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  • 51.
    Lundmark, Jöns
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Clinical and Pharmacological Aspects of Selective Serotonin Reuptake Inhibitors in the Treatment of Depression in Old Age2000Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Objective: The aim of the present thesis is to examine the pharmacokinetic and biochemical effects of the selective serotonin reuptake inhibitors (SSRIs) in the elderly.

    Background: Symptoms of depression are found in up to 15% of the elderly and the prevalence of major depression is reported to be about 3%. At present SSRIs are the pharmacological tools most frequently used for the treatment of depression. Patients in old age account for a relatively higher proportion of SSRI expenditures, although the elderly are seriously underrepresented in pharmacological studies and are increasingly susceptible to adverse drug events.

    Subjects and Methods: Serum concentrations of the SSRis fluoxetine, paroxetine, and sertraline in the elderly were compared to those in younger patients. Effects of paroxetine on cerebrospinal fiuid (CSF) monoamine concentrations were investigated. Influences of therapeutic drug monitoring (TDM) of citalopram, paroxetine, and sertraline on clinical dosing strategies and antidepressant drug costs during a 6-9-month follow-up were studied in depressed elderly patients. Various individual factors, including age, which may influence serum concentrations of fluoxetine and sertraline were evaluated using population TOM data.

    Results: lnterindividual serum concentration variations were pronounced irrespective of age. Compared to the variability between subjects, the intraindividual variability of fiuoxetine and sertraline serum concentrations was found to be low. In the elderly, fiuoxetine, paroxetine, and sertraline serum concentrations were higher than in younger patients. In the case of fluoxetine, gross obesity influenced serum concentrations and sertraline serum concentrations were lower in smokers than in non-smokers. In the case of paroxetine, nonlinear pharmacokinetics were observed in some subjects and paroxetine treatment influenced both serotonergic and noradrenergic neurotransmission, as indicated by 5-HIAA and MHPG concentrations in the CSF. TDM-supported SSRI clinical dosing was found to reduce the doses used and efficacy was sustained when observed during an open follow-up.

    Conclusions: The results reported in the present thesis emphasize the importance of conducting clinical and pharmacological research in the elderly in different phases of drug development. In the postmarketing phase, TOM databases provide important tools for the collection of new pharmacokinetic data from clinical populations and data important for the interpretation of population SS RI serum concentrations. TDM of the SSRis may support individual dose optimization, including assessments of drug compliance.

    Delarbeid
    1. Paroxetine: pharmacokinetic and antidepressant effect in the elderly
    Åpne denne publikasjonen i ny fane eller vindu >>Paroxetine: pharmacokinetic and antidepressant effect in the elderly
    Vise andre…
    1989 (engelsk)Inngår i: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 80, nr S350, s. 76-80Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    To evaluate the pharmacokinetic properties, efficacy, and tolerability of paroxetine in elderly depressed patients, a clinical study was set up - initially at Aalborg Psychiatric Hospital in Denmark, and subsequently at the University Hospital in Linköping, Sweden. A total of 21 patients with a median age of 72 years were included in the study. After a single dose of 20 or 30mg of paroxetine followed by two drug-free days, treatment continued with 20 or 30mg daily for seven weeks. The majority of patients showed a continuous reduction in their HAMD scores, starting in the second week of treatment. Paroxetine was well tolerated at the doses given, and side-effects were mostly mild and transient. Steady-state, pre-dose plasma levels of paroxetine showed considerable variability, and the median steady-state concentration was higher in elderly patients compared with data from a previous study in young volunteers. Elimination half-lives also showed variability between these elderly patients, but tended to be longer after cessation of multiple dosing than after a single dose. They also tended to be longer than in the young volunteers. The results of this study do not advocate reduced doses of paroxetine in the elderly, but further studies are warranted.

    Emneord
    elderly patients, depression, 5-HT uptake inhibitors, paroxetine, efficacy, tolerability, pharmacokinetics
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-79925 (URN)10.1111/j.1600-0447.1989.tb07177.x (DOI)
    Tilgjengelig fra: 2012-08-15 Laget: 2012-08-15 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    2. The effect of paroxetine on cerebrospinal fluid concentrations of neurotransmitter metabolites in depressed patients
    Åpne denne publikasjonen i ny fane eller vindu >>The effect of paroxetine on cerebrospinal fluid concentrations of neurotransmitter metabolites in depressed patients
    Vise andre…
    1994 (engelsk)Inngår i: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 4, nr 1, s. 1-6Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    This paper describes the effect of the selective serotonin reuptake inhibiting drug (SSRI), paroxetine, on cerebrospinal fluid concentrations of neurotransmitter metabolites in depressed patients. 5-Hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were measured at baseline and after 3 weeks of treatment with 30 mg paroxetine daily. In line with similar studies on other SSRIs, influence on both the serotonin and noradrenaline metabolite was found. The mechanism behind the action of paroxetine on both 5-HIAA and MHPG is assumed to be an expression of the linkage between the serotonergic and noradrenergic systems in the brain. A frequently reported correlation between 5-HIAA and HVA was also found. The analysis of paroxetine in CSF proves the transportation of the drug into the central nervous system.

    Emneord
    Cerebrospinal fluid, Serotonin, Selective serotonin reuptake inhibitors, Paroxetine, Major depression
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-79926 (URN)10.1016/0924-977X(94)90308-5 (DOI)7515737 (PubMedID)
    Tilgjengelig fra: 2012-08-15 Laget: 2012-08-15 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    3. Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients
    Åpne denne publikasjonen i ny fane eller vindu >>Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients
    Vise andre…
    2000 (engelsk)Inngår i: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 101, nr 5, s. 354-359Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective: This study was initiated in order to describe and evaluate the effects of a therapeutic drug monitoring (TDM) routine of selective serotonin reuptake inhibitors (SSRIs) on treatment strategies and drug costs in depressed elderly patients.

    Method: Blood samples were drawn from elderly depressed patients and analysed for steady-state trough serum concentrations of citalopram (n=48), paroxetine (n=48) or sertraline (n=39). A global efficacy evaluation was made at baseline and after 6–9 months. Antidepressant drug costs before and after TDM were estimated.

    Results: Eight samples were excluded due to technical problems or non-compliance. In 65 of the 127 (51.2%) remaining cases, the treatment strategy was changed according to the TDM outcome, in most a reduction of the prescribed dose. Bioanalytical TDM costs included the antidepressant drug costs after TDM were reduced by 10.2%.

    Conclusion: The results support the utility of TDM in the search for the individual minimum effective SSRI dose in the elderly.

    Emneord
    antidepressants, serotonin uptake inhibitors, pharmacokinetics, pharmaceutical economics, depression
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-27667 (URN)10.1034/j.1600-0447.2000.101005354.x (DOI)12405 (Lokal ID)12405 (Arkivnummer)12405 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Therapeutic drug monitoring of sertraline: Variability factors as displayed in a clinical setting
    Åpne denne publikasjonen i ny fane eller vindu >>Therapeutic drug monitoring of sertraline: Variability factors as displayed in a clinical setting
    2000 (engelsk)Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 22, nr 4, s. 446-454Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    This report describes sertraline pharmacokinetics derived from routine therapeutic drug monitoring (TDM) data. A high-performance liquid chromatographic method with ultraviolet detection was established for routine sertraline TDM, and 924 analyses were performed from April 1995 to May 1997. Extensive predefined inclusion/exclusion criteria were applied to increase the validity of scientifically evaluated data. Subsequently, 605 samples (65.5%) were excluded. The remaining 319 samples from 319 patients, representative of steady state through specimens and accompanied by essential clinical information provided on request forms, were scrutinized. A pronounced interindividual variability was observed. Smokers had significantly lower concentration-to-dose (C/D) mean ratios of serum sertraline (s-sert) and its main metabolite desmethylsertraline (s-dsert) than nonsmokers. Higher s-sert and s-dsert C/D mean ratios were found in elderly patients than in adults aged less than 65 years. In a subset of 20 patients in whom repeated TDM analyses were performed, observed intraindividual sertraline TDM outcome variability was low. The results highlight sertraline TDM as a tool for individual dose optimization and evaluation of patient drug compliance as well as drug-drug interactions.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-27666 (URN)10.1097/00007691-200008000-00014 (DOI)12404 (Lokal ID)12404 (Arkivnummer)12404 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    5. Serum concentrations of fluoxetine in the clinical treatment setting
    Åpne denne publikasjonen i ny fane eller vindu >>Serum concentrations of fluoxetine in the clinical treatment setting
    2001 (engelsk)Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 23, nr 2, s. 139-147Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    This article discusses fluoxetine serum concentrations as displayed in a clinical setting. A racemic serum fluoxetine and norfluoxetine high-performance liquid chromatography method, including ultraviolet light detection, was used for routine therapeutic drug monitoring (TDM) purposes. In all, 508 samples were analyzed. For the scientific investigation, predefined inclusion and exclusion criteria were applied and 150 samples representative of trough values in steady-state conditions with essential clinical information provided on the assay request forms were evaluated. Fluoxetine plus norfluoxetine concentration-to-dose (C/D) ratio showed Gaussian distribution. Interindividual coefficients of variation of fluoxetine and norfluoxetine serum concentrations after different doses were found to be 40-63%. Intraindividual fluoxetine TDM variability was low. The Spearman rank correlation coefficient for fluoxetine and norfluoxetine C/D ratios in first and second samples was 0.68. Minor increases in norfluoxetine C/D and fluoxetine plus norfluoxetine C/D ratios were found in elderly patients compared with younger adult patients. A higher body-mass index was associated with minor decreases in fluoxetine and fluoxetine plus norfluoxetine C/D ratios. New fluoxetine pharmacokinetic data are added to the results from earlier phases of drug development. Moreover, the results of this study support the usefulness of a fluoxetine TDM procedure for individual dose optimization, detection of drug interactions, and assessments of patient compliance.

    Emneord
    Therapeutic drug monitoring, serum concentration, selective serotonin reuptake inhibitors, fluoxetine, elderly
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-27660 (URN)10.1097/00007691-200104000-00008 (DOI)12398 (Lokal ID)12398 (Arkivnummer)12398 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
  • 52.
    Lundmark, Jöns
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Depression hos äldre.1999Inngår i: Nordisk geriatrik, ISSN 1403-2082, Vol. 2, s. 29-30Artikkel i tidsskrift (Fagfellevurdert)
  • 53.
    Lundmark, Jöns
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Äldrepsykiatrin inventerad i Sverige.2000Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 97, s. 2976-2980Artikkel i tidsskrift (Annet vitenskapelig)
  • 54.
    Lundmark, Jöns
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Nordin, Conny
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Reis, Margareta
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Wålinder, Jan
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients2000Inngår i: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 101, nr 5, s. 354-359Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: This study was initiated in order to describe and evaluate the effects of a therapeutic drug monitoring (TDM) routine of selective serotonin reuptake inhibitors (SSRIs) on treatment strategies and drug costs in depressed elderly patients.

    Method: Blood samples were drawn from elderly depressed patients and analysed for steady-state trough serum concentrations of citalopram (n=48), paroxetine (n=48) or sertraline (n=39). A global efficacy evaluation was made at baseline and after 6–9 months. Antidepressant drug costs before and after TDM were estimated.

    Results: Eight samples were excluded due to technical problems or non-compliance. In 65 of the 127 (51.2%) remaining cases, the treatment strategy was changed according to the TDM outcome, in most a reduction of the prescribed dose. Bioanalytical TDM costs included the antidepressant drug costs after TDM were reduced by 10.2%.

    Conclusion: The results support the utility of TDM in the search for the individual minimum effective SSRI dose in the elderly.

  • 55.
    Lundmark, Jöns
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Geriatrik. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Gunnarsson, Tove
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    A possible interaction between lithium and rofecoxib [1]2002Inngår i: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 53, nr 4, s. 403-404Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    [No abstract available]

  • 56.
    Lundmark, Jöns
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Reis, Margareta
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Serum concentrations of fluoxetine in the clinical treatment setting2001Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 23, nr 2, s. 139-147Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This article discusses fluoxetine serum concentrations as displayed in a clinical setting. A racemic serum fluoxetine and norfluoxetine high-performance liquid chromatography method, including ultraviolet light detection, was used for routine therapeutic drug monitoring (TDM) purposes. In all, 508 samples were analyzed. For the scientific investigation, predefined inclusion and exclusion criteria were applied and 150 samples representative of trough values in steady-state conditions with essential clinical information provided on the assay request forms were evaluated. Fluoxetine plus norfluoxetine concentration-to-dose (C/D) ratio showed Gaussian distribution. Interindividual coefficients of variation of fluoxetine and norfluoxetine serum concentrations after different doses were found to be 40-63%. Intraindividual fluoxetine TDM variability was low. The Spearman rank correlation coefficient for fluoxetine and norfluoxetine C/D ratios in first and second samples was 0.68. Minor increases in norfluoxetine C/D and fluoxetine plus norfluoxetine C/D ratios were found in elderly patients compared with younger adult patients. A higher body-mass index was associated with minor decreases in fluoxetine and fluoxetine plus norfluoxetine C/D ratios. New fluoxetine pharmacokinetic data are added to the results from earlier phases of drug development. Moreover, the results of this study support the usefulness of a fluoxetine TDM procedure for individual dose optimization, detection of drug interactions, and assessments of patient compliance.

  • 57.
    Lundmark, Jöns
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Reis, Margareta
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Therapeutic drug monitoring of sertraline: Variability factors as displayed in a clinical setting2000Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 22, nr 4, s. 446-454Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This report describes sertraline pharmacokinetics derived from routine therapeutic drug monitoring (TDM) data. A high-performance liquid chromatographic method with ultraviolet detection was established for routine sertraline TDM, and 924 analyses were performed from April 1995 to May 1997. Extensive predefined inclusion/exclusion criteria were applied to increase the validity of scientifically evaluated data. Subsequently, 605 samples (65.5%) were excluded. The remaining 319 samples from 319 patients, representative of steady state through specimens and accompanied by essential clinical information provided on request forms, were scrutinized. A pronounced interindividual variability was observed. Smokers had significantly lower concentration-to-dose (C/D) mean ratios of serum sertraline (s-sert) and its main metabolite desmethylsertraline (s-dsert) than nonsmokers. Higher s-sert and s-dsert C/D mean ratios were found in elderly patients than in adults aged less than 65 years. In a subset of 20 patients in whom repeated TDM analyses were performed, observed intraindividual sertraline TDM outcome variability was low. The results highlight sertraline TDM as a tool for individual dose optimization and evaluation of patient drug compliance as well as drug-drug interactions.

  • 58. Nilsson, Linda K
    et al.
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Jönsson, Erik G
    Engberg, Göran
    Linderholm, Klas R
    Erhardt, Sophie
    Cerebrospinal fluid kynurenic acid in male and female controls - Correlation with monoamine metabolites and influences of confounding factors2007Inngår i: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 41, nr 1-2, s. 144-151Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The concentrations of the tryptophan metabolite kynurenic acid (KYNA) and the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were determined in the cerebrospinal fluid (CSF) from 43 healthy volunteers (30 males and 13 females). Healthy female controls displayed higher CSF concentration of KYNA (1.91 nM ± 0.20) compared to healthy male controls (1.06 nM ± 0.07) and lower CSF levels of HMPG (39.2 nM ± 2.0 and 43.4 ± 1.2, respectively). CSF levels of HVA and 5-HIAA did not differ between females (181.3 nM ± 21.9 and 93.7 nM ± 11.4, respectively) and males (138.9 nM ± 12.6 and 74.8 nM ± 5.9, respectively). Positive intercorrelations were found between CSF KYNA, HVA and 5-HIAA while CSF content of HMPG did not correlate with KYNA or the other monoamine metabolites in CSF. A negative correlation was found between back length and CSF concentrations of KYNA, HVA and 5-HIAA and also between CSF KYNA levels and body height. The results of the present study suggest that concentrations of KYNA and the monoamine metabolites in CSF from healthy controls are dependent on gender and back length, which must be taken in consideration when analysing mixed groups of men and women. The higher KYNA concentration found in female controls compared to male might be attributed to a shorter back in women compared to men. Furthermore, these findings suggest that increased KYNA formation is associated with an increased dopamine and serotonin turnover. © 2005 Elsevier Ltd. All rights reserved.

  • 59. Nilsson-Todd, Linda K
    et al.
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Jönsson, Erik G
    Skogh, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Erhardt, Sophie
    Cerebrospinal fluid kynurenic acid in male patients with schizophrenia - Correlation with monoamine metabolites2007Inngår i: Acta Neuropsychiatrica, ISSN 0924-2708, E-ISSN 1601-5215, Vol. 19, nr 1, s. 45-52Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The tryptophan metabolite kynurenic acid (KYNA) is an endogenous glutamate/nicotinic receptor antagonist. Previous studies have shown that the concentration of the compound is increased in cerebrospinal fluid (CSF) of patients with schizophrenia. Furthermore, it has been found that the CSF concentration of KYNA is positively correlated to CSF concentrations of the monoamine metabolites homovanillic acid (HVA) and 5-hydroxy indoleacetic acid (5-HIAA) in healthy control subjects. Objectives: To study the correlations between KYNA and the monoamine metabolites HVA, 5-HIAA and 4-hydroxy-3- methoxyphenylglycol (HMPG) in CSF of male patients (n = 53, ranging from 20 to 48 years of age) with verified schizophrenia. Methods: CSF was obtained by lumbar puncture, and KYNA analysis was performed with an isocratic reversed-phase high-performance liquid chromatography system connected to a fluorescence detector. HVA, 5-HIAA and HMPG concentrations were measured by mass fragmentography with deuterium-labelled internal standards. Results: Positive intercorrelations were found between CSF KYNA, HVA and 5-HIAA, while CSF content of HMPG did not correlate to KYNA or any of the monoamine metabolites in CSF. Conclusion: The results of this study suggest that increased KYNA formation is associated with an increased dopamine and serotonin turnover in male patients with schizophrenia. © 2007 Blackwell Munksgaard.

  • 60.
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    De psykiatriska tvångslagarna: Olustigt med livstestamenten vid återinsjuknande i psykos.2000Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 97, s. 3295-3295Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 61.
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Kapitel 14 - Psykiska störningar.2001Inngår i: Trafikmedicin / [ed] Mariann Almgren; Lars Englund; Sarah Kers, Linköping: Linköpings universitet , 2001, 1, s. 156-160Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 62.
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Kommentar till Torbjörn Tännsjös artikel om "allvarlig psykisk störning". Ett nödvändigt om än ej tillräckligt bidrag till debatten.2000Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 97, s. 2994-2994Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 63.
    Nordin, Conny
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Dahl, Marja-Liisa
    Uppsala.
    Eklundh, Thomas
    KI .
    Eriksson, Mats
    KI .
    Sjöberg, Stefan
    KI .
    CSF taurine level is influenced by plasma cholesterol and the CYP2D6 phenotype2003Inngår i: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 13, nr 5, s. 333-335Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Eight healthy male volunteers, lumbar-punctured before and during simvastatin treatment, were phenotyped for CYP2D6 analysis of the debrisoquine metabolic ratio (the ratio between the urinary recovery of debrisoquine and its 4-hydroxy metabolite) after a single oral dose of debrisoquine. The mean cerebrospinal fluid concentrations of cholesterol and taurine did not differ before and during treatment. During (but not before) treatment taurine in the CSF correlated with the debrisoquine metabolic ratio (r=-0.93, P=0.0007) Our results might indicate an influence of CYP2D6 on the level of taurine in the CSF that was secondary to the change in plasma cholesterol. ⌐ 2003 Elsevier B.V./ECNP. All rights reserved.

  • 64.
    Nordin, Conny
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Eklundh, Thomas
    Altered CSF 5-HIAA disposition in pathologic male gamblers.1999Inngår i: CNS Spectrums, ISSN 1092-8529, E-ISSN 2165-6509, Vol. 4, s. 25-33Artikkel i tidsskrift (Fagfellevurdert)
  • 65.
    Nordin, Conny
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Eklundh, Thomas
    Eriksson, Mats
    Sjöberg, Stefan
    CSF collection time at lumbar puncture is influenced by plasma cholesterol and triglycerides2001Inngår i: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 43, nr 1, s. 19-22Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It is a fairly well-known fact that the CSF collection time (tapping time) at lumbar puncture may influence CSF levels of monoamine compounds (e.g. the serotonin metabolite 5-hydroxyindoleacetic acid, 5-HIAA) and some neuropeptides. Since serum levels of cholesterol and triglycerides and low CSF levels of 5-HIAA have been linked to violent behaviour and impulsivity, we investigated retrospectively whether serum cholesterol and triglycerides affect CSF collection time. The series consists of 14 healthy males lumbar punctured at the L4-5 level. We found that both serum cholesterol and serum triglycerides influenced the CSF collection time for 12 ml of CSF (R = 0.77, p = 0.0067). There was no correlation between cholesterol in serum and CSF, nor between cholesterol in the CSF and collection time. However, we accidentally found a correlation between cholesterol in the CSF and age. The proposed hypothesis tries to explain why cholesterol- and triglyceride-rich lipoprotein particles modify the CSF collection time and influence endothelial function with a subsequent effect on CSF production and/or intraspinal pressure. Thus, it may be of interest to pay attention to serum cholesterol and triglycerides, their effect on CSF collection time and, in the next step, their putative impact on levels of various compounds in the CSF. Copyright ⌐ 2001 S. Karger AG, Basel.

  • 66.
    Nordin, Conny
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Gupta, Ramesh
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan.
    Sjödin, Ingemar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Cerebrospinal fluid amino acids in pathological gamblers and healthy controls2007Inngår i: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 56, nr 2-3, s. 152-158Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amino acids, such as valine, isoleucine and leucine compete with tyrosine and tryptophan for transport into the brain and might thus affect the central serotonin and catecholamine patterns. Furthermore, the excitatory amino acids glutamic acid, aspartic acid and glycine are known to act on the N-methyl-D-aspartate receptor, which is part of the reward system. Based on these facts, we have explored the role of cerebrospinal fluid (CSF) amino acids in pathological gambling. Concentrations of amino acids were determined in CSF obtained from one female and 11 pathological male gamblers and 11 healthy male controls. In an ANCOVA with best subset regression, pathological male gamblers had higher CSF levels of the excitatory glutamic and aspartic acids, as well as of phenylalanine, isoleucine, citrulline and glycine. A negative contribution of glycine in interaction with the neuraxis distance might mirror a reduced spinal supply or an altered elimination of glycine in pathological gamblers. A decreasing CSF gradient from the first (0-6 ml) to the third (13-18 ml) CSF fraction was found for glutamic acid, glycine, leucine, isoleucine, lysine, ornithine and glutamine in both pathological gamblers and healthy controls. A decreasing gradient was found, however, for aspartic acid and phenylalanine in pathological male gamblers. The altered pattern of CSF amino acids in pathological gamblers might exert an influence on central monoamines as well as on N-methyl-D-aspartate receptor function. Copyright © 2008 S. Karger AG.

  • 67.
    Nordin, Conny
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Nylander, Per-Olof
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri.
    Temperament and character in pathological gambling2007Inngår i: Journal of Gambling Studies, ISSN 1050-5350, E-ISSN 1573-3602, Vol. 23, nr 2, s. 113-120Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: We have studied temperament and character in pathological gambling (PG). Methods: Thirty-eight DSM-IV verified pathological gamblers (31 males and 7 females, mean age 35.4 ± 10.4 years) were tested with Cloninger's Temperament and Character Inventory (TCI). Matched controls were chosen from the normal population. Results: Pathological gamblers scored higher on the temperament factors novelty seeking (NS) and harm avoidance (HA). The most pronounced difference was found in the character factor self-directedness (SD). The pathological gamblers differed from controls in cooperativeness and self-transcendence. A personality disorder was found in 29% of the pathological gamblers 84% of whom scored either low on SD and high on impulsivity or had a more dishonest behaviour. Two-thirds of pathological gamblers showed immature character with or without high HA in temperament. The other third showed normal-character extravagant behaviour (86%), high impulsivity (36%) and less responsibility (50%) being the most common personality traits. Conclusion: HA and NS might be trait-like characteristics in PG. © 2007 Springer Science+Business Media, Inc.

  • 68.
    Nordin, Conny
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Sjödin, Ingemar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    CSF cholecystokinin, γ-aminobutyric acid and neuropeptide Y in pathological gamblers and healthy controls2007Inngår i: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 114, nr 4, s. 499-503Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The sulphated cholecystokinin (CCK) octapeptide (CCK-8S), the CCK tetrapeptide (CCK-4), neuropeptide Y (NPY) and γ-aminobutyric acid (GABA) were determined in cerebrospinal fluid (CSF) obtained from 11 pathological male gamblers and 11 healthy male controls. Compared with healthy controls, pathological male gamblers displayed higher concentrations of CCK-8S, CCK-4 and GABA (but not NPY). A gradient with decreasing concentrations from the first to the third 6-ml CSF fraction was found for CCK-8S, CCK-4 and NPY, but only in pathological gamblers. Disrupted gradients were found for GABA and for NPY in healthy controls. Given that CCK is a modulator of dopamine in the reward process, the increase in CCK-8S and CCK-4 is not unexpected. The high level of GABA in pathological gamblers is in conformity with a compensatory inhibitory action on noradrenergic neurons. The CSF gradient of CCK-8S and CCK-4 in pathological male gamblers (but not healthy controls) might indicate a difference in diurnal variation. The results obtained are in line with an altered CCK and GABA function in pathological gambling. © 2006 Springer-Verlag.

  • 69.
    Nordin, Conny
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Sjödin, Ingemar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    CSF monoamine patterns in pathological gamblers and healthy controls2006Inngår i: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 40, nr 5, s. 454-459Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous reports on compounds in the cerebrospinal fluid (CSF) of pathological gamblers have focused on disturbed NA, DA and 5-HT function in the central nervous system. We have analysed precursors, transmitters and transmitter metabolites in 3 × 6 ml of CSF obtained from one female and 11 male pathological gamblers and 11 healthy male controls lumbar punctured at the L4-5 level after 8 h of fasting without preceding strict bedrest. Pathological gamblers displayed lower CSF levels of tryptophan and 5-HT while the opposite was the case for 5-HIAA, tyrosine, DA, HVA, DOPAC and HMPG. In contrast to previous studies, the NA level did not differ between pathological gamblers and healthy controls. A disrupted CSF gradient was noted for tryptophan, 5-HT, DA, HVA, DOPAC, NA and HMPG, but only in pathological gamblers. A disrupted gradient was found for 5-HIAA in both pathological gamblers and healthy controls. The results are in line with the presence of altered indoleamine and cathecholamine function in pathological gamblers as well as an altered CSF transport from the brain to the lumbar compartment in such gamblers. © 2005 Elsevier Ltd. All rights reserved.

  • 70.
    Nordin, Conny
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Sjödin, Ingemar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Letter: Altered CSF taurine function in pathological gambling2006Inngår i: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 40, nr 5, s. 473-474Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    [No abstract available]

  • 71.
    Nordin, Conny
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Sjödin, Ingemar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Letter: Reduced free tri-iodothyronine serum levels are lower in pathological male gamblers than in healthy male controls2005Inngår i: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 39, nr 4, s. 449-Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    [No abstract available]

  • 72. Oreland, Lars
    et al.
    Garpenstrand, H
    Damberg, M
    Alm, Per-Olof
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Thorell, Lars-Håkan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    af Kinteberg, B
    The correlation between platelet MAO activity and personality - the effect of smoking and possible mechanisms behind the correlation.1999Inngår i: Neurobiology (Copenhagen), ISSN 0300-8819, Vol. 7, s. 191-203Artikkel i tidsskrift (Fagfellevurdert)
  • 73.
    Orhagen, Tina
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Working with families in schizophrenic disorders: the practice of psychoeducational intervention1992Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Psychoeducational intervention including educational courses for relatives and individual family sessions was carried out with relatives of patients suffering from schizophrenic disorders. Relatives' Expressed Emotion (BE), amount of illness-related knowledge, burden of care, and satisfaction with the intervention were assessed.

    Relatives' measures of BE (critical remarks, hostility, emotional overinvolvement) and the general BE index decreased significantly after the complete intervention, comprising educational courses for relatives from different families and, for a period of two years, individual family sessions with the participation of the patient. The number of relatives scoring high on the BE index, was significantly reduced after the initial educational courses. The interrater reliability of BE measures, assessed with the Swedish version of the Camberwell Family interview schedule and calculated on data from audiotaped interviews, was generally high.

    The amount of illness-related knowledge increased significantly after the multifamily educational courses. Gain in knowledge and high satisfaction with the intervention were associated with decrease of criticism towards the ill family member, and with relief of relatives' subjective burden. The relatives expressed an appreciative evaluation of the intervention and indicated the socializing and sharing of experiences with other relatives as a most valuable component.

    In the face of relatives' need for information about the illness, the diagnostic process of schizophrenia was studied. Retrospective analyses of case-records from 84 in-patients showed that schizophrenic disorders were ascertained as case-record diagnoses on average six years after the first contact with the mental health service. The findings suggest a propensity to include prolonged course and severe impairment of social functioning in the clinical concept of schizophrenia.

  • 74.
    Phol, Annika
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri.
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Clinical and biochemical observations during treatment of depression with electroacupuncture: A pilot study2002Inngår i: Human Psychopharmacology: Clinical and Experimental, ISSN 0885-6222, E-ISSN 1099-1077, Vol. 17, nr 7, s. 345-348Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Six patients suffering from major depression were treated with electroacupuncture. During 4 weeks of treatment, the total CPRS-S-A score decreased from 23.8 to 13.4 (p = 0.0095). A decrease of neuropeptide Y (NPY) in plasma during the first 2 weeks of treatment was noted in five of the patients, all being women (p = 0.0431). The decrease was negatively correlated with age (rs = -0.29, p = 0.046). The results are in line with a putative antidepressive effect of electroacupuncture, along with an influence on NPY in plasma. Copyright ⌐ 2002 John Wiley & Sons, Ltd.

  • 75.
    Pohl, Annika
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Body mass index influences plasma concentration of neuropeptide Y in healthy female volunteers: A pilot study2003Inngår i: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 17, nr 5, s. 409-412Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuropeptide Y (NPY) was measured in plasma obtained from healthy female volunteers twice in the natural menstrual cycle or the hormonal cycle caused by oral contraceptives about 2 weeks apart. The ratio between the NPY plasma concentration in the second sample and the first sample was influenced negatively by body mass index (BMI). There were no differences in NPY plasma concentrations on comparing the first and second samples. Age and the use or non-use of oral contraceptives did not exert any influence. BMI might be a confounding factor when determining NPY in the plasma of healthy women.

  • 76.
    Reis, Margareta
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Pharmacokinetics of antidepressant drugs: naturalistic and clinical trials2003Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Depression is a major public health problem and it is predicted to be the second leading cause of disease burden by the year 2020. The pharmacological treatment period for major depressive disorder (MDD) is relatively long and sometimes prophylactic over many years. Despite the many drugs introduced on this indication in recent years, details in the drug kinetics linked to the many possible clinical scenarios arising in phase-IV have not been adequately assessed.

    The main objective of this thesis was therefore to focus on the posology of the frequently prescribed antidepressant drugs citalopram (CIT), sertraline (SERT), paroxetine (PAR) and venlafaxine (VEN) in terms of trough level serum concentrations of the parent compound and metabolite(s) under steady state conditions. Therapeutic Drug Monitoring (TDM)-based bioanalytical data were to be linked to clinical information obtained on patients in naturalistic or controlled clinical trial phase-IV settings for evaluation of the inter- as well as intraindividual PK (pharmacokinetic) variance. Specific aims were to identifY and analyze subgroups with possibly deviating PK such as adolescents, elderly patients, and the differences between the sexes. From a controlled trial setting during a six months period a possible serum concentration-effect relationship should be searched for, as well as testing the applicability of a novel type ofTDM procedure based on the metabolite/parent compound ratio to explore both total and partial pharmacological noncompliance.

    Studies I-III were applied on the naturalistic TDM-based trial design. In brief, study I contained 44 adolescents treated with CIT. Study II evaluated trough values in steady state in 749 patients treated with CIT, and study III describes the same parameters for 187 patients treated with VEN. Results revealed that interindividual PK-variations were pronounced for all compounds on all dose levels, but the intraindividual variations were low. Adolescents seemed to have CIT values similar to adults, but old age was correlated with higher dose-corrected serum concentrations of both CIT and VEN. All studied compounds displayed differences between the sexes. Polypharmacy affected the metabolism of CIT and VEN as did smoking.

    Study IV contained 353 patients treated with SERT or PAR in a prospective, randomized multi-center trial with up to eight serum samples each over six months. In study V the TDM-based "compliance method" was tested on the SERT population from the study cohort. Results revealed that no serum concentration - clinical effect relationship could be found for either PAR or SERT. It was observed that the TDM compliance method seemed to detect not only total but also significant partial non-compliance.

    In conclusion, the present thesis describes the possibility for making further PK-assessments on antidepressant drugs commonly prescribed. Thus, by building up drug specific TDM databases in naturalistic clinical phase IV-trials, combined with a structured data analysis a detailed retrospective follow up on the PK of the drugs coming into play in real life emerged. Taken together with the PK-data obtained from a prospective, randomized trial, the overall significance of this thesis may be to forward a new strategy for TDM -related postmarketing surveillance studies. This strategy may also be of interest to explore for other psychoactive drugs as well as for other new drugs commonly used on lager patient groups on chronic medications but outside psychiatric indications.

    Delarbeid
    1. Serum levels of citalopram and its main metabolites in adolescent patients treated in a naturalistic clinical setting
    Åpne denne publikasjonen i ny fane eller vindu >>Serum levels of citalopram and its main metabolites in adolescent patients treated in a naturalistic clinical setting
    Vise andre…
    2002 (engelsk)Inngår i: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 22, nr 4, s. 406-413Artikkel i tidsskrift (Fagfellevurdert) Published
    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.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26736 (URN)10.1097/00004714-200208000-00012 (DOI)11331 (Lokal ID)11331 (Arkivnummer)11331 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Therapeutic drug monitoring of racemic citalopram: a 5-year experience in Sweden, 1992-1997
    Åpne denne publikasjonen i ny fane eller vindu >>Therapeutic drug monitoring of racemic citalopram: a 5-year experience in Sweden, 1992-1997
    2003 (engelsk)Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 25, nr 2, s. 183-191Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Racemic citalopram (CIT) was introduced in Sweden in 1992 for management of major depression. During a 5-year period, 1992 to 1997, serum samples of CIT and desmethylcitalopram (DCIT) were collected for therapeutic drug monitoring (TDM) from patients from all over Sweden. These samples were accompanied by clinical information on a specially designed TDM request form. They represented men and women of various ages (11-94 years) usually on multiple concomitant medications and treated in a naturalistic setting. The TDM samples eligible for evaluation (n = 749), all trough values at steady state, were studied with respect to inter- and intraindividual pharmacokinetic variability. Extensive, interindividual serum concentration variability was seen on all dose levels. For dose-corrected concentrations (C/D) and for clearance (C1) we found the coefficient of variation (CV) to be approximately 55% for all variables (C/D CIT, C/D DCIT, the ratio DCIT to CIT, and for C1 CIT). The intraindividual variations over time for the same parameters were 30% to 35%. On a population level, signs of a possible saturation of CYP2D6 associated with increasing DCIT-to-CIT ratios with increasing daily doses was observed. Age and gender affected the pharmacokinetics of CIT and DCIT. Women showed significantly higher C/D CIT and C/D DCIT and lower C1 CIT values compared with men, and patients aged more than 65 years had higher C/D CIT and C/D DCIT and lower C1 CIT values compared with younger patients. Finally, concomitant medication affected the outcome of serum concentrations by a general increase in C/D CIT and C/D DCIT but without alteration in the DCIT-to-CIT ratio. Thus, this tendency of changes in the CIT disposition when multiple drugs are used (and multiple diseases are prevailing?) seems more general in character than specific for a certain drug or type of drugs.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26797 (URN)10.1097/00007691-200304000-00007 (DOI)11405 (Lokal ID)11405 (Arkivnummer)11405 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Therapeutic drug monitoring of racemic venlafaxine and its main metabolites in an everyday clinical setting
    Åpne denne publikasjonen i ny fane eller vindu >>Therapeutic drug monitoring of racemic venlafaxine and its main metabolites in an everyday clinical setting
    2002 (engelsk)Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 24, nr 4, s. 545-553Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    When Efexor® (venlafaxine) became available in Sweden, a therapeutic drug monitoring (TDM) service was developed in the authors' laboratory. This analytical service was available to all physicians in the country. From March 1996, to November 1997, 797 serum concentration analyses of venlafaxine (VEN) and its main metabolites, O-desmethylvenlafaxine (ODV), N-desmethylvenlafaxine (NDV), and N,O-didesmethylvenlafaxine (DDV) were requested. These samples, each of which was accompanied by clinical information on a specially designed request form, represented 635 inpatients or outpatients, comprising all ages, treated in a naturalistic setting. The first sample per patient, drawn as a trough value in steady state and with documented concomitant medication, was further evaluated pharmacokinetically (n= 187). The doses prescribed were from 37.5 mg/d to 412.5 mg/d. There was a wide interindividual variability of serum concentrations on each dose level, and the mean coefficient of variation of the dose-corrected concentrations (C/D) was 166% for C/D VEN, 60% for C/D ODV, 151% for C/D NDV, and 59% for C/D DDV. The corresponding CV for the ratio ODV/VEN was 110%. However, within patients over time, the C/D VEN and ODV/VEN variation was low, indicating stability in individual metabolizing capacity. Patients over 65 years of age had significantly higher concentrations of C/D VEN and C/D ODV than the younger patients. Women had higher C/D NDV and C/D DDV, and a higher NDV/VEN ratio than men, and smokers showed lower C/D ODV and C/D DDV than nonsmokers. A number of polycombinations of drugs were assessed for interaction screening, and a trend for lowered ODV/VEN ratio was found, predominantly with concomitant medication with CNS-active drug(s) known to inhibit CYP2D6.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-27668 (URN)10.1097/00007691-200208000-00014 (DOI)12406 (Lokal ID)12406 (Arkivnummer)12406 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Serum disposition of sertraline, N-desmethylsertraline and paroxetine: a pharmacokinetic evaluation of repeated drug concentration measurements during 6 months of treatment for major depression
    Åpne denne publikasjonen i ny fane eller vindu >>Serum disposition of sertraline, N-desmethylsertraline and paroxetine: a pharmacokinetic evaluation of repeated drug concentration measurements during 6 months of treatment for major depression
    Vise andre…
    2004 (engelsk)Inngår i: Human Psychopharmacology: Clinical and Experimental, ISSN 0885-6222, E-ISSN 1099-1077, Vol. 19, nr 5, s. 283-291Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Sertraline and paroxetine are frequently prescribed SSRIs for long-term treatment of major depression. Nevertheless, continuous follow-ups of drug concentrations prevailing in patients during the whole treatment period are not available. Hence, in a large phase IV clinical trial, a total of 353 patients with major depression were enrolled for a 6-month comparison of sertraline (50–150 mg daily) and paroxetine (20–60 mg daily). The present study reports the pharmacokinetic results of up to eight serum samples per patient.

    1 A profound variability was found in the interindividual steady state and trough serum levels of sertraline, desmethylsertraline and paroxetine: the coefficient of variation (CV) was 59% for sertraline, 51% for desmethylsertraline, 27% for the ratio desmethylsertraline/sertraline (50 mg/day), and 71% for paroxetine (20 mg/day). The intraindividual CV for the ratio desmethylsertraline/sertraline was only 19%, indicating intraindividual metabolizing stability over time. Both sertraline and paroxetine displayed sex differences in the dose-concentration correlation.

    2 It was possible to predict sertraline, but not paroxetine, steady state levels.

    3 The terminal elimination t½ for both drugs after 6 months of treatments was similar to data previously reported from short-term withdrawal studies.

    4 No correlation between serum drug concentrations and clinical effect was detected for either sertraline or paroxetine.

    For the future, continuous efforts are warranted to perform PK investigations in the natural clinical setting in which the drugs are usually prescribed.

    Emneord
    sertraline, paroxetine, serum concentrations
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-23758 (URN)10.1002/hup.599 (DOI)3270 (Lokal ID)3270 (Arkivnummer)3270 (OAI)
    Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    5. Compliance with SSRI medication during 6 months of treatment for major depression: an evaluation by determination of repeated serum drug concentrations
    Åpne denne publikasjonen i ny fane eller vindu >>Compliance with SSRI medication during 6 months of treatment for major depression: an evaluation by determination of repeated serum drug concentrations
    Vise andre…
    2004 (engelsk)Inngår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 82, nr 3, s. 443-446Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: A recent estimation in a psychiatric cohort showed numbers of noncompliance between 10% and 60%. Therapeutic drug monitoring (TDM) is one method assessing compliance by analysis of drug concentration in the blood.

    Method: During a 24-week phase IV clinical trial, five repeated serum samples of sertraline (SERT) and N-desmethylsertraline (DSERT), trough values in steady state, were collected per patient. Previous results show that the intraindividual variation over time of the ratio DSERT/SERT is low. Hence, we hypothesized that significant partial noncompliance could be scrutinized further by an assessment of the DSERT/SERT ratio. The main aim was to test the applicability of a novel type of TDM procedure based on repeated metabolite/parent compound ratio measurements.

    Result: 9.4% of the per-protocol population in the trial (n=96) were in either hidden total (n=4) or hidden partial (n=5) noncompliance. Only by using the novel TDM ratio screening method could a majority of these patients be identified.

    Emneord
    SSRI, depression, sertraline
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-23759 (URN)10.1016/j.jad.2004.02.003 (DOI)3271 (Lokal ID)3271 (Arkivnummer)3271 (OAI)
    Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
  • 77.
    Reis, Margareta
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Lundmark, Jöns
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Therapeutic drug monitoring of racemic citalopram: a 5-year experience in Sweden, 1992-19972003Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 25, nr 2, s. 183-191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Racemic citalopram (CIT) was introduced in Sweden in 1992 for management of major depression. During a 5-year period, 1992 to 1997, serum samples of CIT and desmethylcitalopram (DCIT) were collected for therapeutic drug monitoring (TDM) from patients from all over Sweden. These samples were accompanied by clinical information on a specially designed TDM request form. They represented men and women of various ages (11-94 years) usually on multiple concomitant medications and treated in a naturalistic setting. The TDM samples eligible for evaluation (n = 749), all trough values at steady state, were studied with respect to inter- and intraindividual pharmacokinetic variability. Extensive, interindividual serum concentration variability was seen on all dose levels. For dose-corrected concentrations (C/D) and for clearance (C1) we found the coefficient of variation (CV) to be approximately 55% for all variables (C/D CIT, C/D DCIT, the ratio DCIT to CIT, and for C1 CIT). The intraindividual variations over time for the same parameters were 30% to 35%. On a population level, signs of a possible saturation of CYP2D6 associated with increasing DCIT-to-CIT ratios with increasing daily doses was observed. Age and gender affected the pharmacokinetics of CIT and DCIT. Women showed significantly higher C/D CIT and C/D DCIT and lower C1 CIT values compared with men, and patients aged more than 65 years had higher C/D CIT and C/D DCIT and lower C1 CIT values compared with younger patients. Finally, concomitant medication affected the outcome of serum concentrations by a general increase in C/D CIT and C/D DCIT but without alteration in the DCIT-to-CIT ratio. Thus, this tendency of changes in the CIT disposition when multiple drugs are used (and multiple diseases are prevailing?) seems more general in character than specific for a certain drug or type of drugs.

  • 78.
    Reis, Margareta
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Lundmark, Jöns
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Björk, Henrik
    Department of Clinical Pharmacology, Lund University, Lund, Sweden.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Therapeutic drug monitoring of racemic venlafaxine and its main metabolites in an everyday clinical setting2002Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 24, nr 4, s. 545-553Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    When Efexor® (venlafaxine) became available in Sweden, a therapeutic drug monitoring (TDM) service was developed in the authors' laboratory. This analytical service was available to all physicians in the country. From March 1996, to November 1997, 797 serum concentration analyses of venlafaxine (VEN) and its main metabolites, O-desmethylvenlafaxine (ODV), N-desmethylvenlafaxine (NDV), and N,O-didesmethylvenlafaxine (DDV) were requested. These samples, each of which was accompanied by clinical information on a specially designed request form, represented 635 inpatients or outpatients, comprising all ages, treated in a naturalistic setting. The first sample per patient, drawn as a trough value in steady state and with documented concomitant medication, was further evaluated pharmacokinetically (n= 187). The doses prescribed were from 37.5 mg/d to 412.5 mg/d. There was a wide interindividual variability of serum concentrations on each dose level, and the mean coefficient of variation of the dose-corrected concentrations (C/D) was 166% for C/D VEN, 60% for C/D ODV, 151% for C/D NDV, and 59% for C/D DDV. The corresponding CV for the ratio ODV/VEN was 110%. However, within patients over time, the C/D VEN and ODV/VEN variation was low, indicating stability in individual metabolizing capacity. Patients over 65 years of age had significantly higher concentrations of C/D VEN and C/D ODV than the younger patients. Women had higher C/D NDV and C/D DDV, and a higher NDV/VEN ratio than men, and smokers showed lower C/D ODV and C/D DDV than nonsmokers. A number of polycombinations of drugs were assessed for interaction screening, and a trend for lowered ODV/VEN ratio was found, predominantly with concomitant medication with CNS-active drug(s) known to inhibit CYP2D6.

  • 79.
    Reis, Margareta
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Olsson, Gunilla
    Division of Child and Adolescence Psychiatry, Department of Neuroscience, Uppsala University, Uppsala.
    Carlsson, Björn
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Lundmark, Jöns
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Dahl, Marja-Liisa
    Clinical Pharmacology, Department of Medical Sciences, Uppsala University, Uppsala.
    Wålinder, Jan
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Ahlner, Johan
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Bengtsson, Finn
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Serum levels of citalopram and its main metabolites in adolescent patients treated in a naturalistic clinical setting2002Inngår i: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 22, nr 4, s. 406-413Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 80. Richter, J
    et al.
    Brändström, Sven
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri.
    Emami, H
    Ghazonour, M
    Temperament and character in cross-cultural comparisons between Swedish and Iranian people and Iranian refugees in Sweden - Personality in transition?2004Inngår i: Collegium Antropologicum, ISSN 0350-6134, E-ISSN 1848-9486, Vol. 28, nr 2, s. 865-876Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of the study was a cross-cultural comparison of personality traits between individuals from two very different cultures and refugees who resettled several years before from one to the other. Four hundred forty four Swedish individuals of the normal population, and 100 Iranian refugees in Sweden, and a group of 335 individuals from Tehran, capital of Iran, were investigated by means of the Temperament and Character Inventory, a questionnaire to assess temperament and character. Iranians are those that are most frequently correctly classified followed by the Swedish based on temperament scores by means of a Discriminance analyses. Iranian refugees in Sweden were classified to about 50 per cent as Swedish and to slightly more then one-third as Iranians. Especially concerning character, 4 per cent only could be correctly classified as refugees. The results give some perspective on the adaptation process and personality changes in refugees several years after resettlement in another country with a complete different culture.

  • 81.
    Rosenqvist, U
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Törnqvist, M
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Therapeutic Drug Monitoring: An interaction between sertraline ana Carbamazepine which resulted in sub-therapeutic concentrations of sertraline and N-desmethyl.2003Inngår i: Skriv in din egen text för ej reg. tidskrift etc.,2003, 2003, s. 527-527Konferansepaper (Fagfellevurdert)
  • 82. Rousseau, A.
    et al.
    Petrén, S.
    Plannthin, J.
    Eklundh, Thomas
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Serum and cerebrospinal fluid concentrations of melatonin: a pilot study in healthy male volunteers.1999Inngår i: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 106, s. 883-888Artikkel i tidsskrift (Fagfellevurdert)
  • 83.
    Rousseau, Andreas
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Anestesiologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Sjödin, Ingemar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    ABC om Konfusion på somatisk vårdavdelning2004Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, s. 2270-2274Artikkel i tidsskrift (Annet vitenskapelig)
  • 84.
    Rutz, Wolfgang
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Evaluation of an educational program on depressive disorders given to general practitioners on Gotland: Short and long-term effects1992Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In the years 1983-1984, the Swedish Comittee for the Prevention and Treatment of Depression (PTD) offered an educational program to all general practitioners (GP:s) on the Swedish island of Gotland. 1982 was used as a baseline year. An evaluation of the short-term effects was made continuously until 1985. The long-term effects were followed 1985-1988. According to the immediate evaluation, 80% considered the practical applicability of the program to be high, and the GP:s achieved increasing competence and stringency in handling depressive states.

    The referrals to the local psychiatric unit decreased to 50% of those at baseline. The total in-patient days due to depressive disorders decreased as well as the average stay. The sick-leave consumption decreased by approximately 50%. In 1982, the prescription of antidepressants was low, 54% of that in the rest of Sweden. In 1985 the corresponding figure was 77%. The prescriptions of lithium remained stable while the prescriptions of sedatives and major tranquilizers decreased as compared to the rest of Sweden. The suicide  rate decreased relative to the trends on Gotland and in the rest of Sweden. During the long-term evaluation, the in-patient care for depressive disorders increased again and the suicidal rate returned almost to control values. The prescriptions of antidepressants stabilised. Thus, the effects were strictly time related to the educational program indicating real effects and not only coincidence with local trends on the island.

    In a cost-benefit analysis the costs for the educational programs, the changes in drug prescriptions and in in-patient care were evaluated as well as indirect costs concerning changes in morbidity and mortality. The results indicate that the PTD educational program on Gotland resulted in savings to the society in the order of about SEK 155 million (USD 26 million). It is concluded that educational programs of this kind should be repeated every second to third year.

  • 85. Rutz, Wolfgang
    et al.
    Wålinder, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Rhimer, Zoltan
    Pestality, P.
    Manlig depression - stressreaktion kombinerad med serotoninsvaghet?1999Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 96, s. 1177-1178Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 86.
    Samuelsson, Martin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Spelberoende - synen på behandlingsansvar och behandling2006Inngår i: Medicinska Riksstämman,2006, 2006, s. 86-86Konferansepaper (Annet vitenskapelig)
    Abstract [sv]

      

  • 87.
    Sjödin, Ingemar
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Kutcher, S.P.
    Canada.
    Ravindran, A
    Canada.
    Burt, T
    USA.
    Efficacy of sertraline in improving quality of life and functioning in generalized anxiety disorder (GAD)2003Inngår i: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 13, s. 365-366Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 88.
    Skogh, Elisabeth
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Could discontinuing smoking be hazardous for patients administered clozapine medication? A case report.1999Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 21, s. 580-582Artikkel i tidsskrift (Fagfellevurdert)
  • 89.
    Skogh, Elisabeth
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Reis, Margareta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri.
    Dahl, Marja-Liisa
    Lundmark, Jöns
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Geriatrik. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Therapeutic drug monitoring data on olanzapine and its N-demethyl metabolite in the naturalistic clinical setting2002Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 24, nr 4, s. 518-526Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Olanzapine (Zyprexa«) was approved for general prescription in Sweden in November 1996, and an HPLC-based therapeutic drug monitoring (TDM) routine for serum olanzapine (OLA) and its major metabolite, N-demethylolanzapine (DMO) was established in February 1997. During 1997 to 1999, a total of 753 TDM requests for a total of 545 Swedish patients was analyzed. Additional patient information on certain clinical variables was collected on specifically designed TDM request forms. After the exclusion process, samples from 194 patients were found to be eligible for further scrutiny. The concentration-to-dose (C/D) ratio for OLA varied 25-fold and that of DMO 22-fold. Women had a higher (P < 0.01) median C/D ratio for OLA than men (median, 7.2 nmol/L/mg vs 5.2 nmol/L/mg). Nonsmokers had a higher (P < 0.001) C/D ratio for OLA than smokers (median, 9,2 nmol/L/mg vs 4.0 nmol/L/mg). Smokers got higher prescribed (P < 0.05) doses of OLA than nonsmokers did. In the group with reported side effects, the median serum OLA concentration was 22% higher (P < 0.05) than in the group without side effects. Patients co-medicated with carbamazepine had a 71% lower median C/D ratio for OLA than patients on OLA monotherapy. The present TDM-based follow-up suggests that the influence of gender, smoking habits, and certain drug interactions may need to be considered for optimal dosage of OLA. TDM may be used for this purpose more readily in the future.

  • 90.
    Sparring Björkstén, Karin
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Neurobiological aspects on brain function in neuro-psychiatric patients and in healthy subjects1995Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The levels of insulin-like growth factor-2 (IGF-2) were assessed in lumbar cerebrospinal fluid (CSF) from children with various kinds of brain damage and from Alzheimer (AD) patients and controls. Whole CSF was separated using acid gel chromatography and the presence of insulin-like growth factor binding protein and two different kinds of free IGF-2 m the CSF was established. The levels of CSF-IGF-2 were higher in the new-born infants than in children aged 6 months - 4 years. This difference was ascribed the immature blood-brain barrier in infants. Older children had levels similar to those reported in adults. Children with hydrocephalus had very low levels of IGF-2. The levels ofiGF in unseparated CSF was similar in AD patients and controls.

    The relationship between CSF spaces and cognitive function was investigated in patients with AD and controls, using a low field magnetic resonance imaging (MRI) technique and psychometric tests. The AD patients had larger relative CSF volumes in all locations investigated. The greatest differences between the two groups were found in the volumes of the temporal horns. The CSF volumes in the basal parts of the brain correlated inversely with episodic memory tests. The relative volumes of the lateral ventricles correlated with the degree of dementia. It was concluded that measurements of the relative CSF volumes of the temporal horns by MRI might be a reliable diagnostic sign of AD as well as providing an estimation of the severity of the disease.

    Demented subjects with either a severely disorganised sleep-wake schedule or regular sleep habits underwent serial blood saropling. The subjects with disorganised sleep-wake schedules had disturbed circadian rhythms of plasma melatonin (MT) and cortisol, whereas those with regular sleep habits had normal plasma MT and cortisol profiles. An 82-year old lady with vascular dementia and a disturbed sleep-wake pattern improved her sleep and normalised plasma MT and cortisol patterns after the removal of a beta-adrenergic blocker, substitution of cobalamin deficiency and cataract surgery. A man with frontal lobe dementia who was assessed repeatedly showed inability to suppress MT as assessed by a light test. A disorganised sleep-wake cycle in demented patients may in some cases be reflected by irregularities in the secretion of MT and cortisol.

    Eleven healthy elderly with normal levels of plasma cobalamin were hospitalised for a serial blood sampling procedure drawing blood every two hours over a 24 hourperiod. It was concluded that there was no circadian variation of plasma cobalamin, unsaturated binding capacity of transcobalamin and haptocorrin, or transcobalamin bound cobalamin other than what can be explained by posture. The proposed role for cobalamin in the regulation of the circadian rhythm could not be confirmed by this study.

    Different methods of assessing the circadian rhytm were reviewed. Awristworn, computerised instrument recording activity and light expsoure was introduced. The light exposure in 14 healthy elderly in Linköping, Sweden, under normal living conditions was analysed using the new instrument. The subjects were exposed to very little light, mostly indoor illumination. The median subject spent 60 % of the time in illumination <:1 Lux, 10 % in <: 100 Lux, and 2 % in <:1000 Lux. Only four subjects were exposed to <: 1000 Lux for 60 minutes or more, which is regarded as a minimum requirement for maximal MT suppression.

    In addition, simultaneous light recording and blood saropling was done over a 24 hour period. All subjects showed low day-time levels and distinct nocturnal rises of MT. Cosinor analysis was applied on the MT and light data. The time interval from the acrophase of light to the acrophase of MT was delayed with the progress of the autunm and diminishing light.

  • 91.
    Spetz, Anna-Clara
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Pettersson, Bill
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Urologi. Linköpings universitet, Hälsouniversitetet.
    Varenhorst, Eberhard
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Urologi. Linköpings universitet, Hälsouniversitetet.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Thorell, Lars-Håkan
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
    Hammar, Mats
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Momentary increase in plasma calcitonin gene-related peptide is involved in hot flashes in men treated with castration for carcinoma of the prostate2001Inngår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 166, nr 5, s. 1720-1723Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose

    In women the vasodilatory neuropeptides calcitonin gene-related peptide and neuropeptide Y seem to be involved in menopausal hot flashes. We assessed whether plasma calcitonin gene-related peptide and neuropeptide Y change during hot flashes in men after castration.

    Materials and Methods

    We evaluated 10 men 61 to 81 years old who underwent castration due to cancer of the prostate and had frequent hot flashes for changes in plasma calcitonin gene-related peptide and neuropeptide Y during 1 day at the outpatient clinic. At least 5 blood samples were obtained between flashes and 4 were obtained during each flash. The samples were analyzed for calcitonin gene-related peptide and neuropeptide Y using radioimmunoassay technique. Hot flashes were objectively recorded by measuring peripheral skin temperature and skin conductance.

    Results

    Plasma calcitonin gene-related peptide increased 46% (95% confidence interval 21 to 71) during flashes in the 6 men in whom it was measurable. This change was statistically significant (p = 0.028). The concentration of neuropeptide Y was below the detection limit. Skin conductance and temperature increased significantly during flashes.

    Conclusions

    Calcitonin gene-related peptide is involved in the mechanisms of hot flashes in men who underwent castration due to prostate carcinoma. Thus, there may be a similar mechanism of hot flashes in women and in men deprived of sex steroids.

  • 92. Strömberg, L
    et al.
    Ohlen, G.
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Lindgren, U.
    Svensson, O.
    Postoperative mental impairment in hip fracture patients: A randomized study of reorientation measures in 223 patients.1999Inngår i: Acta Orthopaedica Scandinavica, ISSN 0001-6470, Vol. 70, s. 250-255Artikkel i tidsskrift (Fagfellevurdert)
  • 93.
    Thorell, Lars-Håkan
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Kjellman, Bengt
    Arned, Marie
    Lindwall-Sundel, K
    Wålinder, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Wetterberg, Lennart
    Light treatment of seasonal affective disorder in combination with citalopram or placebo with 1-year follow-up.1999Inngår i: International Clinical Psychopharmacology, ISSN 0268-1315, E-ISSN 1473-5857, Vol. 14Artikkel i tidsskrift (Fagfellevurdert)
  • 94. Valigi Björck, R
    et al.
    Själin, M.
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Neurological soft signs in schizophrenic patients: Influence of age, age at onset, sex, and family history of schizophrenia.2000Inngår i: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 54, s. 437-440Artikkel i tidsskrift (Fagfellevurdert)
  • 95. Wikell, C
    et al.
    Apelqvist, G
    Carlsson, Björn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Hjorth, S
    Bergqvist, P B F
    Kugelberg, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Pharmacokinetic and pharmacodynamic responses to chronic admininstration of the selective serotonin reuptake inhibitor citalopram in rats.2000Inngår i: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 22, s. 327-336Artikkel i tidsskrift (Fagfellevurdert)
  • 96. Wikell, C
    et al.
    Hjorth, S
    Apelqvist, G
    Kullingsjö, J
    Lundmark, Jöns
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Bergqvist, PBF
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Sustained administration of the antidepressant venlafaxine in rats: pharmacokinetic and pharmacodynamic findings2001Inngår i: Naunyn-Schmiedeberg's Archives of Pharmacology, ISSN 0028-1298, E-ISSN 1432-1912, Vol. 363, s. 448-455Artikkel i tidsskrift (Fagfellevurdert)
  • 97. Wikell, Cecilia
    et al.
    Apelqvist, Gustav
    Hjorth, Stefan
    Kullingsjö, J
    Bergqvist, PB
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Effects on drug disposition, brain monoamines and behavior after chronic treatment with the antidepressant venlafaxine in rats with experimental hepatic encephalopathy2002Inngår i: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 12, nr 4, s. 327-336Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with chronic hepatic encephalopathy (HE) may present affective symptoms and antidepressant drug treatment in this condition is not uncommon. The present microdialysis study investigated treatment with the chronic antidepressant venlafaxine (VEN) in experimental HE with regard to tentative changes in pharmacokinetic and/or pharmacodynamic parameters. Three weeks after portacaval shunt (PCS) or sham operation in rats, VEN (10 mg/kg daily) was administered by implanted osmotic minipumps. VEN treatment for 14 days resulted in higher concentrations of VEN in PCS rats than in sham controls in serum and brain compartments, and the VEN levels in serum and brain were strongly inter-correlated. The serum N-desmethylvenlafaxine concentration did not differ between the groups, but correlated with the serum VEN levels. The other VEN metabolites were below the quantification limits. VEN treatment for 9-12 days significantly stimulated locomotion and rearing in the open field in sham controls, but failed to do so in the PCS rats. The concentrations of noradrenaline, dopamine, 5-HT, and 5-HIAA in neocortical dialysates were higher in PCS than in sham rats after 14 days of VEN treatment, but the elevations reached statistical significance only in the case of dopamine and 5-HIAA. In summary, there were significant pharmacokinetic and pharmacodynamic alterations in rats with experimental HE as compared to controls. The described experimental HE model may be useful for continued pharmacokinetic/pharmacodynamic interaction studies to unravel the pathophysiological consequences of HE on the CNS. Copyright ⌐ 2002 Elsevier Science B.V.

  • 98. Wikell, Cecilia
    et al.
    Kugelberg, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Hjorth, Stephan
    Apelqvist, Gustav
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Effect of halving the dose of venlafaxine to adjust for putative pharmacokinetic and pharmacodynamic changes in an animal model of chronic hepatic encephalopathy2001Inngår i: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 24, nr 6, s. 324-333Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with chronic hepatic encephalopathy display monoaminergic perturbations together with affective symptoms. Thus, these patients belong to a group with a probability of receiving antidepressant drug treatment. The liver impairment may result in pharmacokinetic alterations of the antidepressant drug, which in turn may affect the already perturbed monoaminergic function. Venlafaxine (VEN) was administered as a single subcutaneous challenge to portacaval shunted (experimental hepatic encephalopathy model) rats (5 mg/kg) and sham-operated rats (5 and 10 mg/kg). The aims were to investigate whether a reduced dose in portacaval shunted rats resulted in higher concentrations of VEN and serotonin as compared to control rats, which had been demonstrated earlier when the rats received the same dose (10 mg/kg). A 50% reduction of the dose of VEN administered to portacaval shunted rats resulted in elevated levels of VEN in serum, brain parenchyma, and brain dialysate about 300 minutes after the injection. The VEN challenge increased the serotonin and noradrenaline concentrations in dialysate in portacaval shunted rats and both sham groups, but the three VEN groups did not differ in any major way in serotonin and noradrenaline output. Therefore, when the dose of VEN administered to experimental hepatic encephalopathy was reduced 50% as compared to control rats, mainly pharmacokinetic, and possibly also monoaminergic, alterations were observed.

  • 99.
    Wikström, Sverre
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri.
    Gunnarsson, Tove
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Nordin, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Tactile stimulus and neurohormonal response: A pilot study2003Inngår i: International Journal of Neuroscience, ISSN 0020-7454, E-ISSN 1563-5279, Vol. 113, nr 6, s. 787-793Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The effects of tactile stimuli on plasma oxytocin and neuropeptide Y (NPY) were investigated in 21 volunteers exposed to massage. Blood samples for basal values were drawn immediately before and immediately after finishing the massage. A third sample was drawn after 60 min of restricted rest. On focusing on the difference between oxytocin concentrations before and immediately after massage, we found a sex difference. An opposite sex difference was found for NPY. The results imply that there might be sex-related difference in neurohormonal response to tactile stimuli such as in massage, and the results contradict those of previously reported animal experiments.

  • 100.
    Wålinder, Jan
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Prochazka, J
    Odén, A
    Sjödin, Ingemar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Dahl, ML
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Mirtazapine naturalistic depression study (in Sweden) - MINDS(S): Clinical efficacy and safety2006Inngår i: Human Psychopharmacology: Clinical and Experimental, ISSN 0885-6222, E-ISSN 1099-1077, Vol. 21, nr 3, s. 151-158Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To study how implementation of a naturalistic trial design for mirtazapine treatment in major depressive disorder for six (up to 12) months could be used and evaluated by means of clinical efficacy and safety. Method: An open-labelled, prospective, multicenter, non-comparative trial was conducted during a 2-year period in patients with major depression according to DSM-IV treated in psychiatric departments and primary care in Sweden. Minimal inclusion and exclusion criteria were used in order to diminish the potential patient selection bias. Maximum flexibility of the dosage of mirtazapine was allowed, and clinical assessments included MADRS, CGI, vital signs and spontaneous reporting of adverse events. Results: 192 patients were found eligible and enrolled in the study. A significant improvement in depressive symptoms according to MADRS and CGI was observed including particularly marked sleep improvement early in the treatment. Slight increases in body weight and BMI were observed. The investigational drug was well tolerated overall. Conclusion: The clinical efficacy and safety of mirtazapine found in this naturalistic setting is in line with previously reported data on mirtazapine in traditional controlled clinical trials. The results confirm that the naturalistic study design facilitated conduct of the trial. The authors suggest that this type of study design should also be applied to other antidepressant drugs that are frequently prescribed in the general population. Copyright © 2006 John Wiley & Sons, Ltd.

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