Attention Deficit Hyperactivity Disorder (ADHD) is a neuropsychiatric disability  characterised by difficulties in paying attention, excessive activity and actions without thinking about the consequenses. Symptoms vary among different individuals in how the disability expresses. Symptoms also vary among different age groups. The cause of ADHD is not yet known, but the main theory seems to be due to disturbed dopaminergic transmisson in the regions of the brain that controlls attention, activity control and impulses. Clinical studies show that there seems to be a connection between the etiology of the disability and genetic- and environmental factors. ADHD can’t be cured but a multimodal treatment has been proven to be effective in symptom reduction. The multimodal treatment consist of psychoeducation, psychotherapy and medical treatment. In Sweden methylphenidate is the first choise of drug and if it is not tolerated well by patients in terms of respons or side effects lisdexamfetamine or atomoxetin is choosen. The mechanism of action for these three substances is not completly known but in general they presume to block the reuptake of dopamine and norepinephrine in the presynaptic neurons. This leads to an enhanced transmission at the dopaminergic neurons that in turn stimulates the executive funtions that seem to be deficient in ADHD patients. The aim of this literature study is to investigate how the three substances methylphenidate, lisdexamfetamine and atomoxetine differ in therapeutic effects and side effects profile during long-term treatment for ADHD. Five scientific articles were choosen from the database Pubmed, which analysed the therapeutic effects and side effects of the above choosen drugs during a period of atleast 24 weeks. Participants in the selected studies had a definite diagnosis of ADHD and the participants included were children, adolescents and also adults. Therapeutic efficiency of selected drugs was measured by using different diagnostic scales such as ADHD-RS-IV, CAARS-Inv:SV, AISRS, CGI-S or CGI-I. Therapeutic efficiency was measured by the total reduction of the mean value in the rating scale from start to end of the study. Safety was measured at each follow up session by evaluating the side effects profile and measurements of vital parameters. These studies show statistically significant symptom reductions for all three selected drugs. The results also show differences in therapeutic effects among different drugs. Participants treated with lisdexamfetamine showed greater symptom reduction and thereby the greatest effect. There may be a difference in therapeutic effect between methylphenidate and atomoxetine but more studies are needed to conclude the results. The adverse effects were similar between lisdexamfetamine and methylphenidate but more serious effects were found during treatment with lisdexamfetamine.

Inledning: Attention deficit hyperactivity disorder (ADHD) är en neuropsykiatrisk funktionsnedsättning som sannolikt beror på en annorlunda struktur och funktion av det centrala nervsystemet och en annorlunda utveckling av hjärnan. Tecken på ADHD kan vara svårigheter med uppmärksamhet och koncentration, överaktivitet och impulsivitet. Prevalensen för ADHD kan variera beroende på geografiskt område, i Nordamerika är prevalensen 3 - 7 % av alla barn i skolåldern och i Europa ca 1 - 3 %. Centralstimulerande läkemedel är den vanligaste läkemedelsgruppen vid farmakologisk behandling av ADHD-symptom. Lisdexamfetamin (LDX) är en prodrug till amfetaminderivatet dextroamfetamin, som blockerar återupptag samt ökar utsöndringen av dopamin och noradrenalin. LDX finns i Sverige under namnet Elvanse. Syfte: Nuvarande studie syftade till att undersöka effekt och säkerhet av lisdexamfetamin (Elvanse) för behandling av barn och tonåringar. Metod: Arbetet var en litteraturstudie där fem vetenskapliga artiklar valdes ut i den vetenskapliga databasen pubMed. Kriterier för artiklarna var att de skulle vara randomiserade kontrollerade studier som genomgått peer review. Artiklarna skulle behandla intag av lisdexamfetamin till barn och målet var att hitta studier med så unga deltagare som möjligt. Studier med vuxna uteslöts och likaså studier vars syfte var att jämföra LDX mot ett annat läkemedel. Resultat: Primärt utfall var en skillnad på grad av symptom enligt skalan ADHD-RS-IV i fyra av studierna och samtliga visade en förbättring jämfört med placebo. Flera olika skalor användes för sekundärt utfall och även dessa visade en förbättring vid intag av LDX jämfört med placebo. En av studierna var en post hoc-analys som visade en förbättring av emotionell labilitet hos deltagarna med intag av LDX. Inga nya allvarliga händelser upptäcktes. De vanligaste biverkningarna var liknande de typiska för amfetamin; minskad aptit, insomnia, övre buksmärtor, huvudvärk, irritabilitet och viktnedgång. Slutsats: Farmakologisk behandling med lisdexamfetamin vid ADHD visar minskning av ADHD-symptom mätt i flera olika skalor, främst använd är ADHD-RS-IV. Undersökningen inom ramen för examensarbetet visar att LDX är säkert att använda och tolereras utav barn. I den yngsta målgruppen observerades en mindre effekt på ADHD-symptom jämfört med äldre barn, dock påträffades endast en artikel för åldersgruppen 4 - 5 år. Fler studier krävs för ordentlig slutsats av effekt i just den åldersgruppen men inga nya allvarliga händelser observerades / Introduction: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder. ADHD likely depends on a different structure and function of the central nervous system and a dissimilar brain development. The condition is often characterized by inattention, hyperactivity, and impulsive behavior. The core symptoms are associated with impairments in academic, social, and intrapersonal functioning. ADHD and intelligence do not correlate. Comorbidity is more frequent among people with ADHD; the most common among children are learning disabilities and problems with conduction and defiance. Among adults, more comorbid severe mental disorders such as anxiety, depression, suicidal thoughts, and attempted or completed suicide occur. Different types of abuse are more common among adolescents and adults with ADHD. Studies show that ADHD is hereditary, but exactly how is not clarified. It is probably a combination of several genetic and environmental factors that cause symptoms of ADHD to be expressed. The prevalence of ADHD can vary depending on the geographical area. In North America, the prevalence is 3 – 7 % of all school-age children, and in Europe, about 1 – 3 %. Stimulants are the most common type of drug for pharmacological treatment of ADHD symptoms. Lisdexamfetamine (LDX) is a long-acting prodrug stimulant. It requires enzymatic hydrolysis to yield the therapeutically active metabolite D-amfetamine, which blocks reuptake and increases the secretion of dopamine and norepinephrine. LDX is available in Sweden under the name Elvanse. Aim: This literature study aimed to investigate the efficacy and safety of LDX (Elvanse) in children and adolescents. Methods: Five scientific articles were selected from the scientific database PubMed. Inclusion criteria were that the articles should be randomized controlled trials undergone peer review, and the study population should include children. Key exclusion criteria were studies on adults and studies that compared LDX to other drugs and not placebo. Results: The primary outcome was a change of symptoms according to ADHD-RS-IV scores in four studies. These studies all showed an improvement compared to placebo. Several scales were used for secondary outcomes, and these also showed an improvement in symptoms when taking LDX compared to placebo. One of the studies was a post hoc analysis that showed improved emotional lability in those taking LDX. No new treatment-related adverse events were detected, and the effect was similar to the effect of methylphenidate, a drug for ADHD symptoms that has been on the market for a longer time. The most common side effects were comparable to those typical of amphetamines: decreased appetite, insomnia, upper abdominal pain, headache, irritability, and weight loss. The studies investigate short-term treatment. Conclusion: Lisdexamfetamine shows a reduction of ADHD symptoms measured in several different scales, primarily ADHD-RS-IV. It is safe to use and is tolerated in children. Among the very youngest (4 – 5 years), the effect was less noticeable than for older children, but only one article was found for that age group. More studies are required to conclude efficacy in that particular age group properly, but no new adverse events were observed.