Interaction between mental disorders and social disconnectedness on mortality: a population-based cohort study.

BACKGROUND: Despite the recognised importance of mental disorders and social disconnectedness for mortality, few studies have examined their co-occurrence. AIMS: To examine the interaction between mental disorders and three distinct aspects of social disconnectedness on mortality, while taking into account sex, age and characteristics of the mental disorder. METHOD: This cohort study included participants from the Danish National Health Survey in 2013 and 2017 who were followed until 2021. Survey data on social disconnectedness (loneliness, social isolation and low social support) were linked with register data on hospital-diagnosed mental disorders and mortality. Poisson regression was applied to estimate independent and joint associations with mortality, interaction contrasts and attributable proportions. RESULTS: A total of 162 497 individuals were followed for 886 614 person-years, and 9047 individuals (5.6%) died during follow-up. Among men, interaction between mental disorders and loneliness, social isolation and low social support, respectively, accounted for 47% (95% CI: 21-74%), 24% (95% CI: -15 to 63%) and 61% (95% CI: 35-86%) of the excess mortality after adjustment for demographics, country of birth, somatic morbidity, educational level, income and wealth. In contrast, among women, no excess mortality could be attributed to interaction. No clear trends were identified according to age or characteristics of the mental disorder. CONCLUSIONS: Mortality among men, but not women, with a co-occurring mental disorder and social disconnectedness was substantially elevated compared with what was expected. Awareness of elevated mortality rates among socially disconnected men with mental disorders could be of importance to qualify and guide prevention efforts in psychiatric services.

Prior psychiatric morbidity and differential psychopharmacological treatment patterns: Exploring the heterogeneity of bipolar disorder in a nationwide study of 9594 patients.

OBJECTIVES: Individuals with bipolar disorders (BD) have heterogenic pre-onset illness courses and responses to treatment. The pattern of illness preceding the diagnosis of BD may be a marker of future treatment response. Here, we examined associations between psychiatric morbidity preceding the diagnosis of BD and pharmacological treatment patterns in the 2 years following diagnosis. METHODS: In this register-based study, we included all patients with a diagnosis of BD attending Danish Psychiatric Services between January 1, 2012 and December 31, 2016. We examined the association between a diagnosis of substance use disorder, psychosis (other than schizophrenia or schizoaffective disorder), unipolar depression, anxiety/OCD, PTSD, personality disorder, or ADHD preceding BD and pharmacological treatment patterns following the diagnosis of BD (lithium, valproate, lamotrigine, antidepressants, olanzapine, risperidone, and quetiapine) via multivariable Cox proportional hazards regression adjusted for age, sex, and year of BD diagnosis. RESULTS: We included 9594 patients with a median age of 39 years, 58% of whom were female. Antidepressants, quetiapine, and lamotrigine were the most commonly used medications in BD and were all linked to prior depressive illness and female sex. Lithium was used among patients with less diagnostic heterogeneity preceding BD, while valproate was more likely to be used for patients with prior substance use disorder or ADHD. CONCLUSION: The pharmacological treatment of BD is linked to psychiatric morbidity preceding its diagnosis. Assuming that these associations reflect well-informed clinical decisions, this knowledge may inform future clinical trials by taking participants' prior morbidity into account in treatment allocation.

Association between lithium treatment and renal, thyroid and parathyroid function: A cohort study of 6659 patients with bipolar disorder.

OBJECTIVES: Although potential adverse effects of lithium treatment on renal and endocrine systems have been extensively investigated, most prior studies are limited by selected populations and short follow-up. METHODS: Within the Psychiatric Services of the Central Denmark Region, we identified all patients with bipolar disorder and ≥1 serum-lithium (se-Li) measurements between January 1, 2013, and July 20, 2022, and reference patients with bipolar disorder matched on age, sex, and baseline creatinine. Outcomes were diagnoses of renal, thyroid and parathyroid disease, and blood tests measuring creatinine, estimated glomerular filtration rate (eGFR), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium. Analyses included unadjusted multilevel regression to describe changes in biochemical markers, and adjusted Cox regression to compare rates of disease/biochemical outcomes between lithium users and reference patients. RESULTS: Among 1646 lithium users (median age 36 years, 63% women) and 5013 reference patients, lithium users had decreasing TSH and eGFR, stable PTH, and increasing calcium levels over time. Lithium use was associated with increased rates of renal, thyroid and parathyroid disease, and levels of biochemical markers outside normal ranges (hazard rate ratios: 1.07-11.22), but the absolute number of severe outcomes was low (e.g., chronic kidney disease: N = 10, 0.6%). Notably, the rate of blood testing was substantially higher among lithium users than among reference patients (e.g., mean number of creatinine tests during the second year of follow-up: lithium users = 2.5, reference patients = 1.4). CONCLUSIONS: Severely adverse renal and endocrine outcomes are rare during lithium treatment. Observational studies of long-term lithium treatment are prone to detection bias.

Development and validation of a machine learning model for prediction of type 2 diabetes in patients with mental illness.

BACKGROUND: Type 2 diabetes (T2D) is approximately twice as common among individuals with mental illness compared with the background population, but may be prevented by early intervention on lifestyle, diet, or pharmacologically. Such prevention relies on identification of those at elevated risk (prediction). The aim of this study was to develop and validate a machine learning model for prediction of T2D among patients with mental illness. METHODS: The study was based on routine clinical data from electronic health records from the psychiatric services of the Central Denmark Region. A total of 74,880 patients with 1.59 million psychiatric service contacts were included in the analyses. We created 1343 potential predictors from 51 source variables, covering patient-level information on demographics, diagnoses, pharmacological treatment, and laboratory results. T2D was operationalised as HbA1c ≥48 mmol/mol, fasting plasma glucose ≥7.0 mmol/mol, oral glucose tolerance test ≥11.1 mmol/mol or random plasma glucose ≥11.1 mmol/mol. Two machine learning models (XGBoost and regularised logistic regression) were trained to predict T2D based on 85% of the included contacts. The predictive performance of the best performing model was tested on the remaining 15% of the contacts. RESULTS: The XGBoost model detected patients at high risk 2.7 years before T2D, achieving an area under the receiver operating characteristic curve of 0.84. Of the 996 patients developing T2D in the test set, the model issued at least one positive prediction for 305 (31%). CONCLUSION: A machine learning model can accurately predict development of T2D among patients with mental illness based on routine clinical data from electronic health records. A decision support system based on such a model may inform measures to prevent development of T2D in this high-risk population.

Clinical and Legal Differences in the Use of Involuntary Electroconvulsive Therapy for Life-Threatening Illness Across European Countries.

OBJECTIVES: Electroconvulsive therapy (ECT) can be life-saving in situations where patients are at risk of dying from severe manifestations of psychiatric illness. In some of these cases, patients are unwilling/unable to consent to ECT, and involuntary ECT is required. Such use of involuntary ECT varies substantially across European countries for unclear reasons. The aim of this study was to examine clinical and legal differences in this use of involuntary ECT across European countries. METHODS: A questionnaire based on a case vignette (a 55-year-old female inpatient with psychotic depression at imminent risk of dying from metabolic derangement because of refusal to eat and drink) was sent to an ECT practitioner in each of 31 European countries. RESULTS: We received responses from ECT practitioners in 18 countries. In 7 of these countries, involuntary ECT could be carried out without approval from others and/or involvement of the court system in the case described in the vignette. Practitioners in the remaining 11 countries responded that they either could not carry out involuntary ECT or would have to meet certain requirements before initiating involuntary ECT (e.g., approval from medical/ethics committee and second opinion from an independent psychiatrist). Notably, the rules regarding involuntary ECT differed for adults and minors (more restrictive for the latter) in 6 of the 18 countries. CONCLUSIONS: In many European countries, legislation precludes or delays the use of involuntary ECT. Harmonization of the legislation on involuntary ECT across European countries to allow for better access to this potentially life-saving treatment seems warranted.

Risk of Mania After Methylphenidate in Patients With Bipolar Disorder.

BACKGROUND: Bipolar disorder and attention-deficit/hyperactivity disorder are common comorbidities. Attention-deficit/hyperactivity disorder is commonly treated with stimulants (eg, methylphenidate), which, however, have been suggested to cause treatment-emergent mania in patients with bipolar disorder. Here, we assessed the risk of mania, depressive episodes, and psychiatric admissions after initiation of methylphenidate treatment in patients with bipolar disorder. METHODS: Using Danish health registries, we identified all individuals registered with a diagnosis of bipolar disorder from January 1, 2000, to January 1, 2018, who were treated with methylphenidate. We applied a 1-year mirror-image model to compare the occurrence of mania, depression, and psychiatric admissions in the period leading up to and after methylphenidate treatment initiation. We furthermore assessed the trend in these outcomes from 4 years before to 1 year after initiation of methylphenidate treatment. RESULTS: A total of 1043 patients with bipolar disorder initiated treatment with methylphenidate. The number of manic episodes decreased by 48% after methylphenidate treatment initiation (P = 0.01), both among patients using mood stabilizers (-50%) and among patients not using mood stabilizers (-45%). The number of manic episodes, however, peaked approximately 6 months before methylphenidate. The results were similar for the secondary outcomes. CONCLUSIONS: Initiation of methylphenidate treatment was not associated with an increased risk of mania in patients with bipolar disorder. A decrease in mania, depressive episodes, and psychiatric admissions was observed after methylphenidate. However, these decreases seemed to be driven by regression to the mean after clinical deterioration preceding methylphenidate treatment, rather than by the methylphenidate treatment itself.

Revisiting the association between treatment with antidepressants and mania: A nationwide within-individual study of 3554 patients with bipolar disorder.

INTRODUCTION: Antidepressants are commonly used "off-label" for bipolar depression, despite concerns over the risk of potential treatment-emergent mania (or "manic switch"). Treatment-emergent mania is difficult to study with adequate power in clinical trials as it requires a large group of participants and long follow-up. Therefore, naturalistic register-based studies have been applied to assess this phenomenon. Here, we aimed to replicate previous findings and address key methodological limitations that were not previously taken into account. METHODS: We utilized data from nationwide Danish health registries to identify patients with bipolar disorder treated with an antidepressant, either with or without concomitant treatment with a mood stabilizer (drug treatment proxied via redeemed prescriptions). We plotted the incidence of manic and depressive episodes relative to the initiation of antidepressant treatment and compared the incidence of mania in the period prior to and following initiation of antidepressant treatment (within-individual design). RESULTS: In 3554 patients with bipolar disorder initiating treatment with an antidepressant, the number of manic episodes peaked approximately 3 months prior to initiation of antidepressant treatment, and the number of depressive episodes peaked around the initiation of antidepressant prescription. This temporal pattern suggests that antidepressants were used to treat post-manic depression. CONCLUSION: Within-individual designs do not control sufficiently for confounding by indication, when the treatment indication is time-varying. Thus, results from prior within-individual studies of antidepressant treatment in the context of bipolar disorder may be invalid due to time-varying confounding by indication.

Genetic liability to bipolar disorder and body mass index: A bidirectional two-sample Mendelian randomization study.

OBJECTIVES: Bipolar disorder is associated with increased body mass index (BMI), but it remains undetermined if this association is causal and, if so, in which direction it goes. Here, we sought to answer these questions using bidirectional two-sample Mendelian randomization, a method from genetic epidemiology that uses data from genome-wide association studies (GWAS) to examine whether a risk factor is causal for an outcome METHODS: We used summary statistics from GWAS of bipolar disorder and BMI conducted using data collected by the Psychiatric Genomics Consortium and the UK Biobank, respectively. The genetic instrument for bipolar disorder contained 53 SNPs and explained 0.5% of phenotypic variance, while the genetic instrument for BMI contained 517 SNPs and explained 7.1% of phenotypic variance RESULTS: Our findings suggest that genetic liability to bipolar disorder reduces BMI (slope from Egger regression = -0.195, p = 0.004). It follows that a twofold increase in the genetic liability to bipolar disorder leads to a 0.6 (kg/m2 ) reduction in BMI, predominantly driven by reduced fat mass. Conversely, we found no evidence that BMI causes changes in the risk of developing bipolar disorder CONCLUSION: The results of this study suggest that the increased BMI observed among individuals with bipolar disorder is not a direct consequence of genetic liability to bipolar disorder, but may more likely represent the sum of downstream correlates of manifest bipolar disorder, such as side effects of pharmacological treatment, poor diet, and sedentary lifestyle. As these factors are all modifiable, they can be targeted as part of clinical management.

Pharmacological treatment of bipolar disorder and risk of diabetes mellitus: A nationwide study of 30,451 patients.

OBJECTIVE: While treatment with antipsychotics and antiepileptics have been associated with an increased risk of diabetes mellitus (DM), lithium may have the opposite effect via inhibition of glycogen synthase kinase-3. The aim of this study was to investigate whether treatment of bipolar disorder with lithium, antipsychotics, or antiepileptics is associated with the risk of DM in a real-world clinical setting. METHODS: Using nationwide registers, we identified all patients diagnosed with bipolar disorder in Danish Psychiatric Services from January 1, 1996, to January 1, 2019 (N = 30,451). The risk of developing DM was operationalized via hospital diagnoses and redeemed prescriptions for glucose-lowering drugs. For lithium, antipsychotics, valproate, and lamotrigine, we calculated hazard rate ratios (HRR) for developing DM via adjusted Cox proportional hazards models. Potential cumulative dose-response-like associations were examined using the log-rank test. RESULTS: During follow-up (245,181 person-years), 2107 (6.9%) patients developed DM. Compared with non-users of the respective drugs, we found no clinically or statistically significant difference in the risk of developing DM among patients receiving lithium (n = 11,690; incidence rate of DM/1000 person-years (IR) = 8.87, 95% CI: 8.02-9.90; HRR = 0.94, 95% CI: 0.84-1.06) or lamotrigine (n = 11,785; IR = 7.58, 95% CI: 6.69-8.59; HRR = 0.89, 95% CI: 0.77-1.02), respectively. Conversely, for patients receiving valproate (n = 5171; IR = 12.68, 95% CI: 10.87-14.80; HRR = 1.34, 95% CI: 1.14-1.58) and antipsychotics (n = 22,719; IR = 12.00, 95% CI: 11.14-12.94; HRR = 1.65, 95% CI: 1.45-1.88), respectively, there was increased risk of developing DM. For antipsychotics, we observed a clear cumulative dose-response-like association with the risk of DM. CONCLUSIONS: Treatment with valproate and antipsychotics-but not with lithium and lamotrigine-was associated with increased risk of DM in a real-world cohort of patients with bipolar disorder.

Risk factors for suicide among patients having received treatment with electroconvulsive therapy: A nationwide study of 11,780 patients.

OBJECTIVES: Despite the putative anti-suicidal effect of electroconvulsive therapy (ECT), patients receiving ECT remain at high risk of dying from suicide due to the severity of their underlying mental illness. We aimed to quantify this risk and to identify risk factors for suicide among patients receiving ECT. METHODS: Using nationwide Danish registers, we identified all patients that initiated ECT between 2006 and 2016. These patients were matched on sex and age to 10 reference individuals from the general Danish population. Firstly, we compared 2-year suicide risk between patients initiating ECT and the matched reference individuals. Secondly, we investigated if any patient characteristics were associated with suicide following ECT via Cox proportional hazards regression. RESULTS: A total of 11,780 patients receiving ECT and 117,800 reference individuals were included in the analyses. Among the patients receiving ECT, 161 (1.4%) died from suicide within two years. Compared to the reference individuals, patients having received ECT had a substantially elevated suicide rate (Hazard rate ratio (HRR) = 44.48, 95%CI = 31.12-63.59). Among those having received ECT, the following characteristics were associated with suicide: Male sex (adjusted HRR (AHRR) = 2.32, 95%CI = 1.63-3.30), medium-term higher education (AHRR = 2.64, 95%CI = 1.57-4.44); long-term higher education (AHRR = 3.16, 95%CI = 1.68-5.94), history of substance use disorder (AHRR = 1.51, 95%CI = 1.01-2.26) and history of intentional self-harm/suicide attempt (AHRR = 4.18, 95%CI = 2.76-6.32). CONCLUSIONS: Those who are male, have obtained medium-/long-term higher education, or have a history of substance use disorder or intentional self-harm/suicide attempt, are at particularly elevated risk of suicide following ECT. These findings may guide clinical initiatives to reduce suicides.

Treatment of postpartum psychotic- or mood disorder requiring admission: A nationwide study from Denmark.

BACKGROUND: Postpartum psychotic- or mood disorders are psychiatric emergencies associated with risk of suicide and infanticide. Except from case reports, there are only few descriptions of its treatment. Therefore, we aimed to describe the treatment of women admitted with postpartum psychotic- or mood disorder in Denmark with emphasis on the use of electroconvulsive therapy (ECT). METHODS: We conducted a register-based cohort study of all women with incident postpartum psychotic- or mood disorder (no prior diagnoses of psychotic- or mood disorder or treatment with ECT) requiring admission in the period from 2011 to 2018. For these patients, we described the treatment and the 6-month readmission risk. RESULTS: We identified 91 women with postpartum psychotic- or mood disorder with a median admission length of 27 days (interquartile range: 10-45). Of those, 19% received ECT with a median time from admission to first ECT of 10 days (interquartile range: 5-16). The median number of ECT sessions was eight (interquartile range: 7-12). In the 6 months following discharge, 90% of the women received some form of psychopharmacological treatment (62% antipsychotics, 56% antidepressants, 36% anxiolytics/sedatives, 19% lithium, and 9% mood stabilizing antiepileptics), and 31% were readmitted. CONCLUSION: Psychiatric admission for incident postpartum psychotic- or mood disorder is rare in Denmark. Among those admitted, ECT and psychopharmacological treatment is commonly used. The 6-month readmission risk is high, warranting close follow-up. The fact that there is no international consensus on the optimal treatment of postpartum psychotic- or mood disorder is problematic and calls for action.

Symptom severity and well-being of patients with mental illness during the COVID-19 pandemic: a two-wave survey.

PURPOSE OF THE ARTICLE: To examine changes in symptom severity and well-being during the coronavirus disease 2019 (COVID-19) pandemic among individuals with pre-existing mental illness. MATERIALS AND METHODS: In February 2021, we conducted a follow-up questionnaire-based survey among adults with mental illness, who responded to a similar survey on mental health in June 2020. The participants completed the 18-item Brief Symptom Inventory (BSI-18), the five-item World Health Organization Well-Being Index (WHO-5), and 14 questions evaluating worsening or improvement in mental health using the pre-pandemic period as reference. The survey data were merged with sociodemographic and clinical data from the medical records of all invitees to the first survey, enabling analysis of attrition and weighting of the results. RESULTS: A total of 613 of 992 (62%) invitees participated in the follow-up wave of the survey. The weighted mean WHO-5 and BSI-18 scores were 38 and 27, respectively, and did not differ statistically significantly from the first wave. Multivariate logistic regression showed that having a vocational education (skilled worker/craftsman) was positively associated with reporting deterioration in psychological well-being (OR: 2.95, 95%CI: 1.14-7.81), while being unemployed was negatively associated with reporting deterioration in psychological well-being (OR: 0.20, 95%CI: 0.07-0.56) from the first to the second survey wave. The most common reason for self-reported deterioration in mental health was loneliness (70%). CONCLUSIONS: Approximately one year into the COVID-19 pandemic, the level of symptoms remained high, whereas the level of psychological well-being remained low among patients with mental illness.

The use of electroconvulsive therapy (ECT) en bloc in Denmark: a nationwide register-based study.

OBJECTIVE: Electroconvulsive therapy (ECT) en bloc is defined as ECT administered on 2-3 consecutive days. In Denmark, ECT en bloc is recommended for severe conditions such as catatonia, treatment-resistant mania/psychosis, or imminent risk of suicide. To our knowledge, there are no recent reports on the use of ECT en bloc in clinical practice. Here, we provide such a report. METHODS: We characterized the use of ECT en bloc in the period from 2006-2019 based on data from Danish national registers. Furthermore, we compared mortality rates between patients receiving ECT en bloc and patients receiving standard regimen ECT (not en bloc). RESULTS: We identified 2173 patients who received a total of 2734 ECT en bloc treatment courses in Denmark in the period from 2006 to 2019 (6% of the total number of ECT treatment courses). The use of ECT en bloc was stable over the study period (range: 138-196 patients per year). The most common treatment indications were unipolar depression (41%), psychotic disorder (23%), and bipolar disorder (20%). The vast majority (90%) received ECT en bloc voluntarily. The 1-year mortality rate ratio for ECT en bloc compared to standard regimen ECT was 1.42 (95%CI: 1.03-1.95). CONCLUSION: The use of ECT en bloc in Denmark is stable both in terms of the number of patients treated and treatment indications. In keeping with ECT en bloc being used for severe conditions, those receiving this treatment have a higher mortality rate compared to those receiving standard ECT, warranting careful monitoring during follow-up.

Psychometric validation of the full Yale food addiction scale for children 2.0 among adolescents from the general population and adolescents with a history of mental disorder.

OBJECTIVE: Food addiction is a phenotype characterised by an addiction-like attraction to highly processed foods. Adolescence is a sensitive period for developing addictive disorders. Therefore, a valid measure to assess food addiction in adolescents is needed. Accordingly, the aim of the study was to establish a categorical scoring option for the full version of the Yale Food Addiction Scale for Children 2.0 (YFAS-C 2.0), and to psychometrically validate the full YFAS-C 2.0. METHOD: The data stem from the Food Addiction Denmark (FADK) Project. Random samples of 3750 adolescents from the general population aged 13-17 years, and 3529 adolescents with a history mental disorder of the same age were invited to participate in a survey including the full version of the YFAS-C 2.0. A confirmatory factor analysis was carried out and the weighted prevalence of food addiction was estimated. RESULTS: The confirmatory factor analysis of the YFAS-C 2.0 supported a one-factor model in both samples. The weighted prevalence of food addiction was 5.0% in the general population, and 11.2% in the population with a history of mental disorder. CONCLUSIONS: The full version of the YFAS-C 2.0 is a psychometrically valid measure for assessing clinically significant food addiction in adolescents.

Lexical stability of psychiatric clinical notes from electronic health records over a decade.

OBJECTIVE: Natural language processing (NLP) methods hold promise for improving clinical prediction by utilising information otherwise hidden in the clinical notes of electronic health records. However, clinical practice - as well as the systems and databases in which clinical notes are recorded and stored - change over time. As a consequence, the content of clinical notes may also change over time, which could degrade the performance of prediction models. Despite its importance, the stability of clinical notes over time has rarely been tested. METHODS: The lexical stability of clinical notes from the Psychiatric Services of the Central Denmark Region in the period from January 1, 2011, to November 22, 2021 (a total of 14,811,551 clinical notes describing 129,570 patients) was assessed by quantifying sentence length, readability, syntactic complexity and clinical content. Changepoint detection models were used to estimate potential changes in these metrics. RESULTS: We find lexical stability of the clinical notes over time, with minor deviations during the COVID-19 pandemic. Out of 2988 data points, 17 possible changepoints (corresponding to 0.6%) were detected. The majority of these were related to the discontinuation of a specific note type. CONCLUSION: We find lexical and syntactic stability of clinical notes from psychiatric services over time, which bodes well for the use of NLP for predictive modelling in clinical psychiatry.

A Within-Subject Before-After Study of the Impact of Antidepressants on Hemoglobin A1c and Low-Density Lipoprotein Levels in Type 2 Diabetes.

PURPOSE/BACKGROUND: Data on the effect of treatment with antidepressant drugs on metabolic control in diabetes are sparse. In this controlled within-subject before-after study, the impact of initiation and discontinuation of antidepressant treatment on hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) levels in type 2 diabetes was estimated. METHODS/PROCEDURES: All individuals with newly developed type 2 diabetes (first HbA1c ≥ 6.5%) between 2000 and 2016 in Northern and Central Denmark were identified using register-based health care data. Among these, we identified individuals initiating and discontinuing antidepressant treatment. Using a within-subject before-after design, we examined HbA1c and LDL in the 16 months leading up to and the 16 months after antidepressant treatment initiation or discontinuation, respectively. For comparison, we ran similar time trend analyses in a reference population of age- and sex-matched type 2 diabetes individuals not receiving antidepressant treatment. FINDINGS/RESULTS: Mean HbA1c decreased after initiation of antidepressant treatment (-0.16%; 95% confidence interval [CI], -0.18 to -0.13%). In the reference population, no material change in HbA1c over time (-0.03%; 95% CI, -0.04 to -0.01%) was seen. Mean LDL decreased not only in antidepressant initiators (-0.17 mmol/L; 95% CI, -0.19 to -0.15 mmol/L) but also in the reference population (-0.15 mmol/L; 95% CI, -0.16 to -0.13 mmol/L). Among antidepressant discontinuers, there was also a decrease in HbA1c (-0.32%; 95% CI, -0.37 to -0.28%), with no change in the reference population (-0.02%; 95% CI, -0.04 to 0.00%). Decreases in LDL were found both in antidepressant discontinuers (-0.09 mmol/L; 95% CI, -0.14 to -0.04 mmol/L) and in the reference population (-0.16 mmol/L0; 95% CI, -0.18 to -0.13 mmol/L). IMPLICATIONS/CONCLUSIONS: Antidepressant treatment in type 2 diabetes may have a beneficial effect on glycemic control, as the decrease in HbA1c after discontinuation of antidepressants likely reflects remission of depression. Conversely, antidepressant treatment does not seem to affect LDL levels.

Treatment History Characteristics Associated With Use of Isocarboxazid: A Nationwide Register-Based Study.

PURPOSE/BACKGROUND: The monoamine oxidase inhibitor isocarboxazid (Marplan) is occasionally used in the treatment of depression, but there is only little knowledge on the nature of the use of isocarboxazid in clinical practice. We aimed to identify treatment history characteristics associated with this use. METHODS/PROCEDURES: Via the nationwide Danish registers, we identified all adult incident users of isocarboxazid in the period from 2001 to 2018, as well as up to 5 matched controls using another antidepressant (matched on date of redeemed prescription, age, sex, and region of residence). The 5-year treatment history of the isocarboxazid users and the controls was assessed via the Danish registers. The association between treatment history characteristics and isocarboxazid use was examined by multivariate conditional logistic regression. FINDINGS/RESULTS: We identified 1455 isocarboxazid users and 7045 controls using another antidepressant. The following characteristics were associated with statistically significant increased likelihood of receiving isocarboxazid treatment: Prior treatment with a selective serotonin reuptake inhibitor (odds ratio [OR], 1.80 with 95% confidence interval [CI], 1.46-2.23), a serotonin-norepinephrine reuptake inhibitor (OR, 4.90; 95% CI, 4.08-5.89), a noradrenergic and specific serotonergic antidepressant (OR, 1.56; 95% CI, 1.30-1.88), a tricyclic antidepressant (OR, 5.05; 95% CI, 4.19-6.08), other antidepressants (OR, 4.74; 95% CI, 3.74-6.01), lithium (OR, 6.70; 95% CI, 5.08-8.83), an antipsychotic (OR, 1.43; 95% CI, 1.19-1.73), and each diagnosis of depression received in relation to psychiatric hospital treatment (OR, 1.31; 95% CI, 1.23-1.39). Forty percent of those initiating isocarboxazid had received treatment with drugs from 5 or more different psychopharmacological classes in the 5 preceding years. IMPLICATIONS/CONCLUSIONS: These findings suggest that isocarboxazid is typically used for treatment-resistant depression, consistent with guideline recommendations.

Electroconvulsive therapy following incident bipolar disorder: When, how, and for whom?

OBJECTIVE: The use of electroconvulsive therapy (ECT) in the treatment of bipolar disorder (BD) remains poorly described. Based on data from Danish registries with complete nationwide coverage, this study of patients with incident BD aimed to describe when, how, and for whom ECT is used in the context of BD. METHODS: We identified patients receiving their first diagnosis of BD in the period from 2008 to 2018, who subsequently received ECT. Descriptive statistics were used to clarify when, how, and for whom ECT is used. RESULTS: We identified 1338 patients with incident BD who subsequently received ECT. The median age at the first ECT session was 50.6 years (interquartile range [IQR]: 26.4), and 62% of those treated with ECT were female. The median time from the diagnosis of BD to the first ECT treatment was 0.6 years (IQR: 2.6), and 58% of the patients receiving ECT had the first treatment within the first year after being diagnosed with BD. The most common indication for the first ECT treatment was depression (mainly non-psychotic depression), followed by mania (mainly psychotic mania). The first ECT session was typically provided to inpatients (97%), upon patient consent (98%) and with bilateral electrode placement (60%). CONCLUSIONS: A substantial proportion of the patients with incident BD who receive ECT require this treatment within the first year after the diagnosis. The most common indication for ECT is depression followed by (psychotic) mania. Inpatient voluntary ECT using bilateral electrode placement is the most common form of administration.

Bipolar disorder and regretted behavior in relation to use of social media and online dating.

OBJECTIVES: Individuals with bipolar disorder are prone to risk-taking behavior that is subsequently regretted. Here, we investigated whether this also occurs in relation to the use of social media and online dating. METHODS: A questionnaire-based survey focusing on the use of social media and online dating was conducted among individuals attending an outpatient clinic for bipolar disorder, and among individuals attending two general practices in the same region (controls). The association between bipolar disorder and self-reported regretted behavior on social media/online dating sites was investigated using logistic regression with adjustment for age and sex. RESULTS: A total of 124 individuals with bipolar disorder and 196 individuals without affective disorder from the general practices (controls) formed the study sample. Among the individuals with bipolar disorder who used social media, 66% reported regretted behavior as a consequence of this use, whereas only 31% of the controls reported such behavior. The corresponding numbers for individuals who used online dating were 65% for those with bipolar disorder and 31% for the controls. Following adjustment for age and sex, bipolar disorder was associated with elevated risk of regretted behavior in relation to the use of both social media (adjusted odds ratio: 3.6, 95% CI: 2.2, 5.9) and online dating (adjusted odds ratio: 4.1, 95% CI: 2.1, 8.0). CONCLUSIONS: These findings suggest that risk-taking behavior and subsequent regret among individuals with bipolar disorder extend to social media and online dating. Cautious use of these platforms may be particularly relevant for individuals with bipolar disorder.

How much impairment is required for ADHD? No evidence of a discrete threshold.

BACKGROUND: A diagnosis of attention-deficit/hyperactivity disorder (ADHD) requires the presence of impairment alongside symptoms above a specific frequency and severity threshold. However, the question of whether that symptom threshold represents anything more than an arbitrary cutoff on a continuum of impairment requires further empirical study. Therefore, we present the first study investigating if the relationship between ADHD symptom severity and functional impairment is nonlinear in a way that suggests a discrete, nonarbitrary symptom level threshold associated with a marked step increase in impairment. METHODS: Parent reports on the ADHD-Rating Scale (ADHD-RS-IV), the Weiss Functional Impairment Rating Scale (WFIRS-P), and the Strengths and Difficulties Questionnaire were collected in a general population sample of 1st, 2nd, and 3rd graders (N = 1,914-2,044). RESULTS: Piecewise linear regression analyses and nonlinear regression modeling both demonstrated that the relationship between symptom severity (ADHD-RS-IV total score) and impairment (WFIRS-P mean score) was characterized by a gradual linear increase in impairment with higher symptom severity and no apparent step increase or changing rate of increase in impairment at a certain high ADHD-RS-IV total score level. Controlling for socioeconomic status, sex, and co-occurring conduct and emotional symptoms did not alter these results, though comorbid symptoms had a significant effect on impairment. CONCLUSIONS: There was no clear evidence for a discrete, nonarbitrary symptom severity threshold with regard to impairment. The results highlight the continued need to consider both symptoms and impairment in the diagnosis of ADHD.