Therapy; Delirium; Electroconvulsive Therapy; Humans; Male; Propofol; Schizophrenia

Incidence and risk factors for delirium during clozapine treatment require further clarification.. We used computerized pharmacy records to identify all adult psychiatric inpatients treated with clozapine (1995-96), reviewed their medical records to score incidence and severity of delirium, and tested associations with potential risk factors.. Subjects (n = 139) were 72 women and 67 men, aged 40.8 +/- 12.1 years, hospitalized for 24.9 +/- 23.3 days, and given clozapine, gradually increased to an average daily dose of 282 +/- 203 mg (3.45 +/- 2.45 mg/kg) for 18.9 +/- 16.4 days. Delirium was diagnosed in 14 (10.1 % incidence, or 1.48 cases/person-years of exposure); 71.4 % of cases were moderate or severe. Associated factors were co-treatment with other centrally antimuscarinic agents, poor clinical outcome, older age, and longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical co-morbidity, and daily clozapine dose, which fell with age, were unrelated.. Delirium was found in 10 % of clozapine-treated inpatients, particularly in older patients exposed to other central anticholinergics. Delirium was inconsistently recognized clinically in milder cases and was associated with increased length-of-stay and higher costs, and inferior clinical outcome.

Topics: Adult; Antipsychotic Agents; Clozapine; Delirium; Female; Hospitals, Psychiatric; Humans; Male; Multivariate Analysis; Psychotic Disorders; Retrospective Studies

Between January 1999 and May 2000, the Netherlands Pharmacovigilance Foundation LAREB received five reports of patients with clozapine intoxication attributed to inflammation. The reports all concerned men with schizophrenia, aged 63, 54, 41, 45 en 42 years. The occurrence of increased clozapine levels during inflammation, and normalisation after recovery, strongly suggest a causal relationship. No other possible explanations were found. A three to five-fold increase occurred in most instances, but one patient experienced a ten-fold increase compared with the basal levels of clozapine. Three of the patients developed a delirium as an intoxication symptom, probably due to anticholinergic effects on the central nervous system. In case of an inflammatory reaction in patients on clozapine treatment, the physician should be aware of the possibility of clozapine intoxication and delirium. Measuring clozapine levels during infection and dosing based on these levels can minimise the adverse effects of clozapine intoxication.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Clozapine; Delirium; Humans; Infections; Male; Middle Aged; Netherlands; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Delirium; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Middle Aged; Neurologic Examination; Psychotic Disorders

Topics: Adult; Benzodiazepines; Clozapine; Delirium; Dizziness; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Humans; Hypotension; Male; Middle Aged; Schizophrenia; Schizophrenic Psychology; Unconsciousness

Topics: Antipsychotic Agents; Clozapine; Delirium; Haloperidol; Humans; Male; Middle Aged; Schizophrenia, Paranoid

Clozapine is an atypical antipsychotic agent that is effective in refractory schizophrenic patients. Older patients may have various psychotic manifestations that may not be responsive to typical neuroleptic therapy. There may also be patient-specific factors--declines in reserve capacity and homeostasis, and age-related changes in the pharmacokinetics and pharmacodynamics of drugs--in older patients that increase their susceptibility to the side effects of psychotropic medications. While clozapine has few extrapyramidal side effects, it has other side effects that may be problematic in the older population.. In our geropsychiatric unit, clozapine was prescribed for four patients over the age of 65 years. All patients were either experiencing psychotic symptoms refractory to other antipsychotic medications or had relative contraindications to a typical neuroleptic. Two of the four were chronic schizophrenics, and three of the four also presented with dementia.. Two of the four patients did eventually receive relief of psychotic symptoms from clozapine. All four experienced events after initiation of clozapine therapy, which included falls (2 patients), symptomatic bradycardia (2 patients), and delirium (1 patient). All these adverse effects occurred on doses ranging from 6.25 to 37.50 mg/day, and the three patients with moderate-to-severe dementia experienced these severe adverse effects after administration of the first dose.. Clozapine may be a useful drug for older patients with psychotic symptoms; however, at current dosage recommendations, adverse events may occur, especially on first dose. Well-designed studies need to be performed to assess the effectiveness and dosage ranges for this population.

Topics: Accidental Falls; Age Factors; Aged; Aged, 80 and over; Bradycardia; Clozapine; Delirium; Dementia; Female; Hospitalization; Humans; Male; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

Delirium has many organic causes, one of which is the combination of medications. This is sometimes difficult to differentiate in the psychotic individual. To our knowledge there are no published cases of delirium definitively established by "rechallenge" with a combination of clozapine and benzodiazepines. Lorazepam was given for agitation in two individuals on clozapine. Because of either the short half-life, or the lack of knowledge about this interaction, multiple doses were given. Clonazepam was given to a third individual. Two of the reported individuals developed a delirium associated with the administration and onset of lorazepam. These patients had received both lorazepam and clozapine singularly in the past without the adverse effects seen with the combination. Both patients were rechallenged with second doses of lorazepam, when they again developed a delirium. In one case the patient was admitted on clonazepam and then started on clozapine. A delirium developed at a clozapine dose of 150 mg/day; she was not rechallenged. In all three cases the patients' sensorium cleared when benzodiazepines were discontinued. The combination of benzodiazepines and clozapine should be avoided if possible, and if they are used in combination, it should be with great caution.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Delirium; Drug Interactions; Female; Humans; Male; Middle Aged

Topics: Adult; Clozapine; Delirium; Humans; Male; Neuroleptic Malignant Syndrome; Schizophrenia

Topics: Adult; Clozapine; Delirium; Dose-Response Relationship, Drug; Drug Tolerance; Humans; Male; Schizophrenia

Cerebrospinal fluid 5-hydroxyindoleacetic acid and total blood serotonin levels were measured simultaneously in 11 female patients with delirium tremens and nine schizophrenic women with clozapine-induced acute delirium. Both groups had significantly raised levels of 5HIAA in CSF and significantly reduced blood 5HT levels as compared with normal control subjects, symptom-free alcoholics, or clozapine-treated schizophrenics. The two delirious groups were not distinguishable from each other in respect of their CSF 5HIAA or blood 5HT values. After clinical recovery both values returned to normal levels.

Topics: Adult; Alcohol Withdrawal Delirium; Clozapine; Delirium; Dibenzazepines; Female; Humans; Hydroxyindoleacetic Acid; Psychoses, Alcoholic; Schizophrenia; Serotonin

Clozapine, a new antipsychotic drug without extrapyramidal side effects and with strong sedating potency, can produce acute symptoms of central anticholinergic toxicity. The authors report that physostigmine, a reversible anticholinesterase agent, which can pass the blood-brain barrier, was effective in reversing the clozapine-induced brain syndrome in two patients. Physostigmine also reduced one patient's tachycardia.

Topics: Adult; Bipolar Disorder; Clozapine; Delirium; Dibenzazepines; Female; Humans; Male; Physostigmine

Topics: Adult; Clozapine; Delirium; Dibenzazepines; Drug Antagonism; Female; Humans; Infusions, Parenteral; Physostigmine