The use of uncertain exposure-A method to define switching and add-on in pharmacoepidemiology.

PURPOSE: When defining exposure to pharmacological treatments in pharmacoepidemiology, register data often do not provide information regarding if a pharmacological treatment is a switch or an add-on. This study aims to compare two methods defining switching and add-on therapies and their impact on exposure-outcome associations. Additionally, to guide bias reduction, it aims to describe how the methods relate to immortal time bias and selection bias. METHODS: Cohort study using Swedish population-based health registers to identify antidepressant (AD) prescriptions as exposures while hospitalizations for psychiatric reasons were used as an empirical outcome example. The first method for exposure definition used conditioning on future exposure (FE), the second used the concept of uncertain exposure (UE). To estimate associations between outcome and exposure categories "Use of one AD," "Use of two or more ADs", and "UE" compared to "Unexposed," hazard ratios (HRs) and 95% confidence intervals were estimated using Cox regression adjusted for age and sex. RESULTS: Using the UE method, 7.2% of time periods were classified as "UE" with a notable proportion of psychiatric hospitalizations (7.7%) occurring during this time, while when using the FE method these hospitalizations were distributed over unexposed time and AD use time. The FE method resulted in slightly higher associations than the UE method. The highest HR was found during "UE": HR (95% CI) 5.54 (5.06-6.07). CONCLUSIONS: This study suggests that to reduce the potential immortal time bias, selection bias, and exposure misclassification inherent to the FE method, the UE method could be used for identifying switching and add-on therapies. If not used as a main exposure definition, the UE method may be used to investigate the impact of UE time in a sensitivity analysis.

The value of process evaluation for public health interventions: field-case studies for non-communicable disease prevention and management in five countries.

Complex interventions are needed to effectively tackle non-communicable diseases. However, complex interventions can contain a mix of effective and ineffective actions. Process evaluation (PE) in public health research is of great value as it could clarify the mechanisms and contextual factors associ-ated with variation in the outcomes, better identify effective components, and inform adaptation of the intervention. The aim of this paper is to demonstrate the value of PE through five case studies that span the research cycle. The interven-tions include using digital health, salt reduction strategies, use of fixed dose combinations, and task shifting. Insights of the methods used, and the implications of the PE findings to the project, were discussed. PE of complex interventions can refute or confirm the hypothesized mechanisms of action, thereby enabling intervention refinement, and identifying implementation strategies that can address local contextual needs, so as to improve service delivery and public health outcomes.

Health care utilisation in treatment-resistant depression: a Swedish population-based cohort study.

OBJECTIVE: To investigate the health care utilisation (HCU) among patients with treatment-resistant depression (TRD) compared to patients with depression not meeting TRD criteria. METHODS: Nationwide Swedish registers were used to identify patients 18-69 years old with incident depression and antidepressant treatment. Patients were followed prospectively and defined as having TRD at start of the third distinct consecutive treatment episode. Each of the 16,329 identified TRD patients were matched with five comparators with depression not meeting criteria for TRD. Main outcome measure was total number of inpatient days and outpatient visits, and secondary outcome was HCU in connection with a main diagnosis of depression or suicide attempt. RESULTS: TRD patients had a significantly higher risk of all-cause inpatient care than comparators (first year adjusted risk ratio [aRR] 3.03 [95%CI 3.01-3.05], years 1-3 aRR 2.15 [2.13-2.16]). This was more pronounced when the main diagnosis was depression (first year aRR 4.41 [4.36-4.45]), and after suicide attempt (first year aRR 4.43 [4.26-4.60]). Outpatient visits were also markedly more frequent for patients with TRD (first year aRR 2.05 [2.03-2.07]). Higher HCU among TRD patients persisted throughout follow-up. CONCLUSIONS: Patients with TRD may have a twofold to fourfold higher HCU than other patients with depression.KEYPOINTSThis register-based prospective study investigated health care utilisation (HCU) among patients with treatment-resistant depression (TRD) compared to other patients with depression.Patients with TRD had a two to fourfold higher HCU regarding all measured outcomes, including inpatient hospital days and outpatient visits.The elevated HCU persisted for more than three years, although decreasing gradually. This should correspond to increased costs and individual burden for patients with TRD.

Effect of a Digital Intervention on Depressive Symptoms in Patients With Comorbid Hypertension or Diabetes in Brazil and Peru: Two Randomized Clinical Trials.

Importance: Depression is a leading contributor to disease burden globally. Digital mental health interventions can address the treatment gap in low- and middle-income countries, but the effectiveness in these countries is unknown. Objective: To investigate the effectiveness of a digital intervention in reducing depressive symptoms among people with diabetes and/or hypertension. Design, Setting, and Participants: Participants with clinically significant depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] score ≥10) who were being treated for hypertension and/or diabetes were enrolled in a cluster randomized clinical trial (RCT) at 20 sites in São Paulo, Brazil (N=880; from September 2016 to September 2017; final follow-up, April 2018), and in an individual-level RCT at 7 sites in Lima, Peru (N=432; from January 2017 to September 2017; final follow-up, March 2018). Interventions: An 18-session, low-intensity, digital intervention was delivered over 6 weeks via a provided smartphone, based on behavioral activation principles, and supported by nurse assistants (n = 440 participants in 10 clusters in São Paulo; n = 217 participants in Lima) vs enhanced usual care (n = 440 participants in 10 clusters in São Paulo; n = 215 participants in Lima). Main Outcomes and Measures: The primary outcome was a reduction of at least 50% from baseline in PHQ-9 scores (range, 0-27; higher score indicates more severe depression) at 3 months. Secondary outcomes included a reduction of at least 50% from baseline PHQ-9 scores at 6 months. Results: Among 880 patients cluster randomized in Brazil (mean age, 56.0 years; 761 [86.5%] women) and 432 patients individually randomized in Peru (mean age, 59.7 years; 352 [81.5%] women), 807 (91.7%) in Brazil and 426 (98.6%) in Peru completed at least 1 follow-up assessment. The proportion of participants in São Paulo with a reduction in PHQ-9 score of at least 50% at 3-month follow-up was 40.7% (159/391 participants) in the digital intervention group vs 28.6% (114/399 participants) in the enhanced usual care group (difference, 12.1 percentage points [95% CI, 5.5 to 18.7]; adjusted odds ratio [OR], 1.6 [95% CI, 1.2 to 2.2]; P = .001). In Lima, the proportion of participants with a reduction in PHQ-9 score of at least 50% at 3-month follow-up was 52.7% (108/205 participants) in the digital intervention group vs 34.1% (70/205 participants) in the enhanced usual care group (difference, 18.6 percentage points [95% CI, 9.1 to 28.0]; adjusted OR, 2.1 [95% CI, 1.4 to 3.2]; P < .001). At 6-month follow-up, differences across groups were no longer statistically significant. Conclusions and Relevance: In 2 RCTs of patients with hypertension or diabetes and depressive symptoms in Brazil and Peru, a digital intervention delivered over a 6-week period significantly improved depressive symptoms at 3 months when compared with enhanced usual care. However, the magnitude of the effect was small in the trial from Brazil and the effects were not sustained at 6 months. Trial Registration: ClinicalTrials.gov: NCT02846662 (São Paulo) and NCT03026426 (Lima).

Methods for constructing treatment episodes and impact on exposure-outcome associations.

PURPOSE: To assess the impact on exposure time and outcome misclassifications, and consequent impact on exposure-outcome associations from treatment episode construction. We investigated the dosage assumptions of 1 unit per day, and 1 DDD per day, versus actual prescribed dosage under different handling of gaps and overlaps of prescriptions. METHODS: Data on mirtazapine and citalopram exposure (years 2006-2014) from the Swedish Prescribed Drug register were used. Via a within individuals design we compared method A, based on actual dosage, with methods B and C based on 1 unit of drug per day and 1 DDD per day assumptions, respectively, including consideration of gaps and overlaps. Four outcomes were used, hospitalizations and outpatient visits for all and for psychiatric causes. RESULTS: Relative to method A, both alternative methods lead to misclassification of exposure time. With regard to outcome misclassifications, method B overestimates the effect of the exposure on the outcome in 77% and 100% of exposure definition comparisons for mirtazapine and citalopram respectively, while 23% of the comparisons for mirtazapine results in underestimation of exposure-outcome associations. Conversely, treatment episodes based on DDD (method C) result in underestimation of the exposure-outcome association in 100% and 87.5% of exposure definition comparisons for mirtazapine and citalopram respectively, while 12.5% of the comparisons for citalopram results in overestimation of the exposure-outcome associations. CONCLUSIONS: The study provides results that have consistent clinical relevance. We have showed that a non-accurate construction of exposure time may lead to errors on outcome detection during exposed time, and consequently affect conclusions on safety or efficacy profile of a treatment.

Risk and risk factors for disability pension among patients with treatment resistant depression- a matched cohort study.

BACKGROUND: Treatment resistant depression (TRD) is common among patients with depression, and is associated with clinical and functional disability. However, the risk and risk factors for being granted disability pension (DP) among patients with TRD have not been investigated. METHODS: All antidepressant initiators in Sweden with a diagnosis of depression in specialized care were identified in nationwide registers 2006-2013 and followed regarding treatment trials. TRD was defined as the start of a third sequential trial. Patients with TRD who were not on DP (N = 3204) were matched by age, sex, history of depression, calendar year, and time for treatment start with 3204 comparators with depression and ongoing antidepressant treatment. A proportional Cox Regression was performed with DP as outcome, adjusted for various sociodemographic and clinical covariates. RESULTS: Compared to the comparison cohort, TRD was associated with a doubled risk for all-cause DP (aHR 2.07; 95%CI 1.83-2.35), DP due to depression (2.28; 1.82-2.85) and to any mental disorder (2.24; 1.95-2.57) but not due to somatic diagnoses (1.25; 0.84-1.86). Among significant risk factors for DP in TRD were female sex, being > 29 years of age, unemployment and a diagnosis of comorbid personality disorder (ICD-10 codes F60.0-9). CONCLUSION: TRD is associated with an elevated risk for DP compared to other patients with depression, with large potential costs for the affected patients and for society. Clinical and therapeutic implications for patients with TRD who are granted DP should be further investigated. LIMITATION: No clinical data, e.g. type of depression or reason for treatment switch, was available for this study.

Medication persistence to antihypertensive drug treatment - a cross-sectional study of attitudes towards hypertension and medication in persistent and non-persistent patients.

Purpose: To study the differences in attitudes towards hypertension and drug treatment between patients persistent and non-persistent to antihypertensive drug treatment. Materials and methods: Cross-sectional study on patients with hypertension treated at 25 primary healthcare centres in Stockholm, Sweden. Questionnaires were sent to the patients 3-12 months after initiation of antihypertensive drug treatment. Persistent medication users, defined as patients with less than 30 days without tablet supply between prescription refills, were compared with non-persistent users by scores from Likert scales: Brief-Illness Perception Questionnaire (Brief IPQ, 0-10) and Beliefs about Medicines Questionnaire (BMQ General, 4-20 and BMQ Specific, 5-25). Results: A total of 711 patients were included in the final analyses (mean age: 62 years; 50% women), of whom 609 (86%) were classified as persistent and 102 (14%) as non-persistent by analyses of their filled prescriptions. Likert scales from the Brief-IPQ showed (all p < 0.02) that persistent patients believed that hypertension was a chronic condition (median 6 vs. 4), that hypertension had less consequences on their life (median 2 vs. 3) and that they can prevent cardiovascular disease by taking antihypertensive treatment (median 7 vs. 5). Likert scales from the BMQ General showed (all p < 0.02) that persistent patients believed that there are potential benefits from taking the treatment (median 16 vs. 16), and they did not believe that the doctors put too much trust in drugs (median 12 vs. 13). Further, results from the BMQ Specific showed that they believed that the antihypertensive drugs are necessary for them in order to maintain or improve their own health (median 17 vs. 16). Conclusions: Primary healthcare providers should further emphasize the chronicity of hypertension diagnosis and the benefits of treatment, to improve the patients' medication persistence to antihypertensive treatment.

All-cause mortality in patients with treatment-resistant depression: a cohort study in the US population.

BACKGROUND: Treatment-resistant depression (TRD) may represent a substantial proportion of major depressive disorder (MDD); however, the risk of mortality in TRD is still incompletely assessed. METHODS: Data were obtained from Optum Clinformatics™ Extended, a US claims database. Date of the first antidepressant (AD) dispensing was designated as the index date for study entry and 6 months prior to that was considered the baseline period. Patients with MDD aged ≥ 18 years, index date between January 1, 2008 and September 30, 2015, no AD claims during baseline, and continuous enrollment in the database during baseline were included. Patients who started a third AD regimen after two regimens of appropriate duration were included in the TRD cohort. All-cause mortality was compared between patients with TRD and non-TRD MDD using a proportional hazards model and Kaplan-Meier estimate with TRD status being treated as a time-varying covariate. The model was adjusted for study year, age, gender, depression diagnosis, substance use disorder, psychiatric comorbidities, and Charlson comorbidity index. RESULTS: Out of 355,942 patients with MDD, 34,176 (9.6%) met the criterion for TRD. TRD was associated with a significantly higher mortality compared with non-TRD MDD (adjusted HR: 1.29; 95% CI 1.22-1.38; p < 0.0001). Survival time was significantly shorter in the TRD cohort compared with the non-TRD MDD cohort (p < 0.0001). CONCLUSIONS: Patients with TRD had a higher all-cause mortality compared with non-TRD MDD patients.

Humanistic outcomes in treatment resistant depression: a secondary analysis of the STAR*D study.

BACKGROUND: In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a third of patients did not achieve remission or adequate response after two treatment trials, fulfilling requirements for treatment resistant depression (TRD). The present study is a secondary analysis of the STAR*D data conducted to compare the humanistic outcomes in patients with TRD and non-TRD MDD. METHODS: Patients with major depressive disorder who entered level 3 of the STAR*D were included in the TRD group, while patients who responded to treatment and entered follow-up from level 1 or 2 were included in the non-TRD group. The first visit in level 1 was used for baseline assessments. The time-point of assessments for comparison was the first visit in level 3 for TRD patients (median day: 141), and the visit closest to 141 ± 60 days from baseline for non-TRD patients. Outcomes were assessed by the 12-item Short Form Health Survey (SF12), 16-item Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Work and Social Adjustment Scale (WSAS), and Work Productivity and Activity Impairment scale (WPAI). Scores were compared in a linear model with adjustment for covariates including age, gender, and depression severity measured by the 17-item Hamilton Rating Scale for Depression (HDRS17) and Quick Inventory of Depressive Symptomatology (QIDS). RESULTS: A total of 2467 (TRD: 377; non-TRD: 2090) patients were studied. TRD patients were slightly older (mean age 44 vs 42 years), had a higher proportion of men (49% vs 37%, p < .0001), and baseline depression severity (HDRS17: 24.4 vs 22.0, p < .0001) vs non-TRD patients. During follow-up, TRD patients had lower health-related quality of life (HRQOL) scores on mental (30 vs 45.7) and physical components (47.7 vs 48.9) of the SF12, and lower Q-LES-Q scores (43.6 vs 63.7), greater functional and work impairments and productivity loss vs non-TRD patients (all p < 0.05). CONCLUSION: Patients with TRD had worse HRQOL, work productivity, and social functioning than the non-TRD patients.

Suicide, Self-harm, and Depression After Gastric Bypass Surgery: A Nationwide Cohort Study.

OBJECTIVE: The aim of this study was to examine risk of self-harm, hospitalization for depression and death by suicide after gastric bypass surgery (GBP). SUMMARY OF BACKGROUND DATA: Concerns regarding severe adverse psychiatric outcomes after GBP have been raised. METHODS: This nationwide, longitudinal, self-matched cohort encompassed 22,539 patients who underwent GBP during 2008 to 2012. They were identified through the Swedish National Patient Register, the Prescribed Drug Register, and the Causes of Death Register. Follow-up time was up to 2 years. Main outcome measures were hazard ratios (HRs) for post-surgery self-harm or hospitalization for depression in patients with presurgery self-harm and/or depression compared to patients without this exposure; and standardized mortality ratio (SMR) for suicide post-surgery. RESULTS: A diagnosis of self-harm in the 2 years preceding surgery was associated with an HR of 36.6 (95% confidence interval [CI] 25.5-52.4) for self-harm during the 2 years of follow up, compared to GBP patients who had no self-harm diagnosis before surgery. Patients with a diagnosis of depression preceding GBP surgery had an HR of 52.3 (95% CI 30.6-89.2) for hospitalization owing to depression after GBP, compared to GBP patients without a previous diagnosis of depression. The SMR for suicide after GBP was increased among females (n = 13), 4.50 (95% CI 2.50-7.50). The SMR among males (n = 4), was 1.71 (95% CI 0.54-4.12). CONCLUSIONS: The increased risk of post-surgery self-harm and hospitalization for depression is mainly attributable to patients who have a diagnosis of self-harm or depression before surgery. Raised awareness is needed to identify vulnerable patients with history of self-harm or depression, which may be in need of psychiatric support after GBP.

Mortality in Women With Anorexia Nervosa: The Role of Comorbid Psychiatric Disorders.

OBJECTIVE: To investigate mortality in anorexia nervosa (AN) with a psychiatric comorbidity. METHODS: Using Swedish registers, data for 8069 female inpatients with AN were retrospectively collected for 1973-2010. Mortality patterns were assessed using standardized mortality ratios (SMRs), Cox regression-derived hazard ratios, and incidence rate ratios. A control cohort of 76,995 women was used. RESULTS: Patients with AN and a psychiatric comorbidity had higher mortality rates did than those without a comorbidity. The SMRs for patients with AN and a psychiatric comorbidity were 5.4 (95% confidence interval [CI] = 4.6-6.4) and 18.1 (95% CI = 15.2-21.3) for natural and unnatural causes of death, respectively. The SMRs for patients with AN without a comorbidity were 2.8 (95% CI = 2.3-3.5) and 3.1 (95% CI = 2.2-4.1) for natural and unnatural causes of death, respectively. The adjusted hazard ratios for mortality from natural or unnatural causes were 2.0 (95% CI = 1.5-2.7) and 5.7 (95% CI = 3.9-8.2), respectively. Incidence rate ratios comparing patients with AN and controls, both with psychiatric comorbidities, suggest a negative synergistic effect of comorbid AN and psychiatric disorder on mortality, which was greater for unnatural causes of death. CONCLUSIONS: Mortality in patients with AN was greater in the presence of a psychiatric comorbidity, and even more pronounced for unnatural causes of death and suicides. Substance abuse, especially alcohol use disorder, increased mortality from natural causes of death. These findings highlight the need for early detection and treatment of psychiatric comorbidity in AN, to potentially improve long-term outcomes.

Factors Associated With Adherence to Methylphenidate Treatment in Adult Patients With Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders.

Adherence to treatment is one of the most consistent factors associated with a favorable addiction treatment outcome. Little is known about factors associated with treatment adherence in individuals affected with comorbid attention-deficit/hyperactivity disorder and substance use disorders (SUD). This study aimed to explore whether treatment-associated factors, such as the prescribing physician's (sub)specialty and methylphenidate (MPH) dose, or patient-related factors, such as sex, age, SUD subtype, and psychiatric comorbidity, were associated with adherence to MPH treatment. Swedish national registers were used to identify adult individuals with prescriptions of MPH and medications specifically used in the treatment of SUD or a diagnosis of SUD and/or coexisting psychiatric diagnoses. Primary outcome measure was days in active MPH treatment in stratified dose groups (≤36 mg, ≥37 mg to ≤54 mg, ≥55 mg to ≤72 mg, ≥73 mg to ≤90 mg, ≥91 mg to ≤108 mg, and ≥109 mg). Lower MPH doses (ie, ≤36 mg day 100) were associated with treatment discontinuation between days 101 and 830 (HR≤36 mg, 1.67; HR37-54mg, 1.37; HR55-72mg, 1.36; HR73-90mg, 1.19; HR≥108mg, 1.09). The results showed a linear trend (P < 0.0001) toward decreased risk of treatment discontinuation along with increase of MPH doses. In conclusion, this study shows that higher MPH doses were associated with long-term treatment adherence in individuals with attention-deficit/hyperactivity disorder and SUD.

Suicide risk and antipsychotic side effects in schizophrenia: nested case-control study.

OBJECTIVE: This study explores suicide risk in schizophrenia in relation to side effects from antipsychotic medication. METHODS: Among patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4000), those who died by suicide within 5 years from diagnosis were defined as cases (n = 84; 54% male). For each case, one individually matched control was identified from the same population. Information on antipsychotic side effects, including extrapyramidal symptoms (EPS) and akathisia, as well as prescriptions of anticholinergic medication, was retrieved from clinical records in a blinded fashion. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of the association between suicide and side effects as well as anticholinergic medication were estimated using conditional logistic regression. RESULTS: A lower suicide risk was found in patients with a history of EPS (aOR 0.33, 95% CI 0.12-0.94). There was no statistically significant association between akathisia or anticholinergic medication use and the suicide risk. CONCLUSIONS: A lower suicide risk identified among patients with EPS could potentially reflect higher antipsychotic adherence, exposure to higher dosage, or polypharmacy among these patients. Copyright © 2016 John Wiley & Sons, Ltd.

Cancer incidence and mortality patterns in women with anorexia nervosa.

Caloric restriction in animals is an effective way to reduce carcinogenesis. Anorexia nervosa (AN) is considered a model of extreme caloric restriction in humans. The aim of our study was to assess cancer incidence and mortality in women with AN. A total of 6,009 women with at least one inpatient treatment for AN during the period 1973-2003 were included in the study. Standardized incidence ratios (SIR) and standardized mortality ratios (SMR) were calculated. Overall, there was no statistically significant difference in cancer incidence compared to women in the general population. At a statistically significant or borderline significant level, a higher incidence for lung cancer and cancer of lymphoid, hematopoietic and related tissue was observed along with a reduced breast cancer incidence. Women with AN had twice as high mortality from cancer in general, and more specifically from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites. The increased lung cancer incidence may be due to smoking habits among women with AN. The worse prognosis with higher mortality from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites may be explained by AN-specific attitudes toward seeking medical care, adherence to treatment or worse biological precondition due to starvation and cachexia.

Factors associated with pregabalin dispensing at higher than the approved maximum dose.

PURPOSE: Concerns have been raised about the abuse potential of pregabalin. Therefore, the aim of our study was to characterize patients dispensed pregabalin at higher than the maximum allowed dose in a cohort study based on data extracted from Swedish national registers. METHODS: All patients dispensed at least three prescriptions of pregabalin between July 2006 and December 2009 were included (n = 48,550). The daily dose was defined as the amount of pregabalin dispensed divided by the number of days between the second and third dispensings. Associations between sociodemographic and clinical variables and dispensing pregabalin at a dose exceeding the maximum daily allowed dose (600 mg) were investigated in multivariate regression models. RESULTS: Of the patients dispensed pregabalin during the study period, 8.5 % were dispensed a dose that exceeded the maximum daily allowed dose. A previous addictive disorder drug treatment or diagnosis was present in 20 and 31 % of patients dispensed pregabalin within and exceeding the recommended dose range, respectively. Our analysis revealed that those patients at increased risk of being dispensed pregabalin at higher than the maximum allowed dose were male [adjusted odds ratio (aOR) 1.40, 95 % confidence interval (CI) 1.31-1.49], were between 18 and 29 years of age compared with those aged ≥65 years (aOR 1.62, 95 % CI 1.45-1.82), had a low income (aOR 1.24, 95 % CI 1.10-1.40), had epilepsy compared with no diagnosis (aOR 1.41, 95 % CI 1.10-1.81), had a previous substance use disorder treatment or diagnosis (aOR 1.41, 95 % CI 1.31-1.52) or had previously been dispensed high doses of drugs with abuse potential (aOR 1.77, 95 % CI 1.62-1.94). CONCLUSION: Based on our results we conclude that patients at a high risk of addiction and patients with epilepsy are more likely to be dispensed pregabalin at higher than the maximum approved daily dose.

Randomized controlled trial of transdiagnostic group treatments for primary care patients with common mental disorders.

BACKGROUND: The purpose was to test the effectiveness of two transdiagnostic group interventions compared to care as usual (CAU) for patients with anxiety, depressive or stress-related disorders within a primary health care context. OBJECTIVES: To compare the effects of cognitive-based-behavioural therapy (CBT) and multimodal intervention (MMI) on the quality of life and relief of psychological symptoms of patients with common mental disorders or problems attending primary health care centre. METHODS: Patients (n = 278), aged 18-65 years, were referred to the study by the GPs and 245 were randomized to CAU or one of two group interventions in addition to CAU: (i) group CBT administered by psychologists and (ii) group MMI administered by assistant nurses. The primary outcome measure was the Mental Component Summary score of short form 36. Secondary outcome measures were Perceived Stress Scale and Self-Rating Scale for Affective Syndromes. The data were analysed using intention-to-treat with a linear mixed model. RESULTS: On the primary outcome measure, the mean improvement based on mixed model analyses across post- and follow-up assessment was significantly larger for the MMI group than for the CBT (4.0; P = 0.020) and CAU (7.5; P = .001) groups. Participants receiving CBT were significantly more improved than those in the CAU group. On four of the secondary outcome measures, the MMI group was significantly more improved than the CBT and CAU groups. The course of improvement did not differ between the CBT group and the CAU group on these measures. CONCLUSIONS: Transdiagnostic group treatment can be effective for patients with common mental disorders when delivered in a primary care setting. The group format and transdiagnostic approach fit well with the requirements of primary care.

Symptom reduction due to psychosocial interventions is not accompanied by a reduction in sick leave: results from a randomized controlled trial in primary care.

OBJECTIVE: To investigate whether interventions that have positive effects on psychological symptoms and quality of life compared with usual care would also reduce days on sick leave. DESIGN: A randomized controlled trial. SETTING: A large primary health care centre in Stockholm, Sweden. Intervention. Patients with common mental disorders were recruited by their GPs and randomized into one of two group interventions that took place in addition to usual care. These group interventions were: (a) group cognitive behavioural therapy (CBT), and (b) group multimodal intervention (MMI). Both types of intervention had previously shown significant effects on quality of life, and MMI had also shown significant effects on psychological symptoms. PATIENTS: Of the 245 randomized patients, 164 were employed and had taken sick leave periods of at least two weeks in length during the study period of two years. They comprised the study group. MAIN OUTCOME MEASURES: The odds, compared with usual care, for being sick-listed at different times relative to the date of randomization. RESULTS: The mean number of days on sick leave increased steadily in the two years before randomization and decreased in the two years afterwards, showing the same pattern for all three groups .The CBT and MMI interventions did not show the expected lower odds for sick-listing compared with usual care during the two-year follow-up. CONCLUSION: Reduction in psychological symptoms and increased well-being did not seem to be enough to reduce sickness absence for patients with common mental problems in primary care. The possibility of adding workplace-oriented interventions is discussed.

Association between inflammatory joint disease and severe or treatment-resistant depression: population-based cohort and case-control studies in Sweden.

OBJECTIVE: To investigate whether the association between depression and inflammatory joint disease (IJD; rheumatoid arthritis [RA], psoriatic arthritis [PsA], ankylosing spondylitis/spondyloarthropathies [AS], and juvenile idiopathic arthritis [JIA]) is affected by the severity or treatment-resistance of depression. METHOD: Parallel cohort studies and case-control studies among 600,404 patients with a depressive episode identified in Swedish nationwide administrative registers. Prospective and retrospective risk for IJD in patients with depression was compared to matched population comparators, and the same associations were investigated in severe or treatment-resistant depression. Analyses were adjusted for comorbidities and sociodemographic covariates. RESULTS: Patients with depression had an increased risk for later IJD compared to population comparators (adjusted hazard ratio (aHR) for any IJD 1.34 [95% CI 1.30-1.39]; for RA 1.27 [1.15-1.41]; PsA 1.45 [1.29-1.63]; AS 1.32 [1.15-1.52]). In case-control studies, patients with depression more frequently had a history of IJD compared to population controls (adjusted odds ratio (aOR) for any IJD 1.43 [1.37-1.50]; RA 1.39 [1.29-1.49]; PsA 1.59 [1.46-1.73]; AS 1.49 [1.36-1.64]; JIA 1.52 [1.35-1.71]). These associations were not significantly different for severe depression or TRD. CONCLUSION: IJD and depression are bidirectionally associated, but this association does not seem to be influenced by the severity or treatment resistance of depression.

Antipsychotic prescription filling in patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: Assessment of factors influencing antipsychotic prescription fills in the early phase of schizophrenia or schizoaffective disorder. METHODS: We used the Swedish Patient Register to identify patients younger than 45 years with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 (904 patients). Data on medication were obtained from the Prescribed Drug Register. Filling a prescription of an antipsychotic drug after discharge was used to estimate medication adherence. In Cox regression models, we studied sex, country of birth, metropolitan residence, educational level, age, duration of hospitalization, history of substance use disorder, and previous use of antipsychotic drugs as predictors for antipsychotic fills. RESULTS: Among all patients, 53.1% (95% confidence interval [CI] 49.9%-56.4%) had filled an antipsychotic prescription within 1 week from discharge. After 6 months, the proportion had increased to 80.2% (95% CI, 77.4%-82.8%) with no further increase thereafter. Prescription filling of an antipsychotic drug was primarily associated with antipsychotic use before the hospitalization (hazard ratio, 1.64; 95% CI, 1.33-2.03; for patients with access to antipsychotic drugs at admission compared with no previous use) and with longer hospitalization (hazard ratio, 1.60; 95% CI, 1.27-2.02 for 15-28 days compared with shorter hospitalization). CONCLUSIONS: Among patients who filled a prescription of an antipsychotic drug after discharge, the majority did so within 1 week. Previous adherent use of antipsychotic drugs and longer hospitalization may be predictors of primary adherence to antipsychotic drug treatment in schizophrenia or schizoaffective disorder.

Persistence to antihypertensive drug treatment in Swedish primary healthcare.

PURPOSE: To determine factors associated with low persistence in patients initiated on drug treatment for hypertension. METHODS: Cohort study using medical records for patients with hypertension in 48 Swedish primary healthcare centres. Data were linked to national registers on dispensed drugs, hospitalizations, outpatient hospital consultations, deaths, migration, and socioeconomy. We identified 5225 patients (55 % women, mean age 61 years) initiated on antihypertensive drug treatment during 2006-2007. Persistence was measured for two years by the dispensed drugs. Patients with a gap of >30 days between end of dispensed supply and the next dispensed prescription were classified as non-persistent. This was calculated by Kaplan-Meier analysis. Cox proportional hazard regression was used to estimate hazard ratios for discontinuation. Potential predictors included age, gender, blood pressure before initiation of therapy, cardiovascular comorbidity, educational level, country of birth, and income. RESULTS: Among patients with a dispensed first prescription, 26 % discontinued treatment during the first year, and a further 9 % discontinued during the second year. Discontinuation (all adjusted) was more common in men (P = 0.002) and in younger patients (30-49 years, P < 0.001). Systolic (P < 0.001) but not diastolic blood pressure was positively associated with persistence. Native-born Swedish citizens and patients born in the other Nordic countries had lower discontinuation rates than those born outside the Nordic countries (P < 0.001). CONCLUSION: Major determinants of discontinuation of antihypertensive drug treatment are male sex, young age, mild-to-moderate systolic blood pressure elevation, and birth outside of Sweden.