Efficacy of a synbiotic in the management of adults with Attention-Deficit and Hyperactivity Disorder and/or Borderline Personality Disorder and high levels of irritability: Results from a multicenter, randomized, placebo-controlled, "basket" trial.

Irritability worsens prognosis and increases mortality in individuals with Attention-Deficit and Hyperactivity Disorder (ADHD) and/or Borderline Personality Disorder (BPD). However, treatment options are still insufficient. The aim of this randomized, double blind, placebo-controlled study was to investigate the superiority of a synbiotic over placebo in the management of adults with ADHD and/or BPD and high levels of irritability. The study was conducted between February 2019 and October 2020 at three European clinical centers located in Hungary, Spain and Germany. Included were patients aged 18-65 years old diagnosed with ADHD and/or BPD and high levels of irritability (i.e., an Affectivity Reactivity Index (ARI-S) ≥ 5, plus a Clinical Global Impression-Severity Scale (CGI-S) score ≥ 4). Subjects were randomized 1(synbiotic):1(placebo); the agent was administered each day, for 10 consecutive weeks. The primary outcome measure was end-of-treatment response (i.e., a reduction ≥ 30 % in the ARI-S total score compared to baseline, plus a Clinical Global Impression-Improvement (CGI-I) total score of < 3 (very much, or much improved) at week 10). Between-treatment differences in secondary outcomes, as well as safety were also investigated. Of the 231 included participants, 180 (90:90) were randomized and included in the intention-to-treat-analyses. Of these, 117 (65 %) were females, the mean age was 38 years, ADHD was diagnosed in 113 (63 %), BPD in 44 (24 %), both in 23 (13 %). The synbiotic was well tolerated. At week 10, patients allocated to the synbiotic experienced a significantly higher response rate compared to those allocated to placebo (OR: 0.2, 95 % CI:0.1 to 0.7; P = 0.01). These findings suggest that that (add-on) treatment with a synbiotic may be associated with a clinically meaningful improvement in irritability in, at least, a subgroup of adults with ADHD and/or BPD. A superiority of the synbiotic over placebo in the management of emotional dysregulation (-3.6, 95 % CI:-6.8 to -0.3; P = 0.03), emotional symptoms (-0.6, 95 % CI:-1.2 to -0.05; P = 0.03), inattention (-1.8, 95 % CI: -3.2 to -0.4; P = 0.01), functioning (-2.7, 95 % CI: -5.2 to -0.2; P = 0.03) and perceived stress levels (-0.6, 95 % CI: -1.2 to -0.05; P = 0.03) was also suggested. Higher baseline RANK-L protein levels were associated with a significantly lower response rate, but only in the synbiotic group (OR: 0.1, 95 % CI: -4.3 to - 0.3, P = 0.02). In the placebo group, higher IL-17A levels at baseline were significantly associated with a higher improvement in in particular, emotional dysregulation (P = 0.04), opening a door for new (targeted) drug intervention. However, larger prospective studies are warranted to confirm the findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03495375.

Transcriptomic risk scores for attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. We performed a transcriptome-wide association study (TWAS) using the latest genome-wide association study (GWAS) meta-analysis, in 38,691 individuals with ADHD and 186,843 controls, and 14 gene-expression reference panels across multiple brain tissues and whole blood. Based on TWAS results, we selected subsets of genes and constructed transcriptomic risk scores (TRSs) for the disorder in peripheral blood mononuclear cells of individuals with ADHD and controls. We found evidence of association between ADHD and TRSs constructed using expression profiles from multiple brain areas, with individuals with ADHD carrying a higher burden of TRSs than controls. TRSs were uncorrelated with the polygenic risk score (PRS) for ADHD and, in combination with PRS, improved significantly the proportion of variance explained over the PRS-only model. These results support the complementary predictive potential of genetic and transcriptomic profiles in blood and underscore the potential utility of gene expression for risk prediction and deeper insight in molecular mechanisms underlying ADHD.

Genetic overlap and causality between substance use disorder and attention-deficit and hyperactivity disorder.

Substance use disorder (SUD) often co-occur at high prevalence with other psychiatric conditions. Among them, attention-deficit and hyperactivity disorder (ADHD) is present in almost one out of every four subjects with SUD and is associated with higher severity, more frequent polysubstance dependence and increased risk for other mental health problems in SUD patients. Despite studies suggesting a genetic basis in the co-occurrence of these two conditions, the genetic factors involved in the joint development of both disorders and the mechanisms mediating these causal relationships are still unknown. In this study, we tested whether the genetic liability to five SUD-related phenotypes share a common background in the general population and clinically diagnosed ADHD individuals from an in-house sample of 989 subjects and further explored the genetic overlap and the causal relationship between ADHD and SUD using pre-existing GWAS datasets. Our results confirm a common genetic background between ADHD and SUD and support the current literature on the causal effect of the liability to ADHD on the risk for SUD. We added novel findings on the effect of the liability of lifetime cannabis use on ADHD and found evidence of shared genetic background underlying SUD in general population and in ADHD, at least for lifetime cannabis use, alcohol dependence and smoking initiation. These findings are in agreement with the high comorbidity observed between ADHD and SUD and highlight the need to control for substance use in ADHD and to screen for ADHD comorbidity in all SUD patients to provide optimal clinical interventions.

Association Between Vitamin D Status and Schizophrenia: A First Psychotic Episode Study.

Vitamin D deficiency has been linked with schizophrenia. We aimed to determine whether patients with a first episode of psychosis (FEP) had lower vitamin D levels compared with controls considering their final diagnosis. We conducted a cross-sectional study determining 25-hydroxyvitamin D blood levels. 25-Hydroxyvitamin D levels were considered optimum at 20 ng/mL or greater. A group of 45 adult patients with FEP and a group of 22 healthy controls matched for age were recruited. The patient group was subdivided in two final diagnosis groups (schizophrenia versus other psychoses) after a 6-month follow-up. Average vitamin D values were deficient for FEP patients, especially those 22 with a final diagnosis of schizophrenia. These results relating vitamin D and schizophrenia generate interest to further examine this association.

Risk factors for temporary work disability.

INTRODUCTION: The relationship among labor difficulties and psychiatric disorders is important and bidirectional. However, current information about the influence of psychiatric disorders in temporary work disability in Spain is inconclusive. For this reason, we aimed to describe the prevalence of the conclusions of psychiatric expert’s reports including maintain o revoke the temporary disability (TD). We also aimed to compare sociodemographic, clinical and therapeutic variables according with the decision of maintain or revoke this condition. METHODOLOGY: A descriptive study was conducted in psychiatric patients that were examined by psychiatric experts during one year. At the examination time, the patients had a sick leave mean of 5 months. The psychiatric experts assessed their ability to work according to the interference of the psychiatric symptoms. RESULTS: A total of 380 patients were included (66.8% women, 42±10.9 years), 87.9% had a result of revoke the temporary work disability. No sociodemographic or therapeutic factors were associated with the continuity of sick leave. The most common diagnosis of patients who obtained a revoked temporary work disability was adjustment disorder (66.2% vs 13%, p=0.001) and patients who maintained the temporary work disability was major depressive disorder (45.7% vs 3.9%, p=0.001). CONCLUSIONS: After a psychiatric expert’s examination the most of the results suggest to revoke the temporary work disability. Major depressive disorder is the most commonly diagnostic associated to continue sick leave.

ADHD Rating Scale (ADHD-RS): Validation in Spanish in adult population according to the DSM-5.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is the most common childhood neurodevelopmental disorder, with an estimated prevalence in adulthood of 2.5-3.4%. The Attention Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) is an 18-item self-administered scale that assesses attention deficit and hyperactivity/impulsivity symptoms of ADHD in adults. This study aims to validate the ADHD-RS in Spanish according to the diagnostic criteria established by the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). MATERIALS AND METHODS: A sample of 441 adult patients (mean age 33.34±11.37 years) was included, 396 subjects were diagnosed with ADHD (mean age 33.17±11.18 years), and 45 were controls (mean age 35.40±12.33 years). The clinical diagnosis of ADHD was established according to the DSM-5 criteria. The ADHD-RS was subsequently administered to all participants. A logistic regression study evaluated the model in terms of sensitivity, specificity, positive predictive value, and negative predictive value. The Kaiser-Meyer-Olkin (KMO) measure was performed to assess the adequacy of the data set, and to determine whether factor analysis was applicable, Bartlett's sphericity test was performed. Principal component analysis was used, using the Varimax orthogonal rotation method, which minimizes the number of variables with high loads on each factor, obtaining two factors and thus, simplifying their interpretation. RESULTS: The cut-off point that best discriminates the combined presentation of ADHD was 24 points, with a sensitivity of 94.78%, a specificity of 84.79%, a PPV (positive predictive value) of 93.74%, and an NPV (negative predictive value) of 78.33, with an area under the curve (AUC) of 0.85, and a kappa coefficient of 0.86. Regarding inattentive ADHD, the cut-off point that best discriminates was 21 points, with a sensitivity of 92.56%, a specificity of 76.26%, a PPV of 92.01%, an NPV of 78.33%, an AUC of 0.90, and a kappa coefficient of 0.87. Different cut-off values in the two subgroups suggests that a differentiated cut-off point for the inattentive and combined presentations may be an adequate assessment strategy for ADHD in adulthood. CONCLUSIONS: The Spanish version of the ADHD-RS is a valid instrument to evaluate ADHD in adults according to the diagnostic criteria established by the DSM-5. Differentiated cut-off points for the inattentive and combined presentations discriminate more accurately than a single cut-off point.

Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome.

The association between Attention Deficit Hyperactivity Disorder (ADHD) and low-grade inflammation has been explored in children but rarely in adults. Inflammation is characteristic of some, but not all, patients with ADHD and might be influenced by ADHD medication but also lifestyle factors including nutrition, smoking, and stress. It is also still unclear if any specific symptoms are related to inflammation. Therefore, we assessed 96 inflammatory proteins in a deeply phenotyped cohort of 126 adult ADHD participants with a stable medication status using OLINK technology. A data-based, unsupervised hierarchical clustering method could identify two distinct biotypes within the 126 ADHD participants based on their inflammatory profile: a higher inflammatory potential (HIP) and a lower inflammatory protein potential (LIP) group. Biological processes that differed strongest between groups were related to the NF-κB pathway, chemokine signaling, IL-17 signaling, metabolic alterations, and chemokine attraction. A comparison of sample characteristics revealed that the HIP group was more likely to have higher levels of chronic stress (p < 0.001), a higher clinical global impression scale score (p = 0.030), and a higher risk for suicide (p = 0.032). Medication status did not influence protein levels significantly (p ≥ 0.074), but psychotropic co-medication (p ≤ 0.009) did. In conclusion, our data suggest the presence of two distinct biotypes in adults with ADHD. Higher levels of inflammatory proteins in ADHD are linked to higher levels of chronic perceived stress in a linear fashion. Further research on inflammation in adults with ADHD should take stress levels into account.

Inhaled Loxapine as a Rapid Treatment for Agitation in Patients with Personality Disorder: A Prospective Study on the Effects of Time.

Objective: Agitation in patients diagnosed with personality disorders (PD) is one of the most frequent crises in emergency departments (ED). Although many medications have been tested, their effectiveness has been small or non-significant, and no specific drugs are supported by the available evidence. This study aimed to evaluate the efficacy of Inhaled loxapine (IL) as a therapeutic option for agitated patients with PD. Methods: A naturalistic, unicentric, prospective study was carried out. Thirty subjects diagnosed with PD and attending the ED with episodes of agitation were recruited most of whom were women diagnosed with Borderline Personality Disorder. Subjects were treated with a single dose of IL (9.1 mg). Efficacy was assessed with the Clinical Global Impression scale, the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) and the Agitation-Calmness Evaluation Scale (ACES). Patients were followed 60 minutes after administration to measure IL effect and its duration. Results: IL exhibited an overall efficacy in managing mild to severe agitation, with a quick onset of effect and persistence. 'Effect of time', where IL efficacy is maintained over time, is more marked in higher-severity agitation. No additional treatments were needed to improve agitation during the follow-up time. Conclusion: Results suggest that IL could be a safe and effective option to manage agitation in PD.

Comprehensive analysis of omics data identifies relevant gene networks for Attention-Deficit/Hyperactivity Disorder (ADHD).

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder that results from the interaction of both genetic and environmental risk factors. Genome-wide association studies have started to identify multiple genetic risk loci associated with ADHD, however, the exact causal genes and biological mechanisms remain largely unknown. We performed a multi-step analysis to identify and characterize modules of co-expressed genes associated with ADHD using data from peripheral blood mononuclear cells of 270 ADHD cases and 279 controls. We identified seven ADHD-associated modules of co-expressed genes, some of them enriched in both genetic and epigenetic signatures for ADHD and in biological pathways relevant for psychiatric disorders, such as the regulation of gene expression, epigenetics and immune system. In addition, for some of the modules, we found evidence of potential regulatory mechanisms, including microRNAs and common genetic variants. In conclusion, our results point to promising genes and pathways for ADHD, supporting the use of peripheral blood to assess gene expression signatures in psychiatric disorders. Furthermore, they highlight that the combination of multi-omics signals provides deeper and broader insights into the biological mechanisms underlying ADHD.

Insomnia Disorder in Adult Attention-Deficit/Hyperactivity Disorder Patients: Clinical, Comorbidity, and Treatment Correlates.

Introduction: Several investigations have been performed on insomnia symptoms in adult attention-deficit/hyperactivity disorder (ADHD). However, the relationship between insomnia disorder and adult ADHD has been neglected in research. The main objective of the current study is to analyze the differences between adult ADHD patients with and without insomnia disorder, in terms of ADHD clinical severity, medical and psychiatric comorbidity, psychopharmacological treatment, and quality of life. Material and Methods: Two hundred and fifty-two adult patients with ADHD (mean age 37.60 ± 13.22 years; ADHD presentations-combined: 56.7%, inattentive: 39.7%, hyperactive/impulsive: 3.6%) were evaluated with an exhaustive clinical and psychological evaluation protocol including semistructured interviews (for comorbidities and ADHD assessment) and symptom rating scales for ADHD. The diagnosis of ADHD and insomnia disorder was made according to DSM-5 criteria. Furthermore, the Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Epworth Sleepiness Scale were administered. Results: Insomnia disorder was found in 44.4% of adult ADHD patients and was more common in combined presentation (64.3%) and in patients with more ADHD severity. Comorbidities (both medical and psychiatric), especially mood disorders (42%), anxiety disorder (26.8%), personality disorder (39.3%), and any substance use disorder (11.6%), were associated with a higher insomnia disorder prevalence. ADHD stimulant treatment was related to lower insomnia disorder compared to patients without medication, as well as ADHD stable treatment. Additionally, worse health-related quality of life was associated with insomnia disorder. Conclusion: Insomnia disorder is highly prevalent in adult ADHD and is related to higher ADHD severity and more psychiatric and medical comorbidities. Some stimulants and stable pharmacological ADHD treatment are associated with better outcomes of insomnia disorder.

Gut microbiota signature in treatment-naïve attention-deficit/hyperactivity disorder.

Compelling evidence supports alterations in gut microbial diversity, bacterial composition, and/or relative abundance of several bacterial taxa in attention-deficit/hyperactivity disorder (ADHD). However, findings for ADHD are inconsistent among studies, and specific gut microbiome signatures for the disorder remain unknown. Given that previous studies have mainly focused on the pediatric form of the disorder and involved small sample sizes, we conducted the largest study to date to compare the gastrointestinal microbiome composition in 100 medication-naïve adults with ADHD and 100 sex-matched healthy controls. We found evidence that ADHD subjects have differences in the relative abundance of several microbial taxa. At the family level, our data support a lower relative abundance of Gracilibacteraceae and higher levels of Selenomonadaceae and Veillonellaceae in adults with ADHD. In addition, the ADHD group showed higher levels of Dialister and Megamonas and lower abundance of Anaerotaenia and Gracilibacter at the genus level. All four selected genera explained 15% of the variance of ADHD, and this microbial signature achieved an overall sensitivity of 74% and a specificity of 71% for distinguishing between ADHD patients and healthy controls. We also tested whether the selected genera correlate with age, body mass index (BMI), or scores of the ADHD rating scale but found no evidence of correlation between genera relative abundance and any of the selected traits. These results are in line with recent studies supporting gut microbiome alterations in neurodevelopment disorders, but further studies are needed to elucidate the role of the gut microbiota on the ADHD across the lifespan and its contribution to the persistence of the disorder from childhood to adulthood.

Sleep in adults with autism spectrum disorder and attention deficit/hyperactivity disorder: A systematic review and meta-analysis.

Sleep-related problems have been frequently reported in neurodevelopmental disorders, with special emphasis in Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD). The aim of the present study is to conduct a systematic review and meta-analysis on sleep disturbances in adults with ASD and/or ADHD (PROSPERO's CRD42019132916). PubMed and PsycINFO were searched for studies reporting data on sleep objective/subjective measures, as well as prevalence data of sleep disorders, in adults with ASD and/or ADHD. A manual search was conducted throughout reference lists of eligible studies. A total of 1126 studies and 66 references were identified by electronic and manual searches, respectively. Of these, 42 studies were included in the meta-analysis. Results showed that both disorders share a similar sleep-impaired profile with higher sleep onset latency, poorer sleep efficiency, greater number of awakenings during sleep, and a general lower self-perceived sleep quality compared with healthy controls. A higher proportion of N1 sleep was found in ASD participants, while a greater Periodic Limb Movements in Sleep is specific in ADHD adults. More studies are needed, especially those directly comparing ASD and ADHD participants. Controlling for medication, intellectual disability, and concurrent psychiatric disorders is mandatory.

Transcriptome profiling in adult attention-deficit hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with an estimated heritability of around 70%. Although the largest genome-wide association study (GWAS) meta-analysis on ADHD identified independent loci conferring risk to the disorder, the molecular mechanisms underlying the genetic basis of the disorder remain to be elucidated. To explore ADHD biology, we ran a two-step transcriptome profiling in peripheral blood mononuclear cells (PBMCs) of 143 ADHD subjects and 169 healthy controls. Through this exploratory study we found eight differentially expressed genes in ADHD. These results highlight promising candidate genes and gene pathways for ADHD and support the use of peripheral tissues to assess gene expression signatures for ADHD.

Epigenome-wide association study of attention-deficit/hyperactivity disorder in adults.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder that often persists into adulthood. There is growing evidence that epigenetic dysregulation participates in ADHD. Given that only a limited number of epigenome-wide association studies (EWASs) of ADHD have been conducted so far and they have mainly focused on pediatric and population-based samples, we performed an EWAS in a clinical sample of adults with ADHD. We report one CpG site and four regions differentially methylated between patients and controls, which are located in or near genes previously involved in autoimmune diseases, cancer or neuroticism. Our sensitivity analyses indicate that smoking status is not responsible for these results and that polygenic risk burden for ADHD does not greatly impact the signatures identified. Additionally, we show an overlap of our EWAS findings with genetic signatures previously described for ADHD and with epigenetic signatures for smoking behavior and maternal smoking. These findings support a role of DNA methylation in ADHD and emphasize the need for additional efforts in larger samples to clarify the role of epigenetic mechanisms on ADHD across the lifespan.

Shared genetic background between children and adults with attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.

The Relationship Between Neuropsychological Deficits and Emotional Lability in Adults With ADHD.

Objective: The objective of this study was to investigate the extent to which neuropsychological performance parameters implicated in ADHD might mediate the relationship between emotional lability (EL) and this disorder. Method: Eight hundred twelve adult patients with ADHD were examined. EL was assessed using the EL subscale of Conners' Adult ADHD Rating Scales (CAARS). To assess cognitive and executive functions, a battery of neuropsychological tests was performed in 262 patients with ADHD and high EL symptomatology and 550 patients with ADHD and low EL symptomatology. Results: Several differences between groups were found regarding neuropsychological performance; however, nearly all significant differences disappeared when the effect of gender, inattention, and hyperactive symptoms and psychiatric comorbidities were taken into account. Conclusion: Our results do not support the hypothesis that neuropsychological deficits are associated with EL in adults with ADHD.

Epigenetic signature for attention-deficit/hyperactivity disorder: identification of miR-26b-5p, miR-185-5p, and miR-191-5p as potential biomarkers in peripheral blood mononuclear cells.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood and persists into adulthood in 40-65% of cases. Given the polygenic and heterogeneous architecture of the disorder and the limited overlap between genetic studies, there is a growing interest in epigenetic mechanisms, such as microRNAs, that modulate gene expression and may contribute to the phenotype. We attempted to clarify the role of microRNAs in ADHD at a molecular level through the first genome-wide integrative study of microRNA and mRNA profiles in peripheral blood mononuclear cells of medication-naive individuals with ADHD and healthy controls. We identified 79 microRNAs showing aberrant expression levels in 56 ADHD cases and 69 controls, with three of them, miR-26b-5p, miR-185-5p, and miR-191-5p, being highly predictive for diagnostic status in an independent dataset of 44 ADHD cases and 46 controls. Investigation of downstream microRNA-mediated mechanisms underlying the disorder, which was focused on differentially expressed, experimentally validated target genes of the three highly predictive microRNAs, provided evidence for aberrant myo-inositol signaling in ADHD and indicated an enrichment of genes involved in neurological disease and psychological disorders. Our comprehensive study design reveals novel microRNA-mRNA expression profiles aberrant in ADHD, provides novel insights into microRNA-mediated mechanisms contributing to the disorder, and highlights promising candidate peripheral biomarkers.

Inhaled Loxapine for Agitation in Intoxicated Patients: A Case Series.

OBJECTIVES: Episodes of agitation are frequent in intoxicated patients who have a substance use disorder, a psychiatric disorder or both (dual diagnosis). For managing the agitation, it is necessary to act promptly in a safe environment and addressing any underlying etiology. Inhaled loxapine improves symptoms of agitation in adults with psychiatric disorders (eg, schizophrenia) within 10 minutes of administration. Recently, some reports have documented the usefulness of loxapine in dual diagnoses patients with agitation. However, the efficacy of loxapine in intoxicated patients has not been deeply addressed. METHODS: This report describes a case series of 12 patients (with addiction or dual disorder) who received inhaled loxapine for symptoms of psychomotor agitation during intoxication with different substances (eg, alcohol, cannabis, or cocaine) at 1 center in Spain. RESULTS: Data from 12 patients were reviewed, 5 patients were attended at the emergency room, 4 at the addiction and dual diagnosis unit, and 3 were treated during hospitalization for detoxification. All patients were under effects of substances. They had substance use disorder (including cannabis, cocaine, alcohol, hypnotics, and hallucinogens), and almost all (90%) presented 1 or more psychiatric disorders. One dose of inhaled loxapine was effective in 9 patients (75%), and in 3 patients, a second dose was required. Only mild dizziness was reported in 1 patient after the second dose. CONCLUSIONS: The acute agitation was effectively and quickly managed with inhaled loxapine in all intoxicated patients and enabled the appropriate clinical evaluation of the agitated state and the patient's management.

Effectiveness of Inhaled Loxapine in Dual-Diagnosis Patients: A Case Series.

OBJECTIVES: Episodes of psychotic agitation are frequent in patients with dual diagnosis, that is, in patients with concomitant psychiatric and substance use disorders. Rapid intervention is needed to treat the agitation at a mild stage to prevent the escalation to aggressive behavior. Inhaled loxapine has been demonstrated to rapidly improve symptoms of mild-to-moderate agitation in adults with psychiatric disorders (schizophrenia and bipolar disorder), but data on patients with dual diagnosis are scarce. METHODS: This study is a retrospective review of data from a case series of patients with dual diagnosis, which were attended for symptoms of agitation while at the emergency room (n = 9), in the outpatient clinic (n = 4), or during hospitalization (n = 1) at 1 center in Spain. All patients received inhaled loxapine for treating the agitation episodes. RESULTS: Data from 14 patients with dual diagnosis were reviewed. All patients had 1 or more psychiatric disorders (schizophrenia, bipolar I disorder, drug-induced psychotic disorder, posttraumatic stress, borderline or antisocial personality disorder, depression, or anxiety) along with a variety of substance use disorders (alcohol, cocaine, cannabis, amphetamines, hypnotics and antianxiety drugs, caffeine, or street drugs). Overall, only 1 dose of inhaled loxapine (9.1 mg) was needed to calm each patient during an acute episode of agitation. CONCLUSIONS: Inhaled loxapine was rapid, effective, and well accepted in all dual-pathology patients presenting with acute agitation in the emergency setting. Inhaled loxapine facilitated both patient cooperation and an adequate management of his or her disease.