Side Effects Of Second-generation Antipsychotics Research Articles

Long-term metabolic side effects of second-generation antipsychotics in Chinese patients with schizophrenia: A within-subject approach with modelling of dosage effects

BackgroundSecond-generation antipsychotics (SGAs) are commonly used to treat schizophrenia (SCZ), but SGAs may differ in the severity of side effects. Long-term studies are lacking, and previous observational studies have limitations, such as failure to account for confounding factors and short follow-up durations. AimsTo compare the long-term anthropometric and metabolic side effects of seven SGAs in a Chinese population, using a within-subject approach to reduce the risk of confounding. MethodWe collected longitudinal data of SGA prescriptions, concomitant medications, fasting blood glucose (BG), lipid profiles, and BMI in a cohort of 767 patients with SCZ, with follow-up lasting up to 18.7 years (median ∼6.2 years). A total of 192,152 prescription records were retrieved, with 27,723 metabolic measures analysed. Linear mixed models were used to estimate the effects of SGA on BG, lipid profiles and BMI. Besides studying the effects of SGA medications (as binary predictors), we also investigated the effects of SGA dosage on metabolic profiles. ResultsConsidering SGA medications as binary predictors, clozapine and olanzapine were associated with the most substantial worsening of lipid profiles and BMI. A significant increase in BG was observed with clozapine only. Amisulpride, paliperidone and quetiapine were associated with worsened lipid profiles and increased BMI. Conversely, aripiprazole was associated with significant improvement in lipid profiles but a small increase in BMI.When SGA dosage was considered, the model showed consistent results overall. At the minimum effective dose, clozapine was associated with the most severe metabolic side effects, followed by olanzapine. Risperidone and aripiprazole showed the least metabolic side effects, with aripiprazole being significantly associated with lower lipids. ConclusionsThis study clarified the long-term and dose-dependent effects of different SGAs on anthropometric and metabolic parameters in Chinese SCZ patients. Our findings may inform clinicians and SCZ patients of SGA choices.

Lifestyle and mood correlates of cardiometabolic risk in people with serious mental illness on second-generation antipsychotic medications.

Cardiovascular morbidity and mortality are high in people with serious mental illness (SMI). This problem is mediated, at least in part, by metabolic side effects of second-generation antipsychotics (SGAs) and by unhealthy lifestyle behaviors. We asked whether oral glucose tolerance testing (oGTT) or hemoglobin A1c (HbA1c) is superior in identifying people with SMI at high cardiometabolic risk and whether this risk is shaped by mood, cognition, or lifestyle habits. We evaluated 40 patients with schizophrenia, schizoaffective, or bipolar disorder receiving SGAs by oGTT, HbA1c, comprehensive metabolic and lipid panels, and CRP. Mood was assessed using the Patient Health Questionnaire (PHQ-9), and cognition was assessed using the Saint Louis University Mental Status examination. Diet was assessed using the UK Diabetes and Diet Questionnaire (UKDDQ), and physical activity was assessed using daily step counts. Most patients had prediabetes (preDM) or diabetes mellitus (DM), 72.5% by oGTT, and 52.5% by HbA1c criteria. Pulse rates and insulin resistance indices (Homeostatic Model Assessment of Insulin Resistance, HOMA IR; Matsuda) were significantly different between patients classified as normal or with preDM/DM, using either oGTT or HbA1c criteria. Patients with preDM/DM by HbA1c but not oGTT criteria also had higher waist/hip ratios, triglyceride, and CRP levels (p<0.05). A strong negative correlation was found between average daily step counts and CRP levels (rho = -0.62, p<0.001). Higher UKDDQ scores, or unhealthier diet habits, were associated with higher fasting plasma glucose (rho = 0.28, p = 0.08), triglyceride levels (rho = 0.31, p = 0.05), and insulin resistance (HOMA IR: rho = 0.31, p = 0.06). Higher PHQ-9 scores correlated with lower 2h-oGTT glucose levels (rho = -0.37, p<0.05). OGTT screening is superior to HbA1c screening in detecting preDM and DM early. Patients identified with preDM/DM by oGTT or HbA1c screening are insulin-resistant and have higher pulse rates. Abdominal obesity, unfavorable lipid profiles, and higher CRP levels were noted in patients screened by HbA1c, but not by oGTT. Low physical activity, low depression scores, and unhealthy diet habits were associated with higher CRP and higher glucose and triglyceride levels, respectively. Future studies should assess the impact of specifically tailored individual lifestyle counseling and medical management interventions in this high-risk population.

Breakthrough Psychosis and Long-Acting Injectable Antipsychotics

“Breakthrough” of psychosis despite good compliance of antipsychotics medication for a long time is a major obstacle to the treatment of schizophrenia, whether the mechanism is caused by dopamine hypersensitivity or insufficient dose of antipsychotics. Researchers advocating “Dopamine Supersensitivity Psychosis” (DSP) emphasize to avoid excessive inhibition of dopamine 2 receptors from the beginning of treatment. On the other hand, researchers advocating “Breakthrough psychosis on Antipsychotic Maintenance Medication” (BAMM) in which psychosis recurs due to insufficient medication despite continuous administration of antipsychotics without non-adherence argue that dose of antipsychotics should be increased to enhance therapeutic effect. In patients using long-acting antipsychotics injection (LAI), non-compliance can be ruled out. We believe that in treating non-affective psychosis, it is necessary to continuously maintain the lowest dose possible using the optimal dose considering the side effects of second-generation antipsychotics and the cycle and stage of psychosis, and the optimal formulation such as LAI.

Extreme hyponatraemia due to primary polydipsia and quetiapine-induced SIAD.

SummaryHyponatraemia is the most common electrolyte disturbance in hospitalised patients and is associated with numerous adverse outcomes. Patients with schizophrenia are particularly susceptible to hyponatraemia, in part due to the close association between this condition and primary polydipsia. We report the case of a 57-year-old woman with schizophrenia and primary polydipsia who was receiving inpatient psychiatric care. She became increasingly confused, had multiple episodes of vomiting, and collapsed 1 week after being commenced on quetiapine 300 mg. On examination, she was hypertensive and her Glasgow coma scale was nine. She had a fixed gaze palsy and a rigid, flexed posture. Investigations revealed extreme hyponatraemia with a serum sodium of 97 mmol/L. A CT brain demonstrated diffused cerebral oedema with sulcal and ventricular effacement. A urine sodium and serum osmolality were consistent with SIAD, which was stimulated by the introduction of quetiapine. The antidiuretic effect of vasopressin limited the kidney’s ability to excrete free water in response to the patients' excessive water intake, resulting in extreme, dilutional hyponatraemia. The patient was treated with two 100 mL boluses of hypertonic 3% saline but deteriorated further and required intubation. She had a complicated ICU course but went on to make a full neurological recovery. This is one of the lowest sodium levels attributed to primary polydipsia or second-generation antipsychotics reported in the literature.Learning pointsThe combination of primary polydipsia and SIAD can lead to a life-threatening, extreme hyponatraemia.SIAD is an uncommon side effect of second-generation anti-psychotics.Serum sodium should be monitored in patients with primary polydipsia when commencing or adjusting psychotropic medications.Symptomatic hyponatraemia is a medical emergency that requires treatment with boluses of hypertonic 3% saline.A serum sodium of less than 105 mmol/L is associated with an increased risk of osmotic demyelination syndrome, therefore the correction should not exceed 8 mmol/L over 24 h.

Schizophrenia as a subject of competence of psychiatrist, narcologist, cardiologist, endocrinologist and pathologist

Numerous studies show that people with schizophrenia live 1025 years less than the general population. The significant reduction in life expectancy is due to suicides, frequent comorbidity with heart and vascular diseases, metabolic disorders, including obesity and type 2 diabetes, as well as side effects of second-generation antipsychotics. Conditions for reducing the number of premature deaths in schizophrenia include changing the lifestyle of patients with improved nutrition and increased physical activity, increasing patient adherence to antipsychotic therapy with monitoring of the side effects of second-generation antipsychotics, as well as to the treatment of comorbid substance use disorders and comorbid somatic diseases.

Integrative Management of Metabolic Syndrome in Youth Prescribed Second-Generation Antipsychotics

Weight gain and metabolic syndrome are common side effects of second-generation antipsychotics and carry significant health consequences both in childhood and into adulthood. This review highlights evidence-based, non-pharmacologic interventions to assist in the management of these side effects. Such intervention categories include dietary, physical activity, sleep, stress management, and nutritional supplementation. Interventions with the highest quality evidence include increasing the consumption of fruits, vegetables, and whole grains, increasing physical activity, improving sleep, and fish oil supplementation. We suggest that clinicians work with patients on managing metabolic side effects in a patient-centered way, incorporating principles of motivational interviewing, to reduce the risk of metabolic syndrome.

The impact on functioning of second-generation antipsychotic medication side effects for patients with schizophrenia: a worldwide, cross-sectional, web-based survey

BackgroundIt is well established that the different antipsychotics used for schizophrenia symptoms differ substantially in their side effects. However, relatively little is known about the impact of these side effects on functioning from the patient’s perspective. We aimed to understand how key side effects of second-generation antipsychotics impact the functioning and quality of life (QoL) of patients with schizophrenia.MethodsThis is a cross-sectional, web-based survey of patient-reported side effect burden of antipsychotic drugs in adults with schizophrenia. The survey was deployed in the United States, Canada, Australia, Spain, Italy, Norway, and Denmark. It included sociodemographic and clinical questions, the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), and the Glasgow Antipsychotic Side-Effect Scale (GASS). Eight pre-defined key side effects classified as activating (“Shaky hands or arms,” “Restlessness,” and “Difficulty sleeping”), sedating (“Sleepy during the day”, “Feeling drugged or like a zombie,” and “Feeling dizzy/Fainted”) or other side effects (“Problems enjoying sex” and “Gaining weight”), and additional questions related to impacts on function and quality of life were asked.ResultsIn total, 435 participants (mean age: 38 years, 53.8% female) were included. The total Q-LES-Q-SF score indicated overall medium satisfaction with their quality of life (score of 44.3; possible range 14–70). The most prevalent side effects were “Sleepy during the day” (83.2%), “Difficulty sleeping” (74.7%), “Dry mouth” (63.9%), “Problems enjoying sex” (53.4%) and “Gaining weight” (52.4%). Women reported the side effects of “Sleepy during the day”, “Problems enjoying sex” and “Gaining weight” more frequently than men. Key side effects impacted physical, social, occupational and psychological aspects of functioning. Patients with key side effects often felt frustrated by their experiences. Total Q-LES-Q-SF score showed a significant inverse correlation with the score of pre-defined groups of side effects indicating worse QoL in association with more severe key side effects in these patients.ConclusionStable patients with schizophrenia taking second-generation antipsychotics live with many side effects, including activating and sedating side effects, sexual side effects, and weight gain. Presence of these side effects is associated with substantial impacts across all aspects of daily functioning and lower quality of life and satisfaction.

P.690 Impact of second-generation antipsychotic side effects on functioning from a schizophrenia patient perspective: European perspective of a global patient-centered survey

P.690 Impact of second-generation antipsychotic side effects on functioning from a schizophrenia patient perspective: European perspective of a global patient-centered survey

Understanding and managing cardiac side-effects of second-generation antipsychotics in the treatment of schizophrenia

SUMMARYSecond-generation antipsychotic medications (SGAs) have advanced the treatment of schizophrenia over the past 30 years. However, a number of potentially life-threatening cardiac side-effects associated with these treatments concern and can discourage prescribers from administering these evidence-based treatments. This review provides a practical, psychiatrist-oriented understanding of the relative frequencies, mechanisms, investigations and treatments associated with these cardiac toxicities. We aim to highlight that these are relatively rare complications of an effective class of drug and to promote the advantages of early involvement of cardiologists in the psychiatric multidisciplinary team to guide the investigation and management of these conditions.LEARNING OBJECTIVESAfter reading this article you will be able to: •understand the relative incidence of cardiotoxic side-effects of the various SGAs•perform preliminary investigations to diagnose the common cardiotoxic side-effects of SGAs•understand the treatments for these cardiac side-effects and the role of cardiologists involved the care of these patients.

Cardiovascular and metabolic side effects of second-generation antipsychotics - narrative review

Since the introduction of second generation antipsychotics (SGA) their use have extended far beyond schizophrenia. With increased usage of these agents, particular attention has been paid to their metabolic and cardiac side effects. This narrative review is an attempt to briefly summarize conclusions from recently published systematic reviews on cardio-metabolic side effects of SGAs. Although no SGA is entirely free of these adverse effects, there are major differences in their prevalence among the medications. Numerous studies have showed particularly unfavorable side effects profile for olanzapine and clozapine. The lack of conclusive data was a major limitation for many studies, especially in those on pediatric population. In article we have also discussed the meanings of these findings, suggested recommendations of cardio-metabolic screening during SGA treatment and side effects management strategies.

Debate: Bipolar disorder: extremely rare before puberty and antipsychotics cause serious harms - a commentary on Van Meter etal. (2019).

'Paediatric bipolar disorder' (PBD) remains controversial; because it is based on the hypothesis that bipolar disorder (BD) often begins in childhood with atypical forms of mania. A meta-analysis of 12 epidemiological surveys found a high prevalence of PBD among children and adolescents worldwide (1.8%), however, our study of the measurement issues (Child and Adolescent Mental Health, 23, 2018, 14) found that PBD rates were lower than claimed. Our findings are consistent with the developmental trajectory of BD, as describedbymost longitudinal studies of high-risk offspring. BD is extremely rare in childhood with nearly all index manic/hypomanic episodes being in midadolescence or later. Treatment for BD should not commence until the first well-defined manic/hypomanic episode, because children and younger adolescents are extremely sensitive to the side effects of second-generation antipsychotics including weight gain, metabolic syndrome, extrapyramidal side effects and the risk of cerebral atrophy, as observed in studies of juvenile animals.

59.4 Recognizing and Managing Side Effects of Second-Generation Antipsychotics

This Clinical Perspectives will review tolerability data of antipsychotic medications in children and adolescents and to present evidence-based monitoring and management strategies for selected adverse effects, including extrapyramidal symptoms (EPS), hyperlipidemia, weight gain, and hyperprolactinemia.

Metformin for Weight Gain Associated with Second-Generation Antipsychotics in Children and Adolescents: A Systematic Review and Meta-Analysis.

Weight gain is a potentially concerning side effect of second-generation antipsychotics (SGAs). Metformin, a biguanide with antihyperglycemic effects, is used to manage weight gain in adults treated with SGAs. The objective of this study was to perform the first systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of metformin on weight gain in children and adolescents treated with SGAs. Based on a pre-registered protocol (PROSPERO-CRD42017074839), we searched the PubMed, EMBASE, PsychoINFO, BIOSIS, Science Direct, Cochrane Central, and ClinicalTrials.gov electronic databases through March 2018 (with no restrictions on language, date, or type of publication) for RCTs that assessed the effect of metformin or placebo on body weight in children or adolescents (< 18years of age) treated with selected SGAs (risperidone, aripiprazole, olanzapine, and clozapine) for any psychiatric disorder. We also contacted relevant drug manufacturers for possible additional pertinent studies/data. A random effects model was used and the quality of the included RCTs was assessed using the Cochrane Risk of Bias tool. Five RCTs (205 participants in total) were included in the meta-analysis. We found a significant weight decrease in the metformin group compared with placebo after 4, 12, and 16weeks of treatment {mean difference -0.98kg (95% confidence interval [CI] -1.26, -0.69); -1.83kg (95% CI -2.47, -1.18); and -3.23kg (95% CI -5.59, -0.86), respectively}. A weight decrease at weeks 2 and 8 did not reach statistical significance. The decrease in body mass index (BMI) paralleled that of weight, with a significant effect at weeks 4, 12, and 16. Overall, four studies were rated as unclear, and one study was rated as high, risk of bias. Meta-analytical evidence shows that metformin might decrease weight in children/adolescents treated with SGAs but additional high-quality evidence is needed. Clinicians need to be aware that this use of metformin is currently off-label.

Long-term administration of olanzapine induces adiposity and increases hepatic fatty acid desaturation protein in female C57BL/6J mice.

Objective(s):Weight gain and metabolic disturbances such as dyslipidemia, are frequent side effects of second-generation antipsychotics, including olanzapine. This study examined the metabolic effects of chronic olanzapine exposure. In addition, we investigated the hepatic fatty acid effects of olanzapine in female C57BL/6J mice fed a normal diet.Materials and Methods:Female C57BL/6J mice orally received olanzapine or normal saline for 7 weeks. The effects of long-term olanzapine exposure on body weight changes, food efficiency, blood glucose, triglyceride (TG), insulin, and leptin levels were observed. Hepatic TG and abdominal fat mass were investigated, and fat cell morphology was analyzed through histopathological methods. The levels of protein markers of fatty acid regulation in the liver, namely fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), were measured.Results:Olanzapine treatment increased the food intake of the mice as well as their body weight. Biochemical analyses showed that olanzapine increased blood TG, insulin, leptin, and hepatic TG. The olanzapine group exhibited increased abdominal fat mass and fat cell enlargement in abdominal fat tissue. Western blotting of the mouse liver revealed significantly higher (1.6-fold) levels of SCD-1 in the olanzapine group relative to the control group; by contrast, FAS levels in the two groups did not differ significantly.Conclusion:Enhanced lipogenesis triggered by increased hepatic SCD-1 activity might be a probable peripheral mechanism of olanzapine-induced dyslipidemia. Some adverse metabolic effects of olanzapine may be related to the disturbance of lipid homeostasis in the liver.

F56. IMPACT OF SIDE EFFECTS DUE TO SECOND-GENERATION ANTIPSYCHOTICS ON THE FUNCTIONING OF PATIENTS WITH SCHIZOPHRENIA: AN OBSERVATIONAL, PATIENT CENTERED, WEB SURVEY

BackgroundIn patients with schizophrenia, antipsychotic medications, including second-generation antipsychotics, may cause many side-effects (SE) often leading to treatment discontinuation, and possible relapse as a consequence. The impact of treatments on patient-centered outcomes such as health-related quality of life (HRQOL) is less well understood. Even less well understood is the impact of side effects on patient-centered outcomes such as daily functioning and HRQOL. Therefore, the study’s primary goal was to gain a deeper understanding of the impacts of SEs of second generation antipsychotics on patients’ day to day functioning.MethodsA cross-sectional, web-based, patient-reported survey was fielded in the United States between July and November 2017. The final survey included patient socio-demographics, a quality of life measure (Quality of Life Enjoyment and Satisfaction Questionnaire Short Form, Q-LES-Q-SF), questions on treatment satisfaction, SEs experienced (Glasgow Antipsychotic Side-Effect Scale, GASS), and questions about the impact of SEs on functioning and emotions. Patients were recruited through patient advocacy and support groups, and medical research panels. Patient inclusion criteria: Self-reported schizophrenia diagnosis; 18 to 65 years old; stable for at least one month at time of screening; prescribed a second-generation antipsychotic medication for 1–12 months; the final sample consisted of those individuals who reported experiencing one or more side-effects based on the GASS.ResultsThe total sample (n=180) had a mean age of 35 (range 18–61) years old, of which 58.3% were females. Approximately a quarter (27.8%) of the sample had a college degree or higher; 69.4% identified as White, followed by 16.7% Black/ African American, and 6.1% Native Hawaiian/ Pacific Islanders. Most prevalent SEs reported on the GASS were ‘difficulty sleeping’ (81.1%), ‘feeling sleepy during the day’ (77.2%), ‘dry mouth’ (70.6%), and ‘feeling restless (60.6%). The SEs most commonly reported as distressing, for those patients experiencing that SE, were difficulty passing urine (23.3%), and feeling drugged/like a zombie (19.4%). The minimum impact from SEs on daily functioning was 53.2 on a 0–100 Visual Analogue Scale (higher number reflects more negative impact on daily functioning; 0=no impact and 100=very highly impacted). Across the SEs further probed about, the most severe impact was on one’s ‘ability to get or do a job’; specifically, for the SEs ‘shaky hands or arms’ the mean impact was 76.1, followed by 69.8 for restlessness. ‘Problems enjoying sex’ had the greatest effect on one’s ‘intimate relationships’ (mean 74.8), and feeling drugged/like a zombie had the greatest effect on one’s ‘ability to concentrate’ (mean 70.2).DiscussionThe study indicates the importance of incorporating the patient with schizophrenia’s perspective when assessing SE experiences and impact on functioning due to second generation antipsychotic agents. Findings suggest that both activating SEs (restlessness) and sedating SEs (feeling drugged and sleepiness) have pronounced undesirable impact on daily patient functioning.

Metformin to reduce weight gain and metabolic disturbance in schizophrenia

ABSTRACT FROM: Mizuno Y, Suzuki T, Nakagawa A, et al . Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Schizophr...

Pharmacogenetic study of second-generation antipsychotic long-term treatment metabolic side effects (the SLiM Study): Rationale, objectives, design and sample description

AimWeight gain is an important and common side effect of second-generation antipsychotics (SGAs). Furthermore, these drugs can induce other side effects associated with higher cardiovascular morbidity and mortality, such as insulin resistance, diabetes or metabolic syndrome. Preliminary studies show that inter-individual genetic differences produce varying degrees of vulnerability to the different SGA-induced side effects. The Second-generation antipsychotic Long-term treatment Metabolic side effects (SLiM) study aims to identify clinical, environmental and genetic factors that explain inter-individual differences in weight gain and metabolic changes in drug-naïve patients after six months of treatment with SGAs. Materials and methodsThe SLIM study is a multicenter, observational, six-month pharmacogenetic study where a cohort of 307 drug-naïve pediatric and adult patients (age range 8.8–90.1 years) and a cohort of 150 age- and sex- matched healthy controls (7.8–73.2 years) were recruited. ResultsThis paper describes the rationale, objectives and design of the study and provides a description of the sample at baseline. ConclusionsResults from the SLiM study will provide a better understanding of the clinical, environmental, and genetic factors involved in weight gain and metabolic disturbances associated with SGA treatment.

Hypothalamic ghrelin signalling mediates olanzapine-induced hyperphagia and weight gain in female rats

Excessive weight gain is a major metabolic side effect of second-generation antipsychotics (SGAs) in the treatment of schizophrenia. Ghrelin is an orexigenic hormone secreted mainly from the stomach, which can induce weight gain and hyperphagia through regulating neuropeptides at the hypothalamus. Accumulating evidence implicates a relationship between ghrelin signalling and SGA-induced hyperphagia and weight gain. We report that olanzapine (a SGA with high weight gain liability) potently and time-dependently up-regulate ghrelin and ghrelin signalling, leading to hyperphagia and weight gain in female Sprague-Dawley rats, an action reversed by i.c.v. injection of a ghrelin receptor (GHS-R1a) antagonist. These findings indicate a crucial role of ghrelin signalling in hyperphagia induced by olanzapine, supporting the notion that GHS-R1a antagonist may be useful for pharmacological treatment of SGA-induced weight gain resulted from hyperphagia.

Les recommandations thérapeutiques relatives aux effets secondaires extrapyramidaux associés à l’utilisation d’antipsychotiques de deuxième génération chez les enfants et les adolescents

BACKGROUND/OBJECTIVE: Antipsychotic use in children is increasing. The purpose of the present article is to provide guidance to clinicians on the clinical management of extrapyramidal side effects of second-generation antipsychotics.

Medication Use and Spending Trends Among Children With ADHD in Florida's Medicaid Program, 1996–2005

How the introduction of new pharmaceuticals affects spending for treatment of children with attention-deficit hyperactivity disorder (ADHD) is unknown. This study examined trends in use of pharmaceuticals and their costs among children with ADHD from 1996 to 2005. This observational study used annual cohorts of children ages three to 17 with ADHD (N=107,486 unique individuals during the study period) from Florida Medicaid claims to examine ten-year trends in the predicted probability for medication use for children with ADHD with and without psychiatric comorbidities as well as mental health spending and its components. Additional outcome measures included average price per day and average number of days filled for medication classes. Overall, the percentage of children with ADHD treated with ADHD drugs increased from 60% to 63%, and the percentage taking antipsychotics more than doubled, from 8% to 18%. In contrast, rates of antidepressant use declined from 21% to 15%, and alpha agonist use was constant, at 15%. Mental health spending increased 61%, with pharmaceutical spending representing the fastest-rising component (up 192%). Stimulant spending increased 157%, mostly because of increases in price per prescription. Antipsychotic spending increased 588% because of increases in both price and quantity (number of days used). By 2005, long-acting ADHD drugs accounted for over 90% of stimulant spending. Long-acting ADHD drugs have rapidly replaced short-acting stimulant use among children with ADHD. The use of antipsychotics as a second-tier agent in treating ADHD has overtaken traditional agents such as antidepressants or alpha agonists, suggesting a need for research into the efficacy and side effects of second-generation antipsychotics among children with ADHD.