Identification of primary care patients at risk of nonadherence to antidepressant treatment

Ann-Charlotte Åkerblad1, Finn Bengtsson2, Margareta Holgersson3, Lars von Knorring1, Lisa Ekselius11Department of Neuroscience, Psychiatry, Uppsala University Hospital, Uppsala University, Uppsala, Sweden; 2Division of Clinical Pharmacology, Medicine and Care, Faculty of Health Sciences, Linköping University, Linköping, Sweden; 3Quintiles AB, Uppsala, SwedenIntroduction: Poor adherence to antidepressant treatment is common, and results in increased disability and costs. Several factors are thought to influence patients’ ability and willingness to adhere. So far, however, consensus is lacking regarding patient characteristics that predict nonadherence. The purpose of this study was to identify predictors of nonadherence to antidepressant treatment that can be ascertained at treatment start.Method: The present study used data from a randomized controlled trial with the main objective of studying the effect of two different compliance-enhancing programs on treatment adherence and treatment response in 1031 primary care patients with major depression. In this study, logistic regression analyses were performed to examine patient- and illness-related characteristics potentially associated with nonadherence.Results: Nonadherence to antidepressant treatment was predicted by age under 35 or over 64 years, presence of personality disorder, sensation-seeking personality traits, substance abuse, and absence of concomitant medications.Conclusion: Certain patient- and illness-related characteristics may imply an increased risk of nonadherence to antidepressant treatment. Giving special attention to subjects with such characteristics may improve adherence.Keywords: unipolar depression, antidepressant, adherence, compliance, SSRI, predictor

On the influence of serotonin- and sex steroid-related genetic variation on mood, anxiety, personality, autism and transsexualism

Background: The neurotransmitter serotonin has been related to mood and anxiety, and variation in genes that encode important members of the serotonergic system may hence affect mood- and anxiety-related traits. Sex steroids influence brain development, and variation in genes encoding androgen and estrogen receptors, or enzymes needed for sex steroid synthesis, may be of importance for both personality traits and risk for psychiatric disorders. The specific aims of this thesis were: (i) to investigate the possible influence of serotonin-related genetic variation on the neural correlates of anxiety, and on mood- and anxiety-related phenotypes, including premenstrual dysphoric disorder (PMDD), depression and anxiety-related personality traits, (ii) to investigate the possible influence of sex steroid-related genetic variation on personality, autism spectrum disorder and transsexualism, and (iii) to try to ameliorate the chance of detecting effects of combinations of genetic variations by restricting the statistical analysis to particular patterns. Results: (i) The serotonin transporter (5-HTT) linked polymorphic region (5-HTTLPR) and a polymorphism in an important enzyme for serotonin synthesis (tryptophan hydroxylase 2; TPH2) were associated with amygdala response during presentation of angry faces in subjects with social phobia and controls. (ii) The same polymorphisms were associated with response to placebo and also with placebo-induced changes in amygdala activity during public speaking in subjects with social phobia. (iii) In men, genetic variation in the neurotrophic factor BDNF, which is closely related to the serotonergic system, was associated with the amount of serotonin transporter in the brain. (iv) Polymorphisms in genes that encode proteins important for the development of the serotonergic system (GATA2), for serotonin synthesis (TPH2) and for serotonergic transmission (5-HT3B) were associated with PMDD. (v) The 5-HTTLPR was shown to influence reports of controllable stressful life events in combination with the BDNF Val66Met polymorphism or anxiety-related personality traits in non-depressed men. (vi) Variants that may increase the function of the androgen receptor were associated with extraversion and spiritual acceptance in men. (vii) A variant that is associated with increased androgen receptor function was more common in women with autism spectrum disorder than in controls. (viii) The same androgen receptor polymorphism was associated with transsexualism in combination with polymorphisms in the genes encoding the estrogen receptor β or the testosterone-converting aromatase enzyme. (ix) A method that restricts the search for genetic combinations to monotone effect patterns was shown to increase the probability of finding gene-gene effects. Conclusions: The results support the notion that variation in genes that encode serotonin-related and sex steroid-related proteins are of importance for the psychiatric traits studied in this thesis

The role of sociodemographic and clinical factors in the initiation and discontinuation of attention deficit hyperactivity disorder medication among young adults in Sweden

IntroductionLong-term medication use is a recommended treatment for attention-deficit/hyperactivity disorder (ADHD), however, discontinuation is common. Non-medical factors which might influence initiation and discontinuation are understudied. Therefore, we investigated how different sociodemographic factors and comorbidities were associated with the initiation and discontinuation of ADHD medication use among young adults.Methods and resultsWe conducted a population-based prospective cohort study using individually linked administrative register data, in which we included all individuals residing in Sweden, between the age of 19 and 29 who were first diagnosed with ADHD between January 2006 and December 2016 (n = 59224). ADHD medication initiation was defined as the first prescription of ADHD medication in the period from 3 months before to 6 months after the cohort entry date. Those who initiated ADHD medication were followed up for medication use until discontinuation, death/emigration, or until 2019. Logistic and Cox regression models were used to investigate the associations between sociodemographics, health-related predictors and initiation, as well as discontinuation. Overall, 48.7% of the 41399 individuals initiated ADHD medication, most often methylphenidate (87%). Among the initiators, 15462 (77%) discontinued medication use during the follow-up (median time: 150 days). After mutually adjusting all other predictors, initiation was positively associated with older age, male sex, higher level of education, and negatively associated with living at home with parents, immigrant status, being unemployed during the year before inclusion, being on disability pension, having autism, substance use, schizophrenia-spectrum disorders, other mental disability/developmental disorders, cardiovascular diseases or previous accidents. Discontinuation was positively associated with being born abroad, living in big cities, being unemployed during the year before inclusion, having cancer, and negatively associated with a higher educational level, having depression, anxiety or stress-related disorder, autism spectrum disorder or diabetes.ConclusionBesides medical factors, sociodemographics, such as educational attainment and immigrant status might also play a role in the initiation and discontinuation of ADHD medication use among young adults newly diagnosed with ADHD

Personality disorder : a disease in disguise

Personality disorders (PDs) can be described as the manifestation of extreme personality traits that interfere with everyday life and contribute to significant suffering, functional limitations, or both. They are common and are frequently encountered in virtually all forms of health care. PDs are associated with an inferior quality of life (QoL), poor health, and premature mortality. The aetiology of PDs is complex and is influenced by genetic and environmental factors. The clinical expression varies between different PD types; the most common and core aspect is related to an inability to build and maintain healthy interpersonal relationships. This aspect has a negative impact on the interaction between health-care professionals and patients with a PD. From being discrete and categorical disease entities in previous classification systems, the current concept of PD, reflected in the newly proposed ICD-11, is a dimensional description based on the severity of the disturbed functioning rather than on the type of clinical presentation. Insight about the characteristics of PDs among medical practitioners is limited, which is partly because persons do not seek health care for their PD, but instead for other medical issues which are obscured by their underlying personality problems. What needs to be emphasized is that PDs affect both the clinical presentation of other medical problems, and the outcome of these, in a negative manner and that the integrated effects of having a PD are a shortened life expectancy. Accordingly, PDs need to be recognized in clinical practice to a greater extent than previously

Validity of the personality disorder diagnosis in the Swedish National Patient Register

Aims The Swedish National Patient Register (NPR) is an exceptional source of information in clinical epidemiological research. The register is, however, not validated for the diagnosis of personality disorder (PD). We therefore assessed its validity in this patient group, and the group with emotionally unstable PD (EUPD)/borderline personality disorder (BPD). Methods Records from 100 random adult patients (aged 15-65 years) diagnosed with any PD in the NPR between 1987 and 2015 were analysed using a protocol based on general diagnostic criteria for PD, as well as specific criteria for EUPD/BPD in both ICD and DSM classification systems. Results Of the 100 patients, 27 had been given a diagnosis of EUPD, 23 another specific PD and 50 an unspecified PD. Using ICD criteria, 88 of 95 evaluable patients could be confirmed to have a PD, that is an agreement rate of 93%. Using DSM criteria, the agreement was lower (77 patients or 81%). Of 26 evaluable patients with a diagnosis of EUPD/BPD, the diagnosis was confirmed in all cases when using the ICD criteria, but in only 20 when using the DSM criteria. Conclusions The NPR is a valid source of data for the diagnosis of PD per se and also of EUPD in women

Six-Year Outcome in Subjects Diagnosed with Attention-Deficit/Hyperactivity Disorder as Adults

There are very few studies on the long-term outcome in subjects diagnosed with ADHD as adults. The objective of the present study was to assess this and relate the outcome to whether there was current medication or not and to other potential predictors of favourable outcome. A prospective clinical cohort of adults diagnosed with ADHD according to DSM-IV criteria was followed-up on an average of 6 years after first evaluation (n = 124; mean age 42 years, 51% males). ADHD symptom trajectories were assessed as well as medication, global functioning, disability, health-related quality of life, and alcohol and drug consumption at follow-up. Ninety percent of those diagnosed were initially treated pharmacologically and half of them discontinued treatment. One-third reported remission, defined as not fulfilling any ADHD subtype and a GAF-value last year ≥ 70, which was not affected by comorbidity at baseline. Current medication was not associated with remission. Subjects evaluated and first diagnosed with ADHD as adults are functionally improved at follow-up 6 years later despite a high percentage of psychiatric comorbidity at baseline. Half dropped out of medication, and there was no difference in ADHD remission between subjects with on-going medication at follow-up or subjects without medication, although current medication was related to a higher degree of self-reported global improvement