Tolerability Of Atypical Antipsychotics Research Articles

Efficacy and Tolerability of Atypical Antipsychotics in the Treatment of Delirium: A Systematic Review of the Literature

Although haloperidol is the most widely used drug in the treatment of delirium, evidence on the relevance of atypical antipsychotics (AAPs) is growing. To review the literature on the efficacy and tolerability of AAPs in the treatment of delirium. A systematic search of the literature published before April 2018 was performed on PubMed using the following search strings: "Delirium" and "Atypical antipsychotics", "Novel antipsychotics", "New antipsychotics", "Quetiapine", "Olanzapine", "Aripiprazole", "Risperidone", "Paliperidone", "Clozapine", "Asenapine", "Iloperidone", "Amisulpiride", "Ziprasidone", "Zotepine", "Sertindole", "Lurasidone" or "Perospirone". Twelve randomized controlled trials (RCTs) and 22 open trials were considered. Despite an overall lack of large-scale RCTs, there is some evidence supporting the efficacy of olanzapine and quetiapine in placebo controlled trials. In a recent and large RCT in elderly patients, risperidone and/or haloperidol were associated with a significantly worse outcome than placebo. While preliminary, the current comparative studies suggest that haloperidol and the AAPs olanzapine, quetiapine and risperidone are similarly effective, although treatment with AAPs is associated with a reduced incidence of extrapyramidal symptoms. Ziprasidone was not shown to be effective. No RCTs are available for other AAPs. Although the current evidence of the efficacy and tolerability of AAPs in the treatment of delirium is limited and the heterogeneity of the data precluded a meta-analysis, olanzapine and quetiapine seem to be adequate alternatives to haloperidol, especially in patients who are vulnerable for extrapyramidal symptoms, who require sedation or who have a history of haloperidol intolerance. Evidently, larger-scale RCTs are urgently required.

C.07.01 - Efficacy and tolerability of atypical antipsychotics: research trials and clinical reality

C.07.01 - Efficacy and tolerability of atypical antipsychotics: research trials and clinical reality

Blonanserin Augmentation of Atypical Antipsychotics in Patients with Schizophrenia-Who Benefits from Blonanserin Augmentation?: An Open-Label, Prospective, Multicenter Study.

ObjectiveThe purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients.MethodsaA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to their existing AAP regimen, which was maintained during the study period. Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 2, 4, 8, and 12. Predictors for PANSS response (≥20% reduction) were investigated.ResultsThe PANSS total score was significantly decreased at 12 weeks of blonanserin augmentation (-21.0±18.1, F=105.849, p<0.001). Moreover, 51.0% of participants experienced a response at week 12. Premature discontinuation of blonanserin occurred in 17 patients (17.0%); 4 of these patients dropped out due to adverse events. The patients who benefited the most from blonanserin were those with severe symptoms despite a treatment with a higher dose of AAP.ConclusionBlonanserin augmentation could be an effective strategy for patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP.

Role of atypical antipsychotics in the treatment of generalized anxiety disorder.

Evidence-based treatment approaches for generalized anxiety disorder (GAD) comprise psychotherapy, pharmacotherapy, or a combination of the two. First-line pharmacotherapy agents include selective serotonin reuptake inhibitors, selective serotonin-norepinephrine reuptake inhibitors, and, in certain European guidelines, pregabalin, which gained European Commission approval. Although short- and long-term efficacy have been established for these agents in controlled trials, response rates of 60-70 % are insufficient, remission rates are relatively modest, and relapse rates considerable. Moreover, questions increasingly arise regarding tolerability and side-effect profiles. As an alternative, antipsychotics have long been of interest for the treatment of anxiety disorders, but investigation had been tempered by their potential for irreversible side effects. With the improved side-effect profiles of atypical antipsychotics, these agents are increasingly being investigated across Axis I disorders. Atypical antipsychotics such as quetiapine, aripiprazole, olanzapine, and risperidone have been shown to be helpful in addressing a range of anxiety and depressive symptoms in individuals with schizophrenia and schizoaffective disorders, and have since been used in the treatment of a range of mood and anxiety disorders. In this article, we review the efficacy and tolerability of atypical antipsychotics as adjunctive therapy and/or monotherapy for individuals with GAD, a currently off-label indication. The most evidence has accumulated for quetiapine. Findings suggest that approximately 50 % of participants tolerate the side effects, most commonly sedation and fatigue. Among this subset, those who continue treatment demonstrate significant reductions in anxiety when used as adjunctive therapy or monotherapy. The appropriateness of the use of antipsychotics in the treatment of GAD is discussed.

Deeskalationstechniken und atypische Neuroleptika in der Behandlung der akuten Manie

Agitation is a severe clinical state which represents a therapeutic challenge and often forms part of manic or mixed episodes. Therapeutic options for acute mania have been limited for many years to lithium and typical antipsychotics. Besides anticonvulsants, atypical antipsychotics have been increasingly introduced in the last decade after proving their efficacy in this indication. To avoid intramuscular administration and excessive sedation, a therapeutic contact to the often agitated patient is required. De-escalation techniques can be helpful in this respect but also reduce aggressive behaviour on the ward, improve compliance, reduce relapse rates and lead to a better outcome in the long-term course of the illness. Therefore, a basic knowledge about de-escalation techniques in acute manic patients is an important clinical tool which will be critically reviewed. Furthermore, the efficacy and tolerability of atypical antipsychotics in acute mania, such as olanzapine, zotepine, risperidone, quetiapine, ziprasidone, aripiprazole, paliperidone and asenapine are discussed.

Ziprasidone in Black Patients with Schizophrenia: Analysis of Four Short-term, Double-blind Studies

To better understand the efficacy and tolerability of atypical antipsychotics among racial groups, we reviewed data from four short-term (4-6 weeks), fixed-dose, placebo-controlled trials of ziprasidone for black, white, and overall populations of patients with schizophrenia. Efficacy of ziprasidone in the black, white, and overall schizophrenic populations was compared to placebo using standard efficacy measures (Positive and Negative Syndrome Scale [PANSS] total, PANSS negative, Brief Psychiatric Rating Scale [BPRS], Clinical Global Impression-Severity [CGI-S], CGI-Improvement [CGI-I]). Black patients receiving ziprasidone demonstrated statistically significant improvements from baseline in PANSS total, PANSS negative, and BPRS, and improvements in CGI-S and CGI-I (n=99-149) compared with placebo (n=41-66); improvements were comparable to those observed in the overall population (n=451-639) and the white population (n=310-430). Interaction effect (treatment by race) was not significant for any efficacy variables. Ziprasidone was well-tolerated among black patients (n=175). Adjusted mean (least squares mean) overall weight gain in black patients receiving ziprasidone (n=124) was 1.8 kg. There were no increases in total cholesterol, triglycerides, or random glucose in the black population. Ziprasidone has similar efficacy and safety in black patients with schizophrenia compared with patients in the white and overall populations.

Atypical antipsychotics in the elderly: a review of therapeutic trends and clinical outcomes

Recent emerging data regarding the safety and tolerability of atypical antipsychotics in elderly patients with dementia have called into question common prescribing practices. Although the lifetime risk of developing significant psychopathology in dementia patients approaches nearly 100%, treatment options remain scant and controversial. Millions of people are suffering the consequences of these debilitating dementias. Yet the lack of regulatory approval or even recognition of the problem creates a dilemma for clinicians in practice who are trying to care for severely ill patients. There are data indicating that certain behavioral features can be treated successfully with atypical antipsychotics, offset by a high rate of adversity. This does not lead to the simple conclusion that they should never be used, since the alternatives are either fraught with the same shortcomings or actually lack evidence of benefit altogether. Further, it is not realistic to assume that nonpharmacological approaches, although preferred, will always carry the day. Since we do not have the evidence to define best practice for treating psychopathology, we are forced to make the most of the data we have and exercise best judgment about risk and benefit on a case-by-case basis.

Management of acutely ill patients in the hospital setting: focus on quetiapine

We have considered published work and clinical experience focusing on the atypical antipsychotic quetiapine in order to form a consensus on the most appropriate treatment strategies for hospitalised patients with acute schizophrenia or bipolar disorder. It is important to consider the specific treatment needs of these patients and these are discussed in the context of current treatment guidelines. We will review the efficacy and tolerability of atypical antipsychotics versus conventional antipsychotics and/or benzodiazepines as a first-line treatment, and examine the suitability of oral versus intramuscular formulations in the acute setting. The potentially beneficial properties of specific atypical agents are also considered. Appropriate dosing is particularly important in acutely ill patients as it can help achieve rapid improvement. We will discuss emerging data which show that rapid initiation of quetiapine in patients with acute psychosis or mania is not only as effective as standard initiation, but is also well tolerated. This may be important for treatment in the long term as a positive initial treatment experience can determine patient compliance and treatment adherence. In conclusion, this review recommends that oral atypical antipsychotics should be a first-choice medication for acutely ill cooperative patients in the hospital setting.

Symptom domains of schizophrenia: the role of atypical antipsychotic agents

Given their more obvious presentation, the reduction of positive symptoms and their associated behavioural problems have been considered the most important treatment outcome parameter in patients with schizophrenia. However, the development of the atypical antipsychotic agents in the early 1990s resulted in the adoption of more wide-reaching measures of therapeutic outcome. The aim of this review was to evaluate the efficacy of currently available atypical agents across multiple symptom domains of schizophrenia with a specific focus on negative symptoms, neurocognition, social functioning, quality of life and insight. As such, studies published between January 1990 and December 2005 that evaluated the clinical efficacy and tolerability of atypical antipsychotics in different symptom domains of schizophrenia were reviewed as identified from literature researches using MEDLINE and Embase. Abstracts and posters presented at key psychiatry and schizophrenia congresses during this period were also reviewed where available in the public domain. Results from the studies identified have consistently demonstrated that atypical antipsychotics have substantial advantages over conventional antipsychotics with a broader spectrum of efficacy across symptomatic domains of schizophrenia as proven by greater improvements in negative symptoms and cognitive function and a beneficial effect on affective symptoms and quality of life. However, their clinical advantages have often been limited by patients' partial compliance with therapy. As such, the development of a long-acting atypical antipsychotic agent may provide a new and valuable treatment option for patients with schizophrenia.

Adjunctive risperidone, olanzapine and quetiapine for the treatment of hospitalized patients with bipolar I disorder: A retrospective study

This study evaluated the overall effectiveness and tolerability of atypical antipsychotics (risperidone vs. olanzapine vs. quetiapine) used in the treatment of bipolar inpatients. After screening 463 patients, the medical records of 158 inpatients with bipolar I disorder, who were given olanzapine, risperidone or quetiapine as adjuncts to mood stabilizers for at least 1 month and not administered with any other antipsychotics, were examined. Details of the tolerability and effectiveness were reviewed according to the treatment records during their hospital stay. The results showed equivalent effectiveness based on the Clinical Global Impression (CGI) and Global Assessment Functioning (GAF) score between the three atypical antipsychotics. The frequency of the extrapyramidal symptom-related side effects were higher in the risperidone-treated group than in the olanzapine and quetiapine-treated group. This suggests that risperidone, olanzapine and quetiapine have a comparable effectiveness in inpatients with bipolar I disorder in a naturalistic setting. However, there were some differences in tolerability between these results as reported from previous Western studies.

Amisulpride versus quetiapine for the treatment of delirium: a randomized, open prospective study

The present study aimed to: (i) provide preliminary data on the effectiveness and tolerability of atypical antipsychotics, amisulpride (AMSP) and quetiapine (QTP) for patients with delirium and (ii) investigate whether the two drugs affect sleep differently and further relation with the recovery time of delirium. Forty patients with delirium were randomly assigned to either AMSP or QTP groups, with a flexible dosing schedule. The Delirium Rating Scale-revised-98 (DRS-R-98) and clinical global impression-severity (CGI-S), total sleep time and quality of sleep were assessed daily. Sixteen subjects in the AMSP group and 15 subjects in the QTP group completed the study. The mean daily dose was 156.4 mg/day and 113 mg/day in the AMSP and QTP groups, respectively. There was no significant difference in the baseline DRS-R-98 and CGI scores. After treatment, DRS-R-98 scores were significantly decreased from the baseline in both treatment groups (P<0.001) without group difference. The mean duration of stabilization were 6.3+/-4.4 days for the AMSP group and 7.4+/-4.1 days for the QTP group without group differences. There was no group difference in the mean quality of sleep score and the mean total sleep time. The duration of stabilization was inversely correlated with the mean sleep quality score and the mean total sleep time (P<0.001). Both atypical antipsychotics were generally well tolerated. The present study shows that both amisulpride and quetiapine may be useful drugs for the treatment of delirium on the basis of effectiveness and relative lack of adverse events. Further systematic controlled studies are required.

The safety and tolerability of atypical antipsychotics in bipolar disorder

Atypical antipsychotics (aAPs), have become a first-line treatment option, both in schizophrenia and bipolar disorders. Almost all aAPs now have proven efficacy in acute mania, some also in bipolar depression and in maintenance treatment. This provides reliable data on their safety and tolerability in this particular group of patients. This review focuses on the safety and tolerability of aAPs in the treatment of bipolar disorders. Both tolerability, for example, extrapyramidal symptoms, and safety issues, for example, occurrence of weight gain and hyperglycaemia, will be highlighted for olanzapine, quetiapine, risperidone, ziprasidone and aripiprazole.

Safety and tolerability of atypical antipsychotics in patients with bipolar disorder: prevalence, monitoring and management.

Atypical antipsychotics are associated with fewer movement disorders and a lower risk of tardive dyskinesia than conventional antipsychotics, but are not without side-effects. Metabolic side-effects associated with some of the atypical antipsychotics are a concern for both clinicians and patients. Adverse events related to central nervous system effects, weight gain, and alterations in glucose, lipid, and prolactin levels in patients with depression, bipolar, and anxiety disorders have been reported. Balancing the significant benefits of treatment with these agents against the potential risks of metabolic disturbances and other adverse effects is crucial. Emerging data are making it possible to determine the risk-benefit analysis for specific atypical antipsychotics in individual patients and allow for targeted selection of treatment. A new concept of effectiveness is emerging that attempts to balance adverse effects of treatment with patient quality of life. Patients treated with atypical antipsychotics should have their weight, waist circumference, glucose, and lipids monitored on a regular basis. Monitoring of prolactin levels is not suggested; however, a baseline measurement before initiating treatment can be useful, with subsequent assessment only if a patient demonstrates symptoms. Prevention of weight gain is important. Diet and exercise should be considered for prevention and management, with the use of pharmacologic strategies approached with caution in patients with mood disorders. If a patient is at high risk of developing diabetes, certain pharmacologic agents have been shown to delay the onset of overt diabetes. Once diabetes or dyslipidemia are diagnosed, management should proceed in accordance with approved guidelines for these conditions.

Tolerability of atypical antipsychotics.

Atypical antipsychotics are expected to be better tolerated than older antipsychotics because of their lower propensity to cause certain adverse effects. All atypical drugs have been shown to cause fewer acute extrapyramidal symptoms (EPS) than a standard typical agent (usually haloperidol) and some (clozapine, sertindole and quetiapine) appear to cause these effects no more often than placebo. In the longer term, clozapine, olanzapine and (less robustly) other atypical antipsychotics are thought to cause less tardive dyskinesia than typical antipsychotics. Problems caused by hyperprolactinaemia occur less often with some atypical antipsychotics than with typical drugs although risperidone and amisulpride appear to have no advantages in this respect. Other adverse effects may occur as frequently with some atypical antipsychotics as with some typical drugs. Clozapine, risperidone and quetiapine are known to cause postural hypotension; clozapine, olanzapine and quetiapine are clearly sedative; and anticholinergic effects are commonly seen with clozapine, and, much less frequently, with olanzapine. Some adverse effects are more frequent with atypical drugs. Idiosyncratic effects seem particularly troublesome with clozapine and, to a lesser extent, sertindole, olanzapine and zotepine. Bodyweight gain is probably more problematic with atypical antipsychotics than with typical drugs. Overall tolerability, as judged by withdrawals from therapy, is not clearly proven to be better with atypical drugs, although some individual trials do indicate an advantage with atypical agents. Differences in tolerability between individual atypical antipsychotics have not been clearly shown. The tolerability profile of atypical drugs certainly benefits from a lower incidence of acute EPS effects, along with less certain or less uniform benefits in symptomatic hyperprolactinaemia or tardive dyskinesia. Other, perhaps more trivial, adverse effects militate against their good tolerability, and effects such as bodyweight gain may severely reduce tolerability. Without clear advantages in tolerability in patient groups used in trials, drug choice in regard to adverse effects should continue to be on a patient to patient basis.