Syfte: Att värdera ketamins potential via intranasal administrering och om detta är en effektiv och säker behandlingsmetod mot TRD.Målsättning: Att bedriva en databassökning för att identifiera relevant litteratur, utvärdera studiernas kvalitet och sammanfatta bevisen för utfallet av medicinering av ketamin till patienter med TRD. Design: En systematisk review av randomiserade kontrollerade studier. Datakällor: Cochrane, PubMed, U.S. Food & Drug AdministrationMetod: Litteratursökning med kvantitativ ansats där validering av RCT:s utfördes med hjälp av CONSORT frågeformulär. Data extraherades och kombinerades i text och tabeller med fokus på huvudresultaten som ämnar att svara på syftet.Resultat: Sex randomiserade kontrollerade studier bedömdes ha hög kvalitet enligt CONSORT och inkluderades i denna litteraturstudie. Datan sammanfattades och visar att intranasalt ketamin har en snabbt insättande antidepressiv effekt som kan detekteras redan 40 minuter efter dosering. Det resultat som konventionell antidepressiv behandling kan uppvisa efter åtta veckor uppnår ketamin efter 24 timmar. Ingen av studierna visar att intranasalt ketamin ger allvarliga biverkningar. Dålig smak i munnen och yrsel var de mest rapporterade biverkningarna. De följdverkningar som rapporterats har bedömts milda eller måttliga i intensitet. Intranasal administrering bidrar till mindre obehag för patienten och är ett mer praktiskt alternativ än intravenös tillförsel. Slutsats: Trots missbrukspotentialen kvarstår faktum att ketamin är ett oerhört effektivt och säkert behandlingsalternativ för patienter med TRD och har många fördelar jämfört med den behandling som är tillgänglig för denna patientgrupp idag. / Purpose: To evaluate the drug ketamine and its efficacy and safety in patients with TRD via intranasal administration.Objective: To conduct a database search to identify relevant literature, evaluate the quality of the studies and summarize the evidence for the outcome of the medication of ketamine in patients with TRD.Design: A systematic review of randomized controlled trials.Data sources: Cochrane, PubMed, U.S. Food & Drug AdministrationMethod: Literature search with quantitative approach where validation of RCTs was performed using CONSORT questionnaire. The data was extracted and combined in text and tables focusing on the main results that are intended to answer the purpose.Results: Six randomized controlled studies were considered to be of high quality according to CONSORT and were included in this literature study. The data was summarized and shows that intranasal ketamine has a rapid onset antidepressant effect that can be detected already 40 minutes after dosing. The result of conventional antidepressant treatment after eight weeks reaches ketamine after 24 hours. None of the studies show that intranasal ketamine causes serious side effects. Poor taste in mouth and dizziness were the most commonly reported side effects. The effects reported have been assessed as mild or moderate in intensity. Intranasal administration contributes to less discomfort for the patient and is a more practical alternative than intravenous administration.Conclusion: Despite the potential for abuse, the fact remains that ketamine is an extremely effective and safe treatment option for patients with TRD and has many benefits compared to the treatment recommended for this patient group today

Depression is a potentially life-threatening disease that is one of the leading causes of disability in the world. In 2017, more than 300 million people suffered from depression. That equates to about 4.4% of the world's population, making it the world's second most common public health disease after cardiovascular disease. About 50% who are treated for depression develop unipolar treatment-resistant depression, a type of severe persistent depression in which conventional methods or drugs do not have effect.  Psilocybin is a tryptamine found in a variety of species of psychedelic mushrooms. Psilocybin is a prodrug that breaks down into the active substance psilocin which interacts with serotonin receptors and produces psychoactive effects. Psilocybin is classified as a schedule I drug in most of the world and is therefore not considered to have any medical value. Psilocybin has been researched intensively in recent years, mainly focusing on its potential antidepressant effect. Psilocybin's effects have been widely covered in English literature but hardly at all in Swedish literature. This bachelor thesis will hopefully fill that gap and encourage more research on the subject here in Sweden. The purpose of this bachelor thesis was to evaluate, based on published studies, whether psilocybin potentially can have an effective, safe, and long-lasting antidepressant effect on depressive symptoms. Six studies are presented, and the results indicate that that 20–30 mg of psilocybin together with psychological support in an optimal environment can potentially have a long-acting, safe, and effective antidepressant effect on adult people with moderate to severe unipolar depression. Based on these results, the drug classification of psilocybin should be questioned and investigated.

Inledning: Depression är ett globalt folkhälsoproblem som drabbar människor i alla åldrar oavsett kön. En tredjedel av alla patienter diagnostiserade med depression blir inte hjälpta av dagens behandlingsmetoder och i synnerhet läkemedel. Denna grupp av individer klassificeras som behandlingsresistenta. För individer som lever med behandlingsresistent depression (TRD) är situationen allvarlig. Suicidala tankar (SI) och beteenden är vanligt förekommande och ökar i takt med svårighetsgraden av depressionen. Upptäckten av ketamins snabba effekter mot depression under 2000-talet har givit nytt ljus åt forskningen och mycket forskning görs på området som indikerar på positiva effekter mot TRD och de suicidala benägenheterna. Ketamin är dock ett problematiskt läkemedel med svåra biverkningar som gör situationen mer komplex. Syfte: Syftet med detta litteraturarbete var att undersöka effekterna av intravenöst (iv) ketamin mot TRD och i synnerhet dess antisuicidala effekter. Metod: Fem kliniska studier har analyserats. Två databassökningar gjordes via databasen PubMed med sökorden ”TRD suicidal ideation ketamine infusion treatment” och ” treatment resistant depression ketamine suicidal cognition”. Inkluderade artiklar valdes utifrån fastställda inklusions- och exklusionskriterier. Resultat: Överlag påvisas ett positivt resultat av ketamins antisuicidala effekter vid TRD. Fyra av fem studier visade signifikanta resultat av en singeldos ketamin jämfört med placebo och en studie kunde visa positiva effekter av upprepade infusioner. Medan en studies resultat varken kunde påvisa positiva effekter på kort eller lång sikt. Diskussion: Sammanfattningsvis indikerar resultatet av inkluderade studier på att ketamin i viss grad har positiva effekter på SI vid TRD och att iv ketamin har potential som läkemedel för denna patientgrupp. Dock krävs det mer forskning kring effektens hållbarhet, långtidseffekter, biverkningar och beroenderisken av ketamin. Idag används ketamin i form av det intranasala läkemedlet Spravato mot svår depression, detta med försiktighet på grund av de allvarliga biverkningar som kan följa och dess okända långtidseffekter. / Introduction: Depression is a global public health problem that affects people of all ages regardless of gender. One third of all patients diagnosed with depression are not helped by today's treatment methods. This group of individuals is classified as the treatment resistant. For individuals living with treatment-resistant depression (TRD), the situation is dire. Suicidal thoughts (SI) and behaviors are common and increase with the severity of the depression. The discovery of ketamine's rapid effects against depression in the 21st century has given new light to research and much research are being done in the area that indicates positive effects against TRD and the suicidal tendencies. However, ketamine is a problematic drug with severe side effects that make the situation more complex. Aim: The aim of this review was to investigate the effects of intravenous (iv) ketamine against TRD and in particular its anti-suicidal effects. Method: Five clinical studies have been analyzed. Two database searches were made via the PubMed database with the keywords "TRD suicidal ideation ketamine infusion treatment" and "treatment resistant depression ketamine suicidal cognition". Included articles were selected based on established inclusion and exclusion criteria. Results: Overall, a positive result of ketamine's anti-suicidal effects in TRD is demonstrated. Four out of five studies showed significant results of a single dose of ketamine compared to placebo and one study was able to show positive effects of repeated infusions. While the results of one study could not demonstrate positive effects in the short or long term. Discussion: In summary, the results of included studies indicate that ketamine has, to some extent, positive effects on SI in TRD and that iv ketamine has potential as a drug for this patient group. However, more research is needed concerningdurability of the effect, long-term effects, side effects and the risk of addiction to ketamine. Today, ketamine is used in the form of the intranasal drug Spravato against severe depression, this with caution because of the serious side effects that can follow and its unknown long-term effects.