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Biomedical subjects

Olav Spigset

Publications and source records attributed to Olav Spigset.

At least 37 records · Page 2Linked to original sources
PubMed2005

Pharmacokinetic and behavioral effects of allopregnanolone in healthy women.

RATIONALE: The behavioral effects of allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) in women are not known. OBJECTIVE: Allopregnanolone, a neuroactive steroid secreted by the mammalian ovary, exerts its anesthetic, anxiolytic, and sedative/hypnotic effects through potentiation of GABAA receptors. The purpose of this study was to evaluate the behavioral effects of allopregnanolone in healthy women. METHODS: Ten healthy women were given three increasing intravenous doses of allopregnanolone in the follicular phase of the menstrual cycle. Saccadic eye movement parameters and visual analogue scales of sedation were used to evaluate the behavioral response of allopregnanolone. Repeated blood samples for analyses of allopregnanolone were drawn throughout the study day. RESULTS: Exogenously administered allopregnanolone decreases saccadic eye movement parameters and increases subjective ratings of sedation that correlate with increased serum concentrations of this neuroactive steroid. CONCLUSION: The behavioral effects of allopregnanolone are similar to that of its 5beta-stereoisomer, pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one). Apart from fatigue and mild nausea, allopregnanolone given in a cumulative dose of 0.09 mg/kg did not have any adverse effects.

Adult↗
PubMed2005

[Are mood stabilizers beneficial in the treatment of schizophrenia?].

BACKGROUND: Antipsychotic agents are the drugs of choice in the treatment of schizophrenia. However, some patients profit only modestly from such therapy and thus represent a clinical challenge. MATERIAL AND METHODS: This article is based upon a review of relevant literature on treatment with the mood stabilizers lithium, carbamazepine, valproate and lamotrigine in patients with schizophrenia. RESULTS: Few well-designed studies exist on the use of mood stabilizers in schizophrenia. In monotherapy, these drugs have no documented beneficial effect, but when used as adjunct therapies to antipsychotics, some positive effects are described. Best evidence for an anti-aggressive effect exists for lithium, but it is described also for carbamazepine. Lithium also has some effects on affective symptoms. Valproate has not shown a consistently positive effect. Lamotrigine has demonstrated a beneficial effect in a placebo-controlled study, but this finding should be verified by others before its place in the treatment of schizophrenia can be established. INTERPRETATION: Mood stabilizers are not the drugs of choice in the treatment of schizophrenia but could be considered as potential adjuncts to antipsychotics in patients with treatment-resistant schizophrenia, although the documentation is sparse.

Antimanic Agents↗
PubMed2005

[COX-2 inhibitors--one step forward and two steps back].

BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors are widely used. They have no advantages in terms of efficacy, and it is not documented that they cause fewer adverse effects than conventional NSAIDs. MATERIAL AND METHODS: The adverse effects of rofecoxib, celecoxib and other NSAIDs are reviewed. Relevant literature was identified on Medline and in the reference lists in key articles. RESULTS: Rofecoxib and the novel COX-2 inhibitors etoricoxib and valdecoxib have a higher degree of COX-2 selectivity than traditional NSAIDs. Celecoxib is less COX-2 selective and appears to be similar to diclofenac. Rofecoxib induces thromboembolic adverse effects more frequently than conventional NSAIDs. INTERPRETATION: The cardiovascular problems conferred by rofecoxib are probably a class effect and thus inducible by other selective COX-2 inhibitors. Pending comprehensive safety data, caution is warranted regarding the use of these drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Serum concentrations of risperidone and 9-hydroxyrisperidone after administration of the long-acting injectable form of risperidone: evidence from a routine therapeutic drug monitoring service.

There is limited documentation on the pharmacokinetics of long-acting intramuscular risperidone in a naturalistic setting. The objective of this study was to investigate the concentrations of risperidone and its active metabolite 9-hydroxyrisperidone as well as the concentration/dose (C/D) ratios achieved after intramuscular depot administration in a routine therapeutic drug monitoring setting. Thirty samples were collected from 10 female and 20 male patients receiving depot injections of risperidone. For 6 of the patients, the results could be compared with corresponding data available after previous oral administration of risperidone. In addition, data from a group of 278 patients using oral risperidone were retrieved. The median serum concentrations of risperidone plus 9-hydroxyrisperidone were 38 nmol/L 12-14 days after a intramuscular dose of 25 mg/14 days, 67 nmol/L after a dose of 37.5 mg/14 days, 99 nmol/L after a dose of 50 mg/14 days, and 148 nmol/L after a dose of 75 mg/14 days. The median C/D ratio for risperidone plus 9-hydroxy-risperidone was 22.2 (nmol/L)/(mg/d). In the group on oral medication, the median C/D ratio was 18.6 (nmol/L)/(mg/d). In the 6 patients previously using oral risperidone, switching to depot injections gave an average increase of 33% (range 12%-68%) in the C/D ratio. In conclusion, the authors' data indicate that there are great interindividual differences in the extent to which the daily dose has to be reduced when switching from oral to intramuscular depot administration to achieve the same serum concentrations of risperidone plus 9-hydroxyrisperidone. Because the degree of dose adjustment required for the individual patient so far cannot be predicted, guidance by therapeutic drug monitoring might be helpful.

Administration, Oral↗
PubMed2005

Drug interactions between lamotrigine and psychoactive drugs: evidence from a therapeutic drug monitoring service.

We present a systematic study on the interaction potential of lamotrigine, with focus on psychoactive drugs. A review of routine serum concentration measurements of lamotrigine performed in our laboratory yielded a total of 1733 serum samples from 829 patients (530 women, 299 men) suitable for statistical analysis. Main results for the whole study population were (median; interquartile range in parentheses): dose, 200 (100-300) mg; serum concentration, 2.97 (1.82-4.74) microg/mL; Lamotrigine serum concentration-to-dose ratio (LTG-CDR), 14.8 (9.9-24.6) (ng/mL)/(mg/d). A linear mixed model, allowing multiple observations from the same patient, was used to identify and quantitate the effect of factors influencing the LTG-CDR. In addition to age and gender, a total of 35 different comedications (25 drugs used in psychiatry as well as 10 other drugs) were evaluated. With women younger than 70 years as the reference group, factors found to lower the LTG-CDR significantly were: male gender and comedication with carbamazepine, ethinylestradiol, fluoxetine, lithium, phenytoin, phenobarbital, or topiramate. Factors associated with a significantly higher LTG-CDR were: age > or =70 years, and cotreatment with valproate. No antidepressants other than fluoxetine and none of the antipsychotic drugs included were associated with an altered LTG-CDR. Concerning pharmacokinetic drug interactions, we conclude that lamotrigine can be safely combined with most psychotropic drugs.

Adolescent↗
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↗