Inhaled Loxapine for Agitation in Intoxicated Patients : A Case Series

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. 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. 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. 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

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

Trastorn per dèficit d'atenció i hiperactivitat; Comorbilitat; Trastorn d'insomniTrastorno por déficit de atención e hiperactividad; Comorbilidad; Trastorno de insomnioAttention deficit and hyperactivity disorder; Comorbidity; Insomnia disorderIntroduction: 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.The research leading to these results has received funding from the Instituto de Salud Carlos III (PI18/01788) and supported by the EU's Horizon 2020 Programme (Grant No. 667302, CoCA and Grant No. 728018 Eat2beNICE)

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 ADH

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

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. 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. 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. Results suggest that IL could be a safe and effective option to manage agitation in PD

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

TDAH; Comunitat científicaTDAH; Comunidad científicaADHD; Scientific communityCompelling 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

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

ADHD; Chronic stress; Inflammatory proteomeTDAH; Estrès crònic; Proteoma inflamatoriTDAH; Estrés crónico; Proteoma inflamatorioThe 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.Open Access funding enabled and organized by Projekt DEAL

Preliminary evidence for association of genetic variants in pri-miR-34b/c and abnormal miR-34c expression with attention deficit and hyperactivity disorder

Attention deficit and hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by impairment to sustain attention and inability to control impulses and activity level. The etiology of ADHD is complex, with an estimated heritability of 70-80%. Under the hypothesis that alterations in the processing or target binding of microRNAs (miRNAs) may result in functional alterations predisposing to ADHD, we explored whether common polymorphisms potentially affecting miRNA-mediated regulation are involved in this psychiatric disorder. We performed a comprehensive association study focused on 134 miRNAs in 754 ADHD subjects and 766 controls and found association between the miR-34b/c locus and ADHD. Subsequently, we provided preliminary evidence for overexpression of the miR-34c-3p mature form in peripheral blood mononuclear cells of ADHD subjects. Next, we tested the effect on gene expression of single-nucleotide polymorphisms within the ADHD-associated region and found that rs4938923 in the promoter of the pri-miR-34b/c tags cis expression quantitative trait loci for both miR-34b and miR-34c and has an impact on the expression levels of 681 transcripts in trans, including genes previously associated with ADHD. This gene set was enriched for miR-34b/c binding sites, functional categories related to the central nervous system, such as axon guidance or neuron differentiation, and serotonin biosynthesis and signaling canonical pathways. Our results provide preliminary evidence for the contribution to ADHD of a functional variant in the pri-miR-34b/c promoter, possibly through dysregulation of the expression of mature forms of miR-34b and miR-34c and some target genes. These data highlight the importance of abnormal miRNA function as a potential epigenetic mechanism contributing to ADHD

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

Insomni en adults amb TDAH : comorbiditats i evolució clínica| Insomnia in adults with ADHD : comorbidities and clinical course| Insomnio en adultos con TDAH

El trastorn per dèficit d'atenció i hiperactivitat (TDAH) és un trastorn del neurodesenvolupament caracteritzat per la presència de símptomes d'inatenció i/o hiperactivitat i impulsivitat que generen una disfunció marcada en diversos àmbits de la vida. La seva persistència a l'edat adulta se situa en aproximadament el 65% dels casos, associant una prevalença del 2,5-3%. El trastorn d'insomni és el trastorn del son més prevalent a la nostra societat, caracteritzat per la presència d'una dificultat en la conciliació o en el manteniment del son, o bé per un despertar precoç, que es vincula a un deteriorament diürn clínicament significatiu. Aquestes dificultats es produeixen com a mínim tres nits a la setmana durant un mínim de tres mesos. En els darrers anys hi ha hagut un interès creixent per conèixer la relació entre el TDAH i l'insomni, havent-se realitzat múltiples estudis en població infantojuvenil. Tot i això, en població adulta els estudis són escassos i de vegades amb resultats contradictoris. L'objectiu d'aquesta tesi doctoral és aprofundir en el coneixement del trastorn d'insomni en adults amb TDAH. Això inclou descriure tant la prevalença del trastorn d'insomni com estudiar el conjunt de variables clíniques i sociodemogràfiques associades. També, mitjançant un estudi longitudinal, analitzar la relació que s'estableix entre aquestes variables i la remissió del trastorn d'insomni. El primer estudi apunta una prevalença elevada del trastorn d'insomni (44,4%) a la població adulta amb TDAH. Els resultats assenyalen que el trastorn d'insomni s'associa amb una major severitat clínica del TDAH i una major comorbiditat mèdica i psiquiàtrica, especialment amb els trastorns de l'estat d'ànim, trastorns d'ansietat, trastorns de personalitat i trastorns per ús de substàncies. Així mateix, també es relaciona amb la presentació combinada del TDAH i amb una pitjor qualitat de vida relacionada amb la salut. Per contra, el tractament amb fàrmacs estimulants o l'estabilitat del tractament farmacològic del TDAH s'associen a una presència menor de trastorn d'insomni. El segon estudi valora longitudinalment la relació entre la remissió del trastorn d'insomni i les variables associades al TDAH. L'anàlisi dels resultats mostra una remissió del trastorn d'insomni als 6 mesos al 72,4% dels casos, associant-se a una reducció de la severitat clínica del TDAH, així com a una millora de la comorbiditat psiquiàtrica i de la qualitat de vida relacionada amb la salut. Aquests resultats conclouen que el trastorn d'insomni es presenta amb una elevada prevalença en els pacients adults amb TDAH i que el seu tractament i remissió condicionen una millor evolució clínica del TDAH, amb una reducció de la severitat i de la comorbiditat psiquiàtrica, així com una millora de la qualitat de vida. Aquests resultats poden contribuir a una millor aproximació clínica a ambdós trastorns, la complexa interacció dels quals no ha estat encara ben definida.El trastorno por déficit de atención e hiperactividad (TDAH) es un trastorno del neurodesarrollo caracterizado por la presencia de síntomas de inatención y/o hiperactividad e impulsividad que generan una marcada disfunción en diversos ámbitos de la vida. Su persistencia en la edad adulta se sitúa en aproximadamente el 65% de los casos, asociando una prevalencia del 2,5-3%. El trastorno de insomnio es el trastorno del sueño más prevalente en nuestra sociedad, caracterizado por la presencia de una dificultad en la conciliación o mantenimiento del sueño, o bien un despertar precoz, que se vincula a un deterioro clínicamente significativo durante el día. Estas dificultades se producen al menos tres noches a la semana durante un mínimo de tres meses. En los últimos años ha habido un interés creciente por conocer la relación entre el TDAH y el insomnio, habiéndose realizado múltiples estudios en población infanto-juvenil. Sin embargo, en población adulta los estudios son escasos y en ocasiones con resultados contradictorios. El objetivo de esta tesis doctoral es profundizar en el conocimiento del trastorno de insomnio en adultos con TDAH. Esto incluye describir la prevalencia del trastorno de insomnio como estudiar el conjunto de variables clínicas y sociodemográficas asociadas. También, a través de un estudio longitudinal, analizar la relación que se establece entre estas variables y la remisión del trastorno de insomnio. El primer estudio apunta una elevada prevalencia del trastorno de insomnio (44,4%) en la población adulta con TDAH. Los resultados señalan que el trastorno de insomnio se asocia con una mayor severidad clínica del TDAH y una mayor comorbilidad médica y psiquiátrica, especialmente con los trastornos del estado de ánimo, trastornos de ansiedad, trastornos de personalidad y trastornos por uso de sustancias. Asimismo, también se relaciona con la presentación combinada del TDAH y con una peor calidad de vida relacionada con la salud. Por el contrario, el tratamiento con fármacos estimulantes o la estabilidad del tratamiento farmacológico del TDAH se asocian a una menor presencia de trastorno de insomnio. El segundo estudio valora de forma longitudinal la relación entre la remisión del trastorno de insomnio y las variables asociadas al TDAH. El análisis de los resultados muestra una remisión del trastorno de insomnio a los 6 meses en el 72,4% de los casos, asociándose a una reducción de la severidad clínica del TDAH, así como a una mejoría de la comorbilidad psiquiátrica y de la calidad de vida relacionada con la salud. Estos resultados concluyen que el trastorno de insomnio se presenta con una elevada prevalencia en los pacientes adultos con TDAH y que su tratamiento y remisión condicionan una mejor evolución clínica del TDAH, con una reducción de su severidad y de su comorbilidad psiquiátrica, así como una mejoría de la calidad de vida. Estos resultados pueden contribuir a una mejor aproximación clínica a ambos trastornos, cuya compleja interacción no ha sido todavía bien definida.Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention and/or hyperactivity-impulsivity behavior that interfere with daily life activities. ADHD frequently persists into adulthood up to 65% with a prevalence ranging between 2.5-3%. Insomnia is the most prevalent sleep disorder in our society, characterized by difficulty in sleep-onset, sleep maintenance, or early awakening, causing daily significant discomfort or clinical impairment. These occurs at least three nights a week for a minimum of three months. In the last decades there has been an increased scientific interest in study the relationship between ADHD and insomnia. In children several research has been published; however, few studies have been conducted on this issue and their results are heterogeneous in adult ADHD. Therefore, the objective of this doctoral thesis is to increase the knowledge of the insomnia disorder in adults with ADHD. This includes describe the prevalence of insomnia disorder as well as the set of associated clinical and sociodemographic variables. Also, to analyze the relationship between these variables and the remission of the insomnia disorder through a longitudinal study. The first study points to a high prevalence of insomnia disorder (44.4%) in adult ADHD. The results shows that insomnia disorder is associated with greater ADHD clinical severity and, medical and psychiatric comorbidity, especially with mood disorders, anxiety disorders, personality disorders and substance use disorders. Likewise, it is also related to the ADHD combined presentation and poorer health-related quality of life. On the contrary, stimulant drugs or the pharmacological ADHD treatment stability are associated with a lower prevalence of insomnia disorder. The second study evaluated longitudinally the relationship between the insomnia disorder remission and the ADHD associated variables. The results show a 72.4% remission of the insomnia disorder at 6 months, associated with an ADHD clinical severity reduction, as well as an improvement of the psychiatric comorbidity and health-related quality of life. It can be concluded that insomnia disorder is high prevalent in adult ADHD, and its treatment and remission determine a better clinical ADHD evolution, associating ADHD severity and psychiatric comorbidity reduction, as well as an improvement of quality of life. These results may contribute to a better clinical approach to both disorders, whose complex interaction has not yet been well fixed

Insomni en adults amb TDAH: comorbiditats i evolució clínica| Insomnia in adults with ADHD: comorbidities and clinical course| Insomnio en adultos con TDAH: comorbilidades y evolución clínica|

El trastorn per dèficit d’atenció i hiperactivitat (TDAH) és un trastorn del neurodesenvolupament caracteritzat per la presència de símptomes d’inatenció i/o hiperactivitat i impulsivitat que generen una disfunció marcada en diversos àmbits de la vida. La seva persistència a l’edat adulta se situa en aproximadament el 65% dels casos, associant una prevalença del 2,5-3%. El trastorn d’insomni és el trastorn del son més prevalent a la nostra societat, caracteritzat per la presència d’una dificultat en la conciliació o en el manteniment del son, o bé per un despertar precoç, que es vincula a un deteriorament diürn clínicament significatiu. Aquestes dificultats es produeixen com a mínim tres nits a la setmana durant un mínim de tres mesos. En els darrers anys hi ha hagut un interès creixent per conèixer la relació entre el TDAH i l’insomni, havent-se realitzat múltiples estudis en població infantojuvenil. Tot i això, en població adulta els estudis són escassos i de vegades amb resultats contradictoris. L’objectiu d’aquesta tesi doctoral és aprofundir en el coneixement del trastorn d’insomni en adults amb TDAH. Això inclou descriure tant la prevalença del trastorn d’insomni com estudiar el conjunt de variables clíniques i sociodemogràfiques associades. També, mitjançant un estudi longitudinal, analitzar la relació que s’estableix entre aquestes variables i la remissió del trastorn d’insomni. El primer estudi apunta una prevalença elevada del trastorn d’insomni (44,4%) a la població adulta amb TDAH. Els resultats assenyalen que el trastorn d’insomni s’associa amb una major severitat clínica del TDAH i una major comorbiditat mèdica i psiquiàtrica, especialment amb els trastorns de l’estat d’ànim, trastorns d’ansietat, trastorns de personalitat i trastorns per ús de substàncies. Així mateix, també es relaciona amb la presentació combinada del TDAH i amb una pitjor qualitat de vida relacionada amb la salut. Per contra, el tractament amb fàrmacs estimulants o l’estabilitat del tractament farmacològic del TDAH s’associen a una presència menor de trastorn d’insomni. El segon estudi valora longitudinalment la relació entre la remissió del trastorn d’insomni i les variables associades al TDAH. L’anàlisi dels resultats mostra una remissió del trastorn d’insomni als 6 mesos al 72,4% dels casos, associant-se a una reducció de la severitat clínica del TDAH, així com a una millora de la comorbiditat psiquiàtrica i de la qualitat de vida relacionada amb la salut. Aquests resultats conclouen que el trastorn d’insomni es presenta amb una elevada prevalença en els pacients adults amb TDAH i que el seu tractament i remissió condicionen una millor evolució clínica del TDAH, amb una reducció de la severitat i de la comorbiditat psiquiàtrica, així com una millora de la qualitat de vida. Aquests resultats poden contribuir a una millor aproximació clínica a ambdós trastorns, la complexa interacció dels quals no ha estat encara ben definida.El trastorno por déficit de atención e hiperactividad (TDAH) es un trastorno del neurodesarrollo caracterizado por la presencia de síntomas de inatención y/o hiperactividad e impulsividad que generan una marcada disfunción en diversos ámbitos de la vida. Su persistencia en la edad adulta se sitúa en aproximadamente el 65% de los casos, asociando una prevalencia del 2,5-3%. El trastorno de insomnio es el trastorno del sueño más prevalente en nuestra sociedad, caracterizado por la presencia de una dificultad en la conciliación o mantenimiento del sueño, o bien un despertar precoz, que se vincula a un deterioro clínicamente significativo durante el día. Estas dificultades se producen al menos tres noches a la semana durante un mínimo de tres meses. En los últimos años ha habido un interés creciente por conocer la relación entre el TDAH y el insomnio, habiéndose realizado múltiples estudios en población infanto-juvenil. Sin embargo, en población adulta los estudios son escasos y en ocasiones con resultados contradictorios. El objetivo de esta tesis doctoral es profundizar en el conocimiento del trastorno de insomnio en adultos con TDAH. Esto incluye describir la prevalencia del trastorno de insomnio como estudiar el conjunto de variables clínicas y sociodemográficas asociadas. También, a través de un estudio longitudinal, analizar la relación que se establece entre estas variables y la remisión del trastorno de insomnio. El primer estudio apunta una elevada prevalencia del trastorno de insomnio (44,4%) en la población adulta con TDAH. Los resultados señalan que el trastorno de insomnio se asocia con una mayor severidad clínica del TDAH y una mayor comorbilidad médica y psiquiátrica, especialmente con los trastornos del estado de ánimo, trastornos de ansiedad, trastornos de personalidad y trastornos por uso de sustancias. Asimismo, también se relaciona con la presentación combinada del TDAH y con una peor calidad de vida relacionada con la salud. Por el contrario, el tratamiento con fármacos estimulantes o la estabilidad del tratamiento farmacológico del TDAH se asocian a una menor presencia de trastorno de insomnio. El segundo estudio valora de forma longitudinal la relación entre la remisión del trastorno de insomnio y las variables asociadas al TDAH. El análisis de los resultados muestra una remisión del trastorno de insomnio a los 6 meses en el 72,4% de los casos, asociándose a una reducción de la severidad clínica del TDAH, así como a una mejoría de la comorbilidad psiquiátrica y de la calidad de vida relacionada con la salud. Estos resultados concluyen que el trastorno de insomnio se presenta con una elevada prevalencia en los pacientes adultos con TDAH y que su tratamiento y remisión condicionan una mejor evolución clínica del TDAH, con una reducción de su severidad y de su comorbilidad psiquiátrica, así como una mejoría de la calidad de vida. Estos resultados pueden contribuir a una mejor aproximación clínica a ambos trastornos, cuya compleja interacción no ha sido todavía bien definida.Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention and/or hyperactivity-impulsivity behavior that interfere with daily life activities. ADHD frequently persists into adulthood up to 65% with a prevalence ranging between 2.5-3%. Insomnia is the most prevalent sleep disorder in our society, characterized by difficulty in sleep-onset, sleep maintenance, or early awakening, causing daily significant discomfort or clinical impairment. These occurs at least three nights a week for a minimum of three months. In the last decades there has been an increased scientific interest in study the relationship between ADHD and insomnia. In children several research has been published; however, few studies have been conducted on this issue and their results are heterogeneous in adult ADHD. Therefore, the objective of this doctoral thesis is to increase the knowledge of the insomnia disorder in adults with ADHD. This includes describe the prevalence of insomnia disorder as well as the set of associated clinical and sociodemographic variables. Also, to analyze the relationship between these variables and the remission of the insomnia disorder through a longitudinal study. The first study points to a high prevalence of insomnia disorder (44.4%) in adult ADHD. The results shows that insomnia disorder is associated with greater ADHD clinical severity and, medical and psychiatric comorbidity, especially with mood disorders, anxiety disorders, personality disorders and substance use disorders. Likewise, it is also related to the ADHD combined presentation and poorer health-related quality of life. On the contrary, stimulant drugs or the pharmacological ADHD treatment stability are associated with a lower prevalence of insomnia disorder. The second study evaluated longitudinally the relationship between the insomnia disorder remission and the ADHD associated variables. The results show a 72.4% remission of the insomnia disorder at 6 months, associated with an ADHD clinical severity reduction, as well as an improvement of the psychiatric comorbidity and health-related quality of life. It can be concluded that insomnia disorder is high prevalent in adult ADHD, and its treatment and remission determine a better clinical ADHD evolution, associating ADHD severity and psychiatric comorbidity reduction, as well as an improvement of quality of life. These results may contribute to a better clinical approach to both disorders, whose complex interaction has not yet been well fixed.Universitat Autònoma de Barcelona. Programa de Doctorat en Psiquiatri