Background: The late onset of therapeutic response and a relatively large proportion of nonresponders to antidepressants remain major concerns in clinical practice. Therefore, there is a critical need for effective medication strategies that augment treatment with antidepressants. Methods: To review the available evidence on the use of lithium as an augmentation strategy to treat depressive episodes. Results: More than 30 open-label studies and 10 placebo-controlled double-blind trials have demonstrated substantial efficacy of lithium augmentation in the acute treatment of depressive episodes. Most of these studies were performed in unipolar depression and included all major classes of antidepressants, however mostly tricyclics. A meta-analysis including 10 randomized placebo-controlled trials has provided evidence that lithium augmentation has a statistically significant effect on the response rate compared to placebo with an odds ratio of 3.11, which corresponds to a number-needed-to-treat of 5. The meta-analysis revealed a mean response rate of 41.2% in the lithium group and 14.4% in the placebo group. One placebo-controlled trial in the continuation treatment phase showed that responders to acute-phase lithium augmentation should be maintained on the lithium-antidepressant combination for at least 12 months to prevent early relapses. Preliminary studies to assess genetic influences on response probability to lithium augmentation have suggested a predictive role of the –50T/C single nucleotide polymorphism of the GSK3β gene. Conclusion: Augmentation of antidepressants with lithium is currently the best-evidenced augmentation therapy in the treatment of depressed patients who do not respond to antidepressants. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Mood disorders are serious diseases. Nevertheless, their pathophysiology is not sufficiently clarified. Biological markers that would facilitate the diagnosis or successful prediction of pharmacotherapy are still being sought. The aim of the study was to find out whether mitochondrial functions are affected by antidepressants, mood stabilizers and depression. Our research is based on recent hypotheses of mood disorders, the advanced monoamine hypothesis, the neurotrophic hypothesis, and the mitochondrial dysfunction hypothesis. We assume that impaired function of mitochondria leads to neuronal damage and can be related to the origin of mood disorders. Effects of antidepressants and mood stabilizers on mitochondrial functions can be related to their therapeutic or side effects. In vitro effects of pharmacologically different antidepressants and mood stabilizers on the activities of mitochondrial enzymes were measured in mitochondria isolated from pig brains (in vitro model). Activity of monoamine oxidase (MAO) isoforms was determined radiochemically, activities of other mitochondrial enzymes were measured spectrophotometrically. Overall activity of the system of oxidative phosphorylation was measured electrochemically using high- resolution respirometry. Methods were modified to measure the same...

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Irritable bowel syndrome (IBS) är en av de vanligaste diagnostiserade GI-tillstånden idag och är en störning av gastrointestinalkanalen (GI-kanalen). Det finns inget botemedel mot IBS på grund av att patogenesen är oklar och därför är fokusen symtomlindring vid behandling.  De vanligaste symtom som förekommer är buksmärta, obehag i buk, uppblåsthet, utspänd buk och förändring av avföringens konsistens och frekvens. Patofysiologin är inte fullt klarlagd men en rubbning i tarm-hjärn-axeln kan leda till förändring i GI-rörelser. Neurotransmittorerna noradrenalin och serotonin (5-HT) är troligen viktiga faktorer för patofysiologin kopplad till tarm-hjärn-axeln. Syftet var att undersöka effektiviteten och säkerheten för de antidepressiva läkemedlen vid behandling av IBS. De antidepressiva som undersöktes i arbetet var tianeptin, amitriptylin, escitalopram, venlafaxin, vortioxetin och mirtazapin. De fem artiklarna som användes i detta arbete upptäcktes med hjälp av databaserna Pubmed och Onesearch. Sökord som användes var ”IBS” AND ”antidepressants” och ”IBS” AND ”SSRI”.  Alla antidepressiva visade en signifikant förbättring för livskvalitén hos deltagarna i studierna. Tianeptin, amitriptylin, escitalopram, venlafaxin och mirtazapin undersökte förändring av buksmärta och alla hade en signifikant förbättring förutom escitalopram. Escitalopram jämfördes mot rektal ballongutvidgning vid behandling hos IBS med förstoppning (IBS-C). Ballongutvidgningen visade bättre resultat än escitalopram och denna jämförelse gör det svårt att dra någon slutsats om escitalopram i arbetet. Amitriptylin, tianeptin och mirtazapin undersökte förändring av avföringskonsistensesn och frekvensen och visade en signifikant förbättring hos IBS med diarré (IBS-D). Venlafaxin visade signifikant förbättring för både lös och hård avföringsfrekvens och studerade ingen specifik IBS-grupp. Vortioxetin undersökte alla IBS-grupper och endast förändring av livskvalitén, depression och ångest vilket också gör det svårt att dra slutsats om effekt hos IBS. Det var inga av de depressiva medlen som gav allvarliga biverkningar, dock kan vissa biverkningar tolkas som mer obehagliga än andra. För vissa antidepressiva var det deltagare som avslutade studien på grund av biverkningar. Amitriptylin, tianeptin, venlafaxin vortioxetin och mirtazapin visade alla god effekt och säkerhet. Om effektiviteten ock säkerheten jämförs bland dessa har tianeptin det bästa resultatet. / Irritable bowel syndrome (IBS) is one of the most diagnosed conditions in the gastrointestinal (GI) tract today and is a disorder of the GI tract. There is no cure for IBS, which is probably due to the fact that the pathogenesis is unclear, and therefore the focus has been a symptom-relieving treatment. The most common symptoms that occur are abdominal pain, abdominal discomfort, bloating, distension of the abdomen, and change in the consistency and frequency of the stool. The pathophysiology is not fully understood, but a disorder of the gut-brain axis can lead to a change in GI movements. The neurotransmitters norepinephrine and serotonin (5-HT) are probably important factors for pathophysiology and linked to the gut-brain axis.  The aim was to investigate the effectiveness and safety of antidepressants used in IBS treatment. The antidepressants examined in this literature were tianeptine, amitriptyline, escitalopram, venlafaxine, vortioxetine, and mirtazapine. The five articles on which current litter tour work is based were obtained using the PubMed and OneSearch databases. Keywords used were "IBS" AND "antidepressants" and "IBS" AND "SSRI."  All the antidepressants examined showed a significant improvement in the participants' quality of life in the studies. The studies also examined changes in abdominal pain using tianeptine, amitriptyline, escitalopram, venlafaxine, and mirtazapine. All participants showed a significant improvement and reduced abdominal pain except when ingesting escitalopram. Intake of escitalopram was compared against rectal balloon enlargement as a treatment for IBS with constipation (IBS-C). The balloon expansion showed better results than escitalopram, and this comparison makes it difficult to draw any conclusion about escitalopram and its actual effect in different types of IBS. Amitriptyline, tianeptine, and mirtazapine investigated stool consistency and stool frequency changes and showed a significant improvement in these symptoms in IBS with diarrhea (IBS-D). Venlafaxine showed significant improvement for both loose and hard stool frequency; however, no specific IBS group was studied in this study. When ingesting vortioxetine, all different IBS groups and changes in quality of life, depression, and anxiety were examined, making it difficult to conclude about the effect of the drug in IBS. None of the antidepressant medicines produced severe side effects. However, some side effects can be interpreted as more unpleasant than others, and hence there was some loss during some studies.  Amitriptyline, tianeptine, venlafaxine vortioxetine, and mirtazapine showed good efficacy and safety. If the effectiveness and safety were to be compared between these drugs, tianeptine would be the first choice in treating IBS.

La dépression affecte environ 20 % des femmes en âge de procréer et environ 5 % à 15 % des femmes enceintes. Les troubles anxieux, souvent concomitants de la dépression maternelle sont de l’ordre de 15 % durant la grossesse. Au cours des dernières années, l’utilisation gestationnelle des antidépresseurs s’est accrue, malgré les risques associés pour la mère et l’enfant rapportés dans la littérature. Les risques maternels tels que le risque de diabète gestationnel et de dépression postpartum ont été peu étudiés avec des résultats souvent contradictoires. De plus, les données sur l’évolution dans le temps de la prévalence de la dépression/anxiété et de l’utilisation des antidépresseurs durant la grossesse sont très peu disponibles dans la littérature. La Cohorte des Grossesses du Québec (CGQ) a été utilisée pour cette recherche et la thèse a été organisée en trois volets. Dans un premier volet, nous avons réalisé une étude descriptive pour étudier la prévalence et les tendances d’utilisation des antidépresseurs et de la dépression maternelle/anxiété durant la grossesse, sur la période allant de 1998 à 2015. La prévalence d’utilisation des antidépresseurs durant la grossesse a triplé, allant de 2,2 % en 1998 à 6,2 % en 2015, alors que la prévalence de dépression maternelle/anxiété a été multipliée par 1,3 (de 5 % en 1998 à 7 % en 2015). Le deuxième volet consistait à réaliser une étude utilisant le devis cas-témoins niché dans une cohorte pour évaluer si l’utilisation gestationnelle des antidépresseurs était associée à une augmentation du risque du diabète gestationnel. Nous avons trouvé que l’utilisation des antidépresseurs est associée à une augmentation du risque de diabète gestationnel (aOR = 1,19, IC 95% : 1,08-1,30) et particulièrement pour la venlafaxine (aOR = 1,27, IC 95% :1,09-1,49) et l’amitriptyline (aOR = 1,52, IC 95% :1,25-1,84). Le troisième volet consistait en une analyse de survie pour déterminer si différentes trajectoires d’utilisation d’antidépresseurs durant la grossesse, chez des femmes déprimées avant la grossesse pouvaient affecter le risque de dépression postpartum. Nos résultats montrent que les femmes exposées en continu durant la grossesse (aHR=1,69; IC à 95 % : 1,01-2,84), celles exposées au deuxième/troisième trimestre (aHR=2,56; 95 % CI : 1,33-4,90), et celles avec une exposition intermittente (aHR=2,41; 95 % CI : 1,59-3,66) ont un risque plus élevé de dépression postpartum que les femmes enceintes déprimées, non exposées pendant la gestation. A contrario, celles exposées uniquement au premier trimestre (aHR=1,35; IC à 95 % : 0,81-2,25) étaient moins à risque de dépression postpartum par rapport aux femmes non exposées. En conclusion, les antidépresseurs sont de plus en plus utilisés en grossesse et nous avons observé une augmentation modérée du risque de diabète gestationnel associé à leur utilisation, principalement pour la venlafaxine et l’amitriptyline. En ce qui concerne leur efficacité en vie réelle dans la prévention de la dépression postpartum, nous n’avons pas trouvé de diminution du risque pour les utilisatrices au sein d’une cohorte de femmes avec une dépression prénatale. Néanmoins, malgré certaines limites méthodologiques, ces résultats renforcent la nécessité d’une approche de traitement personnalisée pour chaque femme enceinte souffrant de dépression, afin de faire les meilleurs choix pour sa santé et celle de l’enfant à naitre. / Depression affects about 20% of women of childbearing age and about 5% to 15% of pregnant women. Anxiety disorders, often concomitant with maternal depression, are in the order of 15% during pregnancy. In recent years, gestational use of antidepressants has increased, despite the associated risks to mother and child reported in the literature. Maternal risks such as the risk of gestational diabetes and postpartum depression have been little studied with often contradictory results. In addition, data on the evolution over time of the prevalence of depression / anxiety and the use of antidepressants during pregnancy are very limited in the literature. The Quebec Pregnancy Cohort (QPC) was used for this research and the thesis was organized in three parts. In a first part, we carried out a descriptive study to determine the prevalence and the trends of use of antidepressants and maternal depression / anxiety during pregnancy. over the period from 1998 to 2015. We observed that the prevalence of antidepressants use during pregnancy has tripled, ranging from 2.2% in 1998 to 6.2% in 2015, while the prevalence of maternal depression / anxiety has increased by 1.3 (from 5% in 1998 to 7% in 2015). The second part consisted of carrying out a study using the nested case-control design to assess whether the gestational use of antidepressants was associated with an increased risk of gestational diabetes. We have found that the use of antidepressants is associated with an increased risk of gestational diabetes (aOR = 1.19, 95% CI: 1.08-1.30) and particularly for venlafaxine (aOR = 1.27, 95% CI: 1.09-1.49) and amitriptyline (aOR = 1.52, 95% CI: 1.25-1.84). The third part consisted of a survival analysis to determine whether different trajectories of antidepressant use during pregnancy in women depressed before pregnancy could affect the risk of postpartum depression. Our results show that women exposed continuously during pregnancy (aHR = 1.69; 95% CI: 1.01-2.84), those exposed in the second / third trimester (aHR = 2.56; 95% CI: 1.33-4.90), and those with intermittent exposure (aHR = 2.41; 95% CI: 1.59-3.66) have a higher risk of postpartum depression than depressed pregnant women, not exposed during gestation. Conversely, those exposed only in the first trimester (aHR = 1.35; 95% CI: 0.81-2.25) were less at risk of postpartum depression compared to unexposed women. In conclusion, antidepressants are increasingly used in pregnancy and we have observed a moderate increase in the risk of gestational diabetes associated with their use, mainly for venlafaxine and amitriptyline. Regarding their real-life efficacy in preventing postpartum depression, we found no decreased risk for users in a cohort of women with prenatal depression. Nonetheless, despite some methodological limitations, these results reinforce the need for a personalized treatment approach for each pregnant woman with depression, in order to make the best choices for her health and that of the unborn child.

Psychopharmaca are a large group of drugs widely used not only in psychiatry. Their systemic administration affects both the main diagnosis and the organism as a whole. The subject of our experiments is the effect of psychopharmaca on the changes in mitochondrial functions, which is beneficial for understanding of molecular mechanisms of therapeutic and adverse effects of drugs. The aim of this thesis was to study the in vitro effects of selected drugs on the cell energy metabolism. Selected antipsychotics (chlorpromazine, levomepromazine, haloperidol, risperidone, ziprasidone, zotepine, aripiprazole, clozapine, olanzapine, and quetiapine), antidepressants (bupropion, fluoxetine, amitriptyline, imipramine) and mood stabilizers (lithium, valproate, valpromide, lamotrigine, carbamazepine) were tested. In vitro effects of selected psychopharmaca were measured on isolated pig brain mitochondria. The activities of citrate synthase (CS) and electron transport chain (ETC) complexes (I, II+III, IV) were measured spectrophotometrically. Drug-induced changes of mitochondrial respiration rates linked to complex I (supported by malate and pyruvate) and complex II (supported by succinate) were evaluated by high resolution respirometry. Complex I was significantly inhibited by lithium, carbamazepine, fluoxetine,...

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.

Depressive disorder, etiology, objective criteria for identifying depression, depression and suicide, depression in ICD-10, treatment, chemicals in the brain and transmission of information, action mechanism of antidepressants, cutting depression, comorbidity, biological and psychotherapeutic treatment options, pharmacotherapy, ATC classification drugs, antidepressants,classification according to the distribution of the ATC, guidelines for the treatment of depression. Identifying the trend and volume of consumption of antidepressants - the code N06A in the Czech Republic in the period 2003-2008 using data from the Všeobecná zdravotní pojišťovna ČR and a comparison based on specific criteria: regional (consumption by region), gender (consumption by gender), age (consumption by age groups), season and month (consumption in different seasons and months) and ATC groups (consumption by chemical / therapeutic / pharmacological subgroups N06A * - 4th level ATC class and consumption by subgroups of chemical substances N06A ***, ie . active substances - 5th level ATC classification). A rough estimate of possible share of depressive and neurotic disorders found in consumption, based on additional data from the database of the Všeobecná zdravotní pojišťovna ČR.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Suite aux notifications de cas de comportements suicidaires associés aux antidépresseurs (ADs) chez les jeunes, une mise en garde réglementaire a été émise en mai 2004 au Canada, et deux guides de pratique clinique ont été publiés dans la littérature en novembre 2007. L'objectif de ce mémoire fut d'évaluer l’association entre ces interventions de communication et le suivi médical de la population pédiatrique traitée par ADs au Québec. Une étude de cohorte rétrospective (1998-2008) a été menée chez 4 576 enfants (10-14 ans) et 12 419 adolescents (15-19 ans) membres du régime public d’assurance médicaments du Québec, ayant débuté un traitement par AD. Le suivi médical dans les trois premiers mois de traitement a été mesuré par l’occurrence et la fréquence de visites médicales retrouvées dans les banques de données de la RAMQ. Les facteurs associés à un suivi conforme aux recommandations ont été évalués à partir de modèles de régression logistique multivariés. Seuls 20% des enfants ou adolescents ont eu au moins une visite de suivi à chaque mois, en conformité avec les recommandations. La probabilité de recevoir un suivi médical conforme était plus élevée lorsque le prescripteur initial était un psychiatre. L’occurrence et la fréquence des visites n’ont pas changé après la publication de la mise en garde ou des recommandations. De ce mémoire on conclut que d'autres interventions visant à optimiser le suivi médical devraient être envisagées. / Following reports of a potential association between antidepressants (ADs) and suicidal behaviour in youth, a regulatory warning was issued in Canada in May 2004, and clinical practice guidelines on recommended medical follow-up were published in the literature in November 2007. This Master's thesis aimed at assessing the association between these communication interventions and medical follow-up practices. A retrospective cohort study (1998-2008) was conducted among 4,576 children (10-14 years) and 12,419 adolescents (15-19 years) members of the Quebec public drug plan. Medical follow-up was ascertained through patterns of physician billing practices found in the RAMQ medical services databases. Study outcomes consisted of occurrence and frequency of visits in the first three months of AD treatment. Factors associated with follow-up consistent with recommendations were identified through multivariate logistic regression models. The main independent variable was exposure to each of the communication interventions. Covariates included: gender, class of AD, number of concomitant chronic diseases, psychiatric conditions, prescriber’s specialty, and potential exposure to each intervention. Only 20% of children or adolescents received at least one visit each month. The probability of receiving adequate follow-up was greater when treatment was initiated by a psychiatrist. Occurrence and frequency of visits did not change after the warning nor the publication of the recommendations. From this thesis, one may conclude that further interventions to optimize medical follow-up practices should be envisaged.