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Biomedical subjects

Olav Spigset

Publications and source records attributed to Olav Spigset.

At least 55 records · Page 3Linked to original sources
PubMed2005

Treatment with selective serotonin reuptake inhibitors in the third trimester of pregnancy: effects on the infant.

Pharmacotherapy in pregnant women is often necessary to treat chronic or relapsing depression or anxiety disorders. Studies that have evaluated the safety of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy have not shown an enhanced risk of major congenital malformations and these results may have contributed to the increasing use of these agents during pregnancy. Fewer studies have assessed the safety of SSRIs in the third trimester of pregnancy. This article reviews available human data on the safety of SSRI treatment in the third trimester. The main purpose is to present and discuss the existing literature on the risks to the infant and to suggest treatment guidelines for the use of SSRIs in late pregnancy. The use of SSRIs in the third trimester has shown various perinatal complications, most frequently respiratory distress, irritability and feeding problems. Further studies are needed to evaluate the frequency of these complications and to elucidate whether the symptoms represent a direct serotonergic effect or are a drug withdrawal effect. Studies have shown conflicting results with respect to whether SSRI exposure decreases birthweight and increases the risk of premature delivery. A few case reports have described intracerebral haemorrhage in neonates after maternal SSRI treatment, but it is not known whether the frequency of such complications is higher than in unexposed neonates. Data on possible long-term effects of prenatal SSRI exposure on psychomotor and behavioural development are very sparse. Our interpretation of the current literature suggests that the risk of not receiving adequate antidepressant treatment in the third trimester when indicated outweighs the risks of adverse events in the infant. Thus, adequate pharmacological treatment should not be withheld from a depressed pregnant woman in late pregnancy. However, the neonate should be monitored for possible adverse effects after maternal use of an SSRI in the third trimester.

Female↗
PubMed2004

[Problem forte--is paracetamol-codeine combination rational?].

BACKGROUND: Combination drugs containing codeine and paracetamol are widely prescribed in Norway. MATERIAL AND METHODS: We reviewed relevant literature identified through searches on Medline or found in the reference lists of important articles. RESULTS: Codeine mediates its analgesic effect through the active metabolite morphine, a reaction which is catalysed by the cytochrome P450-isoenzyme CYP2D6. Approximately 7-10 % of the population does not express functional CYP2D6; for them codeine have no analgesic effect. They may, however, experience side effects from codeine. Used alone, codeine is an inefficient analgesic. Meta-analyses have shown little therapeutic advantage by adding codeine to paracetamol. INTERPRETATION: Codeine is an opiate with uncertain and unpredictable effects. The therapeutic benefit from the codeine component in combination with paracetamol is small, even in single dose evaluations. In chronic use, the therapeutic efficacy is most likely outweighed by side effects, including development of tolerance and abuse.

Acetaminophen↗
PubMed2004

[New antidepressive agents during pregnancy and lactation. Drug concentration should be monitored and the lowest possible dose administered].

This article presents a literature review on the treatment with new antidepressants during pregnancy and lactation, focusing on possible unwanted effects to the fetus and infant. Most data is available for the selective serotonin reuptake inhibitors, and particularly for fluoxetine. Some information exists for venlafaxine, whereas no published data was found for other new antidepressants such as reboxetine and mirtazapine. In general, treatment with new antidepressants during the first trimester in pregnancy has not been associated with an increased risk for congenital malformations. In contrast, symptoms such as irritability, respiratory distress and muscular hypotonia have been reported in newborns after third trimester exposure. The excretion of new antidepressants in breast milk seems in most cases to be negligible. However, suspected adverse effects have been reported in a few infants. In conclusion, existing data seems to indicate that the positive effects of maternal drug treatment and of lactation to the infant generally outweigh the risks of possible pharmacological effects. Nevertheless, before a new antidepressant is prescribed to a pregnant or lactating woman, an individual risk/benefit-assessment should always be carried out.

Antidepressive Agents, Second-Generation↗
PubMed2004

Dieting and weight loss do not affect on the platelet serotonin 5-HT2A receptor.

Alterations related to the serotonin 5-HT(2A) receptor have been reported in various psychiatric disorders, and the 5-HT(2A) receptor is also one of the receptors mediating the effects of serotonin on feeding and satiety. The present study was carried out in order to investigate the association between the serotonin 5-HT(2A) receptor and weight loss during dieting in overweight subjects. In nine women studied before, during and after a 6-month period of dieting, body weight loss was not found to affect the platelet 5-HT(2A) receptor status. This finding implies that although body weight decrease is a common feature in many psychiatric disorders, the reported alterations in serotonin 5-HT(2A) receptor status in these disorders do not seem to be caused by the weight loss per se.

Adult↗
PubMed2004

Influence of menstrual cycle on platelet serotonin uptake site and serotonin2A receptor binding.

Depression and anxiety are common health problems affecting women, particularly during the reproductive years. Major depression is two to three times as common in women than in men. Neuroendocrine factors are likely to contribute to this overall increased risk for developing mood disorders in women, and the neuroendocrine influence is most obviously seen in women with premenstrual dysphoric disorder (PMDD) as these women experience depressed mood and anxiety premenstrually only during ovulatory cycles. Moreover, dysfunction of serotonergic transmission has been regarded as an important mechanism in several psychiatric disorders and ovarian steroids have been shown to profoundly influence the activity of the serotonergic system. Given these facts, the purpose of this study was to examine whether binding of [3H]paroxetine to the platelet serotonin transporter or binding of [3H]lysergic acid diethylamide ([3H]LSD) to the platelet 5-HT2A receptor are influenced by the cyclical changes in circulating estradiol and progesterone that occur during the menstrual cycle. We examined 28 healthy women, without oral contraceptives and with regular menstrual cycles. In the late follicular phase, Bmax for [3H]paroxetine binding was significantly higher than in the ovulatory (p<0.01), early luteal phase (p<0.05) and mid-luteal phase (p<0.01). Bmax for [3H]LSD binding was significantly higher in the early follicular phase and the early luteal phase compared to the mid-luteal phase (p<0.001 and p<0.05, respectively). In the early follicular phase and the ovulatory phase, significant correlations between estradiol serum concentrations and Kd for [3H]paroxetine were obtained (p<0.001, respectively). In the luteal phase, significant inverse correlations between progesterone as well as estradiol serum concentrations and Kd for [3H]LSD binding were found (p<0.05, respectively).

Adult↗
PubMed2004

Pulmonary embolism associated with combined oral contraceptives: reporting incidences and potential risk factors for a fatal outcome.

BACKGROUND: It is established that combined oral contraceptive (COC) treatment increases the risk of a pulmonary embolism (PE), but specific risk factors for a fatal outcome from a PE remain to be determined. This study aimed to identify such risk factors, and to calculate the reporting rates of fatal and non-fatal PE. METHODS: Cases of suspected PE during treatment with COCs reported to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) between 1965 and 2001 were included. Medical records were scrutinized for potential risk factors for a venous thromboembolism (VTE). Annual sales data were obtained from the National Corporation of Pharmacies. RESULTS: A total of 248 cases of a suspected PE were reported; 207 non-fatal and 41 fatal. A VTE was verified in all fatal, and in 83.5% of non-fatal cases. The presence of nausea or abdominal pain, an age >35 years, concomitant treatment with other drugs which may increase the VTE risk, vein or lymph vessel malformation, and a deep vein thrombosis above the knee level were positively associated with a fatal outcome. Chest pain and previous COC use were negatively associated with a fatal outcome. The reporting rate of a PE with a verified VTE was 1.72 (95% confidence interval 1.47-2.00) cases per 100 000 treatment years, and of a fatal PE 0.25 (95% confidence interval 0.16-0.37) cases per 100 000 treatment years. CONCLUSION: Several specific potential risk factors for a fatal outcome from a COC-induced PE were identified. Recognition of these in combination with a high suspicion of VTE in COC users may reduce the risk of a fatal outcome.

Adult↗
PubMed2004

Genotyping as a tool to predict adverse drug reactions.

During the last decades, the rapid development in molecular biology has contributed to the understanding of genetic factors underlying many adverse drug reactions. Until recently, most research in this area has focused on genes coding for drug-metabolizing enzymes. Inactivating mutations have been found in genes coding for enzymes belonging to the cytochrome P-450 system, which is the major system for drug metabolism in humans, but also in genes coding for other enzymes. Subjects with a lack of functional activity in these enzymes should be treated with very low doses of drugs metabolized by the same enzyme in order to avoid excessive drug levels and thereby toxic effects. In the last years, increasing attention has been directed towards genes coding for drug targets. Hitherto, most studies have been carried out on single genes known to be or assumed to be functionally related to a given adverse drug reaction. Another approach, which may become more common in the future, is testing for complex single nucleotide polymorphism patterns that may be associated with adverse drug reactions, although the functional relationship between them may be completely unknown. Due to the influence of non-genetic factors in the development of adverse drug reactions, the association between a specific genotype and an adverse drug reaction will always be lower than 100%. Therefore, there is a need for prospective large-scale studies in order to elucidate the extent of environmental influences on the adverse drug reactions for which a genetic basis has been suggested. Despite these obstacles, pharmacogenetic testing will hopefully in the future identify at least some clear-cut situations where a drug should be avoided in certain individuals in order to reduce the risk of adverse drug reactions.

Cytochrome P-450 Enzyme System↗
PubMed2004

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

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.

Adult↗
PubMed2003

[Heroin: a useful analgesic?].

BACKGROUND: In some countries, heroin is widely used as an analgesic agent. MATERIAL AND METHODS: The literature describing the history, pharmacology and analgesic use of heroin was reviewed. RESULTS: Heroin is a semi-synthetic morphine derivative. A century ago it was considered a panacea with numerous indications. Today it is best known as a drug of abuse, but is still in use as an analgesic. Most studies that compare heroin with other analgesics have methodological shortcomings; however, they generally indicate that heroin has a clinical effect not very different from morphine. An better aqueous solubility as compared to morphine may in some situations be advantageous. Because of a proposed incomplete cross-tolerance between heroin and other opioid analgesics, it may be used if the patient shows sub-therapeutic response to first-line opioids. INTERPRETATION: Although not well documented, heroin appears to be an effective analgesic with certain properties different from those of morphine. It may be of clinical value in conditions with acute and/or terminal pain.

Adult↗
PubMed2003

[What information is given on adverse drug reactions from new drugs?].

BACKGROUND: It is not known to what extent information on previously unknown adverse reactions is communicated to doctors after the approval of a new drug. MATERIAL AND METHODS: We included seven drugs, approved between 1982 and 1995 and the first in their class to be approved in Norway. We recorded the number of adverse reactions listed in the annual editions of the Norwegian physicians' desk reference(Felleskatalogen) from the first edition that included the drug and up until the 2001 edition. RESULTS: Only 51 % of the adverse reactions listed in the 2001 edition were included in the first post-approval edition. On average, 1.6 new adverse reactions were added for each drug every year. By contrast: in a group of 12 drugs approved before 1970, 0.14 new adverse reactions were added for each drug every year between 1989 and 2001. INTERPRETATION: With a new drug it is to be expected that many adverse reactions are not acknowledged as such. Caution is warranted because of the fact that even though it is not listed in the physicians' desk reference, any event appearing in a patient exposed to a new drug may be an adverse reaction.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

[Use of antipsychotics during pregnancy and lactation].

BACKGROUND: When a pregnant or lactating woman is treated with an antipsychotic drug, the maternal need of antipsychotics must be weighed against possible risks to the fetus/infant. MATERIAL AND METHODS: Published articles on the use of antipsychotics during pregnancy and lactation were identified by Medline and Embase searches. An overview is presented. RESULTS: Available data do not indicate a clinically significant increased risk of congenital malformations after use of first-generation antipsychotics in pregnancy. However, use in the third trimester increases the risk of extrapyramidal symptoms in the newborn. Epidemiological studies do not indicate long-term effects on psychomotor development or cognitive abilities. For second-generation antipsychotics, data are generally very sparse. The excretion in breast milk of first-generation high potency antipsychotics is generally low and no negative effects have been documented after use in monotherapy. For second-generation antipsychotics, data are sparse or lacking. INTERPRETATION: First-generation antipsychotics do not appear to be teratogenic. If antipsychotics are used in the third trimester, the neonate should be observed for extrapyramidal symptoms. When the use of a first-generation antipsychotic is indicated in a lactating woman, the favourable effects of lactation will most likely in the majority of cases exceed the theoretical risk of detrimental drug effects in the infant. Nevertheless, efforts should always be made to minimise drug exposure to the fetus or suckling infant.

Abnormalities, Drug-Induced↗
PubMed2003

[Psychiatric disorders during pregnancy and lactation].

BACKGROUND: Psychiatric disorders occur both during pregnancy and postpartum. The consequences of inadequate treatment in these periods can be dramatic, not only for the mother but also for the infant. The reference books and textbooks used in Norway provide very scanty information on the treatment of psychiatric disorders during pregnancy and postpartum. The use of drugs is a particularly difficult issue, as detrimental effects may arise in the fetus and in the suckling infant. MATERIAL AND METHODS: This article is based upon a review of relevant literature supplemented by our own experience in the field. RESULTS AND INTERPRETATION: In general, the effect is better documented for drug treatment than for other therapeutic modalities. Some drugs can be used without particular problems during pregnancy and lactation while others have potentially detrimental effects. Often the risk of not giving the mother adequate treatment must be weighed against the potential risks of drug exposure to the infant. Pregnancy-related psychiatric illness would, when recognized, in most cases have a favourable prognosis provided that adequate treatment is given.

Anti-Anxiety Agents↗
PubMed2003

Long-term combination treatment with clozapine and filgrastim in patients with clozapine-induced agranulocytosis.

Short-term treatment with granulocyte colony-stimulating factor has been successful in reducing the duration of clozapine-induced agranulocytosis. Long-term combination treatment with filgrastim and clozapine in patients with clozapine-induced agranulocytosis has only been described in two previous cases. We describe three patients with schizophrenia who developed granulocytopenia or agranulocytosis during treatment with clozapine and who did not respond to other antipsychotics. The patients received long-term combination treatment with clozapine and filgrastim. Using a combination treatment with filgrastim and clozapine, the psychotic symptoms were successfully controlled and no haematological complications were observed during the follow-up periods of 11, 30 and 48 months, respectively. Our cases suggest that long-term treatment with filgrastim might be a useful, but exceptional, treatment approach in patients who have developed clozapine-induced granulocytopenia or agranulocytosis.

Adult↗