Safety Of Second-generation Antipsychotics Research Articles

Use of second-generation antipsychotics in autism spectrum disorder: a systematic review and meta-analysis protocol

IntroductionAtypical antipsychotics have been studied to treat autism spectrum disorder (ASD). However, like little is known about whether these drugs are effective and safe when compared in controlled and non-controlled...

Efficacy and Safety of Second-generation Antipsychotics in Schizophrenia Pharmacotherapy: A Comparative Narrative Review

Antipsychotic medications are essential in schizophrenia pharmacotherapy, with notable differences in efficacy and safety. This review aims to discuss and compare the differences in efficacy and safety among various second-generation antipsychotic drugs (SGAs). A narrative review was conducted involving the English-based published literature in three scientific databases between 2000 and January 2021: Google Scholar, Scopus, and PubMed. Clozapine is widely considered an effective therapy option in cases of resistance. Maintenance of schizophrenia treatment with paliperidone palmitate was effective and resulted in a longer duration between relapses. The risk of weight gain and diabetes mellitus was increased significantly with clozapine and olanzapine. Risperidone caused neuroleptic malignant syndrome (NMS) and significantly elevated prolactin levels. The extent of safety concerns reported varied by study design. While there were minor differences in the dose-dependent role of SGAs in acute episode treatment, there were significant differences in the type and intensity of side effects, and hence adherence determinants.

Efficacy and Safety Considerations With Second-Generation Antipsychotics as Adjunctive Analgesics: A Review of Literature.

Objective: To determine the efficacy and safety of second-generation antipsychotics (SGAs) as adjunctive analgesics. Data Sources: A comprehensive literature review was conducted between August 2020 and January 2021 on PubMed, Scopus, and ProQuest Central. Study Selection and Data Extraction: Keyword and Boolean phrase searches using the following terminology were conducted: "Quetiapine" OR "Risperidone" OR "Olanzapine" OR "Ziprasidone" AND "Analgesia" NOT "Psychosis" NOT "Psych." Articles that involved human adult patients who received any of the SGAs mentioned in the searching filter with an opioid were included. Articles that described pediatrics, pregnant women, patients who received any of these agents for treatment of psychosis and articles that were not in English, or readily translatable to English, were excluded. Data Synthesis: Three articles were selected for inclusion in this review, with 2 articles detailing reports with olanzapine and 1 article describing a randomized, controlled trial with extended-release quetiapine. Both olanzapine and quetiapine were able to decrease pain scores on the numeric rating scale, indicating a reduction pain experienced, and additionally reduced opioid craving behavior in patients. Depression scores and quality-of-life indicators improved with quetiapine, though those metrics were not studied with olanzapine. Conclusions: Select SGAs, specifically extended-release quetiapine and olanzapine, may serve as an appropriate adjunctive analgesic choice in select patients. Further research is required in a clinical setting to determine the exact role of this drug class in pain management.

Affective disorders: A question of continuing treatment during pregnancy (Review).

Fetal development, especially in the first trimester, has proven to be heavily influenced by external factors, such as chemical intake of medication. Chronic psychiatric treatment might interfere with the anatomical and physiological wellbeing of the fetus, because psychotropic medication proceeds past the placenta, into the amniotic fluid, and can enter breast milk. Hence some of the medications prescribed for mood disorders should be reconsidered during pregnancy, without sub-optimally treating when it is needed. A literature review is presented which systematically collects modern data and synthesizes previous interdisciplinary research findings on the safety of psychiatric treatment for affective disorders during pregnancy (term-based) and lactation. Antidepressants and mood stabilizers, fundamental strategies in treating affective disorders, have been classified by the FDA as C respectively D drugs pertaining to their risk, with some exception. Most guidelines recommend pharmacologically treating moderate-severe depression, preferably with SSRIs. Evidence advocates that drugs should be used during pregnancy only if clearly needed and the benefit outweighs the risk to the fetus. However, guidelines the American College of Obstetricians and Gynecologists state that antidepressants are a preferred first course of treatment and does not take into account the severity of the depression. Among mood-stabilizers, lithium is considered to be the safest option for pregnant women. Anticonvulsants have a higher risk of teratogenicity compared with lithium, with lamotrigine being the safest one. All mood stabilizers should be recommended in the lowest effective doses. There is controversy regarding the safety of second-generation antipsychotics during pregnancy and further research is required. Several case reports and meta-reviews have been published in order to emphasize the safety of electroconvulsive therapy (ECT) during pregnancy, but practitioners still stigmatize this procedure. Evaluating the overall risk-benefit ratio should be assessed by the medical care provider, taking into consideration current findings.

98 Monitoring the Safety of Second Generation Antipsychotics in Children and Adolescents with Autism Spectrum Disorder

Approximately 17.5% of youth with autism spectrum disorder (ASD) are treated with second-generation antipsychotics (SGAs). While SGAs have been found to reduce irritability and associated behaviours in youth with ASD, a range of side effects has been reported. Therefore, careful monitoring of youth taking these medications is imperative. However, as the core and associated symptoms of ASD can make medical procedures challenging, monitoring the safety of SGAs may be particularly difficult in this population. To date, there has been little investigation of how closely physicians monitor SGA side effects in youth with ASD or the barriers that they face in doing so. To begin to understand physicians’ current practices in SGA monitoring and the challenges of monitoring SGAs in youth with ASD. An online questionnaire that was completed by 31 specialist physicians serving children and adolescents with ASD in one region of Canada. Our survey examined physicians’ reports of ordering vs. completion of monitoring tasks recommended by the Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotic Medications in Children, as well as their perceptions of factors relevant to SGA safety monitoring in youth with ASD. Of the monitoring tasks queried, physicians were most likely to measure height, weight, and blood pressure at baseline and as part of ongoing follow-up. Waist circumference measurements and electrocardiograms (ECGs) were the monitoring tasks least often carried out at both time points. Fasting and non-fasting bloodwork were frequently not ordered at baseline, but were somewhat more likely to be ordered at follow-up. Neurological exams were attempted more often at baseline than at follow-up. As expected, physicians indicated that ECG and bloodwork were the procedures that youth with ASD have the most difficulty completing successfully. When asked their perspectives on factors that impede completion of these procedures, physicians identified youth distress, activity level, and refusal, as well as family anticipatory anxiety, previous failed attempts, and competing commitments, as the most significant barriers. Our results indicate inconsistent physician practices in ordering/completing SGA various monitoring tasks at baseline and follow-up. Further, our findings suggest that many youth with ASD struggle to complete successfully the medical procedures required for thorough SGA monitoring. Additional research aimed at supporting physicians in their monitoring of SGAs and youth with ASD and their families in successfully completing associated monitoring tasks is indicated.

The Safety of Second-Generation Antipsychotics During Pregnancy: A Clinically Focused Review.

The issue of antipsychotic treatment during pregnancy is subject to substantial uncertainty and some controversy among healthcare providers, specifically pertaining to second-generation antipsychotics (SGAs) that are subject to a large gap in safety data during pregnancy compared with antidepressants. The amount of safety data for the use of SGAs during pregnancy is rapidly increasing, thus constantly changing the level of evidence. We performed a clinically focused review on the safety of SGA during pregnancy. Twenty-three studies provided various pregnancy outcomes for 14,382 pregnant women exposed to an SGA during pregnancy. In utero exposure to aripiprazole, olanzapine, and quetiapine is not associated with increased risks of major congenital malformations, whereas risperidone and paliperidone may be associated with a very minor increased risk of congenital malformations. Safety data on ziprasidone and clozapine remain scarce and insufficient for a quantitative safety evaluation. No or minimal safety data are available for amisulpride, asenapine, lurasidone, and sertindole. For other pregnancy outcomes of interest, e.g. miscarriage, stillbirth, and small for gestational age, the available data overall do not suggest a clinically important increased risk, and do not allow for a meaningful stratification on individual drug level. Furthermore, for neonatal adaption and childhood neurodevelopment, the data do not allow for a meaningful risk assessment. It is imperative that factors in addition to safety data, e.g. individual disease history, characteristics and treatment response, adverse reaction profile, and patient preferences, be considered for the individual patient when choosing specific SGA treatment during pregnancy.

Change in 1-year hospitalization of overall and older patients with major depressive disorder after second-generation antipsychotics augmentation treatment

BackgroundStudies on second-generation antipsychotics (SGA) augmentation treatment for older adults with major depressive disorder (MDD) remain limited. We aimed to investigate the effectiveness of SGA augmentation for overall and older patients with MDD inpatient history by assessing the change in 1-year hospitalization before and after SGA augmentation using the latest National Health Insurance Research Database (NHIRD) in Taiwan. MethodsThe samples were MDD patients (ICD-9 CM code: 296.2 and 296.3) who had psychiatric inpatient history. A total of 2602 MDD patients including 430 elderly subjects (age ≥ 60 years) who received SGA augmentation for 8 weeks between January 1998 and December 2012 were included in this 1-year mirror-image study. Outcome measures included number and length of psychiatric and all-cause hospitalizations. ResultsAfter 8-week continuous SGA augmentation in the study subjects, the total number and days of psychiatric hospitalizations among overall patients reduced by 33.57% (p < .0001) and 18.24% (p < .0001), respectively; the total number and days of psychiatric hospitalizations among older patients (age ≥ 60) reduced by 44.52% (p < .0001) and 27.95% (p < .0001), respectively. Similarly, the total number and days of all-cause hospitalizations were significantly reduced. LimitationsMDD patients without inpatient history were not included due to data limitation; hence, the results may not be generalized to all patients. ConclusionsThe results support that SGA may be effective in reducing psychiatric and all-cause hospitalization among overall and elderly MDD patients. More studies focusing on the safety of SGA among older MDD patients is warranted.

12.5 Efficacy and Safety of Second-Generation Antipsychotics in Youth With Bipolar Depression

Depression associated with bipolar disorder in youth is associated with high rates of suicide attempts and significant functional impairment. Three prior studies have examined the efficacy of second-generation antipsychotic (SGA) drugs in youth with bipolar depression. However, findings from these studies have yielded mixed results. We will present findings from a recent study evaluating the efficacy and safety of lurasidone in youth with bipolar depression and will discuss these results in the context of previous studies of SGAs in youth with bipolar depression.

Update on the safety of second generation antipsychotics in youths: a call for collaboration among paediatricians and child psychiatrists.

During the past decade, a substantial increase in the use of second generation antipsychotics (SGAs) has occurred for a number of juvenile psychiatric disorders, often as off-label prescriptions. Although they were thought to be safer than older, first generation antipsychotics, mainly due to a lower risk of neurological adverse reactions, recent studies have raised significant concerns regarding their safety regarding metabolic, endocrinological and cardiovascular side effects. Aim of this paper is to update with a narrative review, the latest findings on safety of SGAs in youths. Results suggest that different SGAs may present different safety profiles. Metabolic adverse events are the most frequent and troublesome, with increasing evidences of heightened risk for type II diabetes mellitus. Results are discussed with specific emphasis on possible strategies of an active monitoring, which could enable both paediatricians and child psychiatrists to a possible prevention, early detection, and a timely management of such effects.

Seguridad de los antipsicóticos atípicos en el embarazo

IntroductionSince the introduction of second generation antipsychotics (SGAs), prescribing has increased considerably in women with a range of mental illnesses, and now increasingly used by women during pregnancy. However, information regarding the safety of SGAs during pregnancy is limited. ObjectivesTo clarify the impact of SGAs during pregnancy from the available literature, and to provide a clinical support tool. MethodologyAn exhaustive review of the available literature was conducted. Following the PRISMA criteria, literature published from May 1995 to October 2015 was identified from PubMed (Medline), SCOPUS, LILACS and MEDES databases. ResultsThe search yielded a total of 192 studies after duplicates were excluded, and 47 articles were included in the review in accordance with the inclusion criteria. ConclusionsWhile more research is needed, SGAs do not appear to cause marked congenital foetal harm. According to the available literature, in utero exposure to SGAs is associated with some neonatal and obstetric complications. While olanzapine, and clozapine in particular, is associated with increased risk of gestational diabetes and large for gestational age newborns, from this review of the literature it is clear that treating mental illness during pregnancy is vital and promotes better outcomes for both mother and infant. Currently olanzapine and quetiapine are the most frequently used SGAs during pregnancy, and despite some risks observed, overall safety is reported.

Evolution of general practitioners' preferences for antipsychotics in France, 2003-2010.

The study examined changes in French general practitioners' (GPs) antipsychotic preferences between 2003 and 2010, a period when evidence challenging the superiority and safety of second-generation antipsychotics was introduced. Data from the IMS Health Disease Analyzer database for a cohort of 347 GPs (with 12 or more antipsychotic prescriptions in 2003 and in 2010) were used. For each year and GP, preferred antipsychotic was defined as the drug most frequently prescribed at the patient level. Trends in mean number of prescriptions, preferred drug, and changes in preferred antipsychotic class were documented. The mean annual number of antipsychotic prescriptions increased over the period (p<.001). The percentage of GPs who preferred a second-generation antipsychotic tripled, from 16% in 2003 to 50% in 2010. In 2010, 42% of GPs who preferred first-generation antipsychotics in 2003 had switched their preference to second-generation antipsychotics. GPs' preferences for antipsychotics changed dramatically between 2003 and 2010.

Pregnancy outcomes following maternal exposure to second generation antipsychotics: considering polytherapy

Studies on the reproductive safety of second generation antipsychotics (SGAPs) are scarce, and none have compared monotherapy to polytherapy. A cohort study using a prospectively collected database was conducted. Pregnancy outcomes of 133 women exposed to SGAPs and other psychotropic drugs and 133 matched healthy controls were assessed. Psychotropic drug polytherapy was documented in 72% of exposed women. The exposed women had significantly higher pre‐pregnancy weight, smoked more cigarettes, experienced more associated comorbidities and instrumental deliveries and delivered more large for gestational age children. More of the exposed neonates were born premature, admitted to the intensive care unit and presented with poor neonatal adaptation signs and higher major malformations rates. In the monotherapy subgroup, no malformations were reported. In utero exposure to antipsychotic polytherapy is associated with adverse pregnancy outcomes for both mother and child. SGAP monotherapy appears to be associated with less risk to the fetus. Future studies should differentiate among the effects of psychotropic medication exposure and the underlying psychopathology and associated comorbidities.

Antipsychotic-Induced Dyslipidemia Treated with Omega 3 Fatty Acid Supplement in an 11-Year-Old Psychotic Child: A 1-Year Follow-up

Journal of Child and Adolescent PsychopharmacologyVol. 23, No. 2 Letters to the EditorAntipsychotic-Induced Dyslipidemia Treated with Omega 3 Fatty Acid Supplement in an 11-Year-Old Psychotic Child: A 1-Year Follow-upSimone Pisano, Antonella Gritti, Gennaro Catone, and Antonio PascottoSimone PisanoDepartments of Psychiatry, Child Neuropsychiatry, Audiophonology, and Dermatology, Second University of Naples, Naples, Italy.Search for more papers by this author, Antonella GrittiDepartment of Education Sciences, University Suor Orsola Benincasa, Naples, Italy.Search for more papers by this author, Gennaro CatoneDepartments of Psychiatry, Child Neuropsychiatry, Audiophonology, and Dermatology, Second University of Naples, Naples, Italy.Search for more papers by this author, and Antonio PascottoDepartments of Psychiatry, Child Neuropsychiatry, Audiophonology, and Dermatology, Second University of Naples, Naples, Italy.Search for more papers by this authorPublished Online:19 Mar 2013https://doi.org/10.1089/cap.2012.0060AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited ByPutative Mechanisms of Action and Clinical Use of Lithium in Children and Adolescents: A Critical ReviewCurrent Neuropharmacology, Vol. 17, No. 4Weight-Change Trajectories of Pediatric Outpatients Treated with Risperidone or Aripiprazole in a Naturalistic Setting Marco Pozzi, Simone Pisano, Giuseppe Marano, Carla Carnovale, Carmela Bravaccio, Concetta Rafaniello, Annalisa Capuano, Francesco Rossi, Renata Rizzo, Renato Bernardini, Maria Nobile, Massimo Molteni, Emilio Clementi, Elia Biganzoli, and Sonia Radice7 March 2019 | Journal of Child and Adolescent Psychopharmacology, Vol. 29, No. 2Differences in Metabolic Factors Between Antipsychotic-Induced Weight Gain and Non-pharmacological Obesity in Youths12 February 2018 | Clinical Drug Investigation, Vol. 38, No. 5Conduct disorders and psychopathy in children and adolescents: aetiology, clinical presentation and treatment strategies of callous-unemotional traits20 September 2017 | Italian Journal of Pediatrics, Vol. 43, No. 1Different Immune Signature in Youths Experiencing Antipsychotic-Induced Weight Gain Compared to Untreated Obese Patients Simone Pisano, Gennaro Catone, Giangennaro Coppola, Marco Carotenuto, Raffaella Iuliano, Claudia Tiano, Anna Rita Montesanto, Vittoria D'Esposito, Emanuele Miraglia del Giudice, Pietro Formisano, and Carmela Bravaccio1 November 2017 | Journal of Child and Adolescent Psychopharmacology, Vol. 27, No. 9Polyunsaturated fatty acids and recurrent mood disorders: Phenomenology, mechanisms, and clinical applicationProgress in Lipid ResearchUpdate on the safety of second generation antipsychotics in youths: a call for collaboration among paediatricians and child psychiatrists21 May 2016 | Italian Journal of Pediatrics, Vol. 42, No. 1Diffusion Imaging of White Matter in Schizophrenia: Progress and Future DirectionsBiological Psychiatry: Cognitive Neuroscience and Neuroimaging, Vol. 1, No. 3Omega-3 fatty acids in first-episode schizophrenia - a randomized controlled study of efficacy and relapse prevention (OFFER): rationale, design, and methods2 May 2015 | BMC Psychiatry, Vol. 15, No. 1Risperidone11 May 2013 | Reactions Weekly, Vol. 1451, No. 1 Volume 23Issue 2Mar 2013 InformationCopyright 2013, Mary Ann Liebert, Inc.To cite this article:Simone Pisano, Antonella Gritti, Gennaro Catone, and Antonio Pascotto.Antipsychotic-Induced Dyslipidemia Treated with Omega 3 Fatty Acid Supplement in an 11-Year-Old Psychotic Child: A 1-Year Follow-up.Journal of Child and Adolescent Psychopharmacology.Mar 2013.139-141.http://doi.org/10.1089/cap.2012.0060Published in Volume: 23 Issue 2: March 19, 2013Online Ahead of Print:March 12, 2013PDF download

Safety of second-generation antipsychotics in children – questionnaire evaluation in psychiatrists

Safety of second-generation antipsychotics in children – questionnaire evaluation in psychiatrists

Poster #208 NEW RESULTS ALTER BALANCE OF EVIDENCE IN META-ANALYSIS OF LONG-ACTING INJECTABLE VS. ORAL ANTIPSYCHOTICS IN SCHIZOPHRENIA

To review data on efficacy and safety of second-generation antipsychotics (SGAs) in children and adolescents with psychotic and bipolar spectrum disorders.Medline/PubMed/Google Scholar search for studies comparing efficacy and/or tolerability: (i) between two or more SGAs; (ii) between SGAs and placebo; and (iii) between at least one SGA and one first-generation antipsychotic (FGA). The review focused on three major side-effect clusters: 1. body weight, body mass index, and cardiometabolic parameters, 2. prolactin levels, and 3. neuromotor side effects.In total, 34 studies with 2719 children and adolescents were included. Studies lasted between 3 weeks and 12 months, with most studies (79.4%) lasting 3 months or less. Nine studies (n = 788) were conducted in patients with schizophrenia, 6 (n = 719) in subjects with bipolar disorder, and 19 (n = 1212) in a mixed population. Data on efficacy showed that, except for clozapine being superior for refractory schizophrenia, there were no significant differences between SGAs. By contrast, safety assessments showed relevant differences between SGAs. Mean weight gain ranged from 3.8 kg to 16.2 kg in patients treated with olanzapine (n = 353), from 0.9 kg to 9.5 kg in subjects receiving clozapine (n = 97), from 1.9 kg to 7.2 kg in those on risperidone (n = 571), from 2.3 kg to 6.1 kg among patients taking quetiapine (n = 133), and from 0 kg to 4.4 kg in those treated with aripiprazole (n = 451). Prolactin levels increased the most in subjects on risperidone (mean change ranging from 8.3 ng/mL to 49.6 ng/mL), followed by olanzapine (−1.5 ng/mL to + 13.7 ng/mL). Treatment with aripiprazole was associated with decreased prolactin levels, while clozapine and quetiapine were found to be mostly neutral. With respect to neuromotor side effects, SGAs were associated with less parkinsonism and akathisia than FGAs. Most of the studies comparing neuromotor side effects between SGAs found no significant differences.SGAs do not behave as a homogeneous group in children and adolescents with psychotic and mood disorders. Except for clozapine, the heterogeneity within the SGA group is mainly due to differences in the rates and severity of adverse events, especially regarding weight gain as a proxy for the risk of cardiometabolic disturbances.

Evidence-Based Recommendations for Monitoring Safety of Second Generation Antipsychotics in Children and Youth

Evidence-Based Recommendations for Monitoring Safety of Second Generation Antipsychotics in Children and Youth

Second generation antipsychotics in the treatment of bipolar depression: a systematic review and meta-analysis

Depressive symptoms and episodes dominate the course of bipolar disorder. However, the therapeutic armamentarium for bipolar depression is limited. Recent evidence points to the efficacy of second generation antipsychotics (SGAs) for the treatment of bipolar depression. We conducted a systematic review and meta-analysis of the efficacy and safety of SGAs (randomized, double-blind, placebo-controlled trials; used in monotherapy) in the treatment of adult patients with bipolar depression. Publication bias was corrected for by performing similar searches using the clinical trials register of the respective pharmaceutical companies, the Cochrane Database and ClinicalTrials.gov. Seven published papers were identified on the use of aripiprazole, olanzapine and quetiapine. Internal validity of the trials was fairly good, external validity only moderate. Different outcome measures of efficacy and safety were assessed. When the individual trials were looked at, quetiapine and to a lesser extent olanzapine demonstrated significant improvement in MADRS (Montgomery-Åsberg Depression Rating Scale) total scores. This was not demonstrated for aripiprazole. Efficacy was hampered by adverse events, such as weight gain, akathisia and somnolence/sedation. Both clinical heterogeneity of the included trials and statistical heterogeneity of the meta-analytic data were considerable. The number of quetiapine trials was disproportionate to the number of trials of aripiprazole and olanzapine. Further research is needed to assess differential efficacy of the different SGAs and their use in clinical practice.

Second-generation antipsychotics in major depressive disorder: update and clinical perspective.

The aim of this systematic review was to examine the efficacy and safety of second-generation antipsychotics (SGAs) in nonpsychotic major depressive disorder (MDD). In MDD, SGA monotherapy or adjunctive therapy to conventional antidepressants showed rapid onset of antidepressant efficacy. Although maintenance data are limited, quetiapine monotherapy, risperidone adjunctive therapy, and amisulpride adjunctive therapy significantly delayed the time to relapse as compared with placebo. In general, extrapyramidal symptoms appeared to be low with SGAs, but a higher incidence of akathisia was observed with aripiprazole. An elevated risk of weight gain was observed with olanzapine-fluoxetine combination, risperidone, aripiprazole, and quetiapine compared with placebo. At present, there are insufficient data to confidently distinguish between different SGAs in the treatment of MDD. A recent meta-analysis found that adjunctive SGAs were significantly more effective than placebo, but differences in efficacy were not identified among the studied agents, nor were outcomes affected by trial duration or the method of establishing treatment resistance. Both SGA monotherapy and adjunctive therapy showed greater efficacy in the treatment of MDD than placebo, but augmentation is more widely utilized in treatment-resistant depression. Clinicians should routinely monitor for cardiometabolic side-effects and extrapyramidal symptoms during SGA therapy.

Off-Label Use of Second-Generation Antipsychotic Agents Among Elderly Nursing Home Residents

This study examined off-label and evidence-based use of second-generation antipsychotic agents among elderly nursing home residents and factors associated with off-label use. This study involved a retrospective, cross-sectional analysis of data from the 2004 National Nursing Home Survey (NNHS). The sample included nursing home residents 65 years and older who received second-generation antipsychotic agents. This study used an indication-based definition of off-label use established by the U.S. Food and Drug Administration (FDA). Evidence-based use included FDA-approved indications and indications for which the Agency of Healthcare Research and Quality found at least moderate strength of evidence of effectiveness. Descriptive statistics were used to examine the prevalence of off-label and evidence-based use. Multiple logistic regression was used to examine the patient and facility factors associated with off-label use of second-generation antipsychotics. According to the 2004 NNHS, 308,990 (23.5%) elderly nursing home residents received at least one second-generation antipsychotic agent. Of those using second-generation antipsychotics, 86.3% received them for off-label indications and 56.9% received them for an evidence-based use. Multivariate analysis found that age (> or =75 years), self-pay for nursing home care, diagnosis of dementia, and residing in a nonprofit nursing home were positively associated with off-label use, whereas receiving Medicaid benefits was negatively associated with such use. Although second-generation antipsychotics were frequently used for off-label indications, most of the usage was evidence based among elderly nursing home residents. However, the high level of non-evidence-based use combined with recent safety and efficacy data suggests an urgent need to address the evidence base for this vulnerable population.

A systematic review of the efficacy and safety of second generation antipsychotics in the treatment of mania

Second generation antipsychotic agents are increasingly used in the management of acute mania. A systematic review of the efficacy and safety of these agents, as both monotherapy and in combination with mood stabilisers, was performed to establish the evidence for their use. Randomised controlled trials (RCTs) were critically appraised in more detail than studies that presented lower levels of evidence such as case reports, case series and open label follow up studies. We found 11 RCTs reporting on patients treated with second generation antipsychotics for acute bipolar mania, of which three included randomisation between the second generation antipsychotic and placebo, and eight between a mood stabiliser combined with either the second generation antipsychotic or placebo. Data from non-randomised trials is also presented.