Trials Of Antipsychotic Medications Research Articles

Response rates to sequential trials of antipsychotic medications according to algorithms or treatment guidelines in psychotic disorders. A systematic review and meta-analysis

BackgroundThere is a relative lack of research evaluating the outcomes when treatment guidelines or algorithms for psychotic disorders are followed. This systematic review and meta-analysis determined the response rates to antipsychotic medications at different stages of these algorithms and whether these response rates differ in first episode cohorts. MethodsData sources: A systematic search strategy was conducted across four databases PubMed, EMBASE, PsycINFO (Ovid) and CINAHL. Studies that had sequential trials of different antipsychotic medications were included. A meta-analysis of proportions was performed using random effects models and sub-group analysis in first episode psychosis studies. ResultsOf the 4078 unique articles screened, fourteen articles, from nine unique studies, were eligible and included 2522 participants. The proportion who experienced a response to any antipsychotic in the first stage of an algorithm was 0.53 (95 % C.I.:0.38,0.68) and this decreased to 0.26 (95 % C.I.:0.15,0.39) in the second stage. When clozapine was used in the third stage, the proportion that achieved a response was 0.43 (95 % C.I. 0.19, 0.69) compared to 0.26 (95 % C.I.:0.05,0.54) if a different antipsychotic was used. Four studies included 907 participants with a first episode of psychosis and the proportions that achieved a response were: 1st stage: 0.63 (95 % C.I.: 0.45, 0.79); 2nd stage: 0.34 (95 % C.I.:0.16,0.55); clozapine 3rd stage: 0.45 (95 % C.I.:0.0,0.97), different antipsychotic 3rd stage: 0.15 (95 % C.I.,0.01,0.37). DiscussionThese findings support the recommendation to have a trial of clozapine after two other antipsychotic medications have been found to be ineffective.

First generation antipsychotic-associated serious adverse events in women: a retrospective analysis of a pharmacovigilance database.

Women have been under-represented in trials of antipsychotic medications. Our primary objective was toevaluate five adverse events (AE) associated with first-generation antipsychotics (FGAs) among women relative to menthrough an analysis of the FDA Adverse Event Reporting System (FAERS). We queried 24.6 million AE reports from 2000 to 2023 involving FGAs. The study cohort consisted of chlorpromazine (n = 3317), fluphenazine (n = 1124), haloperidol (n = 16,709), loxapine (n = 3151), perphenazine (n = 816), thioridazine (n = 665), thiothixene (n = 244), and trifluoperazine (n = 360). Cases of neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), Torsades de Pointes (TdP), agranulocytosis (AG), and cerebrovascular adverse events (CVAE) were identified. Reporting odds ratios (ROR) and associated 95% confidence intervals (CI) were calculated with logistic regression for each AE among women relative to men. A total of 2,857 serious AEs were evaluated in the study cohort (NMS = 1810, TD = 434, TdP = 260, AG = 149, CVAE = 204). The ROR for women compared to men was 0.79 (95% CI, 0.71-0.87) for NMS, 0.83 (0.68-1.01) for TD, 1.21 (0.94-1.53) for TdP, 0.71 (0.51-0.98) for AG, and 0.91 (0.68-1.19) for CVAE. A secondary analysis revealed a higher odds in women compared to men of hospitalization associated with reports of TD (ROR = 1.95, 1.29-2.94) and death associated with reports of AG (ROR = 2.46, 1.15-5.24). A subgroup analysis of haloperidol revealed an ROR = 1.67 (1.26-2.21) for women relative to men for TdP. The subgroup analysis of haloperidol AEs revealed a significantly higher reporting odds ratio for TdP. Additionally, the secondary study findings suggest that women were more vulnerable to worse outcomes associated with certain AEs of FGAs.

Illusory generalizability of clinical prediction models.

It is widely hoped that statistical models can improve decision-making related to medical treatments. Because of the cost and scarcity of medical outcomes data, this hope is typically based on investigators observing a model's success in one or two datasets or clinical contexts. We scrutinized this optimism by examining how well a machine learning model performed across several independent clinical trials of antipsychotic medication for schizophrenia. Models predicted patient outcomes with high accuracy within the trial in which the model was developed but performed no better than chance when applied out-of-sample. Pooling data across trials to predict outcomes in the trial left out did not improve predictions. These results suggest that models predicting treatment outcomes in schizophrenia are highly context-dependent and may have limited generalizability.

Pharmacological treatment for challenging behavior in adults with intellectual disability: Systematic review and meta-analysis.

Few evidence on the use of antipsychotics in people with intellectual disabilities and challenging behaviors, generates the need to develop studies that contribute to collect, compare and synthesize the available information. The present systematic review and meta-analysis aims to determine the clinical efficacy of antipsychotic medication in reducing critical episodes in this population. We searched Web of Science, Scopus, EBSCO, Embase, and PubMed for randomized controlled trials of antipsychotic medication versus placebo. Preliminarily yielded 1354 abstracts and citations; six studies with 274 subjects met the inclusion criteria of studies with experimental design, longitudinal type, with pre- and post-intervention measurements. There is evidence for the use of psychotropic drugs in the acute management of challenging behaviors in patients with intellectual disability (SMD=-0.85; 95% CI=-1.69 to -0.01; p=0.05). Our results coincide with the recommendations on the efficacy of the use of antipsychotics. Although our study provides evidence, the limited number of studies included in this research does not allow us to obtain totally conclusive results, although it can be considered as a guide for future studies.

Gender differences in the response to antipsychotic medication in patients with schizophrenia: An individual patient data meta-analysis of placebo-controlled studies

ObjectiveTo determine whether gender and menopausal status moderate the response to antipsychotic medication in patients with schizophrenia. MethodsWe analyzed data of 22 short-term placebo-controlled registration trials of antipsychotic medications, which included 5,231 patients with schizophrenia. We applied two-step individual patient data meta-regression analyses to establish the influence of gender and menopausal status on treatment response in mean difference in symptom severity and difference in response (>30% symptom reduction). Analyses were performed both with and without correction for baseline (negative) symptom severity. ResultsAntipsychotic treatment is associated with larger mean symptom reduction in women than in men with schizophrenia. The number needed to treat (NNT) for a response in women was 6.9, in men 9.4. Although, we found an age by gender effect, the gender by treatment effect was independent of premenopausal status and baseline (negative) symptom severity. ConclusionIn the treatment of schizophrenia we found evidence of a higher response to antipsychotic medication in women relative to men. We found no evidence that this effect was driven by menopausal status, or baseline (negative) symptom severity. Despite the impact of gender and age on effect size in acute antipsychotic treatment, efficacy was clinically relevant in all subgroups.

Increased Prevalence of Rare Copy Number Variants in Treatment-Resistant Psychosis.

It remains unknown why ~30% of patients with psychotic disorders fail to respond to treatment. Previous genomic investigations of treatment-resistant psychosis have been inconclusive, but some evidence suggests a possible link between rare disease-associated copy number variants (CNVs) and worse clinical outcomes in schizophrenia. Here, we identified schizophrenia-associated CNVs in patients with treatment-resistant psychotic symptoms and then compared the prevalence of these CNVs to previously published schizophrenia cases not selected for treatment resistance. CNVs were identified using chromosomal microarray (CMA) and whole exome sequencing (WES) in 509 patients with treatment-resistant psychosis (a lack of clinical response to ≥3 adequate antipsychotic medication trials over at least 5 years of psychiatric hospitalization). Prevalence of schizophrenia-associated CNVs in this sample was compared to that in a previously published large schizophrenia cohort study. Integrating CMA and WES data, we identified 47 cases (9.2%) with at least one CNV of known or possible neuropsychiatric risk. 4.7% (n = 24) carried a known neurodevelopmental risk CNV. The prevalence of well-replicated schizophrenia-associated CNVs was 4.1%, with duplications of the 16p11.2 and 15q11.2-q13.1 regions, and deletions of the 22q11.2 chromosomal region as the most frequent CNVs. Pairwise loci-based analysis identified duplications of 15q11.2-q13.1 to be independently associated with treatment resistance. These findings suggest that CNVs may uniquely impact clinical phenotypes beyond increasing risk for schizophrenia and may potentially serve as biological entry points for studying treatment resistance. Further investigation will be necessary to elucidate the spectrum of phenotypic characteristics observed in adult psychiatric patients with disease-associated CNVs.

DNA methylation signature aberration as potential biomarkers in treatment-resistant schizophrenia: Constructing a methylation risk score using a machine learning method

Treatment-resistant schizophrenia (TRS) is defined as a non-response to at least two trials of antipsychotic medication with an adequate dose and duration. We aimed to evaluate the discriminant abilities of DNA methylation probes and methylation risk score between treatment-resistant schizophrenia and non-treatment-resistant schizophrenia. This study recruited 96 schizophrenia patients (TRS and non-TRS) and 56 healthy controls (HC). Participants were divided into a discovery set and a validation set. In the discovery set, we conducted genome-wide methylation analysis (human MethylationEPIC 850K BeadChip) on the subject's blood DNA and discriminated significant methylation signatures, then verified these methylation signatures in the validation set. Based on genome-wide scans of TRS versus non-TRS, thirteen differentially methylated probes were identified at FDR <0.05 and >20% differences in DNA methylation β-values. Next, we selected six probes within gene coding regions (LOC404266, LOXL2, CERK, CHMP7, and SLC17A9) to conduct verification in the validation set using quantitative methylation-specific PCR (qMSP). These six methylation probes showed satisfactory discrimination between TRS patients and non-TRS patients, with an AUC ranging from 0.83 to 0.92, accuracy ranging from 77.8% to 87.3%, sensitivity ranging from 80% to 90%, and specificity ranging from 65.6% to 85%. This methylation risk score model showed satisfactory discrimination between TRS patients and non-TRS patients, with an accuracy of 88.3%. These findings support that methylation signatures may be used as an indicator of TRS vulnerability and provide a model for the clinical use of methylation to identify TRS.

Antipsychotic Optimisation on an Adult Acute Inpatient Ward: A Retrospective Audit

AimsAntipsychotic prescribing in acute inpatient settings is an integral part of patient care. The aim of this audit was to review optimisation of antipsychotics on an acute adult inpatient ward in South West London and St George's NHS Mental Health Trust (SWLSTG). It was ascertained how antipsychotic prescribing on an acute ward meets NICE standards, including duration of antipsychotic use prior to medication change. Furthermore, communication of medication changes was reviewed in the context of the paramount importance of collaborative decision-making in aiding adherence. NICE recommends a 4–6 week trial of antipsychotic medication at optimal dosage. However, it was hypothesised this may vary with side-effects, adherence and risk management in the inpatient environment. To establish the relationship between these factors, data were extracted regarding antipsychotic counselling, baseline physical health investigations, antipsychotic choice, dosage and duration, side-effects and treatment response.MethodsRetrospective data analysis was conducted for patients on an acute adult inpatient ward in SWLSTG. Data extracted from Rio clinical record system and EPMA prescribing software were analysed in Excel. The inclusion criteria were patients admitted or transferred to a 20-bed acute mixed adult ward from 04/08/21 to 04/11/21 with a diagnosis of schizoaffective disorder, schizophrenia, bipolar affective disorder or nonorganic psychosis. This included patients being initiated or continued on antipsychotic medication. From 71 patients, 33 met inclusion criteria. Data were extracted regarding duration of treatment prior to changes in treatment, counselling and pre-treatment investigations. Furthermore, simple statistical analyses were carried out.ResultsThe most commonly initiated antipsychotics on admission were olanzapine (33%), quetiapine (21%), risperidone (15%) and zuclopenthixol decanoate (15%). In those requiring change in antipsychotic regime, mean duration from the start of treatment as inpatient to first change was 11.6 days, time between first and second change 13.8 days, and between second and third change 16.0 days.The data showed in the majority (84.6%) antipsychotics were changed or up-titrated due to inadequate response. Out of the remainder 9.6% were changed due to intolerable side effects and 5.8% due to adherence concerns. In 73% of cases counselling was attempted regarding initial medication changes.ConclusionAntipsychotic therapy was altered more quickly than advised by NICE guidance in the acute inpatient setting evaluated. This can be explained by increased risk, need for intensive management and individual clinical factors including side effects and adherence. Collaborative decision making could be enhanced by ensuring that counselling is attempted for every patient.

Combined use of clozapine and cariprazine in treatment-resistant schizophrenia, is it a good choice?

IntroductionTreatment-resistant schizophrenia (TRS) affects 30% of people with a diagnosis of schizophrenia, and is defined as nonresponse to at least two trials of antipsychotic medication of adequate dose and duration. Clozapine is the only evidence-based treatment for TRS. Cariprazine may be considered significantly more efficacious than risperidone in improving negative symptoms of schizophrenia.ObjectivesTo describe the experience of using cariprazine in combination with clozapine in patients with refractory schizophrenia and negative symptoms.MethodsQualitative design. We present a case report study of a 47-year-old male with a diagnosis of TRS, treated in our outpatient mental health clinic for twenty years. The patient experiences crystallized delusional ideas of harm, self-referential, paranoid and mystical-messianic content, phenomena of theft and thought reading, egodistonic auditory hallucinations. No substance use disorder was observed. He made several suicide attempts in the context of intense suffering and psychotic anguish. Clozapine 400mg/day was instituted after no response to treatment with amisulpride, paliperidone, olanzapine or aripiprazole. The intensity of positive symptoms was reduced (experiences of damage, commenting and insulting auditory hallucinations, self-referentiality), as well as the emotional and behavioral repercussions. Persistent negative symptoms appeared such as apathy, abulia, clinophilia, anergy, social isolation, affective flattening, impairing his functionality.ResultsNeuroimaging and periodic blood tests results were normal. Oral cariprazine was added in ascending doses up to 4.5mg with good tolerance. The patient showed remission of apathy, enhancement of behavioral activation, socialization and motivation to perform occupational activities.ConclusionsCombinations of clozapine with partial agonists may improve the quality of life in refractory schizophrenia.DisclosureNo significant relationships.

Pseudo-Resistant Schizophrenia: Non-Adherence to Treatment

Treatment-resistant schizophrenia (TRS) has been defined as the persistence of positive symptoms despite two or more trials of antipsychotic medication of adequate dose and duration. TRS is a serious clinical problem and occurs in approximately 30% of patients with schizophrenia. It is important that patients who do not adequately respond to antipsychotics be reevaluated to exclude or address causes other than non-responsiveness to medication, that is, the possibility of pseudo-resistance. In particular, non-adherence to oral antipsychotic treatment should be monitored to rule out pseudo-resistant cases of TRS. Moreover, patients with TRS who take their medication as required may have subtherapeutic antipsychotic plasma levels, secondary to pharmacokinetic factors. In this paper, we review the concept and exclusion of pseudo-resistance, especially owing to non-adherence or pharmacokinetic factors, and present methods to enhance drug adherence. Key Words: Adherence · Pharmacokinetics · Pseudo-resistance · Schizophrenia · Treatment-resistance 중심 단어: 순응도 · 약동학 · 조현병 · 치료 ì €í•­ì„± · 치료 ìœ„ì €í•­ì„±

Burying Our Heads in the Sand: The Neglected Importance of Reporting Inter-Rater Reliability in Antipsychotic Medication Trials.

Burying Our Heads in the Sand: The Neglected Importance of Reporting Inter-Rater Reliability in Antipsychotic Medication Trials.

Treatment-Resistant Schizophrenia: Genetic and Neuroimaging Correlates.

Schizophrenia is a severe neuropsychiatric disorder that affects approximately 0.5–1% of the population. Response to antipsychotic therapy is highly variable, and it is not currently possible to predict those patients who will or will not respond to antipsychotic medication. Furthermore, a high percentage of patients, approximately 30%, are classified as treatment-resistant (treatment-resistant schizophrenia; TRS). TRS is defined as a non-response to at least two trials of antipsychotic medication of adequate dose and duration. These patients are usually treated with clozapine, the only evidence-based pharmacotherapy for TRS. However, clozapine is associated with severe adverse events. For these reasons, there is an increasing interest to identify better targets for drug development of new compounds and to establish better biomarkers for existing medications. The ability of antipsychotics to improve psychotic symptoms is dependent on their antagonist and reverse agonist activities at different neuroreceptors, and some genetic association studies of TRS have focused on different pharmacodynamic factors. Some genetic studies have shown an association between antipsychotic response or TRS and neurodevelopment candidate genes, antipsychotic mechanisms of action (such as dopaminergic, serotonergic, GABAergic, and glutamatergic) or pharmacokinetic factors (i.e., differences in the cytochrome families). Moreover, there is a growing body of literature on the structural and functional neuroimaging research into TRS. Neuroimaging studies can help to uncover the underlying neurobiological reasons for such resistance and identify resistant patients earlier. Studies examining the neuropharmacological mechanisms of antipsychotics, including clozapine, can help to improve our knowledge of their action on the central nervous system, with further implications for the discovery of biomarkers and the development of new treatments. The identification of the underlying mechanisms of TRS is a major challenge for developing personalized medicine in the psychiatric field for schizophrenia treatment. The main goal of precision medicine is to use genetic and brain-imaging information to improve the safety, effectiveness, and health outcomes of patients via more efficiently targeted risk stratification, prevention, and tailored medication and treatment management approaches. The aim of this review is to summarize the state of art of pharmacogenetic, pharmacogenomic and neuroimaging studies in TRS.

The Group of Treatment Resistant Schizophrenias. Heterogeneity in Treatment Resistant Schizophrenia (TRS).

Schizophrenia is composed of a heterogeneous group of patient segments. Our current notion of the heterogeneity in schizophrenia is based on patients presenting with diverse disease symptom phenotypes, risk factors, structural and functional neuropathology, and a mixed range of expressed response to treatment. It is important for clinicians to recognize the various clinical presentations of resistance to treatment in schizophrenia and to understand how heterogeneity across treatment resistant patient segments may potentially inform new strategies for the development of effective treatments for Treatment Resistant Schizophrenia (TRS). The heterogeneity of schizophrenia may be reduced by parsing patient segments based on whether patients demonstrate an adequate or inadequate response to treatment. In our current concept of TRS, TRS is defined as non-response to at least two adequate trials of antipsychotic medication and is estimated to affect about 30% of all patients with schizophrenia. In this narrative review, the author discusses that the demonstration of inadequate response to antipsychotic drugs (APDs) may infer that some TRS patients may be suffering from a non-dopamine pathophysiology since D2 receptor antagonist-based treatment is ineffective. Preliminary neurobiological findings may further support the pathophysiologic distinction of TRS from that of general schizophrenia. Investigation of the basis for heterogeneity in TRS through the systematic investigation of relevant “clusters” of similarly at risk individuals may hopefully bring us closer to realize a precision medicine approach for developing effective therapies for TRS patient segments.

Minimal Clinically Important Differences (MCID) in Assessing Outcomes of Post-Traumatic Stress Disorder

This study sought to determine the minimal clinically important difference (MCID) for two frequently used measures of symptom severity in Post-Traumatic Stress Disorder: the Clinician Administered PTSD Scale (CAPS) and the PTSD Symptom Checklist (PCL). Data from a randomized clinical trial of antipsychotic medication in military-related treatment-resistant PTSD (N= 267) included assessments 4 times over 26 weeks. Methods for estimating the MCID were based on both the anchor-based approach, using the Clinical Global Impressions (CGI) severity and improvement scales, rated by both clinicians and patients; and the distribution-based approach (based on standardized z-scores). Severity and change scores on the CAPS and PCL were converted to z-scores and compared across CGI levels using analysis of variance. The average difference in CAPS z-scores between each of three CGI levels between "moderate" to "severe" and from "no change" to "much improved" was 0.758 for clinician CGI ratings and 0.525 for patient CGI ratings and were similar for the PCL (0.483 and 0.471) with all differences significant at p<.0001). Clinically meaningful CAPS and PCL severity and change z-scores range between 0.5-0.8 standard deviations. The MCID estimates suggested here provide an empirical basis for determining whether statistically significant changes in CAPS and PCL scores are clinically meaningful.

A novel approach to measuring response and remission in schizophrenia in clinical trials

BackgroundPharmaceutical companies conduct clinical trials to show the efficacy and safety of new medications for the treatment of schizophrenia. After the new medications are marketed, clinicians treating patients with schizophrenia discover that a considerable number of patients do not respond to these new medications. The goals of the review are to examine the methodology and design of recent antipsychotic clinical trials, identify common flaws, and propose guidelines to fix the flaws and improve the quality of future clinical trials of antipsychotic medications. MethodsA review of recent antipsychotic clinical trials was conducted using a PubMed search. Ten recent trials published in the past four years were reviewed and their methods analyzed and critiqued. ResultsThe authors identified six major methodological flaws that may explain the suboptimal response in many patients after a drug is approved. Most of the flaws are related to eligibility criteria, the misuse of the Positive and Negative Syndromes Scale (PANSS) and the lack of consensus on how to define remission, response and exacerbation in schizophrenia. Proposed guidelines for a more rigorous use of the PANSS are presented and recommendations are proposed for using uniform criteria for remission, response and exacerbation in schizophrenia. ConclusionsThe authors recommend using standardized diagnostic interviews to screen patients for eligibility criteria and using the PANSS according to the author's recommendations and the proposed guidelines. Uniform criteria to define remission, response and exacerbation are recommended for clinical trials examining the efficacy and safety of antipsychotic drugs in schizophrenia.

The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia.

(Reprinted with permission from American Journal of Psychiatry 2016; 173:543-546).

Fifteen minute consultation on children ‘hearing voices’: when to worry and when to refer

Auditory hallucinations are uncommon paediatric presentations, but they can be alarming and lead to emergency consultations. This review outlines the phenomenology of auditory hallucinations, their assessment and clinical significance. Auditory...

Pharmacological interventions for those who have sexually offended or are at risk of offending.

This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the effects of pharmacological interventions on target sexual behaviour for people who have been convicted or at risk of sexual offending.

Placebo response in antipsychotic clinical trials: a meta-analysis.

Because increasing placebo response rates decrease drug-placebo differences and increase the number of failed trials, it is imperative to determine what is causing this trend. To investigate the relationship between antipsychotic medication and placebo response by publication year, and to identify associated study design and implementation variables. MEDLINE, PsycINFO, and PubMed were searched to identify randomized clinical trials of antipsychotic medications published from 1960 to July 2013. Included were randomized clinical trials lasting 4 to 24 weeks, contrasting antipsychotic medication with placebo or an active comparator, and enrolling patients 18 years of age or older with schizophrenia or schizoaffective disorder. Standardized mean change scores were calculated for each treatment arm, plotted against publication year, and tested with Spearman rank correlation coefficients. Hierarchical linear modeling identified factors associated with the standardized mean change across medication and placebo treatment arms. We hypothesized that the mean change in placebo-treated patients would significantly increase from 1960 to the present, that a greater change would be observed in active comparator vs placebo-controlled trials, and that more protocol visits would increase the symptom change observed. In the 105 trials examined, the mean change observed in placebo arms increased significantly with year of publication (n=39, r=0.52, P=.001), while the mean change in effective dose medication arms decreased significantly (n=208, r=-0.26, P<.001). Significant interactions were found between assignment to effective dose medication and publication year (t260=-5.55, P<.001), baseline severity (t260=5.08, P<.001), and study duration (t260=-3.76, P<.001), indicating that the average drug-placebo difference significantly decreased over time, with decreasing baseline severity and with increasing study duration. Medication treatment in comparator studies was associated with significantly more improvement than medication treatment in placebo-controlled trials (t93=2.73, P=.008). The average treatment change associated with placebo treatment in antipsychotic trials increased since 1960, while the change associated with medication treatment decreased. Changes in randomized clinical trials leading to inflation of baseline scores, enrollment of less severely ill participants, and higher expectations of patients may all be responsible.

The relationship between suicide and violence in schizophrenia: Analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) dataset

BackgroundSuicide and violence often co-occur in the general population as well as in mentally ill individuals. Few studies, however, have assessed whether these suicidal behaviors are predictive of violence risk in mental illness. AimsThe aim of this study is to investigate whether suicidal behaviors, including suicidal ideation, threats, and attempts, are significantly associated with increased violence risk in individuals with schizophrenia. MethodData for these analyses were obtained from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial, a randomized controlled trial of antipsychotic medication in 1460 adults with schizophrenia. Univariate Cox regression analyses were used to calculate hazard ratios (HRs) for suicidal ideation, threats, and attempts. Multivariate analyses were conducted to adjust for common confounding factors, including: age, alcohol or drug misuse, major depression, antisocial personality disorder, depression, hostility, positive symptom, and poor impulse control scores. Tests of discrimination, calibration, and reclassification assessed the incremental predictive validity of suicidal behaviors for the prediction of violence risk. ResultsSuicidal threats and attempts were significantly associated with violence in both males and females with schizophrenia with little change following adjustment for common confounders. Only suicidal threats, however, were associated with a significant increase in incremental validity beyond age, diagnosis with a comorbid substance use disorder, and recent violent behavior. ConclusionsSuicidal threats are independently associated with violence risk in both males and females with schizophrenia, and may improve violence risk prediction.