clozapine and Dementia

This is a comprehensive review of antipsychotic (AP)-induced dysphagia and its complications: choking and pneumonia. Areas covered: Four PubMed searches were completed in 2018. The limited literature includes: 1) 45 case reports of AP-induced dysphagia with pharmacological mechanisms, 2) a systematic review of APs as a risk factor for dysphagia, 3) reviews suggesting adult patients with intellectual disability (ID) and dementia are prone to dysphagia (APs are a risk factor among multiple others), 4) studies of the increased risk of choking in patients with mental illness (APs are a contributing factor), 5) naturalistic pneumonia studies suggesting that pneumonia may contribute to AP-increased death in dementia, and 6) naturalistic studies suggesting that pneumonia may be a major cause of morbidity and mortality in clozapine patients. Expert commentary: The 2005 Food and Drug Administration requirement that package inserts warn of AP-induced dysphagia jumpstarted this area, but current studies are limited by: 1) its naturalistic nature, 2) the lack of dysphagia studies of patients with IDs and dementia on APs, and 3) the assumed indirect association between dysphagia with choking and pneumonia. Future clozapine studies on pneumonia, if they lead to a package insert warning, may have high potential to save lives.

Topics: Adult; Airway Obstruction; Antipsychotic Agents; Clozapine; Deglutition Disorders; Dementia; Drug Labeling; Humans; Intellectual Disability; Mental Disorders; Pneumonia; Risk Factors

Persistent violence not due to acute psychosis or mania can be managed only after appropriate characterization of the aggressive episodes (psychotic, impulsive, or predatory/planned/instrumental). The type of violence combined with the psychiatric diagnosis dictates the evidence-based pharmacologic approaches for psychotically motivated and impulsive aggression, whereas instrumental violence mandates forensic/behavioral strategies. For nonacute inpatients, schizophrenia spectrum disorders, traumatic brain injury, and dementia comprise the majority of individuals who are persistently aggressive, with impulsive actions the most common form of violence across all diagnoses. Neurobiological considerations combined with empirical data provide a comprehensive framework for systematic medication trials to manage persistently aggressive patients.

Topics: Aggression; Antimanic Agents; Antipsychotic Agents; Brain Injuries, Traumatic; Carbamazepine; Clozapine; Dementia; Humans; Impulsive Behavior; Neurobiology; Psychopharmacology; Psychotic Disorders; Schizophrenia; Violence

Hallucinations and psychosis are common in patients with Parkinson's disease (PD), with reported prevalences of up to 48% and 80%, respectively. However, few randomized, double-blind, placebo-controlled trials evaluating the treatment options have appeared in the literature. The studies that have been published were complicated by lack of agreement on the diagnosis of psychosis in PD, poor completion rates, mixed populations that included dementia, and other issues. Several reviews, guidelines, and consensus statements have sought to establish standards for treating these symptoms of PD. In 2006, the American Academy of Neurology (AAN) published a practice guideline (based on articles published up to 2004) for management of depression, psychosis, and dementia in patients with PD. Since then, a number of relevant studies have been published.. The purpose of this article was to review data that have appeared in the literature since publication of the AAN guideline regarding the management of hallucinations and psychosis in PD.. A literature search of the PubMed, CINAHL, and PsychInfo databases was conducted for human studies published in English from January 2004 to June 2010. All clinical studies were included except case reports and case series. Studies with <20 participants were also excluded. Search terms included psychosis, hallucinosis, hallucination, delusion, Parkinson, atypical antipsychotic, neuroleptic, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone.. Thirteen studies were included in the review: 3 studies of clozapine, 7 studies of quetiapine, 2 head-to-head trials comparing quetiapine and clozapine, and 1 noncomparative trial of clozapine or quetiapine interventions. Most of the studies included participants with a mean age in the early to mid 70s and a mean duration of PD typically >10 years.. Results of the identified studies suggested that patients with PD might benefit from long-term clozapine therapy. Results of the quetiapine studies were conflicting. However, no statistically significant difference in effectiveness was found between quetiapine and clozapine in comparative trials. The significance of the differences in treatment responses between patients with dementia and those without dementia remains unclear, and it was not possible to draw conclusions for or against other atypical antipsychotics because of insufficient evidence. Further studies are needed to address the methodologic issues in the current trials and to assess safety issues in larger cohorts.

Topics: Aged; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Comorbidity; Delusions; Dementia; Depression; Dibenzothiazepines; Disease Progression; Guidelines as Topic; Hallucinations; Humans; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report; Risperidone

Lewy body dementia and Parkinson disease dementia are frequent causes of degenerative dementia: 20% of the dementias in patients older than 65 years are caused by the former and nearly 80% of patients with advanced Parkinson disease develop the latter. Symptoms of Lewy body dementia include fluctuations of cognitive performance, frontal and visuospatial impairment, visual hallucinations, and parkinsonism. Parkinson disease dementia could be differentiated in two subtypes: a "subcortical" subtype, characterized by frontal impairment with apathy and dullness and a "cortical" subtype with symptoms similar to those of Lewy body dementia. Mastery of potential iatrogenic factors is important: psychotropic drugs must be prescribed at the strict minimum, and L-dopa monotherapy at the minimal dose acceptable for correcting Parkinsonian motor symptoms should be the rule. Acetylcholinesterase inhibitors may be useful in both these types of dementia: rivastigmine is approved for treating Parkinson disease dementia and clozapine for reducing hallucinations.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Cholinesterase Inhibitors; Clozapine; Dementia; Diagnosis, Differential; Disease Progression; Dopamine Agents; Humans; Iatrogenic Disease; Levodopa; Lewy Body Disease; Neuroprotective Agents; Nootropic Agents; Parkinson Disease; Parkinsonian Disorders; Phenylcarbamates; Psychotropic Drugs; Rivastigmine; Serotonin Antagonists

Behavioural symptoms such as anxiety, depression and psychosis are common in Parkinson's disease (PD), and dementia occurs in about 90% of the patients. These symptoms can be more disabling than the motor dysfunction and they negatively impact quality of life, increase caregiver distress and are more frequently associated with nursing home placement. Depression can be treated with counselling and pharmacotherapy. Tricyclic antidepressants or selective serotonin reuptake inhibitors are widely used, but there is still need for controlled clinical trials. Management of psychosis in PD is complex and includes elimination of identifiable risk factors, reduction of polypharmacy and administration of atypical neuroleptics, which can alleviate psychotic symptoms without worsening motor functions. Clozapine is the best documented atypical neuroleptic shown to be effective against psychosis in PD patients. Cholinesterase inhibitors may prove additional benefit in psychotic PD patients. Recent evidence from small double-blind and open-label trials suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD.

Topics: Antipsychotic Agents; Anxiety Disorders; Cholinesterase Inhibitors; Clozapine; Dementia; Depressive Disorder; Humans; Mental Disorders; Parkinson Disease; Psychotic Disorders

The treatment of patients suffering from idiopathic Parkinson's disease has become more and more complex. From its beginning the treatment has to be tailored to the needs of each patient. Not only the individual symptomatology and its course have to be taken into consideration, but also the short- and longtime reaction to treatment.

Topics: Adult; Aged; Antidepressive Agents; Antiparkinson Agents; Antipsychotic Agents; Benserazide; Cholinesterase Inhibitors; Clozapine; Dementia; Depression; Diagnosis, Differential; Dopamine Agents; Dopamine Agonists; Drug Combinations; Humans; Levodopa; Parkinson Disease; Quality of Life; Sleep Wake Disorders; Time Factors

Topics: Antipsychotic Agents; Butyrophenones; Clozapine; Dementia; Diagnostic and Statistical Manual of Mental Disorders; Diagnostic Imaging; Humans; Phenothiazines; Risperidone; Xanthines

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Humans; Olanzapine; Parkinson Disease; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome

With dopaminergic systems, non dopaminergic neurotransmission probably plays a major role in parkinsonian syndromes (Multiple System Atrophy, Progressive Supranuclear Palsy, Pure Autonomic Failure, Cortical basal degeneration, Lewy Body Disease). A better understanding of the pathophysiology of these syndromes led to the development of molecules that interact with non dopaminergic systems. Thus, freezing, gait and balance disorders, dysautonomia and neuropsychiatric disorders are likely to benefit from specific treatments. However, due to methodological difficulties related to the evaluation of such molecules, controlled trials are rather rare and the results are often partial and sometimes unclear.

Topics: Anti-Dyskinesia Agents; Botulinum Toxins; Cholinesterase Inhibitors; Clozapine; Dementia; Depressive Disorder; Dopamine; Glutamic Acid; Humans; Movement Disorders; Parkinsonian Disorders; Selective Serotonin Reuptake Inhibitors; Serotonin; Synaptic Transmission; Treatment Outcome

The use of antipsychotics is common in the elderly Typical antipsychotics are not without risk, especially in tardive dyskinesia, which, when balanced against relatively low efficacy, make their use debatable. Atypical antipsychotics have much less in the way of side-effects and are much less likely to induce tardive dyskinesia. However, there is much less in the published literature about the efficacy of these drugs in the elderly and how best to use them in primary psychosis, Parkinson's disease and the behavioural and psychological symptoms of dementia. This review attempts to summarise the current literature and make some tentative recommendations for each of the commonest atypicals, based on the current evidence.

Topics: Aged; Aged, 80 and over; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition; Dementia; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; United Kingdom

The atypical antipsychotics have a low incidence of extrapyramidal side effects (EPS), have improved tardive dyskinesia profiles, and have a broad range of therapeutic efficacy. These agents offer important therapeutic advantages that extend beyond their initial regulatory approval in several conditions and patient groups. The use of atypical antipsychotics is most relevant in the treatment of mood disorders, where these medications are being used increasingly for acute mood stabilization and in patients who are resistant to other treatments. Similar circumstances and clinical advantages pertain to the use of atypical antipsychotics in the treatment of behavioral disturbances in patients with dementia and in the management of personality disorders-both circumstances where conventional antipsychotics were initially poorly tolerated because of EPS. The low incidence of EPS associated with atypical antipsychotics is highly beneficial in several neuropsychiatric conditions. The extent to which endocrine and metabolic dysregulations associated with atypical antipsychotics will influence antipsychotics' role remains to be determined. As therapeutic opportunities evolve and diversify, atypical antipsychotics, because of favorable adverse-effect profiles, will have enhanced patient tolerability and use in nonpsychiatric conditions.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Child; Child Development Disorders, Pervasive; Clozapine; Dementia; Dibenzothiazepines; Humans; Mood Disorders; Olanzapine; Personality Disorders; Pirenzepine; Quetiapine Fumarate; Risperidone

Elderly patients with schizophrenia and dementia patients with agitation are frequently candidates for antipsychotic treatment. Conventional neuroleptics have relatively little effect on negative symptoms and may cause considerable side effects, especially in elderly patients. The authors have found a 29% cumulative annual incidence of tardive dyskinesia (TD) in middle-aged and elderly outpatients treated with relatively low doses of conventional neuroleptics Newer antipsychotics are less likely to cause extrapyramidal symptoms and may be associated with a lower risk of TD. They are generally effective for both positive and negative symptoms and may also improve some aspects of cognition, but these drugs have their own side effects. Dosing requirements for elderly patients tend to be much lower than those for younger adults.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Significant consequences of untreated psychosis in patients with dementia have led clinicians to seek improved therapeutic options. This review presents the scope of the problem, discusses some of the underlying neurobiology, and highlights the evidence for appropriate therapies. A range of potentially effective pharmacologic therapies is available and is discussed.

Topics: Aged; Antipsychotic Agents; Clozapine; Comorbidity; Delusions; Dementia; Hallucinations; Humans; Psychotic Disorders; Risperidone; Treatment Outcome

Atypical antipsychotics have become the treatment of choice for patients experiencing a first episode of schizophrenia. In addition, they are often prescribed for conditions such as bipolar disorder and dementia. While clinical trials have not yet established the efficacy of the atypical antipsychotics for these uses, a number of reports offer preliminary evidence that the atypical antipsychotics may be beneficial for affective disorders, substance abuse disorder, senile dementia, and pathologic aggression. Atypical agents may be particularly effective and tolerable in elderly patients who are especially susceptible to the adverse effects of conventional antipsychotic medication. Lower dosages are more necessary for the elderly than for younger adults. Current evidence suggests that clozapine is the most effective atypical antipsychotic for neuroleptic-resistant patients. Risperidone, olanzapine, and quetiapine may also be effective in a subset of these patients.

Topics: Adult; Age Factors; Aged; Algorithms; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Decision Trees; Dementia; Dibenzothiazepines; Female; Humans; Male; Mood Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia

Sundowning refers to episodes of agitated behaviour that are more frequent or are more severe at night. Although the effects of different psychoactive medications on agitated behaviour in dementia patients have been documented in hundreds of reports over the last 30 years, less than 20 studies make explicit reference to time of day for which outcome measures were derived, and even fewer have also examined sleep as an outcome. Thus, despite varying claims of efficacy and effectiveness for various medications, there are few data to support informed management of disruptive nocturnal behaviour in these patients. In this brief article, we selectively review those few studies explicitly mentioning temporal dimensions of behavioural outcome, including some newer studies of unconventional types of treatment that may be useful for the treatment of sundowning. We conclude that future pharmacological studies should systematically assess behaviour throughout the 24-hour day to provide outcome data relevant to this phenomenon.

Topics: Antipsychotic Agents; Chlormethiazole; Clozapine; Dementia; Humans; Melatonin; Phototherapy; Psychomotor Agitation

As the world's population ages, increasing numbers of patients with dementia can be expected, the signs and symptoms of which can be extremely disruptive. In particular, behavioral and psychological signs and symptoms of dementia reduce the quality of life of carers (usually family members) and increase the cost of care. Conventional neuroleptics have been used for many years in the management of disturbed and disruptive demented patients, although there are few well-controlled clinical trials demonstrating their efficacy. The use of the low-potency neuroleptics is associated with orthostatic hypotension, cardiac toxicity, anticholinergic side effects and daytime sedation. The high-potency neuroleptics tend to cause extrapyramidal side effects and akathisia. Clozapine although less likely to cause extrapyramidal symptoms than conventional neuroleptics, can cause orthostatic hypotension and requires continual blood monitoring. Early-phase open trials suggest that risperidone is efficacious in patients with behavioral and psychological signs and symptoms of dementia and that it has a low side-effects profile. Further trials are needed to confirm this, but it is likely that the newer antipsychotics, as typified by risperidone, will lead to safer and more effective management of patients with the disruptive and costly behavioral and psychological signs and symptoms of dementia. Non-pharmacologic interventions may also provide benefit, though controls are rare.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dementia; Humans; Olanzapine; Pirenzepine; Risperidone

The atypical antipsychotic clozapine has been reported to be effective in otherwise refractory psychoses. This, and its low potential for inducing extrapyramidal side effects and tardive dyskinesia, predestines this drug for the treatment of psychotic disorders in late life. However, not much is known about the efficacy, safety and pharmacokinetics of clozapine in the treatment of aged patients. There are some studies and reports available about clozapine in the treatment of psychosis in patients suffering from dementia, schizophrenia and Parkinson's disease, which are reported here. They give some evidence that even low doses of clozapine are effective in controlling psychotic symptoms in the elderly. To avoid side effects, patient-specific factors and changes of pharmacokinetics in the elderly have to be considered. However, side effects including sedation, delirium, posturnal hypotension and the risk of agranulocytosis in particular limits the use of clozapine in elderly patients.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Dementia; Female; Humans; Male; Neurocognitive Disorders; Schizophrenia; Treatment Outcome

Symptoms of generalized anxiety disorder are commonly observed in elderly persons and especially in those suffering from dementia. In the demented elderly, these symptoms are often defined as agitation. Approximately 60% of demented persons will present with symptoms of agitation at some point during the course of their illness. The presence of agitation has devastating consequences for the patient and the caregiver. This paper reviews some of the existing literature with regard to the etiology and treatment of agitation in the demented elderly. Agitated behaviors are generally divided in three categories (verbal agitation physically nonaggressive agitation, and aggressive agitation). It is suggested that each category may have a different etiology and treatment; verbal agitation is often related to underlying medical conditions, physically nonaggressive behavior responds to behavioral treatment, and aggressive agitation is more likely to respond to a combination of behavioral and pharmacologic treatment.

Topics: Aged; Aggression; Antipsychotic Agents; Anxiety Disorders; Behavior Therapy; Buspirone; Carbamazepine; Clozapine; Combined Modality Therapy; Decision Trees; Dementia; Humans; Ondansetron; Psychomotor Agitation; Serotonin; Trazodone

Psychotic symptoms such as visual hallucinations and delusions are a relatively common clinical problem in patients with Parkinson's disease (PD). A dilemma arises in the treatment of psychosis in these patients because traditional antipsychotics are dopaminergic antagonists that worsen the motor symptoms of PD. Clozapine, an atypical antipsychotic, has been successfully used in the treatment of psychosis in PD patients. The use of clozapine in these patients differs significantly, however, from its use in young, relatively healthy, treatment-resistant schizophrenic patients in the dosage required, side effects, and other aspects of management.

Topics: Antipsychotic Agents; Clozapine; Dementia; Humans; Parkinson Disease

Agitation or psychosis or both occur in half or more of patients with dementia at some point during the course of illness. The treatment of these signs and symptoms ideally entails identification and alteration of physical, environmental, social, and psychiatric factors. Environmental modification, education of caregivers, and therapeutic activity programs are nonpharmacologic approaches that can effectively reduce some signs and symptoms of this nature. For those that remain, empirical administration of pharmacologic agents may be appropriate. One approach is to inventory the specific behaviors and develop a "therapeutic metaphor," i.e., subtype the agitated behaviors according to the presence of target symptoms likely to respond to specific classes of medication. Available evidence is reviewed regarding the efficacy and safety of somatic therapies for agitation, including antipsychotics, antidepressants, anticonvulsants, benzodiazepines, and cholinesterase inhibitors.

Topics: Aged; Anti-Anxiety Agents; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Clozapine; Dementia; Humans; Psychomotor Agitation; Psychotic Disorders; Risperidone; Selective Serotonin Reuptake Inhibitors; Trazodone

To examine the long-term outcome of PD patients with psychosis requiring antipsychotic therapy; to explore predictors of mortality, nursing home placement, dementia, and persistent psychosis; and to compare outcomes of those with persistent psychosis vs those whose psychosis resolved.. Baseline data available from 59 patients enrolled in the PSYCLOPS (PSychosis and CLOzapine in PD Study) trial included age, age at onset of PD, duration of PD and psychosis, character of psychosis, medications, living setting, and scores for Mini-Mental State Examination (MMSE), Unified Parkinson's Disease Rating Scale, Hoehn and Yahr Scale, and Clinical Global Impression Scale. Longitudinal data were collected 26 months later regarding four outcomes: death, nursing home placement, diagnosis of dementia, and persistence of psychosis. Logistic regression was used to explore whether any baseline characteristics were associated with an increased likelihood of one of these outcomes.. At baseline, 56% of patients had an MMSE score of <25, 12% were in a nursing home, 95% had hallucinations, and 60% had paranoia. On follow-up, 25% were dead, nursing home placement occurred in 42%, psychosis was persistent in 69%, and dementia was diagnosed in 68%. Select baseline characteristics predicted individual outcomes: Nursing home placement was associated with the presence of paranoia and older age; persistent psychosis was associated with younger age at onset of PD and longer disease duration; dementia was associated with older age at PD onset and lower initial MMSE score; no characteristics predicted death. Whether psychosis persisted or not had no significant effect on the development of the other three outcomes. The prevalence of hallucinations at follow-up was not different between groups currently receiving antipsychotics vs those on no treatment.. Psychosis in PD requiring antipsychotic therapy is frequently associated with death, nursing home placement, development and progression of dementia, and persistence of psychosis. Still, it appears the prognosis has improved with atypical antipsychotic therapy based on the finding that 28% of NH patients died within 2 years compared with 100% in a previous study done prior to availability of this treatment.

Topics: Aged; Antipsychotic Agents; Clozapine; Dementia; Double-Blind Method; Female; Hallucinations; Humans; Longitudinal Studies; Male; Nursing Homes; Parkinson Disease; Psychotic Disorders; Treatment Outcome

Two hundred and sixteen psychiatric patients (183 men and 33 women) hospitalized in Sct. Hans Hospital were treated with clozapine between 1971-1983. All had been treated previously with one or more neuroleptic(s) and had either failed to respond adequately, or their response was limited by side effects. Eighty-five patients were treated exclusively with clozapine, while the remaining 131 received additional medication, mainly other neuroleptic drugs. The mean clozapine dosage was 317 mg/day (range 50-1200), and the mean duration of treatment was 23/4 years (range 1/12-12). The tolerability to clozapine was determined by an evaluation of haematological changes, pronounced side effects and mortality. One patient treated with clozapine (8 months) and nitrofurantoin (8 days) developed a reversible granulocytopenia. One patient (treated with a combination of drugs) had clinically insignificant depression of the leucocytes and three of segmented granulocytes. Seven had a reduction in thrombocytes. Two patients developed cardiac insufficiency, and four epileptic seizures. None of the patients treated exclusively with clozapine developed neurological side effects. A global estimation of therapeutic effect revealed that clozapine alone or in combination with other neuroleptic drugs was significantly better than previous antipsychotic therapy, although 47-63% of the patients showed no change. It is concluded that clozapine is a potent antipsychotic drug offering particular advantages in the treatment of schizophrenic patients with a pronounced symptomatology and tendency towards developing extrapyramidal side effects. Caution is advised in patients with cardiac insufficiency and epilepsy. There appears to be a slight risk of granulocytopenia, and therefore the present monitoring of WBC should continue in order to prevent this reaction and to obtain more complete information regarding risk of granulocytopenia.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Clozapine; Dementia; Denmark; Dibenzazepines; Drug Therapy, Combination; Drug Tolerance; Female; Humans; Leukocyte Count; Male; Middle Aged; Paranoid Disorders; Psychoses, Alcoholic; Psychoses, Substance-Induced; Psychotic Disorders; Retrospective Studies; Schizophrenia

Dementia with Lewy bodies (DLB) is characterized by neurocognitive disorders associated with core clinical features including hallucinations. There is currently no cure but a combination of symptomatic treatments: clozapine is commonly used in DLB-related psychosis. Pimavanserin is a serotonin 5HT-2A receptor inverse agonist that has recently been shown to reduce psychosis related to dementia. Trazodone is a serotonin reuptake inhibitor and a 5-HT2 receptor antagonist: it is effective in the treatment of the frontal syndrome and is commonly used in frontotemporal degeneration.. We describe three patients with DLB, hospitalized in the cognitive-behavioral unit of the University Hospitals of Strasbourg, who presented with major visual hallucinations, delusion, and an orbitofrontal syndrome including disinhibition, agitation, and irritability. The 3 patients were intolerant of low-dose Clozapine (neutropenia for one, somnolence for the other and Pisa syndrome and falls for the last one). We evaluated the Neuropsychiatric Inventory (NPI) before and after the introduction of both treatments.. Given their psychotic and frontal symptoms, we used Pimavanserin and Trazodone simultaneously. After 4 to 6 weeks of treatment, a marked improvement was observed in all 3 patients, with a decrease of the NPI scores from a mean of 88 to 38.. To our knowledge, there is no previously described combination of these two treatments in DLB. A clinical trial combining these two molecules against pervasive behavioral disorders in DLB would be interesting in view of these preliminary results.

Topics: Clozapine; Dementia; Drug Inverse Agonism; Hallucinations; Humans; Lewy Body Disease; Trazodone

Distressing behavioural symptoms, particularly agitation and aggressiveness, remain a difficult problem in everyday clinical practice in the treatment of multimorbid patients with dementia. Clozapine may be an effective therapeutic alternative in this context.. In a retrospective study, patients who had a diagnosis of dementia and had been treated in a specialized geriatric psychiatry unit with clozapine between August 2018 and February 2022 were included, and medical records were systematically reviewed. The Clinical Global Impressions Scale was used to assess improvement, and the Pittsburgh Agitation Scale for symptom reduction. In addition, side effects and clinical features were documented in detail.. A total of 31 patients (median age 82 years) were identified with a mean clozapine dose of 47.2 (SD 35.6) mg. A total of 13 patients tolerated clozapine very well, 10 showed tolerable side effects, and in 10 patients side effects were the reason for stopping clozapine. Behavioural symptoms improved significantly, as indicated by the assessment scores.. In summary, clozapine was effective and well tolerated in 23 patients, suggesting that low-dose clozapine may help to alleviate the suffering of difficult-to-treat multimorbid patients with advanced dementia and their caregivers. However, particular attention should be paid to adverse drug reactions, especially in patients with cardiovascular and pulmonary impairment.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Dementia; Humans; Retrospective Studies

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

Behavioural and psychological symptoms of dementia (BPSD) are common and contribute significantly to caregiver burden and institutionalization of the patient. Unfortunately, current guideline-based interventions are sometimes ineffective and BPSD can become extreme.. A 75-year-old man with dementia was admitted to a psychogeriatric unit because of very severe BPSD in a nursing home. Different kinds of pharmaceutical and psychological interventions had been tried but turned out to be ineffective. Therefore, we started with low dose clozapine which improved his behavior. We reduced the dose twice, whereupon the behavior deteriorated. By reintroducing the proper dose, his behavior became better again.. Our case is in accordance with the available literature on Clozapine for BPSD: Six uncontrolled studies have shown a positive effect of clozapine for BPSD, even if other interventions failed. We conclude that clozapine may be tried in cases of serious refractory BPSD when guideline-based interventions are ineffective.

Topics: Aged; Antipsychotic Agents; Clozapine; Dementia; Hospitalization; Humans; Male; Mental Disorders; Nursing Homes

We describe a novel class of designed multiple ligands (DMLs) combining serotonin 5-HT6 receptor (5-HT6R) antagonism with dopamine D2 receptor (D2R) partial agonism. Prototype hybrid molecules were designed using docking to receptor homology models. Diverse pharmacophore moieties yielded 3 series of hybrids with varying in vitro properties at 5-HT6R and D2R, and at M1 receptor and hERG channel antitargets. 4-(piperazin-1-yl)-1H-indole derivatives showed highest antagonist potency at 5-HT6R, with 7-butoxy-3,4-dihydroquinolin-2(1H)-one and 2-propoxybenzamide derivatives having promising D2R partial agonism. 2-(3-(4-(1-(phenylsulfonyl)-1H-indol-4-yl)piperazin-1-yl)propoxy)benzamide (47) exhibited nanomolar affinity at both 5-HT6R and D2R and was evaluated in rat models. It displayed potent antidepressant-like and anxiolytic-like activity in the Porsolt and Vogel tests, respectively, more pronounced than that of a reference selective 5-HT6R antagonist or D2R partial agonist. In addition, 47 also showed antidepressant-like activity (Porsolt's test) and anxiolytic-like activity (open field test) in aged (>18-month old) rats. In operant conditioning tests, 47 enhanced responding for sweet reward in the saccharin self-administration test, consistent with anti-anhedonic properties. Further, 47 facilitated extinction of non-reinforced responding for sweet reward, suggesting potential procognitive activity. Taken together, these studies suggest that DMLs combining 5-HT6R antagonism and D2R partial agonism may successfully target affective disorders in patients from different age groups without a risk of cognitive deficits.

Topics: Animals; Benzamides; Dementia; Dose-Response Relationship, Drug; Drug Partial Agonism; Humans; Indoles; Ligands; Male; Models, Molecular; Molecular Structure; Piperazines; Quinolones; Rats; Rats, Wistar; Receptors, Dopamine D2; Receptors, Serotonin; Structure-Activity Relationship; Swimming

In order to target behavioral and psychological symptoms of dementia (BPSD), we used molecular modeling-assisted design to obtain novel multifunctional arylsulfonamide derivatives that potently antagonize 5-HT(6/7/2A) and D2 receptors, without interacting with M1 receptors and hERG channels. In vitro studies confirmed their antagonism of 5-HT(7/2A) and D2 receptors and weak interactions with key antitargets (M1R and hERG) associated with side effects. Marked 5-HT6 receptor affinities were also observed, notably for 6-fluoro-3-(piperidin-4-yl)-1,2-benzoxazole derivatives connected by a 3-4 unit alkyl linker with mono- or bicyclic, lipophilic arylsulfonamide moieties. N-[4-[4-(6-Fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]butyl]benzothiophene-2-sulfonamide (72) was characterized in vitro on 14 targets and antitargets. It displayed dual blockade of 5-HT6 and D2 receptors and negligible interactions at hERG and M1 receptors. Unlike reference antipsychotics, 72 displayed marked antipsychotic and antidepressant activity in rats after oral administration, in the absence of cognitive or motor impairment. This profile is particularly attractive when targeting a fragile, elderly BPSD patient population.

Topics: Animals; Antidepressive Agents; Antipsychotic Agents; Avoidance Learning; Benzoxazoles; Catalepsy; CHO Cells; Cricetulus; Dementia; Dopamine D2 Receptor Antagonists; HEK293 Cells; Humans; Male; Models, Molecular; Motor Activity; Radioligand Assay; Rats, Wistar; Receptors, Serotonin; Serotonin Antagonists; Structure-Activity Relationship; Sulfonamides

The aim of this study was to review the use of clozapine in a Sydney area old age psychiatry service. Data were extracted from case files of all people who were treated in a health area's old age psychiatry units with clozapine during a 15-year period. Additional details were obtained from clinicians who provided ongoing care after discharge from the hospital. Note was made of psychiatric diagnoses, length of time taking clozapine, dosage, side effects and outcome. Sixteen patients aged over 65 years commenced or continued taking clozapine while inpatients of the service. Of the 13 patients who had a history of schizophrenia or schizoaffective disorder, four patients (all female) developed neutropenia and therefore clozapine was stopped. In one case, neutropenia was first diagnosed 6 years after commencing the medication. Two women died; the nine other women, and one of the deceased, stopped taking clozapine, usually because of side effects. The mean daily dose at cessation was 236 mg. All five men were still taking clozapine (mean 260 mg daily) when followed at a mean age of 72 years, having taken it for an average of 10 years. This case review adds to evidence of the risk of neutropenia when older people are prescribed clozapine.

Topics: Age of Onset; Aged; Clozapine; Dementia; Drug Utilization; Female; Humans; Inpatients; Male; Mental Disorders; Middle Aged; Neutropenia; New South Wales; Psychiatry; Psychotic Disorders; Retrospective Studies; Schizophrenia; Treatment Outcome

Delusional jealousy or Othello syndrome (OS) is a well-described psychiatric disorder with paranoid features reported in both organic and functional psychoses. In organic psychoses, the disorder occurs more frequently among chronic male alcoholics and in demented patients. To date, only 2 anecdotal cases of OS have been reported in Parkinson disease (PD) during dopaminergic treatment.. To investigate the presence of OS in PD patients and to study the relationship between dopaminergic treatment, avoiding the possible influence of dementia.. Five hundred sixty-three PD patients without dementia encountered in our movement disorders practice were included in the study. All patients who developed OS were studied. Relationships between clinical and familial history and dopaminergic therapy and OS were assessed.. Six patients with OS were identified. They were all male, with a relatively recent diagnosis of PD characterized by mild-moderate motor deficit. Dopaminergic treatment had been prescribed at low dosages. Neither confusional states (including agitated confusion) nor delirium were associated with OS. The disorder became manifest mainly at time of introduction/increment of antiparkinson treatment. Invariably, OS decreased or receded after reduction/suspension of the antiparkinson drug and prescription of an atypical neuroleptic, usually clozapine or quetiapine.. We hypothesize that nondemented PD patients affected by OS do not necessarily present with severe motor complications and may well have a biologic predisposition for psychiatric disorders. In our opinion this paranoid delusion is rarely considered in PD.

Topics: Adult; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Delusions; Dementia; Dibenzothiazepines; Humans; Jealousy; Male; Middle Aged; Parkinson Disease; Quetiapine Fumarate; Retrospective Studies; Schizophrenia, Paranoid

Topics: Antipsychotic Agents; Benzodiazepines; Chronic Disease; Clozapine; Cognition Disorders; Dementia; Drug Resistance; Humans; Korsakoff Syndrome; Male; Middle Aged; Neuropsychological Tests; Psychomotor Agitation; Schizophrenia

Few studies have examined the potential role of clozapine in treatment of agitation in dementia patients who have previously failed to respond to standard pharmacotherapy. We conducted a systematic chart review of all elderly patients admitted to our inpatient unit between 2001 and 2004. Of them, 16 dementia patients were treated with clozapine for treatment-resistant agitation, and their charts were blindly rated by 3 clinicians on the Clinical Global Impression (CGI) Scale, Brief Agitation Rating Scale (BARS), and the Cohen-Mansfield Agitation Inventory-Short Form (CMAI-SF). Overall, clozapine therapy seemed beneficial in treatment-resistant agitation in dementia patients.

Topics: Aged; Antipsychotic Agents; Clozapine; Dementia; Drug Resistance; Female; Geriatric Assessment; Humans; Male; Observer Variation; Psychiatric Status Rating Scales; Psychomotor Agitation; Severity of Illness Index; Treatment Outcome

Topics: Administration, Oral; Aged; Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Benzodiazepines; Clozapine; Databases, Factual; Dementia; Dibenzothiazepines; Drug Utilization Review; Health Services for the Aged; Humans; Olanzapine; Pharmaceutical Services; Piperazines; Quetiapine Fumarate; Quinolones; Risk Assessment; Risperidone; Stroke; Thiazoles; Treatment Outcome

Topics: Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dementia; Dibenzothiazepines; Drug Approval; Drug Labeling; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; United States; United States Food and Drug Administration

Concern exists about a possible increased risk of cerebrovascular events (CVEs) among elderly patients receiving risperidone or olanzapine. We estimated the effect of atypical and conventional antipsychotics on the risk of CVEs among elderly nursing home patients with dementia.. We conducted a case-control study on residents of nursing homes in 6 U.S. states by using the Systematic Assessment of Geriatric drug use via Epidemiology database, which includes data from the Minimum Data Set linked to Medicare inpatient claims. Participants were diagnosed with Alzheimer's disease or other forms of dementia on the basis of clinical criteria and medical history (including medical records and neuroradiologic documentation). Cases included patients hospitalized for stroke or transient ischemic attack between June 30, 1998, and December 27, 1999. For each case, we identified up to 5 controls hospitalized for septicemia or urinary tract infection residing in the same facility during the same time period. The sample consisted of 1130 cases and 3658 controls.. After controlling for potential confounders, the odds ratio of being hospitalized for CVEs was 0.87 (95% CI = 0.67 to 1.12) for risperidone users, 1.32 (95% CI = 0.83 to 2.11) for olanzapine users, 1.57 (95% CI = 0.65 to 3.82) for users of other atypical agents, and 1.24 (95% CI = 0.95 to 1.63) for conventional antipsychotic users compared to nonusers of antipsychotics. A history of CVEs appeared to modify the effect of atypical antipsychotics other than risperidone on the risk of new events.. Overall, no increased risk of CVEs seems to be conferred by atypical or conventional antipsychotics. Preexisting cerebrovascular risk factors might interact with some atypical antipsychotics to increase the risk of events. These results should be interpreted in light of the limitations of the study and need to be confirmed.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Cerebrovascular Disorders; Clozapine; Comorbidity; Dementia; Female; Geriatric Assessment; Hospitalization; Humans; Ischemic Attack, Transient; Male; Medical Records Systems, Computerized; Nursing Homes; Odds Ratio; Olanzapine; Risk Factors; Stroke; United States

Clozapine is the gold standard treatment for Parkinson's disease (PD) psychosis based on double blinded, placebo controlled trials, and has also been shown to alleviate tremor and dyskinesia. There is accumulating data suggesting that clozapine may be associated with increased frequency of diabetes mellitus (DM) compared to conventional neuroleptic drugs in treating schizophrenia. Forty-four predominantly geriatric parkinsonian subjects on clozapine for psychosis, tremor or dyskinesia, on an average dose of 50.6 mg/d for a mean duration of 41 months were reviewed. The prevalence of DM in this cohort was 18.1% (8/44). This rate was similar to that reported in the aged-matched general population (prevalence = 19.3% for ages > or = 60 years). In this small study, parkinsonian patients on long-term, low dose clozapine were not at increased risk for developing DM. Larger controlled prospective studies are needed to confirm this.

Topics: Adult; Aged; Antipsychotic Agents; Clozapine; Cohort Studies; Dementia; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Parkinson Disease

Increasingly, atypical antipsychotic drugs are prescribed for elderly patients with symptoms of psychosis and behavioral disturbances. These symptoms often occur in patients with Alzheimer's disease, other dementias, or Parkinson's disease. As the average age of Americans increases, the prevalence of Alzheimer's disease and Parkinson's disease will rise accordingly. Although nonpharmacologic treatments for behavioral disturbances should be tried first, medications often are needed to enable the patient to be adequately cared for. Current guidelines recommend using risperidone and olanzapine to treat psychosis in patients with Alzheimer's dementia. Quetiapine and clozapine are recommended for treatment of psychosis in patients with Parkinson's disease. Additional research is needed for a recently approved agent, ziprasidone. To minimize side effects, these medications should be started at low dosages that are increased incrementally. Drug interactions, especially those involving the cytochrome P450 system, must be considered. Clozapine's potentially lethal side effects limit its use in the primary care setting. Informed use of atypical antipsychotic drugs allows family physicians to greatly improve quality of life in elderly patients with dementia and behavior disturbances.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Comorbidity; Dementia; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone

Topics: Aged; Antipsychotic Agents; Clozapine; Dementia; Dyskinesia, Drug-Induced; Humans; Nursing Homes

Side effects of antipsychotic medications are particularly problematic in elderly patients, who experience many age-related changes that may exacerbate medication side effects. Side effects of particular concern in the elderly include anticholinergic reactions, parkinsonian events, tardive dyskinesia, orthostatic hypotension, cardiac conduction disturbances, reduced bone mineral density, sedation, and cognitive slowing. In addition, elderly patients with schizophrenia often have comorbid medical illnesses-such as cardiovascular disease and dementia of the Alzheimer's type-and are thus likely to be taking multiple medications. The effects of polypharmacy must be carefully considered. Patients, caregivers, and family often have different perspectives on side effects. This article addresses the side effects of the currently available antipsychotic medications in light of these concerns.

Topics: Age Factors; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Clozapine; Comorbidity; Dementia; Dibenzothiazepines; Humans; Movement Disorders; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

The neuroleptic malignant syndrome (NMS) is a side-effect of treatment with neuroleptic drugs. It is infrequent, but underdiagnosed. The diagnosis can be especially difficult to verify, in older patients with dementia because they often have symptoms of NMS, as a consequence of age and dementia. The importance of monitoring serum-creatine-kinase is discussed and proposals for treatment are suggested.

Topics: Aged; Antipsychotic Agents; Clozapine; Creatine Kinase; Dementia; Diagnosis, Differential; Humans; Male; Neuroleptic Malignant Syndrome

In spite of some inherent limitations, naturalistic data can provide information on populations that have greater heterogeneity than can controlled clinical trials and on functional outcomes that may be especially important in clinical practice. In the present retrospective naturalistic study, we evaluated key clinical outcomes among the first wave of risperidone-treated patients at a state psychiatric hospital.. Outcome data were extracted from the charts of 142 patients 2 years after initiation of treatment with risperidone. Their diagnoses included DSM-III-R schizophrenia (57%), schizoaffective disorder (22%), dementia and other organic conditions (7%), bipolar disorder (5%), and other psychiatric disorders (9%).. During the 2-year period, 92 of 142 patients were discharged from the hospital: 61 (43%) were discharged on risperidone treatment and 31 (22%) were discharged on treatment with other drugs. At the time of the study, 50 of 142 patients were still in the hospital: of these, 18 (13%) were still receiving risperidone. The modal maximum daily dose of risperidone was 4.1 mg in patients discharged on risperidone treatment and 7.5 mg in patients still in the hospital. All groups were granted more ward privileges after starting risperidone, the most being granted to patients discharged from the hospital on risperidone treatment (p<.05 versus patients discharged on treatment with other drugs) and those still receiving risperidone in the hospital. Significantly fewer patients discharged on risperidone treatment than on treatment with other drugs were readmitted to the hospital within 2 years after discharge (p<.01).. Improved privilege levels and a reduced readmission rate indicate that risperidone was an effective antipsychotic agent among a heterogeneous patient population in a state hospital. These factors may be especially important to justify use of this agent in the current fiscal climate.

Topics: Adult; Antiparkinson Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dementia; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Hospitalization; Hospitals, Psychiatric; Hospitals, State; Humans; Length of Stay; Male; Mental Disorders; Patient Readmission; Psychotic Disorders; Retrospective Studies; Risperidone; Schizophrenia

Topics: Aged; Antipsychotic Agents; Clozapine; Dementia; Hallucinations; Humans; Male; Parkinson Disease; Seizures

Dementia with Lewy bodies (DLB) may be one of the most common causes of dementia. It should be of particular interest to psychiatrists because hallucinations are common presenting symptoms and because patients with DLB may be particularly sensitive to neuroleptics with respect to developing extrapyramidal symptoms. The authors describe 2 patients with DLB who were intolerant of clozapine, showing not extrapyramidal side effects, but an increase in confusion and behavioral symptoms.

Topics: Aged; Antipsychotic Agents; Clozapine; Confusion; Dementia; Humans; Lewy Bodies; Male; Psychoses, Substance-Induced

Topics: Age Factors; Aged; Clozapine; Dementia; Drug Administration Schedule; Humans; Psychotic Disorders

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

Topics: Aged; Aged, 80 and over; Clozapine; Dementia; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma; Humans; Leukocyte Count; Methazolamide; Neutropenia; Parkinson Disease

Topics: Aged; Antiparkinson Agents; Carbidopa; Clozapine; Dementia; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Levodopa; Male; Middle Aged; Neurologic Examination; Parkinson Disease; Psychoses, Substance-Induced

The short- and long-term treatment tolerance of low-dose clozapine was retrospectively investigated in 18 psychogeriatric patients. Discontinued use of the drug because of side effects or inefficiency was required for only four patients. In the long-term treatment group leukopenia was not observed, and disturbances of liver function appeared to be very infrequent. A second group of seven severely demented psychogeriatric inpatients who were currently being treated with low-dose clozapine underwent a withdrawal study in order to evaluate the therapeutic efficacy of the drug, measured by the NOSIE and the SCAG scales. The results indicate that for patients such as these, with paranoid or socially disturbing behavior who also tend to develop severe neurological side effects with classical neuroleptics, a low-dose administration of clozapine is an acceptable alternative treatment.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Clozapine; Dementia; Dementia, Multi-Infarct; Dose-Response Relationship, Drug; Female; Geriatric Assessment; Hospitalization; Humans; Hydrocephalus, Normal Pressure; Long-Term Care; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Psychotic Disorders; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Social Behavior; Substance Withdrawal Syndrome