Publications by authors named "Trond Aamo"

22 Publications

  • Page 1 of 1

Phosphatidylethanol as Blood Biomarker of Alcohol Consumption in Early Pregnancy: An Observational Study in 4,067 Pregnant Women.

Alcohol Clin Exp Res 2021 04 13;45(4):886-892. Epub 2021 Mar 13.

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology - NTNU, Trondheim, Norway.

Background: The teratogenic effects of alcohol are well documented, but there is a lack of screening methods to detect alcohol use during pregnancy. Phosphatidylethanol 16:0/18:1 (PEth) is a specific and sensitive biomarker reflecting alcohol intake up to several weeks after consumption. The aim of this study was to investigate the prevalence of positive PEth values as an indicator of early prenatal alcohol exposure in a general population of pregnant women.

Methods: Rhesus typing is routinely performed in Norway in all pregnancies around gestational week 12. Rhesus-negative women have an additional test taken around week 24. Blood samples submitted to St. Olav University Hospital in Trøndelag, Norway, for Rhesus typing during the period September 2017 to October 2018 were collected. A total of 4,533 whole blood samples from 4,067 women were analyzed for PEth (limit of quantification of 0.003 µM).

Results: Fifty-eight women had a positive PEth sample. Of these, 50 women were positive around gestational week 12, 3 women were positive around week 24, and in 5 cases, the timing was unknown. There were no significant differences in proportions of women with positive PEth values related to age, or rural versus urban residency.

Conclusion: In an unselected pregnant population in Norway, 1.4% had a positive PEth sample around gestational week 12, whereas 0.4% had a positive sample around week 24. The use of PEth as an alcohol biomarker should be further investigated as a diagnostic tool in the antenatal setting.
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http://dx.doi.org/10.1111/acer.14577DOI Listing
April 2021

Efficacy of Self-Administered Intranasal Oxytocin on Alcohol Use and Craving After Detoxification in Patients With Alcohol Dependence. A Double-Blind Placebo-Controlled Trial.

Alcohol Alcohol 2021 Aug;56(5):565-572

Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology - NTNU, Trondheim, Norway.

Aims: The aim of this study was to assess the efficacy of self-administered intranasal oxytocin on alcohol dependence after detoxification.

Methods: In a double-blind, randomized, placebo-controlled trial, 38 patients fulfilling the criteria for ICD-10 diagnosis of alcohol dependence received either 8 IU oxytocin or placebo at their own discretion up to thrice daily for 4 weeks, after completing detoxification. Primary outcome was alcohol intake specified as the amount of alcohol consumed, the number of days to relapse into alcohol use and the proportion of subjects relapsing. Secondary outcomes were self-reported symptoms of craving, sleep and mental distress.

Results: There were no significant differences between the oxytocin group and the placebo group in daily alcohol intake in total (mean 1.3 ± 2.9 vs. 2.0 ± 5.0 units; P = 0.63) or on drinking days (mean 8.4 ± 2.7 vs. 7.7 ± 6.0 units; P = 0.76), in the number of days until relapse (P = 0.91) or in the proportion of subjects relapsing (37.5 vs. 41.2%; P = 0.84). Neither were there any statistically significant differences in any other outcomes, except a larger decrease in self-reported nervousness in the oxytocin group (P = 0.022).

Conclusion: The results were inconclusive as to whether intranasal oxytocin reduced the time to relapse, degree of craving or total amount of alcohol consumed after detoxification. However, the oxytocin group had a larger decrease in self-reported nervousness.
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http://dx.doi.org/10.1093/alcalc/agaa133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406061PMC
August 2021

Stability of Phosphatidylethanol 16:0/18:1 in Freshly Drawn, Authentic Samples from Healthy Volunteers.

J Anal Toxicol 2021 Apr;45(4):417-421

Department of Clinical Pharmacology, St. Olavs Hospital, 7006 Trondheim, Norway.

Due to its specificity, phosphatidylethanol (PEth) 16:0/18:1 has gained increased popularity as a marker for high alcohol consumption in recent years. As conflicting results regarding the stability of PEth 16:0/18:1 in whole blood have been published, there are still uncertainties related to optimum handling, transport and storage of blood samples for the analysis of PEth 16:0/18:1. A stability study where whole blood samples were drawn from healthy volunteers, who had ingested alcohol, is presented. The samples were collected in tubes with ethylenediamine tetraacetic acid (EDTA) and heparin as additives and stored under standardized conditions within 1 h of blood sampling. Storage times were 28 days in ambient temperature and at 4-8°C, and 90 days at -20°C and -80°C. All samples were analyzed regularly during the storage periods. PEth 16:0/18:1 concentrations were stable (defined as < 15% decrease compared with baseline values) at all temperatures up to 28 days, independent of additive. After 90 days of storage at -20°C, the mean concentrations had decreased by 18.8% in EDTA tubes and by 13.8% in heparin tubes. At -80°C, the concentrations were stable throughout the 90-day period. The present study shows that in samples containing PEth formed in vivo, PEth 16:0/18:1 is stable for 28 days irrespective of storage temperature. During long-term storage, samples should be stored at -80°C.
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http://dx.doi.org/10.1093/jat/bkaa082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040374PMC
April 2021

Actigraphy assessment of motor activity and sleep in patients with alcohol withdrawal syndrome and the effects of intranasal oxytocin.

PLoS One 2020 13;15(2):e0228700. Epub 2020 Feb 13.

Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology-NTNU, Trondheim, Norway.

Background And Aims: The alcohol withdrawal syndrome increases autonomic activation and stress in patients during detoxification, leading to alterations in motor activity and sleep irregularities. Intranasal oxytocin has been proposed as a possible treatment of acute alcohol withdrawal. The aim of the present study was to explore whether actigraphy could be used as a tool to register symptoms during alcohol detoxification, whether oxytocin affected actigraphy variables related to motor activity and sleep compared to placebo during detoxification, and whether actigraphy-recorded motor function during detoxification was different from that in healthy controls.

Methods: This study was a part of a randomized, double blind, placebo-controlled trial in which 40 patients with alcohol use disorder admitted for acute detoxification were included. Of these, 20 received insufflations with intranasal oxytocin and 20 received placebo. Outcomes were actigraphy-recorded motor activity during 5-hour sequences following the insufflations and a full 24-hour period, as well as actigraphy-recorded sleep. Results were related to clinical variables of alcohol intake and withdrawal, including self-reported sleep. Finally, the actigraphy results were compared to those in a group of 34 healthy individuals.

Results: There were no significant differences between the oxytocin group and the placebo group for any of actigraphy variables registered. Neither were there any correlations between actigraphy-recorded motor function and clinical symptoms of alcohol withdrawal, but there was a significant association between self-reported and actigraphy-recorded sleep. Compared to healthy controls, motor activity during alcohol withdrawal was lower in the evenings and showed increased variability.

Conclusion: Intranasal oxytocin did not affect actigraphy-recorded motor activity nor sleep in patients with acute alcohol withdrawal. There were no findings indicating that actigraphy can be used to evaluate the degree of withdrawal symptoms during detoxification. However, patients undergoing acute alcohol withdrawal had a motor activity pattern different from than in healthy controls.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228700PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018062PMC
May 2020

A woman in her forties who used addictive drugs in very high doses.

Tidsskr Nor Laegeforen 2020 01 2;140(1). Epub 2020 Jan 2.

Background: Following a surgical procedure, a female patient in her forties was prescribed opioids (oxycodone). The prescription escalated into doses that were extremely high, and at a level beyond any experienced previously, either at the various hospital units that were involved in the treatment or in the medical literature.

Case Presentation: The patient had no known history of substance abuse. After the surgical procedure, her general practitioner continued to prescribe the drug. The prescriptions escalated over the course of a couple of years, and at the time of our first contact with her, the doses had reached 11 000 mg oxycodone per day.

Interpretation: The high doses were tapered down over the course of around nine months. The spiralling prescriptions had several causes: the oxycodone treatment was initiated without a set plan for withdrawal; the patient had a change of general practitioner during the early stage; and she was a patient without any history of substance abuse. The costs escalated to the extent that the Norwegian Health Economics Administration eventually refused further payments. In such cases there is a need for close cooperation between the inpatient drug rehabilitation care unit and medical and pharmacological units.
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http://dx.doi.org/10.4045/tidsskr.19.0287DOI Listing
January 2020

Effect of intranasal oxytocin on alcohol withdrawal syndrome: A randomized placebo-controlled double-blind clinical trial.

Drug Alcohol Depend 2019 04 13;197:95-101. Epub 2019 Feb 13.

Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology - NTNU, Trondheim, Norway; Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.

Background: In a pilot study, intranasal oxytocin was demonstrated to reduce the benzodiazepine dose needed to relieve withdrawal symptoms during alcohol detoxification. The aim of the present study was to compare the effect of oxytocin and placebo during a three-day period of alcohol detoxification at an addiction treatment center in Norway.

Methods: Randomized, double-blind, placebo-controlled trial with 40 patients fulfilling criteria for ICD-10 diagnosis of alcohol dependence (F10.2), admitted for alcohol detoxification and withdrawal treatment. The benzodiazepine oxazepam was given as symptom-triggered treatment based on the scores of the Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) scale. Participants were randomized to receive either intranasal oxytocin (24 IU twice daily) or placebo.

Primary Outcome: Oxazepam dose required to complete a three-day course of detoxification.

Secondary Outcomes: Scores of the CIWA-Ar, the 10-item Hopkins Symptom Check List (HSCL-10), and self-reported total number of hours of sleep.

Results: The mean total oxazepam dose (± standard deviation) was 56.8 ± 72.8 mg in the oxytocin group and 79.0 ± 122.9 in the placebo group (p = 0.490; difference -22.3 mg; 95% confidence interval (CI) -86.9 to +42.4 mg). The findings were inconclusive as to whether a difference in the CIWA-Ar score (5.94 ± 3.86 vs. 6.48 ± 3.92; p = 0.665) or in any of the other secondary outcomes was present. No serious adverse events were reported.

Conclusion: Compared to placebo, intranasal oxytocin did not significantly reduce the oxazepam dose needed to complete a 3-day course of alcohol detoxification and withdrawal treatment.
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http://dx.doi.org/10.1016/j.drugalcdep.2019.01.003DOI Listing
April 2019

Bruk av fosfatidyletanol i førerkortsaker.

Tidsskr Nor Laegeforen 2019 02 11;139(3). Epub 2019 Feb 11.

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http://dx.doi.org/10.4045/tidsskr.18.0973DOI Listing
February 2019

Conversion factors for assessment of driving impairment after exposure to multiple benzodiazepines/z-hypnotics or opioids.

Forensic Sci Int 2017 Dec 20;281:29-36. Epub 2017 Oct 20.

Oslo University Hospital, Department of Forensic Medicine, Oslo, Norway; Center of Drug and Addiction Research, Faculty of Medicine, University of Oslo, Norway. Electronic address:

Aims: Norway has introduced legal concentration limits in blood for 28 non-alcohol drugs in driving under the influence cases. As of 2016 this legislation also regulates the assessment of combined effects of multiple benzodiazepines and opioids. We herein describe the employed methodology for the equivalence tables for concentrations of benzodiazepines/z-hypnotics and opioids implemented in the Norwegian Road Traffic Act.

Methods: Legislative limits corresponding to impairment at blood alcohol concentrations (BAC) of 0.02%, 0.05% and 0.12% were established for 15 different benzodiazepines and opioids. This was based on a concept of a linear relationship between blood drug concentration and impairment in drug naïve users. Concentration ratios between these drugs were used to establish conversion factors and calculate net impairment using diazepam and morphine equivalents.

Results: Conversion factors were established for 14 benzodiazepines/z-hypnotics (alprazolam, bromazepam, clobazam, clonazepam, etizolam, flunitrazepam, lorazepam, nitrazepam, nordiazepam, oxazepam, phenazepam, temazepam, zolpidem and zopiclone) and two opioids (methadone and oxycodone).

Conclusions: Conversion factors to calculate diazepam and morphine equivalents for benzodiazepines/z-hypnotics and selected opioids, respectively, have been operative in the Norwegian Road Traffic Act as of February 2016. Calculated equivalents can be applied by the courts to meter out sanctions.
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http://dx.doi.org/10.1016/j.forsciint.2017.10.022DOI Listing
December 2017

[New biomarkers for assesing alcohol consumption].

Tidsskr Nor Laegeforen 2016 Oct 25;136(19):1643-1647. Epub 2016 Oct 25.

Avdeling for klinisk farmakologi St. Olavs hospital og Institutt for laboratoriemedisin, barne- og kvinnesykdommer Norges teknisk-naturvitenskapelige universitet.

Alcohol abuse has significant medical, social and socioeconomic consequences. Alcohol biomarkers may serve as a useful tool in identifying individuals with excessive alcohol consumption in medical as well as medico-legal contexts.
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http://dx.doi.org/10.4045/tidsskr.16.0056DOI Listing
October 2016

Medication adherence in outpatients with severe mental disorders: relation between self-reports and serum level.

J Clin Psychopharmacol 2010 Apr;30(2):169-75

Section for Psychosis Research, Department of Psychiatry, Oslo University Hospital-Ulleval, Oslo, Norway.

Medication nonadherence in severe mental disorders is an important clinical issue, but estimates vary between studies. There is a need for valid self-reports for both research and clinical practice. This study examined the level of adherence to prescribed medication in outpatients with severe mental disorders and evaluated the validity of a simple self-report rating of adherence. From an ongoing study of severe mental disorders, 280 patients with schizophrenia and bipolar disorder who were prescribed psychopharmacological agents were included. We assessed adherence with serum concentration of medicines and tested the sensitivity and specificity of a simple self-report questionnaire for patients and compared with a report from health personnel. Adherence rate defined by serum concentrations within reference level was 61.6% in the total sample, 58.4% for schizophrenia and 66.3% for bipolar disorder. The patients' self-report scores overestimated adherence, but correlated significantly to health personnel scores (r = 0.50) and to serum concentration of medication (r = 0.52); the positive predictive value was 70%, and the negative predictive value was 91%. In this naturalistic sample, outpatients with severe mental disorders showed relatively good adherence to prescribed medication, and self-report questionnaires seem to be a valid method for measuring adherence.
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http://dx.doi.org/10.1097/JCP.0b013e3181d2191eDOI Listing
April 2010

Evaluation of a urine on-site drugs of abuse screening test in patients admitted to a psychiatric emergency unit.

J Clin Psychopharmacol 2009 Jun;29(3):248-54

Østmarka Department of Psychiatry, St Olav University Hospital, Trondheim, Norway.

The objective of this study was to characterize the usefulness and reliability of a commonly used urinary on-site drugs of abuse screening test device when used routinely at admittances to a psychiatric emergency unit. Urine samples from 262 emergency psychiatric admittances representing 217 patients were analyzed by a commercially available on-site test for the detection of amphetamines, benzodiazepines, cannabis, cocaine, and opiates in urine. The samples were first screened by nurses at the psychiatric department, thereafter by 2 technicians at the laboratory, and finally, analyzed by liquid chromatography/mass spectrometry. Results of 45.8% of the screening tests were true negative for all 5 drugs/drug groups tested, whereas those of 29.4% were true positive for 1 or several drugs/drug groups and true negative for the others. Thus, in total, 75.2% were correct for all 5 drugs/drug groups. In general, the sensitivities (42.9%-90.0% for the various drug groups) were lower than the specificities (92.7%-100.0%). The accuracies were 86.3% for benzodiazepines, 92.4% for cannabis, 94.7% for opiates, and 97.0% for amphetamines. No cocaine was found in any of the samples. For cannabis, the accuracy was higher among the laboratory technicians than among the nurses. The results from on-site screening testing should not be considered as the final conclusion on the intake of drugs of abuse but must be interpreted with caution.
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http://dx.doi.org/10.1097/JCP.0b013e3181a45e78DOI Listing
June 2009

Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database.

Ther Drug Monit 2009 Feb;31(1):42-56

Department of Forensic Chemistry and Genetics, Swedish National Board of Forensic Medicine, Linköping, Sweden.

A compilation of therapeutic drug monitoring data for 15 antidepressant drugs in a naturalistic routine clinical setting is presented. A substantial number of serum concentrations, at different daily doses, are outlined, and the intraindividual and overall serum concentration coefficient of variation for a respective substance is presented. Also, concentration comparisons between women and men, and patients older or younger than 65 years are made. The drugs included are amitriptyline (n = 394), citalopram (n = 5457), clomipramine (n = 400), escitalopram (n = 3066), fluoxetine (n = 793), fluvoxamine (n = 165), mianserin (n = 1063), mirtazapine (n = 1427), moclobemide (n = 200), nortriptyline (n = 206), paroxetine (n = 1677), reboxetine (n = 85), sertraline (n = 2998), trimipramine (n = 158), and venlafaxine (n = 1781). Of the 9 drugs exhibiting linear (first order) kinetics, all but reboxetine gave a significant negative dose-to-dose-normalized correlation with concentrations, that is an increased clearance with higher dose. When dose was correlated to the metabolite:parent substance ratio for drugs exhibiting linear kinetics, citalopram and mianserin gave a positive slope, contrary to a negative slope shown for sertraline and venlafaxine. The intraindividual variations of the serum concentrations were lower than the overall variations, and the intraindividual variation of the metabolite:parent substance ratio was lower than the intraindividual variation of respective parent substance (except clomipramine and mianserin). Women had significantly higher serum concentrations than men (significant for citalopram, escitalopram, mianserin, mirtazapine, and venlafaxine), and patients older than 65 years had higher serum concentrations than the younger ones for all drugs except amitriptyline, moclobemide, and trimipramine. By presenting a comprehensive compilation of therapeutic drug monitoring data for each drug, a reference tool is created, in addition to improved pharmacokinetic knowledge of antidepressant drugs.
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http://dx.doi.org/10.1097/FTD.0b013e31819114eaDOI Listing
February 2009

[Toxicological screening of medicines and drugs of abuse in emergency cases].

Tidsskr Nor Laegeforen 2008 Jan;128(1):42-5

Avdeling for klinisk farmakologi, St. Olavs Hospital, 7006 Trondheim.

Background: In some situations, and particularly when intoxications are suspected, it would be advantageous if medicines and drugs of abuse could be swiftly detected in serum or urine.

Material And Methods: The Department of Clinical Pharmacology at St. Olav University Hospital has since 2004 been developing a comprehensive toxicology service (at all hours 7-days/week) for immediate quantitative analysis of between 80 and 90 substances. We here present the service in further detail and evaluate its usefulness during its first full year, 2005. Two case reports are presented to further illustrate the possible benefits of this service.

Results: Urgent testing was requested for a total of 390 samples; 351 serum and 39 urine samples. The most common indications for requesting such analyses were suspected acute intoxication (46%) and suspected therapeutic failure/adverse drug reaction (31%). 88% of the serum samples obtained for acute intoxications were positive, and 48 different substances were detected. The substances most often found were various benzodiazepines, various antiepileptic drugs, ethanol, carisoprodol, lithium, and other psychotropic drugs. In urine, amphetamine and zopiclone were the substances most often detected.

Interpretation: The service seems to be used according to its intentions, and the high number of samples received indicate that clinicians consider the service to be useful. An early and continuous dialogue between the clinician and the laboratory physician is a prerequisite for rational use of the service.
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January 2008

Adverse drug reactions of antidepressants and antipsychotics: experience, knowledge and attitudes among Norwegian psychiatrists.

Nord J Psychiatry 2006 ;60(3):227-33

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.

Efficient prevention of adverse drug reactions (ADRs) requires knowledge about their severity and pharmacological mechanisms and is dependent on reliable data on their frequencies and possible risk factors. The study was conducted to investigate the prescribers' experience and understanding of the ADRs of psychotropic drugs, and their attitude towards reporting these. In a questionnaire, physicians treating adult psychiatric patients were asked which ADRs that they regarded bothersome for some of the most widely used antidepressants and antipsychotics. Questions about the relationship between blockade of drug receptors and ADRs, and about the physicians' personal experience of and attitudes towards reporting of ADRs were also included. In total, 70 of 91 questionnaires (78%) were returned. The mean number of ADRs regarded bothersome ranged from 2.4 to 9.3 for the various drugs/drug classes. Qualified psychiatrists stated a significantly higher number of bothersome ADRs than did the residents. The percentage of physicians associating blockade of a receptor with a specific ADR varied from 76% (histamine receptor blockade and sedation) to 37% (alpha(1)-adrenergic blockade and tachycardia). Thirty-nine per cent of the physicians had never reported an ADR to the Norwegian Medicines Agency. The number of ADRs considered bothersome was relatively high. The pattern of these ADRs generally mirrored the typical ADR profiles of the drugs. The knowledge of the underlying mechanisms of ADRs was more or less incomplete. The reporting rate of ADRs to the national regulatory authorities was low.
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http://dx.doi.org/10.1080/08039480600636494DOI Listing
December 2006

Prolonged pharmacokinetic drug interaction between terbinafine and amitriptyline.

Ther Drug Monit 2005 Oct;27(5):680-2

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.

Drugs with long terminal half-lives, such as terbinafine, have a potential for involvement in both long-lasting drug-drug interactions and interactions appearing weeks after discontinuation. We present a case report on a 37-year-old white woman with normal CYP2D6 metabolic capacity who was treated with amitriptyline, valproate, and olanzapine when terbinafine was introduced. Shortly thereafter she experienced extreme dryness of the mouth, nausea, and dizziness accompanied by a large increase in the serum concentrations of amitriptyline and nortriptyline. Terbinafine therapy was discontinued, and the amitriptyline dose was reduced. Surprisingly, the serum concentrations of amitriptyline and nortriptyline did not return to baseline until approximately 6 months later. Studies have shown that terbinafine is a highly potent competitive inhibitor of CYP2D6. CYP2D6 is an important intermediate enzyme in metabolism of amitriptyline to nortriptyline. Nortriptyline is further metabolized to 10-hydroxy metabolites, mainly by CYP2D6. It is, therefore, likely that the concomitant use of terbinafine was the major cause of the increased serum concentrations of amitriptyline and nortriptyline. Very different terbinafine elimination half-lives (17-400 hours) are stated in the physicians' reference guides. If the shortest estimates are used when adjusting the dose of interacting drugs, the risk of underestimating the duration of the interaction is large. Based on our data there is a risk of clinically significant drug-drug interactions for at least 3 months after stopping terbinafine intake.
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http://dx.doi.org/10.1097/01.ftd.0000175910.68539.33DOI Listing
October 2005

Ciprofibrate stimulates the gastrin-producing cell by acting luminally on antral PPAR-alpha.

Am J Physiol Gastrointest Liver Physiol 2005 Dec 11;289(6):G1052-60. Epub 2005 Aug 11.

Dept. of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, St. Olav's Hospital HF, Trondheim, Norway.

The lipid-lowering drug ciprofibrate stimulates gastrin-producing cells in the rat stomach without lowering gastric acidity. Although suggested to be a luminal action on antral peroxisome proliferator-activated receptor-alpha (PPAR-alpha), the mechanism is still not fully elucidated. Gastric bypass was surgically prepared in male Sprague-Dawley rats. Gastric-bypassed and sham-operated rats were either given ciprofibrate (50 mg.kg(-1).day(-1) in methocel) or vehicle alone for 7 wk. PPAR-alpha knockout (KO) and wild-type (WT) mice were either given ciprofibrate (500 mg.kg(-1).day(-1) in methocel) or vehicle alone for 2 wk. The concentration of gastrin in blood was analyzed. Antral G cell density and gastrin mRNA abundance were determined by using immunostaining and Northern blot analysis. Ciprofibrate did not raise plasma gastrin or G cell density in gastric-bypassed rats, although the gastrin mRNA level was slightly increased. In contrast, ciprofibrate induced hypergastrinemia, a 50% increase in G cell density, and a threefold increase in gastrin mRNA in sham-operated rats. In PPAR-alpha KO mice, ciprofibrate did not raise G cell density or the gastrin mRNA level. The serum gastrin level was reduced by ciprofibrate. In WT mice, ciprofibrate induced hypergastrinemia, a doubling of G cell density, and a threefold increase in gastrin mRNA. Comparing animals dosed with vehicle only, PPAR-alpha KO mice had higher serum gastrin concentration than WT mice. We conclude that the main effects of ciprofibrate on G cells are mediated from the antrum lumen, and the mechanism is dependent on PPAR-alpha. The results indicate that PPAR-alpha may have a role in the physiological regulation of gastrin release.
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http://dx.doi.org/10.1152/ajpgi.00268.2005DOI Listing
December 2005

[Drug screening among patients aged 17-40 admitted with psychosis].

Tidsskr Nor Laegeforen 2005 May;125(9):1178-80

Divisjon psykisk helse, Blakstad, Sykehuset Asker og Baerum, 1309 Rud.

Background: High frequency of co-occurring substance use disorders and psychiatric disorders is reported in several studies. An important issue is whether we can rely on patient reports only. The purpose of this investigation was to find the prevalence of substance use among younger psychotic inpatients in Norway and to compare patients' self reports with the results of screening for drugs.

Material And Methods: 65 patients aged 17 to 40, consecutively admitted to Blakstad Psychiatric Hospital in 2001 with psychosis were interviewed with regard to substance use 30 days prior to admittance. The Addiction Severity Index (EuropASI) was used for interviews. Blood and urine samples for drug analysis were taken at admittance.

Results: 54% of the patients reported having used one or more substances for intoxication during the month prior to admittance. 40% of the included patients had used illegal drugs. Laboratory analyses revealed use of illegal drugs, mostly cannabis and amphetamine, in 34% of the patients. Only one patient tested positively for a drug not reported in the interview.

Interpretation: The investigation shows that 54% of the younger psychotic inpatients intoxicate themselves with legal or illegal substances. This fact is important for the total medical management of these patients in psychiatric hospitals. We also found that this group of patients were reliable in reporting their substance use when a standardised interview was used.
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May 2005

Stimulant and relaxant drugs combined with stimulant and relaxant information: a study of active placebo.

Psychopharmacology (Berl) 2004 Nov 5;176(3-4):426-34. Epub 2004 May 5.

Department of Psychology, University of Tromsø, Breivika, 9037 Tromsø, Norway.

Rationale: The active placebo hypothesis states that placebo effects are potentiated when an active drug is administered.

Objective: This hypothesis was tested in an experiment where information about the effect of a drug was combined with administration of an active drug or placebo.

Methods: Information that a drug acted as a relaxant, a stimulant, or as a placebo was crossed with oral administration of a relaxant drug (700 mg carisoprodol), a stimulant drug (400 mg caffeine) or placebo (lactose) in healthy volunteers ( n=94). Dependent variables were subjective and physiological measures of arousal, as well as serum carisoprodol and caffeine levels. Data were collected from 15 to 280 min after administration of drug or placebo.

Results: Caffeine increased alertness, systolic and diastolic blood pressure, startle blink reflexes, and skin conductance responses. Subjects were calmer after carisoprodol, and heart rate was increased. There was a positive correlation between increased arousal and carisoprodol levels when stimulant information had been provided. However, this was only seen when carisoprodol levels were very low. There was no evidence that caffeine modulated the placebo response.

Conclusions: Active placebo responses were seen only transiently when carisoprodol levels were low, and only in the subjective arousal data. Caffeine did not support active placebo responses. The overall findings did not favour the active placebo hypothesis.
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http://dx.doi.org/10.1007/s00213-004-1886-7DOI Listing
November 2004

Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome p450 genotypes.

J Clin Psychiatry 2004 Sep;65(9):1228-34

Centre for Child and Adolescent Mental Health, University of Bergen, Bergen, Norway.

Background: The aims of the study were to quantify the drug exposure in breastfed infants of antidepressant-treated mothers, to identify possible adverse events, and to correlate these variables to maternal and infant drug metabolism-relevant genotypes and milk triglyceride content.

Method: The study included 25 lactating women treated with citalopram (N = 9), sertraline (N = 6), paroxetine (N = 6), fluoxetine (N = 1), or venlafaxine (N = 3) and their 26 breastfed infants. Drug concentrations in maternal and infant serum and milk were analyzed using liquid chromotography mass spectrometry methods; milk triglyceride levels were measured with a commercial kit. Cytochrome P450 (CYP) 2D6 and CYP2C19 activity was determined by polymerase chain reaction-based genotyping of the mothers and infants. An infant adverse event questionnaire was completed by the medication-treated mothers as well as by a control group of medication-free breastfeeding mothers of 68 infants.

Results: Sertraline and paroxetine were not detected in any of the drug-exposed infants. The infant serum level of citalopram was either undetectable (N = 4) or low (N = 6). All venlafaxine-exposed infants had measurable drug concentrations. We identified a paroxetine-treated mother and her infant who were both CYP2D6 poor metabolizers, as well as a citalopram-treated mother with CYP2C19 poor metabolizer status, but the serum drug levels of their infants were still either undetectable (paroxetine) or low (citalopram). There was no evidence of adverse events in the drug-exposed infants.

Conclusion: Serum drug levels in breastfed infants of antidepressant-treated mothers were undetectable or low. This study adds further evidence to previously published data indicating that breastfeeding should not be generally discouraged in women using serotonin reuptake inhibitor anti-depressants.
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http://dx.doi.org/10.4088/jcp.v65n0911DOI Listing
September 2004

Routine drug monitoring of serum concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide do not predict clinical observations in cancer patients.

Palliat Med 2003 Dec;17(8):679-87

Department of Anaesthesia and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

The clinical importance of routine drug monitoring of serum concentrations of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during chronic morphine therapy is not established. We measured morphine, M6G and M3G serum concentrations in cancer pain patients receiving oral (n = 263, median dose 80 mg/24 hours) or subcutaneous (sc) (n = 35, median dose 110 mg/24 hours) morphine. Regression analyses were performed to investigate if serum concentrations of morphine, M3G and M6G predicted pain intensity (Brief Pain Inventory), health-related quality-of-life variables (EORTC QLQ-C30) and cognitive function (Mini-Mental Score). Serum concentrations were also compared in patients categorized as morphine 'treatment successes' and 'treatment failures'. We observed that serum concentrations of morphine, M6G or M3G did not predict pain intensity, cognitive function, nausea or tiredness. 'Treatment failures' caused by nausea, tiredness, cognitive failure or constipation did not have statistically significant different morphine, M6G and M3G serum concentrations than patients classified as 'treatment successes'. In conclusion, this study did not observe any concentration-effect relationships of morphine, M3G or M6G with pain intensity, nausea, constipation, tiredness or cognitive failure in blood samples obtained during routine clinical drug monitoring in cancer patients. This result suggests that therapeutic drug monitoring as a routine tool during chronic morphine treatment has limited value for clinical decision making.
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http://dx.doi.org/10.1191/0269216303pm835oaDOI Listing
December 2003

Valproic acid and risperidone: a drug interaction?

J Am Acad Child Adolesc Psychiatry 2003 Jan;42(1):1-2

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http://dx.doi.org/10.1097/00004583-200301000-00001DOI Listing
January 2003
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