Treatment of adult ADHD: Is current knowledge useful to clinicians?

Psychostimulant drugs have for decades been considered the cornerstone of ADHD treatment. Non-stimulant drugs have also been reported successful. However, many controlled studies exclude patients with comorbidities typical for patients seen in clinical setting. Many patients are also considered non-responders to medication. Current knowledge might not be directly useful to clinicians. The present article reviews the literature on pharmacological and psychotherapeutic treatment in adult ADHD emphasizing comorbidity and other clinically important factors, as well as ADHD specific outcomes. Thirty-three relevant studies of pharmacotherapy and three studies of psychotherapy were included. Most subjects had little current comorbidity, but some studies included subjects with substance use disorder. Significant effect of treatment on ADHD symptoms was found in most studies using pharmacotherapy and all studies of psychotherapy. Both positive and negative effects on comorbid anxiety and depression measures were reported. Pharmacotherapy did not seem to have effect on substance use disorder. Few pharmacotherapy studies conducted any long-term follow-up; two studies that did, found that most subjects had discontinued medication. A clear-cut dose-respons relationship was not substanciated. In conclusion, clinicians have good support for both pharmacological and psychotherapeutic treatment of ADHD in adults, but should take additional measures to deal with comorbidities as well as treatment adherence

ATPase activity of DFCP1 controls selective autophagy

Cellular homeostasis is governed by removal of damaged organelles and protein aggregates by selective autophagy mediated by cargo adaptors such as p62/SQSTM1. Autophagosomes can assemble in specialized cup-shaped regions of the endoplasmic reticulum (ER) known as omegasomes, which are characterized by the presence of the ER protein DFCP1/ZFYVE1. The function of DFCP1 is unknown, as are the mechanisms of omegasome formation and constriction. Here, we demonstrate that DFCP1 is an ATPase that is activated by membrane binding and dimerizes in an ATP-dependent fashion. Whereas depletion of DFCP1 has a minor effect on bulk autophagic flux, DFCP1 is required to maintain the autophagic flux of p62 under both fed and starved conditions, and this is dependent on its ability to bind and hydrolyse ATP. While DFCP1 mutants defective in ATP binding or hydrolysis localize to forming omegasomes, these omegasomes fail to constrict properly in a size-dependent manner. Consequently, the release of nascent autophagosomes from large omegasomes is markedly delayed. While knockout of DFCP1 does not affect bulk autophagy, it inhibits selective autophagy, including aggrephagy, mitophagy and micronucleophagy. We conclude that DFCP1 mediates ATPase-driven constriction of large omegasomes to release autophagosomes for selective autophagy

ADHD in adults; comorbidity and long-term central stimulant treatment: A retrospective, naturalistic study

ADHD hos voksne; samsykelighet og behandling med sentralstimulerende legemidler ADHD er en tilstand som oppstår i barndommen og preges av hyperaktivitet, impulsivitet og oppmerksomhetssvikt. Symptomene på ADHD vedvarer inn i voksen alder hos mange pasienter, og er forbundet med funksjonssvikt på områder som utdannelse og arbeidsliv. Forekomst av andre psykiske lidelser samtidig (samsykelighet) er stor gjennom hele livsløpet. Sentralstimulerende legemidler (SSL) er godt dokumentert behandling av symptomene ved ADHD. Til tross for god symptomatisk effekt slutter mange pasienter tidlig med behandlingen, og mye er uavklart når det gjelder hvordan SSL behandling fungerer i vanlig klinisk praksis hos voksne. Vi ønsket å beskrive forekomst av samsykelighet og funksjonssvikt hos voksne pasienter med ADHD. Videre ønsket vi å se på behandlingsforløp og identifisere variabler som predikerte behandlingsvarighet > 3 år. Det tredje målet med studien var å undersøke forekomsten av rusmisbruk i løpet av behandlingsforløpet og identifisere variabler knyttet til eventuelt misbruk. Vi ønsket også å identifisere kliniske og behandlingsmessige variabler relatert til yrkesmessig fungering i voksen alder. Dette er en retrospektiv, naturalistisk studie på 3 utvalg av voksne pasienter med diagnosen ADHD. Den primære utredningen av pasientene ble gjort i henhold til prosedyrer bestemt av de Sakkyndige team for hyperkinetisk forstyrrelse i perioden 1997-2005. Hovedmengden av data til studien ble retrospektivt hentet fra den psykiatriske journalen. I Paper IV brukte vi i tillegg et spørreskjema. Vi fant at voksne med ADHD hadde lavere utdanningsnivå og yrkesdeltagelse enn den generelle befolkningen. Mange pasienter hadde samsykelighet som rusmisbruk og personlighetsforstyrrelse. Til tross for de høye nivåene av samsykelighet og funksjonssvikt fikk de fleste pasientene behandling med SSL i lang tid (median varighet var 33 måneder). Behandlingsvarighet mer enn 3 år ble positivt predikert av om pasienten brukte langtidsvirkende SSL, og negativt predikert av om pasienten hadde personlighetsforstyrrelse. Hos pasienter uten tidligere rusmisbruk fant vi at behandling med SSL ikke førte til rusmisbruk. Pasienter som tidligere hadde hatt rusmisbruk hadde ikke høyere tilbakefall enn i grupper av voksne pasienter med rusmisbruk alene. Høy alder ved første SSL behandling og høyere grad av oppmerksomhetssvikt var assosiert med redusert yrkesdeltagelse i voksen alder. Avhandlingen understreker det høye nivået av samsykelighet og funksjonssvikt ved ADHD hos voksne. Det viser seg allikevel mulig å behandle pasientene med SSL over lang tid, men det må undersøkes nærmere hvordan behandlingen skal gjennomføres hos pasienter med stor samsykelighet. En lengre periode med rusfrihet før SSL behandling kan redusere risiko for tilbakefall, men dette må undersøkes med kontrollerte studier. Studien antyder at tidlig behandling av ADHD er relatert til bedre yrkesmessig fungering i voksen alder, men i likhet med andre naturalistiske studier er det store metodologiske begrensninger. Vitenskapelig mer robuste studier bør gjøres for å undersøke effekten av SSL behandling av barn og unge på funksjonsnivå og samsykelighet i voksen alder

Optimal management of ADHD in older adults

Background: The manifestation of attention-deficit/hyperactivity disorder (ADHD) among older adults has become an interesting topic of interest due to an increasing number of adults aged 50 years and older (≥50 years) seeking assessment for ADHD. Unfortunately, there is a lack of research on ADHD in older adults, and until recently only a few case reports existed. Method: A systematic search was conducted in the databases Medline/PubMed and PsycINFO in order to identify studies regarding ADHD in adults ≥50 years. Results: ADHD persists into older ages in many patients, but the prevalence of patients fulfilling the criteria for the diagnosis at age ≥50 years is still unknown. It is reason to believe that the prevalence is falling gradually with age, and that the ADHD symptom level is significantly lower in the age group 70–80 years than the group 50–60 years. There is a lack of controlled studies of ADHD medication in adults ≥50 years, but this review suggests that many patients aged ≥50 years experience beneficial effects of pharmacological treatment. The problem with side effects and somatic complications may rise to a level that makes pharmacotherapy for ADHD difficult after the age of 65 years. Physical assessment prior to initiation of ADHD medication in adults ≥50 years should include a thorough clinical examination, and medication should be titrated with low doses initially and with a slow increase. In motivated patients, different psychological therapies alone or in addition to pharmacotherapy should be considered. Conclusion: It is essential when treating older adult patients with ADHD to provide good support based on knowledge and understanding of how ADHD symptoms have affected health, quality of life, and function through the life span. Individualized therapy for each elderly patient should be recommended to balance risk–benefit ratio when pharmacotherapy is considered to be a possible treatment

Psychiatric morbidity, somatic comorbidity and substance use in an adolescent psychiatric population at 3-year follow-up

Knowledge is scarce on the course of psychiatric disorders in adolescence. We aimed to assess changes in the frequency of psychiatric disorders, somatic disorders, pain, and substance use in a clinical psychiatric cohort from adolescence to young adulthood. This study is part of the Health Survey in Department of Children and Youth, St. Olavs Hospital, Norway. At age 13–18 years, 717 (43.5% of eligible) participated in the first study visit (T1) in 2009–2011, 549 were reassessed 3 years later with telephone interview (T2), and 464 had diagnostic evaluation at both time points. Data included: ICD-10 diagnoses (T1), DSM-IV diagnoses (T2), self-reported pain and substance use (T1 and T2). The overall rate of psychiatric disorders decreased (T1 vs. T2: 94.8% vs. 72.2%, p < 0.001); while, an increased rate of anxiety disorders was marked among girls (37.5% vs. 55.9%, p < 0.001), with accompanying raised frequencies of psychiatric comorbidity (14.1% vs. 42.6%, p < 0.001), somatic comorbidity (9.4% vs. 19.5%, p = 0.001), chronic pain (31.6% vs. 49.4%, p < 0.001), smoking, alcohol use and trying illicit drugs. Chronic pain, smoking and trying illicit drugs were associated with persisting psychiatric disorders, with highest risk differences for girls (RD = 25.4%, p = 0.002, RD = 15.6%, p = 0.008, RD = 18.0%, p = 0.001, respectively). Three out of four adolescents still had a psychiatric disorder after 3 years. Unlike boys, girls had an increasing rate of anxiety disorders and comorbidities. Chronic pain, smoking and trying illicit drugs were associated with persisting psychiatric disorders. Despite methodological limitations, these findings emphasize the importance of early targeted intervention for adolescents with psychiatric disorders

Mortality among patients discharged from an acute psychiatric department: A 5-year prospective study

The primary aim of the study was to explore the post discharge standardized mortality ratio of patients from an acute psychiatric department in Norway. The secondary aims were to explore if the standardized mortality ratio is still increasing and to examine the causes of death in the defined population. We conducted a 5-year prospective study among patients admitted to an acute psychiatric department with catchment area responsibilities. A total of 380 patients were included in the study, and the number and causes of deaths were obtained from the Norwegian Cause of Death Registry. Excess mortality was found for the patient group. The standardized mortality ratio for all causes of death was 6.7 (95% CI, 4.6–8.8). The study finds an increased standardized mortality ratio relative to a previous corresponding study in Norway, and the suicide risk was especially elevated the first 2 years after discharge

Suicidality, function and associated negative life events in an adolescent psychiatric population at 3-year follow-up

Background We aimed to examine psychosocial function, suicidality and school dropout in a clinical psychiatric population over a 3-year period from adolescence to young adulthood and explore associations with negative life events. Methods This study is part of the Health Survey in Department of Children and Youth, St. Olavs hospital, Norway. In the first study visit (T1), 717 (43.5% of eligible) participated, aged 13–18 years (2009–2011), and 3 years later (T2), 570 answered a questionnaire (school functioning and negative life events), and 549 completed Kiddie SADS as telephone interview assessing DSM-IV diagnoses, psychosocial functioning and suicidality. Results Suicidal ideation was more frequent among girls (17.9%) than among boys (5.4%) (risk difference; RD = 12.5%, CI (7.2 to 17.7), p < 0.001), as was suicidal behavior (25.0% vs. 9.5%, RD = 15.5%, CI (9.2 to 21.4), p < 0.001). Girls had lower psychosocial functioning than boys (Children’s Global Assessment Scale; Mean score 68.2 vs. 75.2, Mean difference = − 7.0, CI (− 9.4 to − 4.7), p < 0.001), and more school dropout (22.5% vs. 13.2%, RD = 9.3%, CI (2.8 to 15.5), p = 0.006). For those with a psychiatric disorder, 24.8% of girls had suicidal ideation and 30.0% suicidal behavior, which was larger than for boys (RD = 18.0%, CI (10.8 to 24.7), p < 0.001, and RD = 18.3%, CI (10.2 to 25.8), p < 0.001, respectively). Exposure to negative life events was frequent for both genders, but more girls had experienced sexually uncomfortable or abusive situations, the last 3 years (23.5% vs. 2.9%, RD = 20.6%, CI (15.4 to 25.7), p < 0.001), and ever (44.4% vs. 7.9%, RD = 36.5%, CI (29.9 to 42.7), p < 0.001). Suicidal behavior was associated with having been threatened, physically harassed or violently hurt (RD = 16.7%, CI (9.5 to 23.9), p < 0.001), and for girls been put into sexually uncomfortable or abusive situations (RD = 20.1%, CI (10.4 to 29.9), p < 0.001) and seen others violently hurt (RD = 14.6%, CI (3.4 to 25.8), p = 0.011). Conclusions The high frequency of suicidality and school dropout confirms the severity of adolescent psychiatric disorders, especially among girls. Specific life events were associated risk factors and should be target points for prevention and intervention

Psychoeducational Groups versus Waitlist in Treatment of Attention-Deficit Hyperactivity/Impulsivity Disorder (ADHD) in Adults: A Protocol for a Pilot Randomized Waitlist-Controlled Multicenter Trial.

Background Psychoeducation is included in the Norwegian national guidelines for treatment of adult ADHD. Despite some promising results for the treatment of other conditions and ADHD, little is known about the efficacy of such interventions. This paper presents a protocol for a pilot randomized controlled trial featuring a psychoeducational group program for patients with ADHD. The main objective of this pilot trial is to investigate adherence, feasibility, and preliminary efficacy of a ten-session psychoeducational group designed to address specific challenges faced by adults diagnosed with ADHD. Methods This pilot study will evaluate patient satisfaction and preliminary efficacy of a psychoeducational group treatment using a randomized waitlist-controlled trial at two different outpatient clinics in mid-Norway. All participants will receive treatment as usual, concomitant with the intervention and waitlist period. Client satisfaction (CSQ 8), general self-efficacy (GSE-6), ADHD-related quality of life (AAQoL), symptoms of ADHD (SCL-9; ASRS), and work participation will be assessed at the time of recruitment prior to randomization (T0), pre-intervention (T1), post-intervention (T2), and at 10 weeks follow-up (T3). Recruitment and dropout rates along with treatment adherence will also be evaluated. Discussion This study offers valuable insight into the preliminary efficacy of educational programs implemented in outpatient clinics. The aim of the trial is to evaluate adherence, feasibility, patient satisfaction, and the preliminary efficacy of a psychoeducational group intervention for patients with adult ADHD and provide further insight into the design and construction of a large-scale trial. The results also offer preliminary empirical evidence to inform the development of larger and more complex studies