Safety Of Atypical Antipsychotics Research Articles

Safety of Atypical Antipsychotics in a Child and Adolescent Inpatient Setting: A Naturalistic Study.

This study's objective was to investigate the adverse effects of atypical antipsychotics (AAPs) on the metabolic, hematological, and endocrinological systems in the inpatient environment for children and adolescents with diverse psychiatric disorders. A retrospective assessment of 208 children's and adolescents' medical records was conducted. All patients were on AAP monotherapy. At baseline and after treatment, measurements of body weight, height, body mass index (BMI), BMI z-score, fasting blood glucose (FBG), total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, complete blood count, liver functions, thyroid functions, and prolactin levels were made. Scores from the Children's Global Assessment Scale (CGAS) and the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) were preserved. The overall patient population had a mean age of 14.50 ± 2.32 years, 139 girls, and 69 boys. Of the patients, 63 (30.29%) were on risperidone (RIS), 69(33.17%) were on aripiprazole (ARI), 32 (15.39%) were on quetiapine (QUE), 42 (20.19%) were on olanzapine (OLA), and 2 (0.96%) were on clozapine (CLO). In the OLA group, the BMI and BMI z-score increased more than in the RIS, QUE, and ARI groups (P = .030, P = .014, and P = .001, respectively) (P = .001). The mean difference in CGAS and HoNOSCA between the start of antipsychotic medication and hospital discharge was statistically different for all four groups (P = .001 for all). The mean FBG levels in the OLA group increased statistically significantly (P = .013, P = .021) in contrast to the RIS group. In addition, a statistically significant difference in triglycerides across the groups was found (P = .003). According to the findings of our study, children and adolescents appear to be at a significant risk for psychotropic-induced PRL increase, weight gain, metabolic, and hematological consequences. To prevent serious health problems, a meticulous risk-benefit assessment for AAPs treatment should be done between clinicians and patients and their families.

The use of atypical antipsychotics in the therapy of depressive episodes in patients with bipolar disorder

This literature review addresses the effi cacy and safety of atypical antipsychotics in patients with bipolar depression. Th e results of randomized studies and systematic meta-analyses of recent years were revised in detail. The effi cacy of the drug intake was reviewed for the following key research points: Clinical General Impression of Condition Severity Scale (CGI-S) and Montgomery-Asberg Depression Rating Scale (MADRS). A systematic literature search was carried out using Scopus, Web of Science, MedLine, elibrary, and other databases.

New Developments in the Use of Atypical Antipsychotics in the Treatment of Bipolar Disorder: a Systematic Review of Recent Randomized Controlled Trials.

Atypical antipsychotics are increasingly used in the treatment of bipolar disorder (BD). This systematic review provides an overview of recently published randomized controlled trials (RCTs) on the efficacy and safety of atypical antipsychotics in BD. Several studies supported efficacy of quetiapine monotherapy in acute bipolar I (BDI) and bipolar II (BDII) depression. Moreover, quetiapine adjunctive therapy showed superior efficacy to placebo in treatment-resistant bipolar depression. Cariprazine 1.5mg was effective in treating bipolar I depression. Aripiprazole 400mg IM once monthly was effective in preventing manic episodes with minimal metabolic effects. In youth with BD, lurasidone was effective and well-tolerated for acute depression while asenapine showed efficacy in treating acute manic and mixed episodes. Recently published RCTs generally support the efficacy of atypical antipsychotics in different phases of BD. Future studies should focus on understudied populations including pediatric BD and geriatric BD and BDII, as well as a focus on cognitive functioning and quality of life measures.

Risk of pneumonia associated with atypical antipsychotic use in nursing home residents with Parkinson’s disease

According to the American Geriatrics Society (AGS) Beers criteria, most atypical antipsychotic (AAPs) are inappropriate in patients with Parkinson's disease (PD) due to the risk of worsening Parkinsonian symptoms. This study evaluated the risk of pneumonia associated with inappropriate AAP use in elderly nursing home residents with PD. The study population encompassed older adults aged 65 years or older with a diagnosis of PD and with comorbid depression who started the AAP medication. Appropriate AAPs were defined as aripiprazole, clozapine or quetiapine according to 2015 Beers criteria, and inappropriate AAPs included olanzapine, asenapine, brexpiprazole, iloperidone, lurasidone, paliperidone, risperidone, or ziprasidone. Cox regression analyses involved propensity score-matched users of inappropriate and appropriate AAPs to examine the association between AAP use and risk of pneumonia. The mean age of patients in propensity-matched cohort (n = 12,076) was 82.15 years (SD = 6.97). The pneumonia incidence rates were 37.19 and 45.92 per person-year in appropriate and inappropriate AAP groups, respectively. Multivariable Cox regression analyses revealed increased risk of pneumonia [Hazard Ratio (HR) 1.20 (1.08–1.34)] for nursing home residents who were taking inappropriate compared to those taking appropriate AAP. In sensitivity analyses, the pneumonia risk was 1.28 (1.12–1.47) for risperidone vs. quetiapine and 1.29 (1.06–1.57) for olanzapine vs. quetiapine. The risk of pneumonia was significantly higher for patients with PD who used inappropriate AAP in comparison to appropriate AAP group in all analyses. This investigation warrants further attention regarding safety of atypical antipsychotics in PD.

Assessment of Reported Comparative Effectiveness and Safety of Atypical Antipsychotics in the Treatment of Behavioral and Psychological Symptoms of Dementia

Atypical antipsychotics offer modest effectiveness compared with placebo but with serious safety risks, including a boxed warning for the risk of death in the treatment of behavioral and psychological symptoms of dementia (BPSD). Their comparative effectiveness and safety are not fully known. To assess the relative benefits and safety of atypical antipsychotics in the treatment of BPSD shown in randomized clinical trials using network meta-analysis. PubMed/MEDLINE, Embase, PsychINFO, and Cochrane Library were searched from their inception until May 31, 2018. Key terms included dementia and atypical antipsychotics. Randomized clinical trials comparing any atypical antipsychotic with another atypical antipsychotic or with placebo were included in the analysis. Two independent reviewers used a standardized data extraction and quality assessment form. Random-effects network meta-analyses were performed. Effect sizes were reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% CIs. In addition to ORs, the surface under the cumulative ranking curve (SUCRA) was ascertained, which represents the percentage of the effectiveness or safety for each treatment compared with a hypothetical treatment that would be ranked first without uncertainty. The primary effectiveness outcome assessed was the Neuropsychiatric Inventory (NPI); secondary effectiveness outcomes were the Brief Psychiatric Rating Scale (BPRS) and Cohen-Mansfield Agitation Inventory (CMAI). The primary safety outcomes were death and cerebrovascular adverse events (CVAEs). Secondary safety outcomes were extrapyramidal signs/symptoms; somnolence/sedation; falls, fracture, or injury; and urinary tract infection/incontinence. Seventeen studies (5373 patients) were included. The mean (SD) age of all participants was 80.8 (3.1) years, and most were women (3748 [69.8%]). Compared with placebo, aripiprazole was associated with improvement in outcomes on the NPI (SMD, -0.17; 95% CI, -0.31 to -0.02), BPRS (SMD, -0.20; 95% CI, -0.35 to -0.05), and CMAI (SMD, -0.30; 95% CI, -0.55 to -0.05); quetiapine was associated with improvement in outcomes on the BPRS (SMD, -0.24; 95% CI, -0.46 to -0.01), and risperidone was associated with improvement in outcomes on the CMAI (SMD, -0.26; 95% CI, -0.37 to -0.15). Differences between atypical antipsychotics were not significant for effectiveness, death, or CVAE. Compared with placebo, risperidone (OR, 3.85; 95% CI, 1.55-9.55) and olanzapine (OR, 4.28; 95% CI, 1.26-14.56) were associated with increased risk of CVAEs. The SUCRA estimated relative ranking of treatments suggested that aripiprazole might be the most effective and safe atypical antipsychotic and that olanzapine provides the least benefit overall; however, these results should be interpreted with caution where point estimates (OR and SMD) show that there is no statistically significant difference. This network meta-analysis supports the existence of a trade-off between the effectiveness and safety of atypical antipsychotics in the treatment of BPSD and confirms that a single most effective and safe treatment option does not exist. Clinicians should individualize the assessment of safety risks against expected benefits when prescribing these medications to patients with dementia.

Atypical Antipsychotics for Irritability in Pediatric Autism: A Systematic Review and Network Meta-Analysis.

Irritability is common in pediatric autism spectrum disorder (ASD) patients. This can have major implications in child development, receptivity to behavioral therapy, as well as child and caregiver well-being. A systematic review and network meta-analysis were conducted to assess the efficacy and safety of atypical antipsychotics in treating irritability in these patients. Studies were identified from Medline, Embase, and PsycINFO from inception to March 2018. The clinical trials database was reviewed. Studies were included if they were a double-blind, randomized controlled trial utilizing the Aberrant Behavior Checklist Irritability (ABC-I) to measure the efficacy of atypical antipsychotic monotherapy. Data extraction was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-analyses for network meta-analysis guidelines. The main outcome was the reduction in irritability score using the ABC-I subscale from baseline. Eight trials comparing four interventions-risperidone, aripiprazole, lurasidone, and placebo in 878 patients, were included. Both risperidone and aripiprazole had significantly reduced ABC-I scores than placebo. Estimates of mean differences (95% credible intervals) were risperidone, -6.89 (-11.14, -2.54); aripiprazole, -6.62 (-10.88, -2.22); and lurasidone, -1.61 (-9.50, 6.23). Both risperidone and aripiprazole had similar safety. There were only eight studies included in the analysis, however, sample sizes were not small. Variance in reporting of adverse effects limited the quality of safety analysis. Risperidone and aripiprazole were the two best drugs, with comparable efficacy and safety in pediatric ASD patients. These two medications could be beneficial in improving irritability in these patients.

Efficacy and Safety of Atypical Antipsychotics in Bipolar Disorder With Comorbid Substance Dependence: A Systematic Review

Bipolar disorder (BD) patients with a comorbid substance use disorder (SUD) are notoriously difficult to treat. Atypical antipsychotics (AAPs) are widely prescribed in BD, but their efficacy in patients with comorbid SUD is still debated. The aim of the present article is to systematically review the literature findings on the efficacy and safety of AAPs in BD patients with comorbid SUD. We searched PubMed to identify original studies focused on the treatment of dual diagnosed BD with AAPs. Ten articles met our inclusion/exclusion criteria, involving a total of 969 subjects, 906 affected by BD and 793 with comorbid SUD: 4 were randomized controlled trials, 4 were open label trials and 2 were observational studies, published between 2002 and 2017. The most commonly abused substances were alcohol and cocaine. The AAPs used to treat patients were quetiapine (n = 337), asenapine (n = 119), olanzapine (n = 80), risperidone (n = 62), and aripiprazole (n = 48). In terms of safety, AAPs were usually well tolerated. Atypical antipsychotics were usually efficacious on acute mood symptoms, whereas their impact on substance-related issues was reported only in those studies without a placebo comparison. According to our results, even though AAPs are widely used and efficacious in treating the clinical symptoms of BD, there are not enough data to suggest their adjunctive benefit on craving and substance consumption.

Safety of atypical antipsychotics in the treatment of behavioral and psychological symptoms in dementia: a meta-analysis

Objective: To assess the safety of olanzapine, risperidone and quetiapine drugs in dementia patients with behavioral and psychological symptoms. Methods: The EMBASE, Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews, Medline, CNKI, Wang Fang were systematically searched for eligible randomized controlled trials of olanzapine, risperidone and quetiapine drugs therapy in patients with psychotic symptoms of dementia before February 2016. Two reviewers independently assessed the quality of the trials and extracted information. All the data was analyzed with meta analysis and software of the Revman5.3 provided by Cochrane network. Results: Overall, 16 relevant RCTs with 1 727 participants were identified (olanzapine group: 672; quetiapine group: 395; risperidone group: 660). (1)Olanzapine group had higher incidence of somnolence than risperidone group (OR=1.49, 95% CI [-1.01-2.21], P=0.05), while for the dizziness, agitation, accidental injury, weight gain, abnormal gait, weakness, sleep disorders, extrapyramidal symptoms, there were no significant difference. (2) Risperidone had higher incidence of extrapyramidal symptoms than quetiapine group (OR=0.11, 95% CI [0.04-0.27], P=0.64), the incidence of somnolence was lower than quetiapine group (OR=0.03, 95% CI [1.06-3.51], P=0.03), while for accidental injury, dizziness, fatigue, insomnia, constipation, there were no significant difference. (3) Olanzapine group had higher incidence of extrapyramidal symptoms than quetiapine group (OR=11.10, 95% CI [3.35-36.75], P<0.000 1), while for somnolence, sleep disturbances, constipation, agitation, weight gain, dizziness, there was no significant difference. (4) The subgroup analysis showed that in the Chinese population, compared with the population in Europe and America, risperidone group had higher incidence of agitation, sleep disorders than olanzapine (agitation: [OR= 0.26, 95% CI [0.08-0.82]; sleep disorders: OR= 0.31, 95% CI [0.10-0.99]), olanzapine group had higher incidence of weight gain than quetiapine (OR=6.8, 95% CI [2.00-23.14]). Conclusions: Among olanzapine, risperidone and quetiapine, risperidone has lowest incidence of somnolence, quetiapine has lowest incidence of extrapyramidal symptoms. In the Chinese population, compared with the population in Europe and America, risperidone group has higher incidence of agitation, sleep disorders than olanzapine, and olanzapine group has higher incidence of weight gain than quetiapine.

Atypical antipsychotics for disruptive behaviour disorders in children and youths.

Atypical antipsychotics for disruptive behaviour disorders in children and youths.

Atypical antipsychotics in the treatment of delirium

The aim of this study was to review the efficacy and safety of atypical antipsychotics, comparing within class, placebo, or compared to another active treatment for delirium. A literature search was conducted using PubMed, EMBASE, and the Cochrane database (1 January 1990-5 November 2012). Selection criteria for review were prospective, controlled studies (comparison studies), using validated delirium rating scales as outcome measures. A total of six prospective, randomized controlled studies were included in the review. It was found that atypical antipsychotics are effective and safe in treating delirium, even though there seemed to be no difference between each agent. In particular, comparison studies with haloperidol showed that the efficacy of atypical antipsychotics was similar to that of low-dose haloperidol. It was concluded that atypical antipsychotics appear to be effective and tolerable in the management of delirium, even though the evidence is limited.

The safety of atypical antipsychotics: does QTc provide all the answers?

Drug safety of atypical antipsychotics is important due to the increasing mortality gap between patients with schizophrenia and the general population. This editorial discusses the safety evaluation of ziprasidone with a focus on the risk of the potentially fatal cardiac arrhythmia, torsades de pointes (TdP). The exact incidence of antipsychotic-induced TdP remains unknown because capturing TdP warrants continuous monitoring and tens of thousands of patient-years due to the rarity of TdP. For this reason, surrogate markers such as the QTc interval are used despite their limitations. New surrogate markers Tpeak-Tend and T-wave morphology have seen the light of day but their validity remain unknown. Large pragmatic trials have been conducted, but their contributions to drug safety evaluations are controversial. Finally, psychiatrists should have in mind that safety evaluation should include more than the risk of TdP. Some atypical antipsychotics are associated with life-shortening side effects, such as severe weight gain and type 2 diabetes, which may contribute more to the overall mortality than TdP. In addition to this, suboptimal treatment may result in life-shortening behaviors such as suicide. A shared decision including a thorough discussion of risks and benefits with the patients is essential.

Use of Atypical Antipsychotics in the Treatment of Autistic Disorder

To review clinical trials and reports describing the efficacy and safety of atypical antipsychotics (olanzapine, ziprasidone, quetiapine, aripiprazole) in the treatment of autistic or other pervasive developmental disorders. English-language publications from the MEDLINE database (1966-February 2007) including clinical trials, case reports, and retrospective series were reviewed. Relevant data were extracted from studies of selected atypical antipsychotics in the treatment of autistic disorder in children, adolescents, and adults. Most literature found was in the form of case reports or case series; however, several open-label and double-blind trials were also identified. Autistic disorder is a chronic neurodevelopmental disorder with limited treatment options. Nonpharmacologic approaches may be the most beneficial, but pharmacologic agents are needed for some patients with significant behavioral manifestations of the disorder. The atypical antipsychotics (olanzapine, ziprasidone, quetiapine, aripiprazole) have shown some efficacy in improving certain behavioral symptoms of autistic disorder--primarily aggressiveness, hyperactivity, and self-injurious behavior. Efficacy was based on observation or changes from baseline in behavioral rating scores. Data appear to be strongest for olanzapine compared with quetiapine, with several open-label trials suggesting its efficacy. Weight gain and sedation were frequently reported adverse events with both agents. Aripiprazole has demonstrated efficacy in limited case series, with minimal adverse effects reported. Atypical antipsychotics represent a treatment option for symptoms associated with autistic disorder. However, these drugs do not affect the core symptoms of autistic disorder and are associated with potentially significant adverse effects. In addition, there is a lack of randomized controlled trials to determine the true efficacy and long-term safety of these agents in the pediatric population.

Behavioral and psychological symptoms of dementia (BPSD) in elderly demented subjects: Is the long lasting use of atypical antipsychotic drugs useful and safe?

The use of atypical antipsychotics (AA) is suggested in the treatment of BPSD, although controversial data are available on their safety and efficacy. The aim of this study was to assess the efficacy and safety of AA and whether this therapy could modify cognitive and functional domains in parallel with BPSD modifications. Out of 1,100 patients followed by the psychogeriatric ambulatory of our hospital, 69 patients (6.2%) were in therapy with AA and only 32 of them fulfilled the inclusion criteria of this study. Namely, the availability was required of a complete geriatric assessment, including the evaluation of cognitive (mini mental state examination = MMSE), emotional (the Italian “scala di valutazione del benessere emotivo nell’anziano” = SVEBA), functional (basic and instrumental activities of daily living = ADL and IADL), as well as behavioral (neuropsychological inventory = NPI) status, at the beginning (T 0) and after a 6 month therapy (T 1). The AA prescribed were risperidone (42.8%), olanzapine (31.3%), quetiapine (25.9%). The mean age was 80.1 years; 34.4% male; 65.6% female. Educational level was elementary in 90.6% of cases. Only 21.9% were institutionalized. 15.6% had 1 cardiovascular risk factor (CVRF), 50% more than 1, and the remaining with no CVRF. More than the half of them were diagnosed with degenerative dementia (D) (40.6% Alzheimer D = AD; 15.6% fronto-temporal dementia (FTD); 34.4% with vascular dementia (VD) (9.4%) or combined D (25%); 3,1 % with mild cognitive impairment (MCI), classified as F06.7 by the ICD-10 (International Classification of Diseases) and 6.2% with psychiatric disturbances. The most common BPSD were hallucinations, delusions, agitation, verbal and physical aggression. A paired t-test was applied to analyze data. There was a significant improvement with all 3 AA on NPI (mean NPI T 0 = 27.50 vs. T 1 = 12.13; t = 7.49). An improvement was also observed on SVEBA ( t = 1.97), close to significance. Most people did not have any adverse effects; 5 patients (15.6%) had extrapyramidal symptoms and 1 (3.1%) showed ginecomasty, clinically so relevant to cause the interruption of the treatment. The profile of safety and efficacy described on the whole sample was confirmed when it was subdivided according to kind of drug, illness severity and presence/absence of CVRF. In a large sample of the “real” subjects attending a geriatric service for dementia, the accurate selection of patients treatable with AA leads to identification of a population with a negligible rate of adverse effects in presence of a high rate of efficacy with respect not only to BPSD but also to cognitive and functional domains.

A Systematic Review of the Efficacy and Safety of Atypical Antipsychotics in Patients with Psychological and Behavioral Symptoms of Dementia

Although the Food and Drug Administration (FDA) has not approved atypical antipsychotics for use in patients with dementia, they are commonly prescribed in this population. Recent concerns about increased risk of cerebrovascular events and mortality have led to warnings. A systematic review was conducted to assess the benefits and harms of atypical antipsychotics when used in patients with behavioral and psychological symptoms of dementia. Electronic searches (through March 2005) of the Cochrane Library, Medline, Embase, and PsycINFO were supplemented with hand searches of reference lists, dossiers submitted by pharmaceutical companies, and a review of the FDA Website and industry-sponsored results database. Using predetermined criteria, each study was assessed for inclusion, and data about study design, population, interventions, and outcomes were abstracted. An overall quality rating (good, fair, or poor) was assigned based on internal validity. The evidence for olanzapine and risperidone supports their effectiveness compared with placebo. Short-term adverse events were similar to placebo. Risperidone had no advantage over haloperidol on efficacy measures in the better-quality studies. Risperidone had an advantage over haloperidol on some measures of extrapyramidal symptoms. Evidence for the other atypical antipsychotics is too limited to assess efficacy and safety. Trials were short term and conducted in highly selected populations. The potential for increased risk of cerebrovascular adverse events and mortality is a serious concern. To make judgments about when the benefits of atypical antipsychotics outweigh the potential harms, clinicians need more information. Additional data from existing trials and more-complete reporting of trial results could provide this information.

Treatment Recommendations for the Use of Antipsychotics for Aggressive Youth (TRAAY), Part I: A Review

Objectives: To review the evidence for the safety and efficacy of nonpharmacological and pharmacological treatments for aggression in children and adolescents. Method: Medline and PsycINFO searches (1990–present) were conducted for double-blind, placebo-controlled studies of atypical antipsychotics for aggression and for literature on the use of other pharmacological agents and psychosocial interventions for aggression. Case reports and adult literature regarding the safety of atypical antipsychotics were used where controlled data for youth were lacking. Results: Controlled data on the treatment of aggression in youth is scarce. Psychosocial interventions may be effective alone or in combination with pharmacological treatments. Psychotropic agents (e.g., stimulants, mood stabilizers, β-blockers) have also been shown to have limited efficacy in reducing aggression. Antipsychotics, particularly the atypical antipsychotics, show substantial efficacy in the treatment of aggression in selected pediatric populations. Atypical antipsychotics are generally associated with fewer extrapyramidal symptoms than are typical antipsychotics. Conclusions: Psychosocial interventions and atypical antipsychotics are promising treatments for aggression in youth. Double-blind studies should examine the safety and efficacy of atypical antipsychotics compared to each other and to medications from other classes, the efficacy of specific medications for different subtypes of aggression, combining various psychotropic medications, optimal dosages, and long-term safety.

Clinical utilization of atypical antipsychotics in pregnancy and lactation.

To analyze the available literature regarding the safety of atypical antipsychotics in pregnancy and lactation in order to recommend evidence-based strategies for pharmacologic management of psychosis in these conditions. We summarized the results from articles identified via MEDLINE/PubMed/TOXNET (1993-January 31, 2004), using the key terms pregnancy, lactation, breast-feeding, human milk, psychotropic drugs, atypical antipsychotics, olanzapine, quetiapine, risperidone, clozapine, ziprasidone, and aripiprazole. Retrospective studies, clinical observations, and case reports regarding the 6 atypical antipsychotics mentioned above were selected and analyzed. Extensive manual review of pertinent journals and textbooks was also performed. Reviewed studies show that olanzapine and clozapine apparently do not increase the teratogenic risk if administered to pregnant women, while evidence on quetiapine, risperidone, aripiprazole, and ziprasidone is still limited. In contrast, available information is not able to exclude unwanted serious effects associated with the use of all atypical antipsychotics on mother-infant dyads. Furthermore, more than a few studies suggest increased hyperglycemic risk for pregnant women related to atypical antipsychotic therapy during gestation. Finally, published evidence about the effects on long-term infant neurodevelopment of drug exposure through both placenta and breast milk is represented only by sporadic case reports. It is well known that potential consequences of an untreated psychotic episode may be severe and may lead to the mother attempting suicide and/or infanticide. For these reasons, clinicians need to help mothers weigh both fetal and neonatal risks of exposure to drugs against the potential risk they and their infant may incur if the psychiatric illness is not treated. On the other hand, atypical antipsychotics in pregnancy and breast-feeding do not show evident advantages in safety when compared with typical neuroleptic agents. Therefore, we suggest that the most relevant parameters for selecting the best clinical option for pregnant and breast-feeding women with schizophrenia and related disorders remain strongly related to 3 main points: (1). cautious evaluation of the risk/benefit ratio of fetal and neonatal drug exposure, (2). degree of severity of maternal psychiatric illness, and (3). careful preliminary choice of drugs characterized by a balanced safety/efficacy profile.

Benefit-Risk Assessment of Atypical Antipsychotics in the Treatment of Schizophrenia and Comorbid Disorders in Children and Adolescents

Evidence on the efficacy and safety of atypical antipsychotics in children and adolescents with schizophrenia is limited. The purpose of this review is to assess the published data on the use of atypical antipsychotics in children and adolescents with schizophrenia alone and with comorbid disorders, and to establish benefit-risk guidelines for clinicians.Risperidone, olanzapine and clozapine were found to be effective in the treatment of aggression and mania. Risperidone, and possibly also olanzapine, may be the drugs of choice in children with comorbid tic disorders. Ziprasidone has some monoamine reuptake inhibition properties and may be administered as an augmenting agent in children and adolescents with schizophrenia and comorbid anxiety and mood disorders. Compared with the typical antipsychotics, the atypical drugs seem to be more effective, better tolerated and lead to better patient adherence. Importantly, the atypical antipsychotics have a lower propensity to induce extrapyramidal symptoms and a potential (shown so far only in adults) to improve cognitive function and inhibit suicidal behaviour (especially clozapine). Yet, the adverse effects associated with these agents, especially weight gain, which may also have long-term effects, can lead to non-compliance in the young population. In children and adolescents receiving clozapine, olanzapine and quetiapine (but not ziprasidone, which does not have a pro-appetite effect), particularly those with obesity or a family history of diabetes mellitus, fasting blood glucose and lipid levels must be monitored frequently. Weight gain might be better controlled when the children and their parents are properly informed about this adverse effect and diet is regulated. Another major disadvantage of the atypical antipsychotics, especially risperidone, is their association with hyperprolactinaemia, which can lead to hypogonadism-induced osteoporosis, galactorrhoea, gynaecomastia, irregular menstruation and sexual dysfunction, all seen also with typical antipsychotics. Other atypical antipsychotics, namely olanzapine and ziprasidone, have been reported to be prolactin sparing in adults, but may not be completely devoid of hyperprolactinaemic effects in children and adolescents. Thus, prolactin levels should be assessed routinely in young patients treated with atypical antipsychotics. Further, children and adolescents with hyperprolactinaemia-related effects should be switched to a prolactin-sparing agent, such as quetiapine. All atypical antipsychotics may induce sedation and they are not devoid of extrapyramidal symptoms (especially risperidone). The use of typical antipsychotics has been limited to patients who are resistant to atypical antipsychotics, intolerant to their adverse effects, or require injections or depot preparations. Further double-blind, placebo-controlled trials and long-term safety assessments are needed before definitive conclusions can be reached about the place of atypical antipsychotics in the therapeutic armamentarium of childhood-onset schizophrenia.

Review: atypical antipsychotics and psychosocial interventions, alone or in combination, may reduce youth aggression

Schur SB, Sikich L, Findling RL et al. Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY). Part 1: a review. J Am Acad Child Adolec Psychiatry,2003 Feb;...

Treatment Recommendations for the Use of Antipsychotics for Aggressive Youth (TRAAY). Part I: A Review

To review the evidence for the safety and efficacy of nonpharmacological and pharmacological treatments for aggression in children and adolescents. and searches (1990-present) were conducted for double-blind, placebo-controlled studies of atypical antipsychotics for aggression and for literature on the use of other pharmacological agents and psychosocial interventions for aggression. Case reports and adult literature regarding the safety of atypical antipsychotics were used where controlled data for youth were lacking. Controlled data on the treatment of aggression in youth is scarce. Psychosocial interventions may be effective alone or in combination with pharmacological treatments. Psychotropic agents (e.g., stimulants, mood stabilizers, beta-blockers) have also been shown to have limited efficacy in reducing aggression. Antipsychotics, particularly the atypical antipsychotics, show substantial efficacy in the treatment of aggression in selected pediatric populations. Atypical antipsychotics are generally associated with fewer extrapyramidal symptoms than are typical antipsychotics. Psychosocial interventions and atypical antipsychotics are promising treatments for aggression in youth. Double-blind studies should examine the safety and efficacy of atypical antipsychotics compared to each other and to medications from other classes, the efficacy of specific medications for different subtypes of aggression, combining various psychotropic medications, optimal dosages, and long-term safety.