Comparative efficacy and tolerability of 32 oral and long-acting injectable antipsychotics for the maintenance treatment of adults with schizophrenia: a systematic review and network meta-analysis
Johannes Schneider‐ThomaKonstantina ChalkouCarola DörriesIrene BighelliAnna CerasoMaximilian HuhnSpyridon SiafisJohn M. DavisAndrea CiprianiToshi A. FurukawaGeorgia SalantiStefan Leucht
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Onabotulinumtoxin A (onabotA) has shown efficacy in chronic migraine (CM), with good tolerability and a low rate of adverse effects, most of them not severe. The aim of this study is to evaluate tolerability and adverse effects of onabotA in clinical practice and to analyze if there is a relationship between tolerability to treatment administration, adverse effects' (AEs) occurrence and clinical response. We included patients with CM that received treatment with onabotA for the first time. Tolerability to treatment was evaluated by a 0-10 numeric rating scale (0: worst possible, 10: optimal tolerability). We assessed the presence of AEs by using a standardized questionnaire. Treatment response was based on the 50 and 75% responder rate between weeks 20 and 24, compared with the baseline, according to headache diaries. We analyzed whether the tolerability was associated with a higher frequency of AEs or a higher probability of clinical response. We included 105 patients, 87.7% female, with an age of 43.9 ± 10.7 years. Mean tolerability was 7.8/10 and 7.2/10 in the first and second onabotA administration, respectively. AEs were reported by (first-second) 71.4-68.6% patients. The percentage of patients with a 50% response was 56.3%. There was no association between tolerability and AEs' occurrence or clinical response.
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Objective: This study describes antipsychotic prescribing practices for outpatients with schizophrenia over a 3 year period in two large mental health catchment areas of Auckland. Methods: All community files were reviewed at three time points. Patient characteristics, diagnosis and antipsychotic treatment information were recorded and analysed. Results: Over the three time periods, the number of outpatients with a diagnosis of schizophrenia or schizoaffective disorder was stable. There was a marked change in the type of antipsychotic prescribed, with an 18.6% increase in atypical antipsychotics and a decrease in both intramuscular and oral typical antipsychotics. Clozapine was the most commonly prescribed antipsychotic in 2003 (35%). Despite the fact that polypharmacy was relatively low (14.6% in 2003), those receiving more than one antipsychotic had a greater likelihood of being prescribed a higher total daily dose. Conclusions: This study describes a change in antipsychotic prescribing towards recommended practice guidelines for the treatment of schizophrenia over a 3 year period.
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Assessment of factors influencing antipsychotic prescription fills in the early phase of schizophrenia or schizoaffective disorder.We used the Swedish Patient Register to identify patients younger than 45 years with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 (904 patients). Data on medication were obtained from the Prescribed Drug Register. Filling a prescription of an antipsychotic drug after discharge was used to estimate medication adherence. In Cox regression models, we studied sex, country of birth, metropolitan residence, educational level, age, duration of hospitalization, history of substance use disorder, and previous use of antipsychotic drugs as predictors for antipsychotic fills.Among all patients, 53.1% (95% confidence interval [CI] 49.9%-56.4%) had filled an antipsychotic prescription within 1 week from discharge. After 6 months, the proportion had increased to 80.2% (95% CI, 77.4%-82.8%) with no further increase thereafter. Prescription filling of an antipsychotic drug was primarily associated with antipsychotic use before the hospitalization (hazard ratio, 1.64; 95% CI, 1.33-2.03; for patients with access to antipsychotic drugs at admission compared with no previous use) and with longer hospitalization (hazard ratio, 1.60; 95% CI, 1.27-2.02 for 15-28 days compared with shorter hospitalization).Among patients who filled a prescription of an antipsychotic drug after discharge, the majority did so within 1 week. Previous adherent use of antipsychotic drugs and longer hospitalization may be predictors of primary adherence to antipsychotic drug treatment in schizophrenia or schizoaffective disorder.
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Summary: Purpose: To evaluate the tolerability and safety of gabapentin (GBP) as add‐on therapy for seizure control. Methods: Conducted in an outpatient setting and reflecting usual practice, this study compared tolerability of GBP dosages ≤1,800 versus >1,800 mg/day, when these doses were required to achieve the most effective seizure control. Two analyses of adverse events are presented: tolerability and safety. In the tolerability analysis, each patient served as his or her own control to compare the occurrence of adverse events at GBP ≤1,800 versus >1,800 mg/day. The safety analysis required patients to receive at least one dose of GBP and have a follow‐up contact. Results: A total of 2,216 patients enrolled in this open‐label, 16‐week study and were evaluable for safety. Of these, 74.0% completed the 16‐week study, and 281 met the tolerability criteria. Within these 281 patients, two mutually exclusive groups were compared (a) those reporting adverse events at only ≤1,800 mg/day (low dose); and (b) those reporting adverse events at only >1,800 mg/day (high dose). Three adverse events (asthenia, headache, and dizziness) were observed in a statistically significantly larger number of patients at only the low dose than in the group reporting these same adverse events at only the high dose, suggesting that patients who tolerated GBP at ≤1,800 mg/day did not experience a significant increase in adverse events with dosages >1,800 mg/day. Overall, 10.6% of the 2,216 patients in the safety population prematurely withdrew because of adverse events, and 3.5% discontinued because of lack of efficacy. Safety and tolerability of GBP was rated as excellent or good for 78.5% of all patients. Conclusions: Gabapentin doses >1,800 mg/day were as well tolerated as doses ≤1,800 mg/day and were not associated with more adverse events.
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Drug tolerability refers to the degree to which drugs' overt adverse effects can be tolerated by patients. The tolerability profile is of comparative importance to its efficacy and safety, as it largely determines adherence to treatment and ultimately treatment success or failure. However, the term is frequently used imprecisely, and it is unclear if tolerability is limited to subjective patient-reported symptoms or also covers certain objective signs and findings. The aim of this systematic review was to assess how clinical studies define, evaluate and present drug tolerability.The study consisted of a systematic review of clinical studies in PubMed® reporting the term "tolerability".Eighty clinical studies were screened and 56 studies reporting drug tolerability were retained. None of the retained studies defined events encompassed by the term tolerability by making a distinction between safety and tolerability. Twenty-five studies claimed to evaluate tolerability, but none of them described how to evaluate tolerability from the patient perspective. Most studies (54 out of 56) concluded that the treatment was well tolerated, apparently implying favourable safety. However, none of them actually presented tolerability in terms of a contrast between safety and tolerability.Tolerability is used frequently, albeit incorrectly, to refer to a drug's favourable safety profile. Focused evaluation of drug tolerability (i.e., the patient perspective of adverse drug reactions) should become routine. Presentation in regulatory documents, such as risk management plan summaries, product information and patient leaflets should be a continuation of the process of patient-centred healthcare.
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Objective: This study describes antipsychotic prescribing practices for outpatients with schizophrenia over a 3 year period in two large mental health catchment areas of Auckland. Methods: All community files were reviewed at three time points. Patient characteristics, diagnosis and antipsychotic treatment information were recorded and analysed. Results: Over the three time periods, the number of outpatients with a diagnosis of schizophrenia or schizoaffective disorder was stable. There was a marked change in the type of antipsychotic prescribed, with an 18.6% increase in atypical antipsychotics and a decrease in both intramuscular and oral typical antipsychotics. Clozapine was the most commonly prescribed antipsychotic in 2003 (35%). Despite the fact that polypharmacy was relatively low (14.6% in 2003), those receiving more than one antipsychotic had a greater likelihood of being prescribed a higher total daily dose. Conclusions: This study describes a change in antipsychotic prescribing towards recommended practice guidelines for the treatment of schizophrenia over a 3 year period.
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To review the evidence base for the efficacy and tolerability of antipsychotic medication for the treatment of the first episode of schizophrenia.MEDLINE databases were searched for published articles in English over the last 25 years, from January 1986 to January 2011, on choice of antipsychotic treatment for the first episode of schizophrenia, with an emphasis on efficacy and tolerability of antipsychotic drugs in the acute phase of psychotic illness.The keywords antipsychotic drugs and schizophrenia were used in combination with drug treatment, pharmacologic treatment, efficacy, and tolerability in addition to atypical antipsychotics, first-generation antipsychotics, second-generation antipsychotics, first-episode psychosis, and acute psychotic episode.At present, there is no convincing evidence to guide clinicians in choosing a single first-line antipsychotic that is effective in treating the positive and negative symptoms of the first episode of schizophrenia. Even though second-generation antipsychotic drugs offer potential benefits in terms of less extrapyramidal side effects and some benefits in treating negative, affective, and cognitive symptoms, these drugs are not without their own side effects.With the introduction of a number of second-generation antipsychotic drugs there have been significant advances in antipsychotic drug treatment over the last decade. Despite these advances, there are still a number of limitations in continued use of some antipsychotic medications due to their efficacy and tolerability issues in the acute and early maintenance phases of psychosis. Active research in this area would provide more promising results of improved efficacy and tolerability of antipsychotic medication.
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Antipsychotic polypharmacy (APP) is employed routinely, although it remains controversial because robust evidence supporting its efficacy is lacking. In addition, it is associated with increased costs, higher antipsychotic dosing, and greater risk of side effects. Surprisingly, no prospective, randomized, double-blind studies have addressed this issue; the present investigation set out to fill this gap in knowledge.A 12-week, double-blind, randomized, placebo-controlled, single-site study was carried out in individuals with schizophrenia or schizoaffective disorder (DSM-IV) receiving a designated primary antipsychotic plus a secondary antipsychotic, with doses stabilized for each. Individuals were randomly assigned to APP (N = 17), reflecting current treatment, or antipsychotic monotherapy (APM) (N = 18), in which the secondary antipsychotic was discontinued. Assessments occurred weekly during month 1 and every 2 weeks during months 2 and 3; the primary outcome measure was the Brief Psychiatric Rating Scale (BPRS) total score. Other measures included the Clinical Global Impressions (CGI) scale, Simpson-Angus Scale, and Barnes Akathisia Scale. The study was carried out between August 2006 and March 2011.Withdrawal due to clinical deterioration occurred in 1 individual receiving APP (5.8%) and in 4 individuals in the APM group (22.2%). Overall, however, there was no indication of clinical worsening with APM, as measured using BPRS and CGI scale.Almost 80% (n = 14) of individuals with schizophrenia or schizoaffective disorder currently receiving APP could be safely transitioned to APM with no clinical deterioration. For those who do deteriorate, risk appears greatest in the first several months. From another perspective, results also indicate that a minority of individuals benefit from APP, and research focusing on identifying this group may represent the best strategy to curb excessive use of APP.ClinicalTrials.gov identifier: NCT00493233.
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Abstract Background: Schizophrenia is a severe psychiatric condition with devastating consequences for the individual's functionality and leading to severe disability. Lack of insight and non-adherence to treatment remain the most important factors in the progression of the disease to chronicity.Despite their proven effectiveness in preventing relapses, reducing morbidity and mortality, long acting injectable antipsychotics (LAIs) are still underused. One of the causes invoked is the lack of guidelines or protocols for initiating LAIs. Objective: The aim of this article is to present Schizophrenia long-acting injectable antipsychotic initiation index (SLAII), a clinician-rated index that rates the important factors of the disorder across seven items: age, duration of illness, relapses, antipsychotic treatment response, family support, antipsychotic existing formulation and adherence. Method: A retrospective study in which all patients with schizophrenia discharged on oral antipsychotics without LAIs treatment lifetime were evaluated with SLAII for opportunity for LAIs initiation. Results: Of 225 consecutive patients, 144 patients (64%) had a strong indication for initiating LAI and 76 (34%) had moderate indication. 203 patients (90.2 %) had more than 2 relapses. The results of our research showed that 177 patients (78.7%) received at discharge an oral antipsychotic that also had a long-acting formula. Conclusion: This paper proposed an instrument designed to improve treatment in schizophrenia using a simple conceptual model which integrates important predictors of good or poor outcomes.
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