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  • 1.
    Chermá Yeste, Maria Dolores
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Löfgren, Ulla-Britt
    n/a.
    Almkvist, Göran
    n/a.
    Hallert, Claes
    Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland. Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Bengtsson, Finn
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Assessment of the prescription of antidepressant drugs in elderly nursing home patients2008In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 28, no 4, p. 424-431Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate the use of antidepressant drugs among elderly people in nursing homes. Elderly residents who where found to have been prescribed at least one antidepressant drug according to the specific medication dispensing system were identified in 8 nursing homes in the county of Östergötland, Sweden. Data were collected from the medical record forms at the nursing home. Blood samples were drawn for the assessment of drug concentration, blood chemistry parameters and cytochrome P450 expression. At least one antidepressant drug was prescribed to 38% of elderly people in the nursing home studied. A total of 71 patients were evaluated, 80% women and 20% men. The median age was 84 years (range, 71-100 years). Indications for antidepressant drug treatment were found on 96% of medical record forms (depression, 60%); however, information relating to when treatment was initiated could not be found on 34% of medical record forms and a clear time schedule for how long this drug treatment was planned to continue could not be found either. A possible adverse effect of antidepressant drug treatment was retrieved in at least 77% of patients. Polypharmacotherapy was common; median number of drugs per patient was 11. Concentrations of drugs were higher than expected in 73%. Most patients were medicated with citalopram (n = 44). A clear interindividual variability of concentrations at each dose level was found for citalopram and for the metabolites desmethylcitalopram and didesmethylcitalopram. A significant correlation was found between the estimation of creatinine clearance and concentration-dose ratio of citalopram. Poor metabolizers, who had been prescribed an antidepressant drug that are substrate for the cytochrome P450 isoenzyme examined, have higher concentrations of prescribed antidepressant drug than do non-poor metabolizers in relation to dose. An increase in quality contribution to follow-up at antidepressant medications is needed. A more frequent clinical use of therapeutic drug monitoring and pharmacogenetic tests in addition to therapeutic drug monitoring may be one important tool in this process.

  • 2.
    Fazel, S.
    et al.
    Department of Psychiatry, University of Oxford, Oxford, United Kingdom, Centre for Violence Prevention, Karolinska Institute, Stockholm, Sweden, University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, United Kingdom.
    Grann, M.
    Centre for Violence Prevention, Karolinska Institute, Stockholm, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Goodwin, G.
    Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
    Suicides by violent means in individuals taking SSRIs and other antidepressants: A postmortem study in Sweden, 1992-20042007In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 27, no 5, p. 503-506Article in journal (Refereed)
    Abstract [en]

    A number of reports have linked consumption of selective serotonin reuptake inhibitors (SSRIs) with suicide by violent methods. We aimed to determine whether suicides with postmortem evidence of SSRI consumption are more likely to have used violent methods compared with suicides with no detectable antidepressants. Blood samples from all suicides in Sweden during 1992-2004 were examined. Suicides were classified into those who died by violence and nonviolent (self-poisoning) methods using information from police records and autopsy. In addition, we investigated proportions of violent suicide in individuals who died with detectable levels of tricyclic and other antidepressants.The sample consisted of 14,691 suicides. Of the 1958 suicides with detectable levels of SSRIs, 1247 were by violent means (63.7%) compared with 7835 of 11,045 suicides (70.9%) in antidepressant-free group (?1 = 7.6, P < 0.01). We found no significant differences in the proportion of violent suicides in the SSRI group compared with the antidepressant-free group by sex or age band (15-24, 25-39, and over 40 years). When subdivided by gender and age-bands, we found specific groups with significantly lower proportions of violent suicides compared with the antidepressants-free group, including men aged 15-24 years. © 2007 Lippincott Williams & Wilkins, Inc.

  • 3.
    Fazel, Seena
    et al.
    Univ Oxford, Dept Psychiat, Oxford, England.
    Grann, Martin
    Karolinska Inst, Ctr Violence Prevent, Stockholm, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Goodwin, Guy
    Univ Oxford, Dept Psychiat, Oxford, England.
    Letter: SSRI-induced violent suicide: Does forensic toxicology hold the answer? Reply to comments by Mr Carlin and Mr Hardisty2008In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 28, no 4, p. 477-477Article in journal (Other academic)
    Abstract [en]

    n/a

  • 4.
    Jones, Alan Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Holmgren, Anita
    National Board of Forensic Medicine, Linköping, Sweden.
    Amphetamine Abuse in Sweden: Subject Demographics, Changes in Blood Concentrations Over Time, and the Types of Coingested Substances2013In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 33, no 2, p. 248-252Article in journal (Refereed)
    Abstract [en]

    Amphetamine is a major drug of abuse in Sweden and in the other Nordic countries. The demographics of amphetamine abusers in Sweden and the concentrations of this stimulant in blood are reported for 10 years of forensic blood samples (2001-2010). Using a forensic toxicology database (TOXBASE), we studied 1183 amphetamine-related deaths, 20,452 users of illicit drugs, and 47,366 people arrested for driving under the influence of drugs (DUID). Most amphetamine abusers were male (82%-87%), and their average age was 33 to 39 years with males being 2 to 3 years older than females (P andlt; 0.001). Mean (median) concentrations of amphetamine in blood were 1.25 (0.40) mg/L in autopsy cases, 0.61 (0.40) mg/L in users of illicit drugs, and 0.76 (0.58) mg/L in DUID suspects. Median concentration in DUB) suspects was significantly higher than in the other forensic materials (P andlt; 0.001). Women also had higher median concentrations of amphetamine in blood than male abusers of this central stimulant (P andlt; 0.001). The major coingested drugs were benzodiazepines (41%), cannabis (26%), opiates (21%), and alcohol (18%) in autopsy cases. Polydrug use was less common in DUID suspects and users of illicit drugs, although benzodiazepines (13%), tetrahydrocannabinol (12%), and opiates (5%) were often identified along with amphetamine. Because median concentration of amphetamine was higher in living subjects (DUID suspects) compared with amphetamine-related deaths, this points toward toxicity of coingested drugs or adverse drug-drug interaction as being responsible for death.

  • 5.
    Kallen, Bengt
    et al.
    Lund University, Sweden .
    Reis, Margareta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Neonatal Complications After Maternal Concomitant Use of SSRI and Other Central Nervous System Active Drugs During the Second or Third Trimester of Pregnancy2012In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 32, no 5, p. 608-614Article in journal (Refereed)
    Abstract [en]

    Drugs acting on the central nervous system(CNS) and given to a pregnant woman during the latter part of pregnancy may affect neonatal morbidity of the infant. Little is known on the combined effects of different categories of such drugs. The redeeming of prescriptions for CNS-active drugs during the second or third trimester of pregnancy was studied by linkage between a register of prescribed drugs and the Swedish Medical Birth Register for the deliveries during 2006-2008 (n - 15,045 live-born infants). Neonatal morbidity was defined as the presence of neonatal diagnoses of respiratory problems, hypoglycemia, convulsions, or other CNS pathologic abnormalities including intraventricular hemorrhage, or low 5-minute Apgar score. The risk of such neonatal morbidity after maternal use of selective serotonin reuptake inhibitors (SSRIs) with or without other CNS-active drugs were evaluated as odds ratios or risk ratios, comparing with unexposed infants or infants only exposed to SSRI drugs. An increased risk for neonatal morbidity was seen for most studied groups of CNS-active drugs when used alone. Benzodiazepines seemed to have a stronger effect than other sedatives/hypnotics. The combination of SSRIs with 1 or more other CNS-active drug groups increased the risk for neonatal morbidity. This was seen for all types of sedatives/hypnotics, which may suggest a confounding by indication. Polypharmacy with CNS-active drugs during the later part of the pregnancy seems to increase the occurrence of neonatal morbidity but difference in nature or strength of underlying psychiatric pathology may confound the findings.

  • 6.
    Mao, Mao
    et al.
    Uppsala University.
    Skogh, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Scordo, Maria Gabriella
    Uppsala University.
    Dahl, Marja-Liisa
    Karolinska University.
    Letter: Interindividual Variation in Olanzapine Concentration Influenced by UGT1A4 L48V Polymorphism in Serum and Upstream FMO Polymorphisms in Cerebrospinal Fluid2012In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 32, no 2, p. 287-289Article in journal (Other academic)
    Abstract [en]

    n/a

  • 7.
    Reis, Margareta
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Akerblad, Ann-Charlotte
    Uppsala University.
    Ekselius, Lisa
    Uppsala University.
    von Knorring, Lars
    Uppsala University.
    Letter: Partial Compliance as Determined From Plasma Levels of Sertraline and Its Metabolite in Depressed Patients in Primary Care2010In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 30, no 6, p. 746-748Article in journal (Other academic)
    Abstract [en]

    n/a

  • 8.
    Reis, Margareta
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Kallen, B.
    Maternal use of antipsychotics in early pregnancy and delivery outcome.2008In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 28, no 3, p. 279-288Article in journal (Refereed)
    Abstract [en]

    The effect of various antipsychotics during pregnancy has repeatedly been studied, but for most atypical antipsychotics, only little information is available. We identified from the Swedish Medical Birth Register 2908 women who had reported the use of any antipsychotic or lithium in early pregnancy and studied malformation rates with data also from the Register of Congenital Malformations and the Hospital Discharge Register. Comparisons were made with all births (n = 958,729) after adjustment for some confounders. Risks were expressed as odds ratios (ORs).Most women had used dixyrazine or prochlorperazine mainly because of nausea and vomiting in early pregnancy. Seventy-nine women had used lithium, and these outcomes are reported separately. Hence, the main analysis was restricted to 570 women (576 infants) using other antipsychotics. There was a statistically significant increase in the risk for a congenital malformation-after exclusion of some common and minor conditions, the OR was 1.52 (95% confidence interval, 1.05-2.19). Exclusion of infants exposed to anticonvulsants reduced the OR only slightly. Most of the increased risk was caused by cardiovascular defects, mainly atrium or ventricular septum defect. No certain drug specificity was found. Except for an increased risk for congenital malformations, a nearly doubling of the risk for gestational diabetes and a 40% increased risk for cesarean delivery was noted. Because there seems to be little drug specificity, it is possible that underlying pathology or unidentified confounding explains the excess risk.

  • 9.
    Reis, Margareta
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Olsson, Gunilla
    Division of Child and Adolescence Psychiatry, Department of Neuroscience, Uppsala University, Uppsala.
    Carlsson, Björn
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lundmark, Jöns
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Dahl, Marja-Liisa
    Clinical Pharmacology, Department of Medical Sciences, Uppsala University, Uppsala.
    Wålinder, Jan
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Finn
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Serum levels of citalopram and its main metabolites in adolescent patients treated in a naturalistic clinical setting2002In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 22, no 4, p. 406-413Article in journal (Refereed)
    Abstract [en]

    The prescribing of selective serotonin reuptake inhibitors for adolescents is extensive despite the fact that there are few pharmacokinetic (PK), effi]cacy, safety, or tolerability studies on this group. This study reports the PK findings from two trials in adolescents treated with citalopram (CIT) in naturalistic clinical settings: one retrospective and one prospective. The aim of our study was to describe serum concentrations of CIT, desmethylcitalopram (DCIT), and didesmethylcitalopram (DDCIT) (trough values in steady state) in adolescents in relation to daily dose and clinical information obtained from therapeutic drug monitoring request forms. Altogether, 44 patients younger than 21 years were scrutinized using this combined open-label approach. The main findings were that (1) there was a pronounced interindividual variability of serum CIT, DCIT, and DDCIT concentrations in all doses prescribed, in agreement with previous studies on adults; on correcting for dose, the coefficient of variance was about 50% for CIT, DCIT, and DDCIT; (2) the transformation of CIT to DCIT and of DCIT to DDCIT was similar within the dose range 20 to 60 mg/day; (3) there was a difference between the sexes on comparing the dose-corrected concentrations of CIT and DCIT, with girls presenting significantly higher values than boys; and (4) there was a strong dose-serum concentration relationship in three identified subgroups of adolescents: (a) nonsmokers (CIT, r 2 = 0.71; DCIT, r 2 = 0.81), (b) girls not taking oral contraceptives (CIT, r 2 = 0.75; DCIT, r 2 = 0.71,), and (c) girls in the last 14 days of the menstrual cycle (CIT, r 2 = 0.68; DCIT, r 2 = 0.64). In summary, the present study tentatively supports influences of sex, oral contraceptives, and smoking habits on the disposition of CIT in younger patients. Hence, future studies on CIT should assess these parameters.

  • 10.
    Skogh, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Sjödin, Ingemar
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Dahl, Marja-Liisa
    University Uppsala Hospital.
    High Correlation Between Serum and Cerebrospinal Fluid Olanzapine Concentrations in Patients With Schizophrenia or Schizoaffective Disorder Medicating With Oral Olanzapine as the Only Antipsychotic Drug2011In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 31, no 1, p. 4-9Article in journal (Refereed)
    Abstract [en]

    The primary aim of the present study was to investigate the relationship between steady state serum and cerebrospinal fluid (CSF) concentrations of olanzapine (OLA) and its metabolite 4-N-desmethylolanzapine (DMO) in patients with schizophrenia or schizoaffective disorder treated with oral OLA as the only antipsychotic drug. The influence of smoking, gender, age, as well as polymorphisms in cytochrome P450 CYP2D6, CYP1A2, and ABCB1 genes on the serum and CSF drug levels was also analyzed. Thirty-seven white outpatients (10 smokers and 27 nonsmokers) were included. From 29 of them, CSF was collected successfully. A strong correlation (Spearman rank correlation [r(s)] = 0.93; P = 0.05) was found between serum and CSF concentrations of OLA and a somewhat weaker correlation (r(s) = 0.5; P = 0.05) between those of DMO. The CSF concentrations of OLA and DMO were on average 12% and 16% of those in serum. Extensive metabolizers of CYP2D6 had higher (P = 0.05) daily doses than poor metabolizers when the influence of smoking was taken into account. Smokers had lower (P = 0.01) concentration-to-dose ratios of OLA in serum (mean, 2.23 ng/mL per mg vs 3.32 ng/mL per mg) and CSF (0.27 ng/mL per mg vs 0.41 ng/mL per mg) than nonsmokers. The concentration-to-dose ratio for serum DMO decreased with increasing age (r(s) = -0.41; P = 0.05). Carriers of ABCB1 1236T/2677T/3435T haplotype had higher serum (mean, 37.7 ng/mL vs 22.5 ng/mL; P = 0.035) and CSF (4.7 ng/mL vs 2.6 ng/mL; P = 0.018) OLA concentrations than patients without this haplotype. The present study shows a strong correlation between serum and CSF concentrations of OLA, indicating that concentrations of OLA in serum reflect those in CSF.

  • 11. Åberg-Wistedt, Anna
    et al.
    Ågren, Hans
    Ekselius, Lisa
    Bengtsson, Finn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Åkerblad, AC
    Sertraline versus paroxetine in major depression: Clinical outcome after six months of continuous therapy2000In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 20, no 6, p. 645-652Article in journal (Refereed)
    Abstract [en]

    Relatively little research is available comparing the efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) during continuation therapy. This investigation reports the differential effect of 6 months of treatment with sertraline versus paroxetine for symptoms of depression, quality of life, and personality outcomes. Outpatients with unipolar major depression (DSM-III-R) were randomly assigned to receive 24 weeks of double-blind treatment with flexible doses of paroxetine (20-40 mg) or sertraline (50-150 mg). Assessments included the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Scale, the Battelle Quality of Life Questionnaire, and the Structured Clinical Interview for DSM-III-R Personality Disorders screen questionnaire. One hundred seventy-six patients (mean age, 43 years, 64% female, baseline MADRS, 30.3) were treated with sertraline and 177 patients (mean age, 42 years, 71% female, MADRS, 30.7) with paroxetine. Antidepressant efficacy during continuation therapy was sustained, with only 2% of patients receiving sertraline and 9% of patients receiving paroxetine suffering a relapse. Continuation therapy resulted in a substantial conversion of responders during short-term treatment to full remission: remitter rates increased from 52% to 80% for sertraline and from 57% to 74% for paroxetine. The improvements in quality of life were related to a reduced depression score. SSRI treatment had significant beneficial effects on both categorical and dimensional measures of personality. A logistic regression analysis identified early response (25% reduction in MADRS scores at week 2) as the most important predictor of treatment response, whereas high severity, chronicity, and poor baseline quality of life had no effect. Both treatments were well-tolerated, with sertraline having a somewhat lower side effect profile. Sertraline and paroxetine demonstrated comparable efficacy during short-term and continuation therapy. Treatment was associated with significant improvement in quality of life and with reductions in axis II personality psychopathology.

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