This article presents a study conducted on data containing drug concentrations. The data was obtained from femoral venous blood samples collected at medico legal autopsies in Sweden. Cases positive for antidepressant drugs were scrutinized and divided in to two groups for 15 antidepressant drugs: B‑cases, where the cause of death was intoxication with more than one drug detected in the blood sample. C‑cases, where the cause of death was NOT intoxication and at least one drug (the antidepressant) was detected in the blood sample. This data was then processed to find frequencies of concomitant drugs taken together with the antidepressant drugs. Frequencies of the most common concomitant drugs were then compared between B-cases and C-cases for each antidepressant drug. This revealed that the drugs dextropropoxyphene, ethanol, codeine, flunitrazepam, paracetamol, propiomazine and alimemazine were signifcantly more common as concomitant drugs in B-cases (intoxications) than in C‑cases (non‑intoxications). With regards to unknown interactions the most interesting combinations were: Propiomazine with mirtazapine, venlafaxine, citalopram or fluoxetine; Paracetamol with paroxetine; Flunitrazepam with mirtazapine, venlafaxine or citalopram; Codeine with mirtazapine or sertraline. These combinations should be further investigated.

Fibromyalgi är ett kroniskt smärtsyndrom med prevalens i Sverige och internationellt kring 2 %. Karakteristiskt är långvarig, utbredd och generaliserad smärta, dock förekommer andra psykiska och fysiska symtom som gör syndromets symtombild varierad. Syndromet har i decennier inte accepterats på grund av dess oklara etiologi. Avvikelser har beskrivits i centrala nervsystemet och i periferin hos fibromyalgipatienter. Det finns också teorier om att psykiska mekanismer kan vara involverade. Vad som saknas är kausalsamband mellan fynden som rapporterats. Behandlingen är symtomatisk i form av icke-farmakologiska eller farmakologiska alternativ. Val av intervention avgörs utefter patientens symtombild. I Europa finns idag inget godkänt läkemedel för behandling av fibromyalgi och läkemedelsterapi sker utanför godkänd indikation. I USA har tre läkemedel godkänts för behandling av fibromyalgi och två av dessa är duloxetin och pregabalin. Båda dessa läkemedel inkluderas i en nyligen uppdaterad europeisk rekommendation som ligger till grund för läkemedelsverkets rekommendationer i Sverige. Läkemedelsföretagen bakom duloxetin och pregabalin har år 2008 och 2009 ansökt om godkännande till försäljning av läkemedlen till fibromyalgipatienter i Europa, dock avslogs ansökningarna. Trots avslag fortsätter läkemedelsföretagen driva forskning om dessa läkemedel vid fibromyalgi. Denna litteraturundersöknings syfte var att utvärdera effekt och säkerhet för duloxetin och pregabalin vid symtomatisk behandling av smärta orsakad av fibromyalgi. Utvärderingen inkluderar åtta kliniska studier som publicerats från och med år 2008, fyra studier med duloxetin och fyra med pregabalin. Resultat från litteraturundersökningen visar att varken duloxetin eller pregabalin har någon stor effekt, jämfört med placebo, på fibromyalgins främsta symtom smärta. Placeboeffekten är relativt stor och dossamband saknas för läkemedlen. / Fibromyalgia is a chronic pain syndrome characterized by widespread generalized pain. Patients also experience other both mental and physical symptoms making the syndrome heterogeneous. Co-morbidity examples are somnolence, gastrointestinal problems and psychiatric conditions including depression and anxiety. The prevalence of fibromyalgia in Sweden is 2,0 % of the population and the international prevalence is similar. Of these 2,0 % almost 80 % are women and the average age of the patients is middle-age. For decades fibromyalgia has not been accepted because of its unknown etiology. Abnormalities have been found in both the central nervous system and in the periphery of fibromyalgia patients. There are also theories that a mental mechanism like poor well-being and stress can cause local pain that can spread and develop into widespread pain. Currently a causal relationship behind the clinical findings is missing.   The treatment of fibromyalgia is often symptomatic according to the patient’s symptoms and needs. The treatment can either be non-pharmacological or pharmacological. In Sweden and the rest of Europe there is no drug approved by the European Medicines Agency for the treatment of fibromyalgia. In the United States three drugs are approved by the Food and Drugs Administration, the two antidepressants milnacipran and duloxetine and the anticonvulsant pregabalin. In a recent update by the European League Against Rheumatism (EULAR) both duloxetine and pregabalin are listed as recommended drugs for the treatment of symptoms of fibromyalgia. The Swedish medical agency has in their recommendations for Swedish healthcare followed the update from EULAR. The pharmaceutical companies have applied for authorization to market the drugs in Europe for treatment of fibromyalgia but the Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion to all applications on the grounds that there was poor benefit, due to poor evidence of effect from clinical trials, compared to the side effects of the drugs. Despite this assessment, the companies are supporting new clinical trials. This literature study examined eight clinical trials published from year 2008 and later, conducted to assess the effect and safety of the two drugs duloxetine and pregabalin compared to placebo. The aim of this literature study was to analyze the effect and safety of these drugs for symptomatic treatment of pain caused by fibromyalgia. The aggregated results show that neither duloxetine nor pregabalin had any major effect on pain caused by fibromyalgia, nor on other symptoms. There was a lack of dose response relationship and several parameters also improved with placebo treatment.

Fler än 350 miljoner människor i världen hade en depression 2012 och sjukdomen tillhör tillsammans med hjärt-kärlsjukdom de mest kostsamma sjukdomarna i västvärlden. 2007 behandlades över 700 000 personer i Sverige med antidepressiva läkemedel till en kostnad av 990 miljoner kronor. Depression kan vara unipolär (endast nedstämdhet) eller bipolär (även med maniska inslag). En primär ”egentlig” depression, major depression, MDD, har ofta en biologisk orsak. Bland annat har man funnit att halterna av signalsubstanserna serotonin och noradrenalin är lägre hos deprimerade. Behandling av depression idag inkluderar antidepressiva läkemedel, elektrokonvulsiv behandling (eng. electroconvulsive therapy (ECT)) och psykoterapi. Syftet med denna litteraturstudie var att jämföra venlafaxin, som är en selektiv serotonin- och noradrenalinåterupptagshämmare (SNRI), med traditionella selektiva serotoninåterupptagshämmare (SSRI) i effekt och säkerhet vid behandling av unipolär depression hos vuxna.  Sju studier, som hämtades från Pubmed och Medline, granskades i detta arbete. De utgjordes av två meta-analyser och fem randomiserade kliniska prövningar. Resultatet visade att i fyra studier hittades ingen statistiskt signifikant skillnad i respons mellan de patienter som fick venlafaxin och de som fick SSRI. I de tre studier som uppvisade en statistiskt signifikant skillnad var venlafaxin effektivare än SSRI. I studie 2 hittades skillnaden i en subgrupp med de sjukaste patienterna (p=0.0121),  i studie 6: RR=1.06, 95% KI 1.01-1.12 och i studie 7: OR=1.15, 95% KI 1.02-1.29.  Endast en av studierna påvisade en statistiskt signifikant skillnad i remission, studie 7, och även här till fördel för venlafaxin  (OR=1.19, 95% KI 1.06-1.34). Dock orsakade venlafaxin fler bortfall p.g.a. biverkningar än SSRI i sex av studierna. Sammanfattningsvis kan venlafaxin anses något effektivare än SSRI, men detta har troligtvis ingen stor klinisk betydelse förutom eventuellt vid behandling av svårare depressioner. Biverkningarna bör vägas in i valet av behandling. Det vore intressant att se fler studier som jämför venlafaxin med SSRI vid svårare depressioner.

Bakgrund: Globalt drabbas 300 miljoner av depression och sjukdomen kan idag behandlas med både antidepressiva läkemedel och psykoterapi. Depression diagnosticeras utifrån klassificeringssystemen ICD-10 och DSM-5 och självskattats utifrån MADRS-skala. Sjukdomen kan delas in i följande svårighetsgrader: lätt/lindrig depression, medelsvår/måttlig depression och svår/djup depression. Vid val av antidepressiva läkemedel är det viktigt att ta hänsyn till svårighetsgrad, biverkningar och interaktioner.  Syfte: Syftet med denna studie är att kartlägga läkemedelslistor framtagna av Sveriges olika läkemedelskommittéer och beskriva val av läkemedelsbehandling vid depression för vuxna och äldre.  Metod: En dokumentanalys utfördes som lämpar sig till att kunna jämföra aktuell offentlig information. Datainsamlingen utfördes hösten 2022 med hjälp av Sveriges 21 olika regioners behandlingsrekommendationer för vuxna och äldre. En egen bedömningsskala med maximalt tre poäng utfördes för att lyckas bedöma regionernas läkemedelsrekommendationer.  Resultat: För vuxna rekommenderar 19 regioner vid lindrig-medelsvår depression sertralin, vid medelsvår-svår rekommenderar 13 regioner venlafaxin och vid svår rekommenderar sex regioner TCA där amitriptylin/klomipramin är mest förekomna. För äldre rekommenderar 13 regioner sertralin/mirtazapin/escitalopram vid lindrig-medelsvår depression, vid medelsvår-svår rekommenderar 13 regioner duloxetin/venlafaxin och vid svår rekommenderar två regioner duloxetin. Enligt den egna bedömningsskalan uppnås varierande antal poäng där totalt sju regioner uppnår maximal poäng.  Slutsats: SSRI var den vanligaste preparatgruppen som rekommenderades av regionerna vid medelsvår depression hos både vuxna- och äldre. Vid svår depression var den vanligaste preparatgruppen SNRI för äldre och TCA för vuxna. Enligt den egna bedömningsskalan var Läkemedelverkets och Socialstyrelsens rekommendationer mest vanligt förekomna källorna hos regionerna. / Background: Globally, 300 millions of people suffer from depression and the disease can today be treated with both antidepressants and psychotherapy. Depression is diagnosed from the classification system ICD-10 and DSM-5 and is self-assessed based on the MADRS-scale. The disease can be divided into the following difficulty level: light/mild depression, medium/moderate depression, and severe/deep depression. It is very important to consider difficulty level, side effects and interactions when choosing an antidepressant.  Aim: The aim of this study is to identify drug lists produced by Sweden’s different pharmaceutical committees and describe the choice of drug treatment for depression for adults and the elderly.  Materials and methods: A document analysis was performed which is suitable to be able to compare public information. The collection of data was performed autumn 2022 with the help of Sweden’s 21 different regions treatment recommendations for adults and the elderly. An own assessment scale was accomplished to judge the regions drug treatment recommendations. Results: For the adults, 19 regions primarily recommend sertraline for mild-moderate depression, for moderate-deep depression 13 regions recommend venlafaxine and for deep depression six regions recommend TCA where amitriptyline/clomipramine are most common. For the elderly, 13 regions primarily recommend sertraline/mirtazapine/escitalopram for mild-moderate depression, for moderate-deep depression 13 regions recommend duloxetine/venlafaxin and for deep depression two regions recommend duloxetine. According to the own assessment scale a varying number of points were achieved, were a total of seven regions achieved maximum points.  Conclusions: SSRIs were the most common drug group recommended by the regions for moderate depression for both adults and the elderly. In deep depression the most common drug group was SNRIs for the elderly and TCAs for adults. According to the own assessment scale the Swedish- Medicines Agency and Social Welfare Board are most common sources in the regions.

Major depressive disorder (MDD) is a mood disorder majorly responsible for disability and mortality worldwide. With a lifetime prevalence of 15-20%, it is the main cause of functional impairment in Western societies as well as the fourth most debilitating illness in the world. Although the pathophysiology of MDD is not yet fully understood, some evidence that suggest the presence of a neuroanatomical deficiency have given rise to the theory of a specific imbalance in the monoamine neurotransmitters noradrenaline (NA) and/or serotonin (5-HT) levels in the brain. Overall, the various classes of antidepressant agents that have been developed to increase monoamine levels on the basis of this proposal have been successful. However, facts relating to prevalent escalation in the illness and recurring episodes of depression point towards a need to enhance clinical treatment. Most conventional antidepressants such as selective serotonin reuptake inhibitors (SSRI) and selective serotonin and noradrenaline inhibitors (SNRI) pose problems in symptomatic improvement. These include therapeutic lag, safety and tolerability issues, making more than 30% patients with MDD unable to reach adequate relief. In this respect, the action mechanism has moved beyond conventional SSRI and lead to the introduction of vilazodone, a novel antidepressant with an additional 5-HT1A partial agonist profile argued to be of potential benefit for a greater efficacy, faster onset of action and better tolerability. Using secondary data, this project aimed to evaluate the role of vilazodone as a SPARI-drug in the overall clinical treatment of MDD as well as its potential in addressing some of the most common obstacles in antidepressant treatment. Study results proved vilazodone’s efficacy to be superior to placebo. Patients across all studies showed significant improvement in depressive symptoms measured in MADRS and HAMD17. Vilazodone was also shown to be generally safe and tolerable but was not positively distinguished from placebo with regards to adverse effects. An overall, meaningful improvement in depressive symptoms was demonstrated in vilazodone, which reinforces its merit as an important treatment option for patients with MDD.

Major depressive disorder (MDD) is a mood disorder majorly responsible for disability and mortality worldwide. With a lifetime prevalence of 15-20%, it is the main cause of functional impairment in Western societies as well as the fourth most debilitating illness in the world. Although the pathophysiology of MDD is not yet fully understood, some evidence that suggest the presence of a neuroanatomical deficiency have given rise to the theory of a specific imbalance in the monoamine neurotransmitters noradrenaline (NA) and/or serotonin (5-HT) levels in the brain. Overall, the various classes of antidepressant agents that have been developed to increase monoamine levels on the basis of this proposal have been successful. However, facts relating to prevalent escalation in the illness and recurring episodes of depression point towards a need to enhance clinical treatment. Most conventional antidepressants such as selective serotonin reuptake inhibitors (SSRI) and selective serotonin and noradrenaline inhibitors (SNRI) pose problems in symptomatic improvement. These include therapeutic lag, safety and tolerability issues, making more than 30% patients with MDD unable to reach adequate relief. In this respect, the action mechanism has moved beyond conventional SSRI and lead to the introduction of vilazodone, a novel antidepressant with an additional 5-HT1A partial agonist profile argued to be of potential benefit for a greater efficacy, faster onset of action and better tolerability. Using secondary data, this project aimed to evaluate the role of vilazodone as a SPARI-drug in the overall clinical treatment of MDD as well as its potential in addressing some of the most common obstacles in antidepressant treatment. Study results proved vilazodone’s efficacy to be superior to placebo. Patients across all studies showed significant improvement in depressive symptoms measured in MADRS and HAMD17. Vilazodone was also shown to be generally safe and tolerable but was not positively distinguished from placebo with regards to adverse effects. An overall, meaningful improvement in depressive symptoms was demonstrated in vilazodone, which reinforces its merit as an important treatment option for patients with MDD.

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