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  • 1.
    Bengtsson, Cecilia
    et al.
    St Gorans Univ Hosp, Stockholm Ctr Dependency Disorders, Stockholm, Sweden..
    Nilsson, Björn Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Boden, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Postinjection Delirium Syndrome Associated With Olanzapine Long-Acting Injectable2016In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 36, no 4, p. 388-389Article in journal (Refereed)
  • 2.
    Bengtsson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Olsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Wass, Caroline
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Theta burst transcranial magnetic stimulation of the dorsomedial prefrontal cortex in schizophrenia and depression2015Conference paper (Refereed)
    Abstract [en]

    Negative symptoms in schizophrenia and core depressive symptoms share phenomenology and repetitive transcranial magnetic stimulation (rTMS) is a treatment modality for both conditions. The most common treatment site has been the dorsolateral prefrontal cortex (DLPFC) but there might be more optimal targets. Furthermore, the implementation of the currently approved protocols is hampered by the long duration. More intense stimulation protocols such as the theta burst stimulation (TBS) are significantly shorter and may be as effective and safe.

    The overall aim of this project is to evaluate the treatment effect of TBS on poor motivation and anhedonia in schizophrenia and depression and to explore the neurobiological correlates of these deficits.

    The dorsomedial prefrontal cortex (dmPFC) is a key cortical area in networks associated with motivation and anhedonia and it is affected in both schizophrenia and depression. The dmPFC has recently been identified as a possible site of stimulation and is now within reach by new angled coils that have deeper tissue penetration.

    Our study will enroll 38 patients with schizophrenia, 38 patients with depression and 38 healthy volunteers. Patients will be given daily TBS (totally 2400 pulses, 1200 on each hemisphere) over the dmPFC during 10 days. Target symptoms will be assessed with the Clinical Assessment Interview for Negative Symptoms (CAINS). We will also assess cortical excitability with paired-pulse stimulation and the pre-attentive memory function with mismatch negativity (MMN), spontaneous motor activity (assessed with 24 hours accelerometer) as well as autonomic nervous system tone (assessed by skin conductance, heart rate variability and breathing pattern). In addition, we will evaluate cognitive function (speed of processing, verbal fluency, auditory and working memory, visuospatial ability) during rest and stress.

  • 3. Bjorkenstam, C.
    et al.
    Bjorkenstam, E.
    Hjern, A.
    Boden, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Reutfors, J.
    Suicide in first episode psychosis: A nationwide cohort study2014In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 157, no 1-3, p. 1-7Article in journal (Refereed)
    Abstract [en]

    Background: Relatively little is known about suicide in diagnostic subtypes of first episode psychosis (FEP). Our aim was to assess suicide rates and potential risk factors for suicide in FEP. Methods: This is a national register-based cohort study of patients born in 1973-1978 in Sweden and who were hospitalized with a FEP between ages 15 and 30 years (n = 2819). The patients were followed from date of discharge until death, emigration, or 31st of December 2008. The suicide rates for six diagnostic subtypes of FEP were calculated. Suicide incidence rate ratios (IRRs) were calculated to evaluate the association between suicide and psychiatric, familial, social, and demographic factors. Results: In total 121 patients died by suicide. The overall suicide rate was 4.3 (95% confidence interval [CI] 3.5-5.0) per 1000 person-years. The highest suicide rates were found in depressive disorder with psychotic symptoms and in delusional disorder. In an adjustedmodel, the strongest risk factors for suicide were self-harm (IRR 2.7, CI 1.7-4.4) or a conviction for violent crime (IRR 2.0, CI 1.3-3.2). Also having a first-degree relative with a schizophrenia/bipolar diagnosis (IRR 2.1, CI 1.2-3.6) or substance use disorder (IRR 2.0, CI 1.2-3.2) were significant risk factors for suicide. Conclusions: Impulsive behavior such as self-harm as well as having a family history of severe mental disorder or substance use are important risk factors for suicide in FEP. (C) 2014 Elsevier B.V. All rights reserved.

  • 4.
    Boden, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Brandt, Lena
    Kieler, Helle
    Andersen, Morten
    Reutfors, Johan
    Early non-adherence to medication and other risk factors for rehospitalization in schizophrenia and schizoaffective disorder2011In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 133, no 1-3, p. 36-41Article in journal (Refereed)
    Abstract [en]

    Non-adherence to antipsychotic medication and hospitalization in psychotic disorders are common and costly problems. Our aim was to identify risk factors for rehospitalization of patients with recent onset schizophrenia or schizoaffective disorder in a population-based cohort study. All patients with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 were included (n = 861). Patients were identified through and data retrieved from national Swedish health and population registers. We investigated how socio-demographic variables, duration of first hospitalization and prescription fills of antipsychotics were associated with rehospitalization in Cox regression models. A higher risk for rehospitalization within 28 days was observed in patients with a first hospitalization that was shorter than two weeks compared with patients who were hospitalized for more than four weeks: hazard ratio (HR) 2.30,95% confidence interval (CI) 1.42 to 3.74. Further, patients who did not fill a prescription of antipsychotics within the first week after discharge had a higher risk of early rehospitalization than patients who were given antipsychotics (HR 1.75, 95% CI 1.13 to 2.72). More than 12 years of education was associated with a lower risk of early rehospitalization (HR 0.44,95% CI 0.26 to 0.77). Sex, age, being born in Sweden, urban area residence and prescription fills of antipsychotics prior to first admission did not significantly affect the risk of early rehospitalization. In conclusion, we identified two potentially modifiable risk factors for rehospitalization: short duration of initial hospitalization and early non-adherence to medication.

  • 5.
    Boden, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Edman, Gunnar
    Reutfors, Johan
    Ostenson, Claes-Goran
    Osby, Urban
    A comparison of cardiovascular risk factors for ten antipsychotic drugs in clinical practice2013In: Neuropsychiatric Disease and Treatment, ISSN 1176-6328, E-ISSN 1178-2021, Vol. 9, p. 371-377Article in journal (Refereed)
    Abstract [en]

    It is well known that abdominal obesity, dyslipidemia, and insulin resistance are highly prevalent in patients receiving maintenance treatment with antipsychotics, but there is limited knowledge about the association between cardiovascular risk factors and treatment with antipsychotic drugs. In this naturalistic study we investigated a sample of 809 antipsychotic-treated patients from Swedish psychosis outpatient teams. Cardiovascular risk factors (eg, metabolic syndrome, homeostasis model assessment of insulin resistance, and low-density lipoprotein values) were measured, and their associations to current antipsychotic pharmacotherapy were studied. Ten antipsychotic drugs were compared in a stepwise logistic regression model. For the patients, the presence of the components of metabolic syndrome ranged from 35% for hyperglycemia to 64% for elevated waist circumference. Hypertriglyceridemia was associated with clozapine (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.08-3.04), reduced high-density lipoprotein with both clozapine and olanzapine (OR = 1.73, 95% CI 1.01-2.97; and OR = 2.03, 95% CI 1.32-3.13), hypertension with perphenazine (OR = 2.00, 95% CI 1.21-3.59), and hyperglycemia inversely with ziprasidone (OR = 0.21, 95% CI 0.05-0.89) and positively with haloperidol (OR = 2.02, 95% CI 1.18-3.48). There were no significant relationships between any of the antipsychotic drugs and increased waist circumference, homeostasis model assessment of insulin resistance, or low-density lipoprotein levels. In conclusion, treatment with antipsychotic drugs is differentially associated with cardiovascular risk factors, even after adjusting for waist circumference, sex, age, and smoking.

  • 6.
    Boden, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lundgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Brandt, Lena
    Reutfors, Johan
    Andersen, Morten
    Kieler, Helle
    Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study2012In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 345, p. e7085-Article in journal (Refereed)
    Abstract [en]

    Objective To investigate the risks of adverse pregnancy and birth outcomes for treated and untreated bipolar disorder during pregnancy. Design Population based cohort study using data from national health registers. Setting Sweden. Participants 332 137 women with a last menstrual period anytime after 1 July 2005 and giving birth anytime before the end of 31 December 2009. Women with a record of at least two bipolar diagnoses were identified and grouped as treated (n=320)-those who had filled a prescription for mood stabilisers (lithium, antipsychotics, or anticonvulsants) during pregnancy-or untreated (n=554). Both groups were compared with all other women giving birth (n=331 263). Main outcome measures Preterm birth, mode of labour initiation, gestational diabetes, infants born small or large for gestational age, neonatal morbidity, and congenital malformations. Results Of the untreated women, 30.9% (n=171) were induced or had a planned caesarean delivery compared with 20.7% (n=68 533) without bipolar disorder (odds ratio 1.57, 95% confidence interval 1.30 to 1.90). The corresponding values for the treated women were 37.5% (n=120) (2.12, 1.68 to 2.67). The risks of preterm birth in both treated and untreated women were increased by 50%. Of the untreated women, 3.9% (n=542) had a microcephalic infant compared with 2.3% (324 844) of the women without bipolar disorder (1.68, 1.07 to 2.62). The corresponding values for the treated women were 3.3% (n=311) (1.26, 0.67 to 2.37). Similar trends were observed for risks of infants being small for gestational age infants for weight and length. Among infants of untreated women, 4.3% (n=24) had neonatal hypoglycaemia compared with 2.5% (n=8302) among infants of women without bipolar disorder (1.51, 1.04 to 2.43), and 3.4% (n=11) of the treated women (1.18, 0.64 to 2.16). The analyses of variation in outcomes did not support any significant differences between treated and untreated women. Conclusions Bipolar disorder in women during pregnancy, whether treated or not, was associated with increased risks of adverse pregnancy outcomes.

  • 7.
    Boden, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Molin, E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Jernberg, T.
    Kieler, H.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Higher mortality after myocardial infarction in patients with severe mental illness: a nationwide cohort study2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 6, p. 727-736Article in journal (Refereed)
    Abstract [en]

    ObjectivesThe aim of this study was to explore the impact of severe mental illness (SMI) on myocardial infarction survival and determine the influence of risk factor burden, myocardial infarction severity and different treatments. Design, setting and participantsThis population-based cohort study, conducted in Sweden during the period 1997-2010, included all patients with a first diagnosis of myocardial infarction in the Swedish nationwide myocardial infarction register SWEDEHEART (n=209592). Exposure was defined as a diagnosis of SMI (i.e. bipolar disorder or schizophrenia) in the national patient register prior to infarction. Bias-minimized logistic regression models were identified using directed acyclic graphs and included covariates age, gender, smoking, diabetes, previous cardiovascular disease, myocardial infarction characteristics and treatment. Main outcome measuresThe outcomes were 30-day and 1-year mortality, obtained through linkage with national population registers. ResultsPatients with bipolar disorder (n=442) and schizophrenia (n=541) were younger (mean age 68 and 63years, respectively) than those without SMI (n=208609; mean age 71years). The overall 30-day and 1-year mortality rates were 10% and 18%, respectively. Compared with patients without SMI, patients with SMI had higher 30-day [odds ratio (OR) 1.99, 95% confidence interval (CI) 1.55-2.56] and 1-year mortality (OR 2.11, 95% CI 1.74-2.56) in the fully adjusted model. The highest mortality was observed amongst patients with schizophrenia (30-day mortality: OR 2.58, 95% CI 1.88-3.54; 1-year mortality: OR 2.55, 95% CI 1.98-3.29). ConclusionSMI is associated with a markedly higher mortality after myocardial infarction, also after accounting for contributing factors. It is imperative to identify the reasons for this higher mortality.

  • 8. Boden, Robert
    et al.
    Molina, E.
    Jernberg, T.
    Kieler, H.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Myocardial infarction survival in patients with bipolar disorder or schizophrenia spectrum disorders- a nationwide cohort study2014In: Bipolar Disorders, ISSN 1398-5647, E-ISSN 1399-5618, Vol. 16, p. 62-63Article in journal (Other academic)
  • 9.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Prognostic Factors in First-Episode Schizophrenia: Five-year Outcome of Symptoms, Function and Obesity2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Our knowledge of prognostic factors and optimal treatment organisation in schizophrenia is incomplete. The disparity of outcome measures used has been a major obstacle for research. Increasing evidence has shown that schizophrenia is associated with increased cardiovascular mortality, development of obesity and autonomic nervous system imbalance. Assertive community treatment (ACT) has been suggested as a promising direction for organising treatment services for first-episode schizophrenia, but its long-term effect has not been evaluated.

    One aim of the present thesis was to investigate prognostic factors for 5-year symptomatic and functional outcome and obesity development. A further aim was to evaluate a recently proposed definition of remission and examine the long-term effects of introducing a modified ACT programme (mACT). Thus, we performed a follow-up study of all consecutive first-episode psychosis patients in Uppsala County, Sweden during 1995-2000 (n=144).

    In the first study we investigated the changes in a broad 5-year outcome of symptoms and function among patients presenting first time ever to psychiatric health care during 3 years before and during 3 years after the implementation of mACT. This change in the psychiatric service, however, was not followed by any long-term clinical benefits.

    In the second study, we examined the association between remission of eight core schizophrenia symptoms and functional outcome. Remission was strongly associated with having good function and having a higher self-rated satisfaction with life.

    In the third study, we explored a set of biochemical markers as predictors of weight gain and development of obesity. Haemoglobin, red blood cell count, hematocrit, γ-glutamyltransferase and creatinine were associated with the development of obesity in first-episode schizophrenia.

    In the fourth and final study, we tested electrocardiographic measures of autonomic imbalance as predictors of symptomatic remission. Higher heart rate and high ST and T-wave amplitudes were related to symptomatic remission, indicating that cardiac autonomic imbalance at baseline may have a prognostic value in first-episode schizophrenia.

  • 10.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Abrahamsson, Tore
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Holm, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Borg, Jacqueline
    Psychomotor and cognitive deficits as predictors of 5-year outcome in first-episode schizophrenia2014In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 68, no 4, p. 282-288Article in journal (Refereed)
    Abstract [en]

    Background: Cognitive deficits are common in schizophrenia but the predictive value of these deficits for long-term outcome in first-episode patients is unclear. Aims: We aimed to investigate associations of performance in psychomotor and cognitive tests with a 5-year functional and symptomatic outcome. Methods: After clinical stabilization, patients with a first schizophrenia spectrum diagnosis (n = 46) were assessed for global cognitive function [Synonyms, Reasoning, and Block Design (SRB)], psychomotor speed [Trail Making Test (TMT) and finger tapping] and verbal learning (Claeson-Dahl Verbal Learning Test). The subsequent 5-year outcome regarding independent living, occupational and social function, and symptomatic remission status was assessed. Results: Low psychomotor speed was associated with poor social function 5 years later, with an odds ratio (OR) of 3.37 and a 95% confidence interval (CI) of 1.08-10.51, adjusted for antipsychotic drug use. Better performance on finger tapping with the non-dominant hand was associated with an increased risk of a 5-year symptomatic non-remission (adjusted OR = 0.42, CI 0.19-0.96). Occupational function and independent living were not significantly associated with any of the investigated tests. Conclusions: Psychomotor speed is associated with a long-term outcome regarding social function and symptom remission in patients with first-episode schizophrenia.

  • 11.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Bexelius, Tomas S
    Mattsson, Fredrik
    Lagergren, Jesper
    Lindblad, Mats
    Ljung, Rickard
    Antidopaminergic drugs and acute pancreatitis: a population-based study2012In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 3, p. e000914-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the suggested association between antidopaminergic drugs and acute pancreatitis.

    DESIGN: A large population-based nested case-control study.

    SETTING: Swedish nationwide study from 2006 to 2008.

    PARTICIPANTS: The Patient Register was used to identify 6161 cases of acute pancreatitis. The 61 637 control subjects were randomly selected from the Register of the Total Population by frequency-based density sampling, matched for age, sex and calendar year.

    EXPOSURE: Exposure data were extracted from the Prescribed Drug Register. Antidopaminergic drugs were grouped into antiemetic/anxiolytic and other antipsychotics. Current use of antidopaminergic drugs was defined as filling a prescription 1-114 days before index date, while previous use was 115 days to 3.5 years before index date.

    MAIN OUTCOME MEASURES: Cases were defined as being diagnosed as having acute pancreatitis. ORs and 95% CIs were calculated using unconditional logistic regression.

    RESULTS: The unadjusted OR indicated an increased risk of acute pancreatitis among current users of antiemetic/anxiolytics (OR 1.9, 95% CI 1.4 to 2.6), but not in the multivariable model adjusting for alcohol-related comorbidity, chronic obstructive lung disease, ischaemic heart disease, obesity, diabetes, opioid use, gallstone disease, educational level, marital status and number of concomitant medications (OR 0.9, 95% CI 0.6 to 1.2). Similarly, among current users of other antipsychotics, the unadjusted OR was 1.4 (95% CI 1.1 to 1.6), while the adjusted OR was 0.8 (95% CI 0.6 to 0.9). Results regarding previous use of antidopaminergic drugs followed a similar risk pattern as for current use.

    CONCLUSIONS: The lack of association between antidopaminergic drugs and acute pancreatitis after adjustment for confounding factors in this study suggests that the previously reported positive associations might be explained by confounding.

  • 12.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lindström, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Rautaharju, Pentti
    Wake Forest Univ, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Electrocardiographic signs of autonomic imbalance in medicated patients with first-episode schizophrenia spectrum disorders: relations to first treatment discontinuation and five-year remission status2012In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 27, no 3, p. 213-218Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To explore measures in electrocardiograms (ECG) influenced by autonomic balance in early schizophrenia spectrum disorders and to examine their relation to subsequent first antipsychotic pharmacotherapy discontinuation and five-year remission status.

    SUBJECTS AND METHODS:

    Twelve-lead ECGs were recorded at baseline in 58 patients with first-episode schizophrenia spectrum disorders and in 47 healthy controls of similar age. Selected ECG variables included heart rate and measures of repolarization. Pharmacotherapy data were extracted from medical records. At a five-year follow-up the patients were interviewed and assessed with the Positive and Negative Syndrome Scale.

    RESULTS:

    Patients had higher heart rate and a different ST-T pattern than the controls. High T-wave amplitudes in the leads aVF and V5 and ST-elevations in V5 were associated both with higher risk of an earlier discontinuation of first antipsychotic pharmacotherapy and with non-remission five years later.

    DISCUSSION AND CONCLUSION:

    In this longitudinal cohort study, simple ECG measures influenced by autonomic balance in the early phase of schizophrenia spectrum disorders contained prognostic information. As this is the first report of this association and is based on a relatively small sample, the results should be interpreted with caution.

  • 13.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lundgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Brandt, Lena
    Reutfors, Johan
    Kieler, Helle
    Antipsychotics During Pregnancy Relation to Fetal and Maternal Metabolic Effects2012In: Archives of General Psychiatry, ISSN 0003-990X, E-ISSN 1538-3636, Vol. 69, no 7, p. 715-721Article in journal (Refereed)
    Abstract [en]

    Context: Knowledge about the effects of exposure to the newer antipsychotics during pregnancy is limited. Objective: To investigate the effects of maternal use of antipsychotics during pregnancy on gestational diabetes and fetal growth. Design: Population-based cohort study comparing women exposed and not exposed to antipsychotics during pregnancy. Exposure was defined as prescriptions filled. Setting: Swedish national health registers. Participants: All women giving birth in Sweden from July 1, 2005, through December 31, 2009, grouped by filled prescriptions for (1) olanzapine and/or clozapine, the most obesogenic and diabetogenic antipsychotics (n=169), (2) other antipsychotics (n=338), or (3) no antipsychotics (n=357 696). Main Outcome Measures: Odds ratios (ORs) with 95% CIs for gestational diabetes and being small for gestational age (SGA) and large for gestational age for birth weight, birth length, and head circumference. Results: Exposure to other antipsychotics was associated with an increased risk of gestational diabetes (adjusted OR, 1.77 [95% CI, 1.04-3.03]). The risk increase with olanzapine and/or clozapine was of similar magnitude but not statistical significance (adjusted OR, 1.94 [95% CI, 0.97-3.91]). Infants exposed to either group of antipsychotics had increased risks of being SGA on birth weight, whereas only exposure to other antipsychotics yielded increased risks of being SGA for birth length and head circumference. None of the risks for SGA measurements remained significant after adjusting for maternal factors. There were no increased risks of being large for gestational age for birth weight or birth length after exposure to olanzapine and/or clozapine, but the risk increased for head circumference (OR, 3.02 [95% CI, 1.60-5.71]). Conclusions: Women who used antipsychotics during pregnancy had increased risks of gestational diabetes. The increased risks of giving birth to an SGA infant seemed to be an effect of confounders, such as smoking. Except for macrocephaly, olanzapine and/or clozapine exposure was not associated with anabolic fetal growth.

  • 14.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Persson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Uppsala Univ, Uppsala, Sweden..
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Striatal Phosphodiesterase 10A and Medial Prefrontal Cortical Thickness in Patients with Schizophrenia: A PET and MRI Study2017In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, p. S386-S387Article in journal (Other academic)
  • 15.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Persson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Striatal phosphodiesterase 10A and medial prefrontal cortical thickness in patients with schizophrenia: a PET and MRI study2017In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 7, no 3, article id e1050Article in journal (Refereed)
    Abstract [en]

    The enzyme phosphodiesterase 10A (PDE10A) is abundant in striatal medium spiny neurons and has been implicated in the pathophysiology of schizophrenia in animal models and is investigated as a possible new pharmacological treatment target. A reduction of prefrontal cortical thickness is common in schizophrenia, but how this relates to PDE10A expression is unknown. Our study aim was to compare, we believe for the first time, the striatal non-displaceable binding potential (BPND) of the new validated PDE10A ligand [(11)C]Lu AE92686 between patients with schizophrenia and healthy controls. Furthermore, we aimed to assess the correlation of PDE10A BPND to cortical thickness. Sixteen healthy male controls and 10 male patients with schizophrenia treated with clozapine, olanzapine or quetiapine were investigated with positron emission tomography (PET) and magnetic resonance imaging (MRI). Striatal binding potential (BPND) of [(11)C]Lu AE92686 was acquired through dynamic PET scans and cortical thickness by structural MRI. Clinical assessments of symptoms and cognitive function were performed and the antipsychotic dosage was recorded. Patients with schizophrenia had a significantly lower BPND of [(11)C]Lu AE92686 in striatum (P=0.003) than healthy controls. The striatal BPND significantly correlated to cortical thickness in the medial prefrontal cortex and superior frontal gyrus across patients with schizophrenia and healthy controls. No significant correlation was observed between the BPND for [(11)C]Lu AE92686 in striatum and age, schizophrenia symptoms, antipsychotic dosage, coffee consumption, smoking, duration of illness or cognitive function in the patients. In conclusion, PDE10A may be important for functioning in the striato-cortical interaction and in the pathophysiology of schizophrenia.

  • 16.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Persson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Striatal Phosphodiesterase 10A and Thinning of the medial Prefrontal Cortex in Schizophrenia - a PET and MRI study2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, p. S48-S49Article in journal (Refereed)
  • 17.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Lindström, Eva
    Wieselgren, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Lindström, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Five-year outcome of first-episode psychosis before and after the implementation of a modified assertive community treatment programme2010In: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 45, no 6, p. 665-674Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Assertive community treatment programmes are increasingly common worldwide but without much knowledge of their long-term effect. We investigated whether the implementation of such a programme would improve symptomatic and functional outcome 5 years later. METHODS: Naturalistic cohort study between 1995 and 2000 of all first-episode psychosis patients (n = 144) in Uppsala County, Sweden. We compared a 3-year period before (non-mACT) and after the introduction of a modified assertive community treatment (mACT) programme in 1998. Five-year outcome was assessed for symptoms and functioning and the two co-primary outcome measures were positive and negative symptoms. Regression models were adjusted for a propensity score based on multiple baseline variables and use of antipsychotics at 5-year follow-up. RESULTS: Contrary to our hypothesis, patients in the mACT group, compared to those in the non-mACT group, had a borderline significant increased risk of having a poor 5-year outcome regarding positive psychotic symptoms [adjusted odds ratio (OR) 3.21, 95% confidence interval (CI) 0.97-10.63]. There was no difference at the 5-year follow-up between the mACT and non-mACT group regarding negative symptoms (adjusted OR 1.65, 95% CI 0.48-5.66), or any of the secondary outcome measures: global assessment of functioning, hazardous alcohol use, use of illicit drugs, working or being in education, independent living, subjective satisfaction with life or suicide. Results were similar in subgroup analyses. CONCLUSIONS: The implementation of a modified assertive community treatment was not followed by subsequent improvements of 5-year outcome on a group level for patients with first-episode psychosis.

  • 18.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Wettermark, Bjorn
    Brandt, Lena
    Kieler, Helle
    Factors associated with pregabalin dispensing at higher than the approved maximum dose2014In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 70, no 2, p. 197-204Article in journal (Refereed)
    Abstract [en]

    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. 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. 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 a parts per thousand yen65 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). 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.

  • 19.
    Brenner, Philip
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Brandt, Lena
    Karolinska Inst, Stockholm, Sweden.
    Hägg, David
    Karolinska Inst, Stockholm, Sweden.
    Li, Gang
    Janssen, Global Serv, Titusville, NJ USA.
    DiBernardo, Allitia
    Janssen, Global Serv, Titusville, NJ USA.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Reutfors, Johan
    Karolinska Inst, Stockholm, Sweden.
    Substance use disorders are risk factors for treatment resistant depression2018In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 27, no Suppl. 2, p. 153-153, article id 331Article in journal (Other academic)
  • 20.
    Brenner, Philip
    et al.
    Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Brandt, Lena
    Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Li, Gang
    Janssen Res & Dev LLC, Titusville, NJ USA.
    DiBernardo, Allitia
    Janssen Res & Dev LLC, Titusville, NJ USA.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry. Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Reutfors, Johan
    Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Treatment-resistant depression as risk factor for substance use disorders: a nation-wide register-based cohort study2019In: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 114, no 7, p. 1274-1282Article in journal (Refereed)
    Abstract [en]

    Background and aims Treatment-resistant depression (TRD) is common among patients with major depressive disorder (MDD). MDD may increase the risk for developing substance use disorders (SUD). The aim of this study was to investigate the risk for developing SUD among patients with TRD compared with other depressed patients.

    Design Observational cohort study.

    Setting Nation-wide governmental health registers in Sweden.

    Participants All patients aged 18-69 years with an MDD diagnosis in specialized health care who had received at least one antidepressant prescription during 2006-14 were identified. Patients with at least three treatment trials within a single depressive episode were classified with TRD.

    Measurements Patients with TRD were compared with the whole MDD cohort regarding risk for obtaining a SUD diagnosis or medication using survival analyses adjusted for socio-demographics and comorbidities.

    Findings Of 121 669 MDD patients, 13% were classified with TRD. Among the patients without any history of SUD, patients with TRD had a risk increase for any SUD both ≤ 1 and > 1 year after antidepressant initiation [> 1 year hazard ratio (HR) = 1.4; 95% confidence interval (CI) = 1.3-1.5]. Risks were elevated for the subcategories of opioid (HR = 1.9, 95% CI = 1.4-2.5) and sedative SUD (HR = 2.7, 95% CI = 2.2-3.2). Patients with a history of SUD had a risk increase for any SUD ≤ 1 year after start of treatment (HR = 1.2, 95% CI = 1.1-1.4), and both ≤ 1 year and > 1 year for sedative (> 1 year HR = 2.0, 95% CI = 1.3-3.0) and multiple substance SUD (HR = 1.9, 95% CI = 1.4-2.5).

    Conclusions Patients with treatment-resistant depression may be at greater risk for substance use disorders compared with other patients with major depressive disorder. Patterns may differ for patients with and without a history of substance use disorders, and for different categories of substance use disorder.

  • 21.
    Brenner, Philip
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Hagg, David
    Karolinska Inst, Stockholm, Sweden.
    DiBernardo, Allitia
    Janssen, Global Serv, Titusville, NJ USA.
    Li, Gang
    Janssen, Global Serv, Titusville, NJ USA.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Brandt, Lena
    Karolinska Inst, Stockholm, Sweden.
    Reutfors, Johan
    Karolinska Inst, Stockholm, Sweden.
    Treatment resistant depression as a risk factor for substance use disorders-A national register-based cohort study2018In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 27, no Suppl. 2, p. 152-152, article id 329Article in journal (Other academic)
  • 22.
    Clapham, Eric
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry. Uppsala Univ, Dept Neurosci, Psychiat, Ing 10,Van 3, SE-75185 Uppsala, Sweden;Karolinska Inst, Karolinska Univ Hosp, Ctr Pharmacoepidemiol CPE, Dept Med Solna, Stockholm, Sweden.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry. Uppsala Univ, Dept Neurosci, Psychiat, Ing 10,Van 3, SE-75185 Uppsala, Sweden;Karolinska Inst, Karolinska Univ Hosp, Ctr Pharmacoepidemiol CPE, Dept Med Solna, Stockholm, Sweden.
    Brandt, Lena
    Karolinska Inst, Karolinska Univ Hosp, Ctr Pharmacoepidemiol CPE, Dept Med Solna, Stockholm, Sweden.
    Jonsson, Erik G.
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden;Univ Oslo, KG Jebsen Ctr Psychosis Res, NORMENT, Inst Clin Med,Psychiat Sect, Oslo, Norway.
    Bahmanyar, Shahram
    Karolinska Inst, Karolinska Univ Hosp, Ctr Pharmacoepidemiol CPE, Dept Med Solna, Stockholm, Sweden.
    Ekbom, Anders
    Karolinska Inst, Karolinska Univ Hosp, Ctr Pharmacoepidemiol CPE, Dept Med Solna, Stockholm, Sweden.
    Osby, Urban
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
    Reutfors, Johan
    Karolinska Inst, Karolinska Univ Hosp, Ctr Pharmacoepidemiol CPE, Dept Med Solna, Stockholm, Sweden.
    Suicide Ideation and Behavior as Risk Factors for Subsequent Suicide in Schizophrenia: A Nested Case-Control Study2019In: Journal of Suicide and Life-threatening Behaviour, ISSN 0363-0234, E-ISSN 1943-278X, Vol. 49, no 4, p. 996-1005Article in journal (Refereed)
    Abstract [en]

    Objective To investigate suicide ideation and behavior as risk factors for suicide in schizophrenia during varying time periods. Method Cases were 84 patients who died by suicide within 5 years from diagnosis in a source population of patients discharged for the first time from psychiatric hospitals in Stockholm County, Sweden, with a schizophrenia spectrum diagnosis. One control was individually matched with each suicide case. Data were retrieved from clinical records in a blind fashion. Thoughts of death, thoughts of suicide, suicide plan, and suicide attempt during varying time periods were investigated as risk factors for subsequent completed suicide. Results In adjusted analyses, thoughts of suicide, suicide plan, and suicide attempt were significantly associated with subsequent completed suicide in the following year. The highest suicide risk was found within a year following suicide attempt (adjusted OR 9.9, 95% confidence interval 2.5-39.0). The association between suicide ideation and behavior and subsequent suicide declined over time. Conclusions Several types of suicide ideation and behavior were associated with suicide, and the association was stronger for suicidal behavior. The clinical significance of suicidal communication appears highest during the following month or/and year. Many suicides occurred without recorded short-term suicidal communication.

  • 23.
    DiBernardo, Allitia
    et al.
    Janssen Res & Dev LLC, Titusville, NJ 08560 USA.
    Lin, Xiwu
    Janssen Res & Dev LLC, Titusville, NJ 08560 USA.
    Zhang, Qiaoyi
    Janssen Res & Dev LLC, Titusville, NJ 08560 USA.
    Xiang, Jim
    Janssen Res & Dev LLC, Titusville, NJ 08560 USA.
    Lu, Lang
    Janssen Res & Dev LLC, Titusville, NJ 08560 USA.
    Jamieson, Carol
    Janssen Res & Dev LLC, Titusville, NJ 08560 USA.
    Benson, Carmela
    Janssen Sci Affairs LLC, Titusville, NJ USA.
    Lee, Kwan
    Janssen Res & Dev LLC, Titusville, NJ 08560 USA.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol Clin Epidemiol, Stockholm, Sweden.
    Brandt, Lena
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol Clin Epidemiol, Stockholm, Sweden.
    Brenner, Philip
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol Clin Epidemiol, Stockholm, Sweden.
    Reutfors, Johan
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol Clin Epidemiol, Stockholm, Sweden.
    Li, Gang
    Janssen Res & Dev LLC, Titusville, NJ 08560 USA;Janssen R&D US, Real World Evidence Stat & Decis Sci, 920 US Highway 202 S, Raritan, NJ 08869 USA.
    Humanistic outcomes in treatment resistant depression: a secondary analysis of the STAR*D study2018In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 18, article id 352Article in journal (Refereed)
    Abstract [en]

    BackgroundIn 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.MethodsPatients 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 14160days 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).ResultsA total of 2467 (TRD: 377; non-TRD: 2090) patients were studied. TRD patients were slightly older (mean age 44 vs 42years), 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.

  • 24. Fleischhacker, W Wolfgang
    et al.
    Siu, Cynthia O
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Pappadopulos, Elizabeth
    Karayal, Onur N
    Kahn, René S
    Metabolic risk factors in first-episode schizophrenia: baseline prevalence and course analysed from the European First-Episode Schizophrenia Trial2013In: International Journal of Neuropsychopharmacology, ISSN 1461-1457, E-ISSN 1469-5111, Vol. 16, no 5, p. 987-995Article in journal (Refereed)
    Abstract [en]

    Available data on antipsychotic-induced metabolic risks are often constrained by potential confounding effects due to prior antipsychotic treatment. In this study, we assessed the baseline prevalence of metabolic abnormalities and changes following treatment with five commonly-used antipsychotic drugs (haloperidol, amisulpride, olanzapine, quetiapine or ziprasidone) in first-episode, partially antipsychotic-naive patients with schizophrenia in the European first-episode schizophrenia trial (EUFEST). Overall baseline prevalence of metabolic syndrome (MetS) was 6.0%, with similar rates observed in the antipsychotic-naive patients (5.7%, 9/157) and in the other patients with only a brief prior exposure to antipsychotics (6.1%, 20/326). These results are consistent with the MetS prevalence rate estimated in a general population of similar age. Examination of individual risk factors showed 58.5% of subjects had one or more elevated metabolic risks at baseline: 28.5% demonstrated suboptimal HDL; 24.2% hypertension; 17.7% hypertriglyceridemia; 8.2% abdominal obesity; 7.3% hyperglycaemia. Increase in body weight (kg/month) occurred in patients treated with haloperidol (0.62 s.e. 0.11), amisulpride (0.76 s.e. 0.08), olanzapine (0.98 s.e. 0.07) and quetiapine (0.58 s.e. 0.09), which was significantly greater than that in the ziprasidone group (0.18 s.e. 0.10). The incidence rate of new diabetes cases over a 52-wk follow-up period was 0.82% (4/488). More patients experienced worsening rather than improvement of hypertriglyceridemia or hyperglycaemia in all treatment groups. Our findings suggest that in first-episode, partially antipsychotic-naive patients, the baseline prevalence rate of MetS appears to be no higher than that in the general population, but serious underlying individual risk factors nevertheless existed.

  • 25.
    Lagerros, Ylva Trolle
    et al.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden; Karolinska Univ Hosp Huddinge, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.
    Brandt, Lena
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    Hedberg, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    Suicide, Self-harm, and Depression After Gastric Bypass Surgery: A Nationwide Cohort Study2017In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 265, no 2, p. 235-243Article in journal (Refereed)
    Abstract [en]

    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.

  • 26. Lagerros, Ylva Trolle
    et al.
    Brandt, Lena
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Hedberg, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Boden, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Risk of Suicide, Self-Harm and Depression after Gastric Bypass2015In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 25, p. S127-S127Article in journal (Other academic)
  • 27.
    Neider, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lindström, Leif H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Boden, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Risk factors for suicide among patients with schizophrenia: a cohort study focused on cerebrospinal fluid levels of homovanillic acid and 5-hydroxyindoleacetic acid2016In: Neuropsychiatric Disease and Treatment, ISSN 1176-6328, E-ISSN 1178-2021, Vol. 12, p. 1711-1714Article in journal (Refereed)
    Abstract [en]

    Background: The objective of this study was to investigate the association between 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid (CSF), bullying, and later suicide among patients with schizophrenia. Methods: Ninety-nine patients with schizophrenia were included. Correlations of clinical factors, 5-HIAA and HVA, and later suicide were investigated. Results: Twelve patients committed suicide (12%) during a 28-year follow-up period. Later suicide was correlated to bullying in childhood (P=0.02) and a lower quotient of HVA/5-HIAA in CSF (P<0.05). Conclusion: Suicide in schizophrenia is related to childhood exposedness and CSF neurotransmitter levels.

  • 28.
    Nilsson, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Edström, Oscar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lindström, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Wernegren, Petter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Tachycardia in Patients Treated with Clozapine versus Antipsychotic Long-Acting Injections2017In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10 S, p. S408-S409Article in journal (Other academic)
  • 29.
    Nilsson, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lindström, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Persistent Clozapine Associated Tachycardia Investigated with 24 Hour Ambulatory Electrocardiogram2017In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, p. S408-S408Article in journal (Other academic)
  • 30.
    Nilsson, Björn M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lindström, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Mohsen, Issam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Holmlöv, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Persistent tachycardia in clozapine treated patients: A 24-hour ambulatory electrocardiogram study2018In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 199, p. 403-406Article in journal (Refereed)
    Abstract [en]

    Tachycardia is associated with cardiovascular mortality. Tachycardia is also a known clozapine adverse effect. However, whether clozapine-associated tachycardia is persistent is not known. Thirty clozapine-treated patients with clinical tachycardia were investigated with 24-hour ambulatory electrocardiography (ECG). Baseline peripheral heart rate (HR) was 106.7 +/- 7.8. The ambulatory ECG 24-hour-HR was 98.7 +/- 9.7. Baseline HR and 24-hour-HR correlated strongly (r = 0.74, p = 0.000003). Daytime HR was 106.4 +/- 9.9 and nighttime HR 89.2 +/- 12.0. Low dose bisoprolol reduced HR significantly. The high 24-hour-HR indicates a persistent tachycardia. Tachycardia should not discourage from clozapine use but the findings indicate a need of guidelines for detection and treatment of clozapine-associated tachycardia.

  • 31. Olsson, Eric
    et al.
    Westman, Jeanette
    Sudic Hukic, Dzana
    Eriksson, Sven V
    Edman, Gunnar
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Centre for pharmacoepidemiology, Karolinska Institutet.
    Jedenius, Erik
    Reutfors, Johan
    Berntsson, Anders
    Hilding, Agneta
    Schalling, Martin
    Östenson, Claes-Göran
    Ösby, Urban
    Diabetes and glucose disturbances in patients with psychosis in Sweden2015In: BMJ Open Diabetes Research & Care, ISSN 2052-4897, Vol. 3, article id e000120Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    The objectives of this study were to (1) analyze the prevalence of diabetes, prediabetes, and antidiabetic medication in patients with psychosis compared with control subjects and (2) determine what factors in patients with psychosis were associated with antidiabetic medication.

    METHOD:

    We studied 977 patients with psychosis recruited from outpatient clinics in Stockholm County, Sweden, and they were compared with 3908 non-psychotic control subjects for fasting plasma glucose levels; prevalence of diabetes, prediabetes, antidiabetic treatment, and tobacco use; and blood pressure, weight, height, and waist circumference. Group differences were evaluated with analysis of variance and χ(2) test, and factors associated with antidiabetic treatment were evaluated with logistic regression.

    RESULTS:

    Diabetes was observed in 94 (10%) patients with psychosis, 2.7 times the prevalence observed in control subjects. Among patients with psychosis, 87 (10%) had prediabetes (fasting glucose, 6.1-6.9 mmol/L) compared with 149 (3.8%) control subjects. Most patients with psychosis (77%) who had prediabetes fulfilled criteria for metabolic syndrome. In patients with psychosis, both lipid-lowering medication and fasting glucose were significantly associated with antidiabetic treatment. There was no significant relation between antidiabetic treatment and lifestyle factors such as smoking or degree of psychiatric illness.

    CONCLUSIONS:

    The high prevalence of impaired fasting glucose and metabolic syndrome in patients with psychosis warrants further clinical research in preventing or delaying the onset of diabetes in these patients by pharmacotherapy and/or lifestyle intervention.

  • 32.
    Persson, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Szalisznyo, Krisztina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Zora, Hatice
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Phosphodiesterase 10A levels are related to striatal function in schizophrenia: a combined positron emission tomography and functional magnetic resonance imaging study2019In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491Article in journal (Refereed)
    Abstract [en]

    Pharmacological inhibition of phosphodiesterase 10A (PDE10A) is being investigated as a treatment option in schizophrenia. PDE10A acts postsynaptically on striatal dopamine signaling by regulating neuronal excitability through its inhibition of cyclic adenosine monophosphate (cAMP), and we recently found it to be reduced in schizophrenia compared to controls. Here, this finding of reduced PDE10A in schizophrenia was followed up in the same sample to investigate the effect of reduced striatal PDE10A on the neural and behavioral function of striatal and downstream basal ganglia regions. A positron emission tomography (PET) scan with the PDE10A ligand [11C]Lu AE92686 was performed, followed by a 6 min resting-state magnetic resonance imaging (MRI) scan in ten patients with schizophrenia. To assess the relationship between striatal function and neurophysiological and behavioral functioning, salience processing was assessed using a mismatch negativity paradigm, an auditory event-related electroencephalographic measure, episodic memory was assessed using the Rey auditory verbal learning test (RAVLT) and executive functioning using trail-making test B. Reduced striatal PDE10A was associated with increased amplitude of low-frequency fluctuations (ALFF) within the putamen and substantia nigra, respectively. Higher ALFF in the substantia nigra, in turn, was associated with lower episodic memory performance. The findings are in line with a role for PDE10A in striatal functioning, and suggest that reduced striatal PDE10A may contribute to cognitive symptoms in schizophrenia.

  • 33.
    Pottegård, A.
    et al.
    Univ Southern Denmark, Dept Publ Hlth, Clin Pharmacol & Pharm, Odense, Denmark..
    Tjäderborn, M.
    Linkoping Univ, Dept Drug Res, Clin Pharmacol, Linkoping, Sweden..
    Schjerning, O.
    Aalborg Univ Hosp, Psychiat, Aalborg, Denmark.;Aalborg Univ, Dept Clin Med, Aalborg, Denmark..
    Nielsen, J.
    Aalborg Univ Hosp, Psychiat, Aalborg, Denmark.;Aalborg Univ, Dept Clin Med, Aalborg, Denmark..
    Damkier, P.
    Univ Southern Denmark, Dept Publ Hlth, Clin Pharmacol & Pharm, Odense, Denmark.;Odense Univ Hosp, Dept Clin Chem & Pharmacol, Odense, Denmark..
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Re: Pregabalin prescriptions in the United Kingdom - a drug utilisation study of The Health Improvement Network (THIN) primary care database by Asomaning et al.2016In: International journal of clinical practice (Esher), ISSN 1368-5031, E-ISSN 1742-1241, Vol. 70, no 8, p. 696-696Article in journal (Refereed)
  • 34.
    Reutfors, Johan
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Andersson, Therese M-L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Brenner, Philip
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Brandt, Lena
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    DiBernardo, Allitia
    Janssen, Global Serv, Titusville, NJ USA.
    Li, Gang
    Janssen, Global Serv, Titusville, NJ USA.
    Hagg, David
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Wingard, Louise
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Mortality in treatment-resistant unipolar depression: A register-based cohort study in Sweden2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 238, p. 674-679Article in journal (Refereed)
    Abstract [en]

    Background: The impact of treatment resistant depression (TRD) on mortality is not established. Methods: Using Swedish national registers, 118,774 patients between 18-69 years of age who had been prescribed an antidepressant and been diagnosed with depression in specialized care were identified. Patients with at least two additional treatment trials during the same depressive episode were classified as having TRD. Data on the covariates of sex, age, history of depression, self-harm, substance use disorders, and other psychiatric and somatic comorbidities was also used. Relative risks comparing TRD patients with other depressed patients were calculated as hazard ratios (HR) for all-cause mortality and for external and non-external causes of death, as well as excess mortality rate ratios (EMRR), with 95% confidence intervals (CI). Results: In total 15,013 patients (13%) were classified with TRD. Adjusted HR for all-cause mortality was 1.35 (95% CI 1.21-1.50). Mortality from external causes (including suicides and accidents) was markedly higher in TRD patients than in other depressed patients (HR 1.97; 1.69-2.29), while mortality from non-external causes was similar. The adjusted EMRR was 1.52 (1.31-1.76), highest among patients 18-29 years old (EMRR 2.03; 1.31-1.76) and patients without somatic comorbidity (EMRR 1.99; 1.63-2.43). Limitations: Severity of depression and adherence to treatment were not available in the data. Conclusions: Patients with TRD may have an increased all-cause mortality compared to other depressed patients, mainly for external causes of death. The relative mortality is highest among young and physically healthy patients.

  • 35.
    Reutfors, Johan
    et al.
    Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Bahmanyar, Shahram
    Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Brandt, Lena
    Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Clapham, Eric
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Jönsson, Erik G.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Boden, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Ekbom, Anders
    Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Osby, Urban
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Suicide Risk and Side Effects from Antipsychotics in Schizophrenia: A Nested Case-Control Study2015In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 24, p. 333-333Article in journal (Other academic)
  • 36. Reutfors, Johan
    et al.
    Bahmanyar, Shahram
    Jönsson, Erik G
    Brandt, Lena
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Centre for pharmacoepidemiology, Karolinska Institutet.
    Ekbom, Anders
    Ösby, Urban
    Medication and suicide risk in schizophrenia: A nested case-control study2013In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 150, no 2-3, p. 416-420Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Patients with schizophrenia are at increased risk of suicide, but data from controlled studies of pharmacotherapy in relation to suicide risk is limited.

    AIM: To explore suicide risk in schizophrenia in relation to medication with antipsychotics, antidepressants, and lithium.

    METHODS: Of all patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n=4000), patients who died by suicide within five years from diagnosis were defined as cases (n=84; 54% male). Individually matched controls were identified from the same population. Information on prescribed medication was retrieved from psychiatric records in a blinded way. Adjusted odds ratios [OR] of the association between medication and suicide were calculated by conditional logistic regression.

    RESULTS: Lower suicide risk was found in patients who had been prescribed a second generation antipsychotic (clozapine, olanzapine, risperidone, or ziprasidone; 12 cases and 20 controls): OR 0.29 (95% confidence interval [CI], 0.09-0.97). When the 6 cases and 8 controls who had been prescribed clozapine were excluded, the OR was 0.23 (95% CI 0.06-0.89). No significant association was observed between suicide and prescription of any antipsychotic, depot injection antipsychotics, antidepressants, SSRI, or lithium.

    CONCLUSIONS: Lower suicide risk for patients who had been prescribed second generation antipsychotics may be related to a pharmacological effect of these drugs, to differences in adherence, or to differences in other patient characteristics associated with lower suicide risk.

  • 37. Reutfors, Johan
    et al.
    Brandt, Lena
    Stephansson, Olof
    Kieler, Helle
    Andersen, Morten
    Boden, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Antipsychotic Medication Adherence in Patients with Schizophrenia or Schizoaffective Disorder2012In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 21, no SI:3, p. 437-438Article in journal (Other academic)
  • 38. Reutfors, Johan
    et al.
    Brandt, Lena
    Stephansson, Olof
    Kieler, Helle
    Andersen, Morten
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Centre for pharmacoepidemiology, Karolinska Institutet.
    Antipsychotic Prescription Filling in Patients With Schizophrenia or Schizoaffective Disorder2013In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 33, no 6, p. 759-765Article in journal (Refereed)
    Abstract [en]

    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.

  • 39.
    Reutfors, Johan
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol CPE, SE-17176 Stockholm, Sweden.
    Clapham, Eric
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Bahmanyar, Shahram
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol CPE, SE-17176 Stockholm, Sweden.; Golestan Univ Med Sci, Fac Med, Gorgan, Iran..
    Brandt, Lena
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol CPE, SE-17176 Stockholm, Sweden.
    Jönsson, Erik G
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.; Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, NORMENT, Oslo, Norway.
    Ekbom, Anders
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol CPE, SE-17176 Stockholm, Sweden.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol CPE, SE-17176 Stockholm, Sweden.
    Ösby, Urban
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.; Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.; PRIMA Psychiat AB, Dept Adult Psychiat, Stockholm, Sweden.
    Suicide risk and antipsychotic side effects in schizophrenia: nested case-control study.2016In: Human Psychopharmacology: Clinical and Experimental, ISSN 0885-6222, E-ISSN 1099-1077, Vol. 31, no 4, p. 341-345Article in journal (Refereed)
    Abstract [en]

    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.

  • 40. Reutfors, Johan
    et al.
    Tiihonen, Jari
    Brandt, Lena
    Scheen, Louise
    Tanskanen, Antti
    Andersen, Morten
    Boden, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Medication and Risk of Rehospitalization in Bipolar Disorder: A Nationwide Cohort Study2014In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 23, no S1, p. 251-251Article in journal (Other academic)
  • 41. Scheen, Louise
    et al.
    Boden, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Brandt, Lena
    Tiihonen, Jari
    Andersen, Morten
    Kieler, Helle
    Reutfors, Johan
    Clinical Factors Associated with Prescription Filling of Mood-Stabilizers in Bipolar Disorder - A Population-Based Cohort Study2014In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 23, no S1, p. 368-369Article in journal (Other academic)
  • 42. Scheen, Louise
    et al.
    Brandt, Lena
    Boden, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Tiihonen, Jari
    Andersen, Morten
    Kieler, Helle
    Reutfors, Johan
    Predictors for initiation of pharmacological prophylaxis in patients with newly diagnosed bipolar disorder-A nationwide cohort study2015In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 172, p. 204-210Article in journal (Refereed)
    Abstract [en]

    Background: Treatment guidelines state that all patients with bipolar disorder should use pharmacological prophylaxis; however the actual use of prophylactic drugs after bipolar disorder diagnosis is unknown. Our aim was to assess the use of, and predictors for, pharmacoprophylaxis in newly diagnosed bipolar disorder patients. Methods: Data from three Swedish nationwide registers were obtained. We identified patients aged 18-75 with a first time diagnosis of bipolar disorder between 2006 and 2012 (n=31,770) and reviewed subsequent mood-stabilizer and antipsychotic prescription fills. In multivariable Cox regression models, we studied demographic and illness related factors as predictors of prescription fills after diagnosis. Results: In total, 72.2% (95% confidence interval [Cl] 71.7-72.7%) of the patients filled a prescription of a prophylactic drug within 3 months after diagnosis. Pharmacological prophylaxis was mainly associated with a longer duration of hospitalization at bipolar disorder diagnosis (adjusted hazard ratio [AHR] 2.18; Cl 2.02-2.35 for a hospitalization of >28 days compared to < 7 days) and previous use of any moodstabilizer or antipsychotic (inpatients: AHR 1.24; Cl 1.17-1.31 and outpatients: AHR 1.78; Cl 1.73-1.84). Limitations: We had no information on drug prescriptions that were never filled. Conclusions: The proportion of newly diagnosed bipolar disorder patients without pharmacological prophylaxis is substantial. Patients who are naive to mood-stabilizers and antipsychotics and are hospitalized for a brief period at diagnosis are the ones least likely to initiate pharmacoprophylaxis, suggesting that this group deserves attention in order to improve the long term prognosis. (C) 2014 Elsevier B.V. All rights reserved.

  • 43.
    Stålberg, Gabriella
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lindström, Leif H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Larhammar, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Neuropeptide Y, social function and long-term outcome in schizophrenia2014In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 156, no 2-3, p. 223-227Article in journal (Refereed)
    Abstract [en]

    There is a lack of biomarkers in schizophrenia and the mechanisms underlying the observed deficits in social functioning are poorly understood. This cohort study aimed to explore whether neurotransmitter neuropeptide Y (NPY) in cerebrospinal fluid (CSF) from patients with schizophrenia is correlated to social function and clinical variables. A further aim was to determine whether baseline levels of NPY were associated with subsequent 3-year outcome. Fifty-six consecutively admitted patients with schizophrenia were included and underwent lumbar puncture and symptom ratings before antipsychotic treatment. NPY levels in CSF were determined by radioimmunoassay. Social function (Social Competence and Social Interest) was assessed by Nurses' Observation Scale for Inpatient Evaluation while psychiatric symptoms were rated using the Comprehensive Psychopathological Rating Scale. Three-year outcome was assessed with the Strauss–Carpenter Outcome Scale. Cross-sectional analysis showed a correlation between level of NPY and Social Competence at index admission (rs = 0.37, p < 0.05). The longitudinal analysis (i.e. at the 3-year follow-up) indicated that, for each standard deviation increase in baseline NPY, there was an increased risk of being unemployed (odds ratio [OR] 2.02, 95% confidence interval [CI] 1.07–3.82), having moderate or severe symptoms (OR 3.09, CI 1.30–7.32) or being hospitalized at least 6 months the previous year (OR 3.24, CI 1.09–9.64). However, NPY was not correlated to Social Interest or clinical variables at index admission. In conclusion, NPY levels in CSF are correlated to Social Competence and seem to predict some aspects of longitudinal outcome in schizophrenia.

  • 44. Wettermark, B
    et al.
    Brandt, L
    Kieler, H
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Centre for pharmacoepidemiology, Karolinska Institutet.
    Pregabalin is increasingly prescribed for neuropathic pain, generalised anxiety disorder and epilepsy but many patients discontinue treatment2014In: International journal of clinical practice (Esher), ISSN 1368-5031, E-ISSN 1742-1241, Vol. 68, no 1, p. 104-110Article in journal (Refereed)
    Abstract [en]

    AIM: To assess prescribing patterns, sociodemographic characteristics and previous disease history in patients receiving pregabalin.

    METHODS: An observational study using register data on dispensed drugs and recorded diagnoses for all patients in Stockholm, Sweden, who filled at least one prescription of pregabalin between July 2005 and December 2009. Analyses focused on prevalence, incidence, diagnosis patterns, prior dispensing of other analgesics/psychotropics and persistence to treatment over time.

    RESULT: A total of 18,626 patients (mean age 55 years, 63% women) were initiated on treatment between July 2006 and December 2009. Approved indications were recorded in hospital and/or primary care within 1 year prior to the first dispensing for 40% of the patients (epilepsy 1.3%, neuropathic pain 35.5% and generalised anxiety disorder (GAD) 3.6%). Antidepressants were used by 55%, opioids by 49% and sedatives by 48% prior to initiation of pregabalin. One-third (34%) only purchased one prescription and the proportion purchasing pregabalin 1 year after initiation was 42.1% for epilepsy, 36.3% for GAD, 21.5% for neuropathic pain and 25.6% for those without any of the included diagnoses.

    CONCLUSION: Pregabalin was mainly used as a second-line drug for the treatment of GAD or neuropathic pain and to a lesser extent as add-on therapy in epilepsy. However, a large proportion of all patients only purchased one prescription and the persistence declined rapidly over time. The issue of potential off-label prescribing or poor registration of diagnoses should also be noted as a high proportion had been prescribed the drug without a record of any of the approved indications.

  • 45.
    Wingard, Louise
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol CPE, Stockholm, Sweden.
    Taipale, Heidi
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden;Univ Eastern Finland, Niuvanniemi Hosp, Dept Forens Psychiat, Kuopio, Finland;Univ Eastern Finland, Sch Pharm, Kuopio, Finland.
    Reutfors, Johan
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol CPE, Stockholm, Sweden.
    Westerlund, Anna
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol CPE, Stockholm, Sweden.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol CPE, Stockholm, Sweden.
    Tiihonen, Jari
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden;Univ Eastern Finland, Niuvanniemi Hosp, Dept Forens Psychiat, Kuopio, Finland.
    Tanskanen, Antti
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden;Univ Eastern Finland, Niuvanniemi Hosp, Dept Forens Psychiat, Kuopio, Finland.
    Andersen, Morten
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol CPE, Stockholm, Sweden;Univ Copenhagen, Dept Drug Design & Pharmacol, Fac Hlth & Med Sci, Copenhagen, Denmark;Univ Southern Denmark, Res Unit Gen Practice, Odense, Denmark.
    Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder2018In: Bipolar Disorders, ISSN 1398-5647, E-ISSN 1399-5618, Vol. 20, no 7, p. 634-646Article in journal (Refereed)
    Abstract [en]

    Objectives

    Increasing evidence points to the harmful effects of long‐term benzodiazepine treatment. Our objective was to study the incidence of, and predictors for, long‐term use of benzodiazepines and Z‐drugs in bipolar disorder.

    Methods

    We conducted a population‐based cohort study, using data from Swedish national registers. Swedish residents aged 18‐75 years with a recorded diagnosis of bipolar disorder or mania between July 2006 and December 2012, and no history of benzodiazepine/Z‐drug use in the past year, were included. Patients were followed for 1 year with regard to prescription fills of benzodiazepines/Z‐drugs. Initiators were followed for another year during which continuous use for >6 months was defined as “long‐term”. Patient and prescription characteristics were investigated as potential predictors for long‐term use in multivariate logistic regression models.

    Results

    Out of the 21 883 patients included, 29% started benzodiazepine/Z‐drug treatment, of whom one in five became long‐term users. Patients who were prescribed clonazepam or alprazolam had high odds for subsequent long‐term use (adjusted odds ratios [aORs] 3.78 [95% confidence interval (CI) 2.24‐6.38] and 2.03 [95% CI 1.30‐3.18], respectively), compared to those prescribed diazepam. Polytherapy with benzodiazepines/Z‐drugs also predicted long‐term use (aOR 2.46, 95% CI 1.79‐3.38), as did age ≥60 years (aOR 1.93, 95% CI 1.46‐2.53, compared to age <30 years), and concomitant treatment with psychostimulants (aOR 1.78, 95% CI 1.33‐2.39).

    Conclusions

    The incidence of subsequent long‐term use among bipolar benzodiazepine initiators is high. Patients on clonazepam, alprazolam or benzodiazepine/Z‐drug polytherapy have the highest risk of becoming long‐term users, suggesting that these treatments should be used restrictively.

  • 46.
    Wingård, L.
    et al.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Brandt, L.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Kieler, H.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Andersen, M.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Reutfors, J.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Comparative risks of treatment failure in bipolar 1 disorder: a population based study of lithium, valproate, olanzapine, quetiapine and aripiprazole in post mania relapse prevention2017In: Bipolar Disorders, ISSN 1398-5647, E-ISSN 1399-5618, Vol. 19, no S1, p. 100-101Article in journal (Other academic)
  • 47.
    Wingård, Louise
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol, T2, SE-17176 Stockholm, Sweden.
    Brandt, Lena
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol, T2, SE-17176 Stockholm, Sweden.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry. Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol, T2, SE-17176 Stockholm, Sweden.
    Kieler, Helle
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol, T2, SE-17176 Stockholm, Sweden.
    Andersen, Morten
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol, T2, SE-17176 Stockholm, Sweden;Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Copenhagen, Denmark.
    Reutfors, Johan
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Pharmacoepidemiol, T2, SE-17176 Stockholm, Sweden.
    Monotherapy vs. combination therapy for post mania maintenance treatment: A population based cohort study2019In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, no 6, p. 691-700Article in journal (Refereed)
    Abstract [en]

    In recent years, the use of atypical antipsychotics and combination therapy for relapse prevention in bipolar disorder has increased substantially. However, real-world data on the comparative effectiveness of these treatment options are largely non-existent. We conducted a population-based cohort study, using data from Swedish national registers. All patients aged 18-75 years who were hospitalized for mania 2006-2014 and filled at least one prescription of lithium, valproate, olanzapine, quetiapine, aripiprazole or any combination of these drugs were included, and followed for up to one year after hospital discharge, generating follow-up data from 5 713 hospitalizations. We used Cox proportional hazard regression models to study time to treatment failure for each individual drug and combination therapy, using lithium as comparator. Treatment failure was defined as treatment discontinuation, switch, or rehospitalization, and the results were adjusted for clinical and sociodemographic factors. We found that treatment failure occurred in 85% of cases and that the majority of combination therapies were associated with lower risks of treatment failure compared to monotherapies. Patients combining lithium + valproate + quetiapine had the lowest risk of treatment failure (adjusted HR [AHR] 0.40, 95% CI 0.30-0.54), followed by patients on lithium + valproate + olanzapine (AHR 0.55, 95% CI 0.45-0.68). In contrast, monotherapies with antipsychotics were associated with significantly higher risks of treatment failure compared to single use of lithium. In conclusion, our results support experimental findings, suggesting that combination therapy is more effective than monotherapy after a manic episode.

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