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John M. Kane - One of the best experts on this subject based on the ideXlab platform.

  • blood levels to optimize Antipsychotic treatment in clinical practice a joint consensus statement of the american society of clinical psychopharmacology and the therapeutic drug monitoring task force of the arbeitsgemeinschaft fur neuropsychopharmako
    The Journal of Clinical Psychiatry, 2020
    Co-Authors: Georgios Schoretsanitis, Christoph U Correll, John M. Kane, Stephen R Marder, Leslie Citrome, John W Newcomer, Delbert G Robinson
    Abstract:

    Objective The quantification of Antipsychotic levels in blood, also known as therapeutic drug monitoring (TDM), is a potentially useful tool of modern personalized therapy that can be applied to augment Antipsychotic use and dosing decisions. The application of TDM for Antipsychotics can be helpful in numerous challenging clinical scenarios, such as lack of therapeutic response, relapse, or adverse drug reactions (ADRs) related to Antipsychotic treatment. The benefits of TDM may be particularly evident in the treatment of highly vulnerable patient subgroups, such as children, adolescents, pregnant women, and the elderly. The main aim of this article is to aid clinicians who routinely prescribe Antipsychotics to successfully apply TDM in routine clinical practice in order to help optimize the efficacy and safety of those Antipsychotics. Participants Participants were clinicians and researchers, members of the American Society of Clinical Psychopharmacology, and the Therapeutic Drug Monitoring Task Force of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (Association of Neuropsychopharmacology and Pharmacopsychiatry). Evidence TDM literature on Antipsychotics was critically reviewed to provide a condensed clinical decision-making algorithm with therapeutic reference ranges for blood Antipsychotic levels, within which patients are most likely to respond and tolerate treatment, although TDM is not equally recommended/supported for all Antipsychotics. Consensus process A preliminary draft was prepared and circulated to the writing group members. Consensus was achieved in all cases, and resulting recommendations focused on following areas: steady-state and sampling time, levels of recommendations, indications, therapeutic reference ranges and laboratory alert levels, practical issues, and interpretation, as well as limitations. Conclusions The utilization of TDM as a tool for problem solving in Antipsychotic treatment offers a unique method to improve safety and efficacy. This consensus statement summarizes essential information on the routine use of TDM for Antipsychotics and encourages clinicians to perform TDM with the appropriate indications as part of the clinical decision-making process.

  • What is the risk-benefit ratio of long-term Antipsychotic treatment in people with schizophrenia?
    World psychiatry : official journal of the World Psychiatric Association (WPA), 2018
    Co-Authors: Christoph U Correll, Jose M. Rubio, John M. Kane
    Abstract:

    The long-term benefit-to-risk ratio of sustained Antipsychotic treatment for schizophrenia has recently been questioned. In this paper, we critically examine the literature on the long-term efficacy and effectiveness of this treatment. We also review the evidence on the undesired effects, the impact on physical morbidity and mortality, as well as the neurobiological correlates of chronic exposure to Antipsychotics. Finally, we summarize factors that affect the risk-benefit ratio. There is consistent evidence supporting the efficacy of Antipsychotics in the short term and mid term following stabilization of acute psychotic symptoms. There is insufficient evidence supporting the notion that this effect changes in the long term. Most, but not all, of the long-term cohort studies find a decrease in efficacy during chronic treatment with Antipsychotics. However, these results are inconclusive, given the extensive risk of bias, including increasing non-adherence. On the other hand, long-term studies based on national registries, which have lower risk of bias, find an advantage in terms of effectiveness during sustained Antipsychotic treatment. Sustained Antipsychotic treatment has been also consistently associated with lower mortality in people with schizophrenia compared to no Antipsychotic treatment. Nevertheless, chronic Antipsychotic use is associated with metabolic disturbance and tardive dyskinesia. The latter is the clearest undesired clinical consequence of brain functioning as a potential result of chronic Antipsychotic exposure, likely from dopaminergic hypersensitivity, without otherwise clear evidence of other irreversible neurobiological changes. Adjunctive psychosocial interventions seem critical for achieving recovery. However, overall, the current literature does not support the safe reduction of Antipsychotic dosages by 50% or more in stabilized individuals receiving adjunctive psychosocial interventions. In conclusion, the critical appraisal of the literature indicates that, although chronic Antipsychotic use can be associated with undesirable neurologic and metabolic side effects, the evidence supporting its long-term efficacy and effectiveness, including impact on life expectancy, outweighs the evidence against this practice, overall indicating a favorable benefit-to-risk ratio. However, the finding that a minority of individuals diagnosed initially with schizophrenia appear to be relapse free for long periods, despite absence of sustained Antipsychotic treatment, calls for further research on patient-level predictors of positive outcomes in people with an initial psychotic presentation.

  • pharmacoepidemiology of Antipsychotic use in youth with adhd trends and clinical implications
    Current Psychiatry Reports, 2013
    Co-Authors: Michael L Birnbaum, Mark Olfson, John M. Kane, Tobias Gerhard, Ema Saito, Almut G Winterstein, Christoph U Correll
    Abstract:

    Although concern has been raised about Antipsychotic prescribing to youth with attention-deficit/hyperactivity disorder (ADHD), the available database is limited to individual studies. Therefore, in order to provide a synthesis of prevalence and time trends, we conducted a systematic review and pooled analysis of pharmaco-epidemiologic data on Antipsychotic use in ADHD youth. Of 1806 hits, 21 studies (N) were retained that reported analyzable data for three separate populations: 1) Antipsychotic-treated youth (N = 15, n = 341,586); 2) ADHD youth (N = 9, n = 6,192,368), and 3) general population youth (N = 5, n = 14,284,916). Altogether, 30.5 ± 18.5 % of Antipsychotic-treated youth had ADHD. In longitudinal studies, this percentage increased over time (1998–2007) from 21.7 ± 7.1 % to 27.7 ± 7.7 %, ratio = 1.3 ± 0.4. Furthermore, 11.5 ± 17.5 % of ADHD youth received Antipsychotics. In longitudinal studies, this percentage also increased (1998–2006) from 5.5 ± 2.6 % to 11.4 ± 6.7 %, ratio = 2.1 ± 0.6. Finally, 0.12 ± 0.07 % of youth in the general population were diagnosed with ADHD and received Antipsychotics. Again, in longitudinal studies, this percentage increased over time (1993–2007): 0.13 ± 0.09 % to 0.44 ± 0.49 %, ratio = 3.1 ± 2.2. Taken together, these data indicate that Antipsychotics are used by a clinically relevant and increasing number of youth with ADHD. Reasons for and risk/benefit ratios of this practice with little evidence base require further investigation.

  • does Antipsychotic polypharmacy increase the risk for metabolic syndrome
    Schizophrenia Research, 2007
    Co-Authors: Christoph U Correll, John M. Kane, Anne M Frederickson, Peter Manu
    Abstract:

    The prescribing of more than one Antipsychotic at the same time is becoming common in the treatment of patients with severe mental illnesses, despite authoritative treatment guidelines that advocate for Antipsychotic monotherapy, recommending Antipsychotic cotreatment as the last option after other strategies, including clozapine, have failed (1–3). Depending on treatment settings, populations, time of study and study methodology, prevalence rates of Antipsychotic polytherapy for schizophrenia and other chronic psychotic disorders range between 3% and 71% (4–19). The increased cost of combining two atypical Antipsychotics and the lack of substantial proof of the efficacy and safety of Antipsychotic polytherapy has raised considerable reservations regarding this practice (20–22). Among the four controlled studies in patients with clozapine-refractory schizophrenia, two trials demonstrated a moderate benefit of augmentation with sulpiride (23) and risperidone (24), while the other two trials did not find clozapine augmentation with risperidone to be superior compared to augmentation with placebo (25,26). However, since only less than 5% of patients are treated with clozapine in the US, these controlled trials are limited in addressing the efficacy of combining two Antipsychotics in patients with schizophrenia and other severe mental disorders who are either not considered fully treatment refractory, or in those unwilling or unable to benefit from clozapine. On the other hand, the safety of Antipsychotic polytherapy has received scant attention in published work. In several studies, Antipsychotic combination treatment has been associated with higher rates of extrapyramidal side effects, as well as increased use of anticholinergic agents (12,17,27) compared to Antipsychotic monotherapy. In addition, sedation (25) and hyperprolactinemia (23,28) have been observed more often in patients treated with Antipsychotic polytherapy. In addition, recent data suggest that Antipsychotic polytherapy may be associated with greater metabolic risk. In a case-control study of patients treated with Antipsychotics, including 181 cases with new antidiabetic prescriptions and 1,448 matched controls, an elevated risk for treatment-emergent diabetes mellitus was found in association with Antipsychotic combination treatment (29). The association of Antipsychotic treatment with weight gain, hyperglycemia, dyslipidemia, and the metabolic syndrome (30–34), as well as naturalistic reports linking cardiovascular mortality to Antipsychotic polytherapy (35,36), suggest that combining Antipsychotics, particularly second-generation Antipsychotics, could be associated with an increased risk of metabolic syndrome, which is linked with coronary heart disease and diabetes (37,38). However, the Antipsychotics used in polytherapy may produce different effects on the prevalence of metabolic syndrome (39,40), because clozapine and olanzapine are associated with greater weight increase and metabolic abnormalities than other SGAs, particularly ziprasidone and aripiprazole (41). The relationship between Antipsychotic polytherapy and metabolic syndrome has not been examined. In this cross-sectional study of an inpatient population treated with second-generation Antipsychotics, we aimed to determine whether Antipsychotic polytherapy is associated with an increased point prevalence of metabolic syndrome and lipid markers of insulin resistance. We hypothesized that the frequency of metabolic syndrome and insulin resistance would be elevated in patients receiving more than one Antipsychotic for the treatment of a severe mental disorder.

  • tardive dyskinesia rates with atypical Antipsychotics in adults prevalence and incidence
    The Journal of Clinical Psychiatry, 2004
    Co-Authors: John M. Kane
    Abstract:

    Both conventional and atypical Antipsychotics cause an up-regulation of dopamine-2 receptors and have been associated with tardive dyskinesia. Studies of adult and elderly subjects have shown a greater incidence of tardive dyskinesia among patients who were administered conventional Antipsychotic drugs than those given atypical Antipsychotic drugs. This article will review studies of the prevalence and incidence of tardive dyskinesia in patients taking Antipsychotic agents.

Christoph U Correll - One of the best experts on this subject based on the ideXlab platform.

  • mortality risk of Antipsychotic augmentation for adult depression
    PLOS ONE, 2020
    Co-Authors: Tobias Gerhard, Christoph U Correll, Scott T Stroup, Soko Setoguchi, Brian L Strom, Cecilia Huang, Zhiqiang Tan, Stephen Crystal, Mark Olfson
    Abstract:

    Importance Randomized controlled trials have demonstrated increased all-cause mortality in elderly patients with dementia treated with newer Antipsychotics. It is unknown whether this risk generalizes to non-elderly adults using newer Antipsychotics as augmentation treatment for depression. Objective This study examined all-cause mortality risk of newer Antipsychotic augmentation for adult depression. Design Population-based new-user/active comparator cohort study. Setting National healthcare claims data from the US Medicaid program from 2001–2010 linked to the National Death Index. Participants Non-elderly adults (25–64 years) diagnosed with depression who after ≥3 months of antidepressant monotherapy initiated either augmentation with a newer Antipsychotic or with a second antidepressant. Patients with alternative indications for Antipsychotic medications, such as schizophrenia, psychotic depression, or bipolar disorder, were excluded. Exposure Augmentation treatment for depression with a newer Antipsychotic or with a second antidepressant. Main outcome All-cause mortality during study follow-up ascertained from the National Death Index. Results The analytic cohort included 39,582 patients (female = 78.5%, mean age = 44.5 years) who initiated augmentation with a newer Antipsychotic (n = 22,410; 40% = quetiapine, 21% = risperidone, 17% = aripiprazole, 16% = olanzapine) or with a second antidepressant (n = 17,172). The median chlorpromazine equivalent starting dose for all newer Antipsychotics was 68mg/d, increasing to 100 mg/d during follow-up. Altogether, 153 patients died during 13,328 person-years of follow-up (newer Antipsychotic augmentation: n = 105, follow-up = 7,601 person-years, mortality rate = 138.1/10,000 person-years; antidepressant augmentation: n = 48, follow-up = 5,727 person-years, mortality rate = 83.8/10,000 person-years). An adjusted hazard ratio of 1.45 (95% confidence interval, 1.02 to 2.06) indicated increased all-cause mortality risk for newer Antipsychotic augmentation compared to antidepressant augmentation (risk difference = 37.7 (95%CI, 1.7 to 88.8) per 10,000 person-years). Results were robust across several sensitivity analyses. Conclusion Augmentation with newer Antipsychotics in non-elderly patients with depression was associated with increased mortality risk compared with adding a second antidepressant. Though these findings require replication and cannot prove causality, physicians managing adults with depression should be aware of this potential for increased mortality associated with newer Antipsychotic augmentation.

  • blood levels to optimize Antipsychotic treatment in clinical practice a joint consensus statement of the american society of clinical psychopharmacology and the therapeutic drug monitoring task force of the arbeitsgemeinschaft fur neuropsychopharmako
    The Journal of Clinical Psychiatry, 2020
    Co-Authors: Georgios Schoretsanitis, Christoph U Correll, John M. Kane, Stephen R Marder, Leslie Citrome, John W Newcomer, Delbert G Robinson
    Abstract:

    Objective The quantification of Antipsychotic levels in blood, also known as therapeutic drug monitoring (TDM), is a potentially useful tool of modern personalized therapy that can be applied to augment Antipsychotic use and dosing decisions. The application of TDM for Antipsychotics can be helpful in numerous challenging clinical scenarios, such as lack of therapeutic response, relapse, or adverse drug reactions (ADRs) related to Antipsychotic treatment. The benefits of TDM may be particularly evident in the treatment of highly vulnerable patient subgroups, such as children, adolescents, pregnant women, and the elderly. The main aim of this article is to aid clinicians who routinely prescribe Antipsychotics to successfully apply TDM in routine clinical practice in order to help optimize the efficacy and safety of those Antipsychotics. Participants Participants were clinicians and researchers, members of the American Society of Clinical Psychopharmacology, and the Therapeutic Drug Monitoring Task Force of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (Association of Neuropsychopharmacology and Pharmacopsychiatry). Evidence TDM literature on Antipsychotics was critically reviewed to provide a condensed clinical decision-making algorithm with therapeutic reference ranges for blood Antipsychotic levels, within which patients are most likely to respond and tolerate treatment, although TDM is not equally recommended/supported for all Antipsychotics. Consensus process A preliminary draft was prepared and circulated to the writing group members. Consensus was achieved in all cases, and resulting recommendations focused on following areas: steady-state and sampling time, levels of recommendations, indications, therapeutic reference ranges and laboratory alert levels, practical issues, and interpretation, as well as limitations. Conclusions The utilization of TDM as a tool for problem solving in Antipsychotic treatment offers a unique method to improve safety and efficacy. This consensus statement summarizes essential information on the routine use of TDM for Antipsychotics and encourages clinicians to perform TDM with the appropriate indications as part of the clinical decision-making process.

  • What is the risk-benefit ratio of long-term Antipsychotic treatment in people with schizophrenia?
    World psychiatry : official journal of the World Psychiatric Association (WPA), 2018
    Co-Authors: Christoph U Correll, Jose M. Rubio, John M. Kane
    Abstract:

    The long-term benefit-to-risk ratio of sustained Antipsychotic treatment for schizophrenia has recently been questioned. In this paper, we critically examine the literature on the long-term efficacy and effectiveness of this treatment. We also review the evidence on the undesired effects, the impact on physical morbidity and mortality, as well as the neurobiological correlates of chronic exposure to Antipsychotics. Finally, we summarize factors that affect the risk-benefit ratio. There is consistent evidence supporting the efficacy of Antipsychotics in the short term and mid term following stabilization of acute psychotic symptoms. There is insufficient evidence supporting the notion that this effect changes in the long term. Most, but not all, of the long-term cohort studies find a decrease in efficacy during chronic treatment with Antipsychotics. However, these results are inconclusive, given the extensive risk of bias, including increasing non-adherence. On the other hand, long-term studies based on national registries, which have lower risk of bias, find an advantage in terms of effectiveness during sustained Antipsychotic treatment. Sustained Antipsychotic treatment has been also consistently associated with lower mortality in people with schizophrenia compared to no Antipsychotic treatment. Nevertheless, chronic Antipsychotic use is associated with metabolic disturbance and tardive dyskinesia. The latter is the clearest undesired clinical consequence of brain functioning as a potential result of chronic Antipsychotic exposure, likely from dopaminergic hypersensitivity, without otherwise clear evidence of other irreversible neurobiological changes. Adjunctive psychosocial interventions seem critical for achieving recovery. However, overall, the current literature does not support the safe reduction of Antipsychotic dosages by 50% or more in stabilized individuals receiving adjunctive psychosocial interventions. In conclusion, the critical appraisal of the literature indicates that, although chronic Antipsychotic use can be associated with undesirable neurologic and metabolic side effects, the evidence supporting its long-term efficacy and effectiveness, including impact on life expectancy, outweighs the evidence against this practice, overall indicating a favorable benefit-to-risk ratio. However, the finding that a minority of individuals diagnosed initially with schizophrenia appear to be relapse free for long periods, despite absence of sustained Antipsychotic treatment, calls for further research on patient-level predictors of positive outcomes in people with an initial psychotic presentation.

  • pharmacoepidemiology of Antipsychotic use in youth with adhd trends and clinical implications
    Current Psychiatry Reports, 2013
    Co-Authors: Michael L Birnbaum, Mark Olfson, John M. Kane, Tobias Gerhard, Ema Saito, Almut G Winterstein, Christoph U Correll
    Abstract:

    Although concern has been raised about Antipsychotic prescribing to youth with attention-deficit/hyperactivity disorder (ADHD), the available database is limited to individual studies. Therefore, in order to provide a synthesis of prevalence and time trends, we conducted a systematic review and pooled analysis of pharmaco-epidemiologic data on Antipsychotic use in ADHD youth. Of 1806 hits, 21 studies (N) were retained that reported analyzable data for three separate populations: 1) Antipsychotic-treated youth (N = 15, n = 341,586); 2) ADHD youth (N = 9, n = 6,192,368), and 3) general population youth (N = 5, n = 14,284,916). Altogether, 30.5 ± 18.5 % of Antipsychotic-treated youth had ADHD. In longitudinal studies, this percentage increased over time (1998–2007) from 21.7 ± 7.1 % to 27.7 ± 7.7 %, ratio = 1.3 ± 0.4. Furthermore, 11.5 ± 17.5 % of ADHD youth received Antipsychotics. In longitudinal studies, this percentage also increased (1998–2006) from 5.5 ± 2.6 % to 11.4 ± 6.7 %, ratio = 2.1 ± 0.6. Finally, 0.12 ± 0.07 % of youth in the general population were diagnosed with ADHD and received Antipsychotics. Again, in longitudinal studies, this percentage increased over time (1993–2007): 0.13 ± 0.09 % to 0.44 ± 0.49 %, ratio = 3.1 ± 2.2. Taken together, these data indicate that Antipsychotics are used by a clinically relevant and increasing number of youth with ADHD. Reasons for and risk/benefit ratios of this practice with little evidence base require further investigation.

  • national trends in the office based treatment of children adolescents and adults with Antipsychotics
    Archives of General Psychiatry, 2012
    Co-Authors: Mark Olfson, Shuai Wang, Christoph U Correll
    Abstract:

    sonsincreasedfrom0.24to1.83forchildren,0.78to3.76 for adolescents, and 3.25 to 6.18 for adults. The proportion of total visits that included a prescription of Antipsychotics increased during this period from 0.16% to 1.07% for youths and from 0.88% to 1.73% for adults. From 2005 to 2009, disruptive behavior disorders were the most common diagnoses in child and adolescent Antipsychotic visits, accounting for 63.0% and 33.7%, respectively, while depression (21.2%) and bipolar disorder (20.2%) were the 2 most common diagnoses in adult Antipsychotic visits. Psychiatrists provided a larger proportion of the Antipsychotic visits for children (67.7%) andadolescents(71.6%)thantoadults(50.3%)(P.001). From2005to2009,Antipsychoticswereincludedin28.8% of adult visits and 31.1% of youth visits to psychiatrists. Conclusions: On a population basis, adults make considerably more medical visits with a prescription of Antipsychotics than do adolescents or children. Yet Antipsychotic treatment has increased especially rapidly among young people, and recently Antipsychotics have been prescribed in approximately the same proportion of youth and adult visits to psychiatrists.

Joseph R Calabrese - One of the best experts on this subject based on the ideXlab platform.

  • Antipsychotic drug induced somnolence incidence mechanisms and management
    CNS Drugs, 2016
    Co-Authors: Fang Fang, Zuowei Wang, Joseph R Calabrese
    Abstract:

    Somnolence is a common side effect of Antipsychotics. To assess the incidence of this side effect, we performed a MEDLINE search for randomized, double-blinded, placebo- or active-controlled studies of adult patients treated with Antipsychotics for schizophrenia, mania, bipolar depression, or bipolar disorder. We extracted rates of somnolence from original publications and pooled them based on the dose of each Antipsychotic in the same psychiatric condition, then estimated the absolute risk increase (ARI) and the number needed to harm (NNH) of an Antipsychotic relative to placebo or an active comparator in the same psychiatric condition. According to the ARI in acute schizophrenia, bipolar mania, and bipolar depression, Antipsychotics can be classified as high somnolence (clozapine), moderate somnolence (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone), and low somnolence (aripiprazole, asenapine, haloperidol, lurasidone, paliperidone, cariprazine). The risk of somnolence with blonanserin, brexpiprazole, chlorpromazine, iloperidone, sertindole, and zotepine needs further investigation. The rates of somnolence were positively correlated to dose and duration for some Antipsychotics, but not for others. Many factors, including Antipsychotic per se, the method used to measure somnolence, patient population, study design, and dosing schedule, might affect the incidence of Antipsychotic-induced somnolence. The mechanisms of Antipsychotic-induced somnolence are likely multifactorial, although the blockade of histamine 1 receptors and α1 receptors may play a major role. The management of Antipsychotic-induced somnolence should include sleep hygiene education, choosing an Antipsychotic with a lower risk for somnolence, starting at a lower dose with a slower titration based on psychiatric diagnoses, adjusting doses when necessary, and minimizing concurrent somnolence-prone agents. Since most cases of somnolence were mild to moderate, allowing tolerance to develop over at least 4 weeks is reasonable before discontinuing an Antipsychotic.

  • typical and atypical Antipsychotics in bipolar depression
    The Journal of Clinical Psychiatry, 2005
    Co-Authors: Keming Gao, Prashant Gajwani, Omar Elhaj, Joseph R Calabrese
    Abstract:

    Background: Symptomatic bipolar patients experience more depressive than manic symptoms, but fewer studies have been designed for bipolar depression than for bipolar mania. Since the Antipsychotic agents have been shown to diminish depressive symptoms during the treatment of mania, atypical agents are now being studied for use in bipolar depression. Data Sources: English-language articles published from 1980 through July 2004 and cited in MEDLINE were searched using the keywords Antipsychotics, typical Antipsychotics, atypical Antipsychotics, bipolar depression, bipolar disorder, manic-depressive illness, placebo, and clinical trial. The generic and brand names of individual Antipsychotics were also entered as keywords . Peer-reviewed abstracts of placebo-controlled studies assessing acute or long-term efficacy in bipolar depression presented at major scientific meetings were also reviewed. Study Selection: Use of a depression rating scale was required for inclusion of studies of the atypical Antipsychotic agents in our analysis. Data Synthesis: Twenty-one randomized trials and 13 nonrandomized prospective trials were identified. In the only 2 acute, double-blind, placebo-controlled studies of Antipsychotics in bipolar depression, the effect size of olanzapine was small (0.32) compared with the effect sizes of quetiapine (0.91-1.09, depending on dose). The effect size in acute mania of olanzapine at week 4 and quetiapine at week 3 was 0.50 and 0.39, respectively. Both olanzapine and quetiapine have been shown to be superior to placebo in the acute treatment of bipolar I depression. In addition, olanzapine has been shown to be more effective than placebo in delaying relapse into bipolar depression. With the exception of a 6-month perphenazine study, there are no other randomized studies of typical Antipsychotics that support the conclusion that this class of medication worsens bipolar depression. Conclusion: Emerging data suggest that the atypical Antipsychotic agents have a role in the acute and long-term treatment of bipolar depression. No convincing data support the impression that the typical Antipsychotic agents worsen bipolar depression.

Mark Olfson - One of the best experts on this subject based on the ideXlab platform.

  • mortality risk of Antipsychotic augmentation for adult depression
    PLOS ONE, 2020
    Co-Authors: Tobias Gerhard, Christoph U Correll, Scott T Stroup, Soko Setoguchi, Brian L Strom, Cecilia Huang, Zhiqiang Tan, Stephen Crystal, Mark Olfson
    Abstract:

    Importance Randomized controlled trials have demonstrated increased all-cause mortality in elderly patients with dementia treated with newer Antipsychotics. It is unknown whether this risk generalizes to non-elderly adults using newer Antipsychotics as augmentation treatment for depression. Objective This study examined all-cause mortality risk of newer Antipsychotic augmentation for adult depression. Design Population-based new-user/active comparator cohort study. Setting National healthcare claims data from the US Medicaid program from 2001–2010 linked to the National Death Index. Participants Non-elderly adults (25–64 years) diagnosed with depression who after ≥3 months of antidepressant monotherapy initiated either augmentation with a newer Antipsychotic or with a second antidepressant. Patients with alternative indications for Antipsychotic medications, such as schizophrenia, psychotic depression, or bipolar disorder, were excluded. Exposure Augmentation treatment for depression with a newer Antipsychotic or with a second antidepressant. Main outcome All-cause mortality during study follow-up ascertained from the National Death Index. Results The analytic cohort included 39,582 patients (female = 78.5%, mean age = 44.5 years) who initiated augmentation with a newer Antipsychotic (n = 22,410; 40% = quetiapine, 21% = risperidone, 17% = aripiprazole, 16% = olanzapine) or with a second antidepressant (n = 17,172). The median chlorpromazine equivalent starting dose for all newer Antipsychotics was 68mg/d, increasing to 100 mg/d during follow-up. Altogether, 153 patients died during 13,328 person-years of follow-up (newer Antipsychotic augmentation: n = 105, follow-up = 7,601 person-years, mortality rate = 138.1/10,000 person-years; antidepressant augmentation: n = 48, follow-up = 5,727 person-years, mortality rate = 83.8/10,000 person-years). An adjusted hazard ratio of 1.45 (95% confidence interval, 1.02 to 2.06) indicated increased all-cause mortality risk for newer Antipsychotic augmentation compared to antidepressant augmentation (risk difference = 37.7 (95%CI, 1.7 to 88.8) per 10,000 person-years). Results were robust across several sensitivity analyses. Conclusion Augmentation with newer Antipsychotics in non-elderly patients with depression was associated with increased mortality risk compared with adding a second antidepressant. Though these findings require replication and cannot prove causality, physicians managing adults with depression should be aware of this potential for increased mortality associated with newer Antipsychotic augmentation.

  • treatment of young people with Antipsychotic medications in the united states
    JAMA Psychiatry, 2015
    Co-Authors: Mark Olfson, Marissa King, Michael Schoenbaum
    Abstract:

    DESIGN, SETTING, AND PARTICIPANTS A retrospective descriptive analysis of Antipsychotic prescriptions among patients aged 1 to 24 years was performed with data from calendar years 2006 (n = 765 829), 2008 (n = 858 216), and 2010 (n = 851 874), including a subset from calendar year 2009 with service claims data (n = 53 896). Data were retrieved from the IMS LifeLink LRx Longitudinal Prescription database, which includes approximately 60% of all retail pharmacies in the United States. Denominators were adjusted to generalize estimates to the US population. MAIN OUTCOMES AND MEASURES The percentage of young people filling 1 or more Antipsychotic prescriptions during the study year by sex and age group (younger children, 1-6 years; older children, 7-12 years; adolescents, 13-18 years; and young adults, 19-24 years) was calculated. Among young people with Antipsychotic use, percentages with specific clinical psychiatric diagnoses and 1 or more Antipsychotic prescriptions from a psychiatrist and from a child and adolescent psychiatrist were also determined. RESULTS The percentages of young people using Antipsychotics in 2006 and 2010, respectively, were 0.14% and 0.11% for younger children, 0.85% and 0.80% for older children, 1.10% and 1.19% for adolescents, and 0.69% and 0.84% for young adults. In 2010, males were more likely than females to use Antipsychotics, especially during childhood and adolescence: 0.16% vs 0.06% for younger children, 1.20% vs 0.44% for older children, 1.42% vs 0.95% for adolescents, and 0.88% vs 0.81% for young adults. Among young people treated with Antipsychotics in 2010, receiving a prescription from a psychiatrist was less common among younger children (57.9%) than among other age groups (range, 70.4%-77.9%). Approximately 29.3% of younger children treated with Antipsychotics in 2010 received 1 or more Antipsychotic prescriptions from a child and adolescent psychiatrist. Among young people with claims for mental disorders in 2009 who were treated with Antipsychotics, the most common diagnoses were attention-deficit/hyperactivity disorder in younger children (52.5%), older children (60.1%), and adolescents (34.9%) and depression in young adults (34.5%).

  • pharmacoepidemiology of Antipsychotic use in youth with adhd trends and clinical implications
    Current Psychiatry Reports, 2013
    Co-Authors: Michael L Birnbaum, Mark Olfson, John M. Kane, Tobias Gerhard, Ema Saito, Almut G Winterstein, Christoph U Correll
    Abstract:

    Although concern has been raised about Antipsychotic prescribing to youth with attention-deficit/hyperactivity disorder (ADHD), the available database is limited to individual studies. Therefore, in order to provide a synthesis of prevalence and time trends, we conducted a systematic review and pooled analysis of pharmaco-epidemiologic data on Antipsychotic use in ADHD youth. Of 1806 hits, 21 studies (N) were retained that reported analyzable data for three separate populations: 1) Antipsychotic-treated youth (N = 15, n = 341,586); 2) ADHD youth (N = 9, n = 6,192,368), and 3) general population youth (N = 5, n = 14,284,916). Altogether, 30.5 ± 18.5 % of Antipsychotic-treated youth had ADHD. In longitudinal studies, this percentage increased over time (1998–2007) from 21.7 ± 7.1 % to 27.7 ± 7.7 %, ratio = 1.3 ± 0.4. Furthermore, 11.5 ± 17.5 % of ADHD youth received Antipsychotics. In longitudinal studies, this percentage also increased (1998–2006) from 5.5 ± 2.6 % to 11.4 ± 6.7 %, ratio = 2.1 ± 0.6. Finally, 0.12 ± 0.07 % of youth in the general population were diagnosed with ADHD and received Antipsychotics. Again, in longitudinal studies, this percentage increased over time (1993–2007): 0.13 ± 0.09 % to 0.44 ± 0.49 %, ratio = 3.1 ± 2.2. Taken together, these data indicate that Antipsychotics are used by a clinically relevant and increasing number of youth with ADHD. Reasons for and risk/benefit ratios of this practice with little evidence base require further investigation.

  • national trends in the office based treatment of children adolescents and adults with Antipsychotics
    Archives of General Psychiatry, 2012
    Co-Authors: Mark Olfson, Shuai Wang, Christoph U Correll
    Abstract:

    sonsincreasedfrom0.24to1.83forchildren,0.78to3.76 for adolescents, and 3.25 to 6.18 for adults. The proportion of total visits that included a prescription of Antipsychotics increased during this period from 0.16% to 1.07% for youths and from 0.88% to 1.73% for adults. From 2005 to 2009, disruptive behavior disorders were the most common diagnoses in child and adolescent Antipsychotic visits, accounting for 63.0% and 33.7%, respectively, while depression (21.2%) and bipolar disorder (20.2%) were the 2 most common diagnoses in adult Antipsychotic visits. Psychiatrists provided a larger proportion of the Antipsychotic visits for children (67.7%) andadolescents(71.6%)thantoadults(50.3%)(P.001). From2005to2009,Antipsychoticswereincludedin28.8% of adult visits and 31.1% of youth visits to psychiatrists. Conclusions: On a population basis, adults make considerably more medical visits with a prescription of Antipsychotics than do adolescents or children. Yet Antipsychotic treatment has increased especially rapidly among young people, and recently Antipsychotics have been prescribed in approximately the same proportion of youth and adult visits to psychiatrists.

  • national trends in the outpatient treatment of children and adolescents with Antipsychotic drugs
    Archives of General Psychiatry, 2006
    Co-Authors: Mark Olfson, Carlos Blanco, Carmen Moreno, Gonzalo Laje
    Abstract:

    Context Although there are indications that Antipsychotic drugs are increasingly used to treat children and adolescents, little is known about the characteristics of those who receive them. Objective To examine national trends and patterns in Antipsychotic treatment of youth seen by physicians in office-based medical practice. Design Analysis of national trends of visits (1993-2002) that included prescription of Antipsychotics, and comparison of the clinical and demographic characteristics of visits (2000-2002) that included or did not include Antipsychotic treatment. Setting Outpatient visits to physicians in office-based practice. Participants Patient visits by persons 20 years and younger from the National Ambulatory Medical Care Surveys from 1993 to 2002. Main Outcome Measures Visits that included prescription of Antipsychotics. Results In the United States, the estimated number of office-based visits by youth that included Antipsychotic treatment increased from approximately 201 000 in 1993 to 1 224 000 in 2002. From 2000 to 2002, the number of visits that included Antipsychotic treatment was significantly higher for male youth (1913 visits per 100 000 population) than for female youth (739 visits per 100 000 population), and for white non-Hispanic youth (1515 visits per 100 000 population) than for youth of other racial or ethnic groups (426 visits per 100 000 population). Overall, 9.2% of mental health visits and 18.3% of visits to psychiatrists included Antipsychotic treatment. From 2000 to 2002, 92.3% of visits with prescription of an Antipsychotic included a second-generation medication. Mental health visits with prescription of an Antipsychotic included patients with diagnoses of disruptive behavior disorders (37.8%), mood disorders (31.8%), pervasive developmental disorders or mental retardation (17.3%), and psychotic disorders (14.2%). Conclusions There has been a sharp national increase in Antipsychotic treatment among children and adolescents in office-based medical practice. Second-generation Antipsychotics are being widely prescribed, and emerging empirical evidence provides a base of support that is limited to short-term safety and efficacy.

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  • incidence of tardive dyskinesia with typical versus atypical Antipsychotics in very high risk patients
    Biological Psychiatry, 2003
    Co-Authors: Christian R Dolder, Dilip V Jeste
    Abstract:

    Our aim was to study the risk of developing tardive dyskinesia in highly vulnerable patients (i.e., middle-aged and older adults with borderline dyskinesia) treated with conventional versus atypical Antipsychotics.We examined the cumulative incidence of definitive tardive dyskinesia at 1, 3, and 6 months during Antipsychotic treatment among 240 outpatients at least 45 years of age who had borderline tardive dyskinesia at baseline. Patients treated with conventional Antipsychotics were approximately two times more likely to develop definitive tardive dyskinesia during the study period compared with those treated with atypical Antipsychotics (p <.001). This difference was found despite patients in the atypical Antipsychotic group being significantly older and having more severe extrapyramidal symptoms at baseline than those prescribed typical Antipsychotics. Among patients at a very high risk for worsening tardive dyskinesia, the use of atypical Antipsychotics was associated with a significantly lower risk of developing definitive tardive dyskinesia compared with conventional Antipsychotics.