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Hans Agren

Publications and source records attributed to Hans Agren.

54 records · Page 3Linked to original sources
PubMed2004

Compliance with SSRI medication during 6 months of treatment for major depression: an evaluation by determination of repeated serum drug concentrations.

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.

Adolescent↗
PubMed2004

Calculations of static and dynamic polarizabilities of excited states by means of density functional theory.

We present density functional theory and calculations for excited state second order, static or dynamic, properties. The excited state properties are identified from a double residue of a cubic response function. The performance of various functionals, including the generalized gradient approximation and fractional exact Hartree-Fock exchange, is compared to coupled cluster calculations. Applications on excited state polarizabilities of s-tetrazine and pyrimidine show a good agreement with ab initio correlated, coupled cluster, results.

Journal Article↗
PubMed2004

Density functional theory for hyperfine coupling constants with the restricted-unrestricted approach.

This work presents derivation, implementation, and the first applications of the restricted-unrestricted approach based on restricted Kohn-Sham formalism for evaluation of hyperfine coupling constants. By using the spin-restricted Kohn-Sham method the well-known spin contamination problem existing in the unrestricted Kohn-Sham formalism is avoided and a proper description of spin polarization is achieved via the restricted-unrestricted approach without introducing spin contamination into the evaluation of the hyperfine coupling constants. The performance of the proposed formalism is evaluated for a set of organic radicals and transition metal compounds. The results of this investigation indicate promising accuracy of the restricted-unrestricted approach for calculation of the isotropic hyperfine coupling constants in organic radicals as well as transition metal compounds.

Journal Article↗
PubMed2004

Few-states models for three-photon absorption.

Few-states models are derived for the calculation of three-photon absorption matrix elements. Together with earlier derived few-states models for two-photon absorption, the models are evaluated against results from response theory calculations that provide the full sum-over-states values. It is demonstrated that not even for systems with charge-transfer character, where few-states models for two-photon absorption are in excellent agreement with response theory, do the models provide a quantitatively correct description for three-photon absorption. The convergence behavior, merits, and shortcomings of the models are elucidated in some detail. The role of various characteristics of the electronic structure, such as symmetry, charge transfer, and conjugation--important for the formation of a large three-photon cross section--is analyzed. As for two-photon absorption cross sections, it is essential to consider generalized few-states models also for three-photon absorption, that is, to account for dipolar directions and laser beam polarization. Despite their poor quantitative performance, it is argued that few-states models at times can be useful for interpretation purposes when applied to three-photon absorption.

Journal Article↗
PubMed2004

Serum disposition of sertraline, N-desmethylsertraline and paroxetine: a pharmacokinetic evaluation of repeated drug concentration measurements during 6 months of treatment for major depression.

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 t(1/2) 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.

Adolescent↗
PubMed2003

Increased incidence of CYP2D6 gene duplication in patients with persistent mood disorders: ultrarapid metabolism of antidepressants as a cause of nonresponse. A pilot study.

OBJECTIVE: Recent studies have revealed that genetic polymorphisms of cytochrome P(450) 2D6 (CYP2D6) are among the factors that determine the interindividual differences in the metabolism and response to antidepressants. We investigated the relationship between persistent mood disorders and the duplication of the CYP2D6 gene, which encodes an enzyme with increased activity. METHODS: We screened the prevalence of the CYP2D6 genotypes in 108 patients with persistent mood disorders using long polymerase chain reaction (PCR) and the real-time PCR methods. Clinical correlates with the genotypes were also analyzed. RESULTS: Among the 108 patients, 81 had failed to respond to antidepressants shown to be metabolized by CYP2D6. Of those 81, 8 had a CYP2D6 gene duplication (9.9%, 95% confidence interval 3.4-16.4%) which was higher than the 0.8-1.0% incidence previously observed in healthy Nordic Caucasians. The worst week scores of the Hamilton Depression Rating Scale were higher in the patients with the duplication compared with those without the duplication ( P=0.026, student's t-test). CONCLUSION: These results suggest that the CYP2D6 gene duplication is a possible factor that influences the development of persistence in patients with mood disorders probably by ultrarapid drug metabolism.

Antidepressive Agents↗
PubMed2003

Self-rated aggression and cerebral monoaminergic turnover. Sex differences in patients with persistent depressive disorder.

OBJECTIVE: Outward-directed violence and impulsivity in humans and primates has frequently been related to abnormal brain monoaminergic turnover. Self-rated aggression is likely to be clinically relevant,and its psychobiological basis needs investigation. SUBJECTS: Sixty-six patients (40 women and 26 men) with persistent depressive disorder (PDD) were compared with 497 control subjects from the general Swedish population. METHODS: We administered the Aggression Questionnaire - Revised Swedish Version (AQ-RSV) to patients and control subjects. In patients, CSF 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-5-hydroxyphenylglycol (MHPG) in CSF were analyzed. Total Aggression score and Aggression subfactors 'Physical Aggression','Verbal Aggression','Anger', and 'Hostility'were correlated with CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA),and 3-methoxy-5-hydroxyphenylglycol (MHPG). RESULTS: Overall, Hostility was positively related to CSF MHPG (t=2.27, p=0.015). Split by sex,Hostility was related with 5-HIAA in males (r=0.62,p=0.003),and with MHPG in females (r=0.38, p=0.03). Comparing self rated aggression with age- and sex-matched data from the general Swedish population, the most prominent deviation was increased Hostility score among PDD patients. Among patients, all aggression factors were nominally higher in women than in men, with the most pronounced sex difference in Hostility (t=-1.89, p=0.04). CONCLUSIONS: Results suggest a clinically meaningful sex difference in a positive relationship between hostility and serotonergic/noradrenergic turnover in PDD patients.

Adult↗
PubMed2003

Lifetime burden of mood swings and activation of brain norepinephrine turnover in patients with treatment-refractory depressive illness.

BACKGROUND: We tested if duration and intensity of episodes in treatment-resistant affectively ill patients were related to cerebrospinal fluid (CSF) concentrations of monoamine metabolites. METHOD: In retrospective life charts were recorded every previous episode of 37 patients with severe treatment-refractory affective disorders. 'Accumulated burden of mood swings' (ABMS, sum of each episode length x episode depth) was used to estimate the accumulated illness burden. Homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were analyzed in CSF of all patients and compared with 27 healthy controls. Data were analyzed using multiple regression analysis. RESULTS: CSF MHPG contributed strongly significant and positively to the ABMS. LIMITATIONS: The retrospective nature of the study. CONCLUSION: CSF concentrations of MHPG is positively related to ABMS over life. Thus, a specific involvement of norepinephrine in the long-term burden of affective illness is a likely reality.

Antidepressive Agents↗
PubMed2003

Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study.

This multinational, randomized, double-blind study was specifically designed to prospectively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice. A total of 345 patients with major depressive episode (DSM-IV) received mirtazapine (30-45 mg/d) or sertraline (50-150 mg/d) for 8 weeks. Mirtazapine was administered in the newly developed fast dissolving, orally disintegrating tablet formulation. Assessments were performed at baseline and on days 4, 7, 10, 14, 28, 42, and 56. The primary efficacy variable (mean absolute change from baseline in the Hamilton Depression Rating Scale [HAMD] total score [17 items]) showed that mirtazapine was significantly (P < 0.05) more effective than sertraline at all assessments during the first 2 weeks of the study. After this time, HAMD total scores were similar in both groups. These findings were supported by analysis of the HAMD response rate (ie, > or =50% reduction in HAMD total score from baseline), HAMD remission rate (HAMD total score of < or =7), and the Montgomery-Asberg Depression Rating Scale (MADRS). Both treatments were well tolerated. In addition, mirtazapine had a greater effect than sertraline on sexual functioning. In conclusion, this first prospective onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect than sertraline. The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient.

Adolescent↗
PubMed2003

Self-rated aggression related to serum testosterone and platelet MAO activity in female patients with the fibromyalgia syndrome.

To investigate self-rated aggression in relation to platelet MAO activity and serum testosterone in patients with fibromyalgia syndrome (FMS), we administered the Aggression Questionnaire - Revised Swedish Version (AQ-RSV) to 30 female patients with FMS. After correction for age, significant positive correlations were seen between serum testosterone concentrations and the AQ-RSV scores for Verbal Aggression (r=0.36, p<0.05) and Anger (r=0.37, p<0.05), whereas the platelet MAO activity was negatively correlated with the score for Verbal Aggression (r=-0.44, p<0.05). Our results suggest that aggression and irritability in female FMS patients might be increased by elevated testosterone concentrations in combination with reduced capacity of the serotonergic system as reflected by low platelet MAO activity.

Adult↗
PubMed2002

Physical properties and spectra of IO, IO- and HOI studied by ab initio methods.

Structure and properties of the IO, IO- and HOI species, which are of potential importance for the ozone destruction catalytic cycle in the troposphere, have been calculated together with the EPR, NMR and UV-visible spectra by ab initio methodology with account of spin-orbit coupling (SOC) effects. Multi-configuration self-consistent field calculations with linear and quadratic response techniques and the multi-reference configuration interaction method have been employed. Photodissociation of these species, crucial for the catalytic ozone-destruction cycle, is critically reviewed and analyzed. Calculations predict that the singlet-triplet (S-T) transition to the lowest triplet state (X1 A' --> 3A'') should be responsible for the weak long-wavelength tail absorption (approximately 450-560 nm) and photodissociation of the HOI molecule. The second, more intense, band around 400 nm is produced by two overlapping S-S and S-T transitions. In order to check this assignment of the HOI photodissociation the isoelectronic IO- anion and IO radical have been studied by the same methods. Comparison with the EPR spectrum of the IO radical indicates that the methods are reliable which gives credit to the accuracy of the HOI spectral interpretation. NMR spectra of HOI and IO- molecules and some other properties are calculated for the first time.

Biophysics↗
PubMed2002

Patterns of sensitisation in the course of affective illness. A life-charting study of treatment-refractory depressed patients.

BACKGROUND: A 'sensitisation' process over time has been suggested by Post and collaborators--the affective illness course shows a tendency towards more frequent, deeper, and less stress-related episodes over time. The main aim of the present study was to test the sensitisation hypothesis using a Swedish Life Charting program. METHODS: Thirty patients with treatment-refractory affective disorder, of whom four had bipolar I disorder, were first interviewed using a semistructural interview manual covering episodes, treatment and stress. All previous psychiatric records were then recruited. Information from the records and from the interview was coalesced into individual, retrospective life charts. RESULTS: Twenty patients showed a sensitisation course and 10 patients showed a non-sensitisation course. In both groups, almost 90% of illness episodes had undergone treatment. Time spent in illness since onset of the affective disorder was about 33% for the sensitisation group and more than 50% for the non-sensitisation group. LIMITATIONS: The retrospective nature of the study is a limitation. The results apply to patients with severe treatment-refractory affective disorder and may not be generalisable to general patients with less-severe mood disorders. CONCLUSIONS: Our results partially validate the Post hypothesis of affective sensitisation in demonstrating this phenomenon in more than half of our affectively recurring patients. However, a substantial minority were clearly non-sensitisers showing a stable but more malignant illness course. Future studies need to elucidate whether these two groups benefit from different kinds of treatment.

Adaptation, Psychological↗
PubMed2002

Calcitonin gene-related peptide and calcitonin in the CSF of patients with dementia and depression: possible disease markers.

Cerebrospinal fluid (CSF) was obtained from 32 patients with dementia, 19 healthy controls that were age-matched with the dementia patients, and 29 DSM-IV major depression patients and calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and calcitonin-like immunoreactivity (CT-LI) measured by RIA. CGRP-LI was lower in the dementia group compared to both the controls and depressed patients (P<.01) after covarying out sex and age. CT-LI was decreased in the dementia and depressed patients (P<.05) compared to the controls. A positive relationship between CGRP-LI and CT-LI was found in dementia. A logistic discriminant analysis with calcitonin gene-related peptide (CGRP) and log calcitonin (CT) predicting diagnosis (three classes) revealed a significant overall fit (chi2 = 18.08, P = .0011), with an effect test showing contributions of both independent variables: CGRP (chi2 = 10.03, P<.007), log CT (chi2 = 8.63, P = .013). In dementia, both CGRP-LI and CT-LI were decreased and their concentration ratio did not differ from that in controls, likely reflecting a general neuronal loss. Alternatively and more speculatively, but theoretically possible, expression of the alpha-CGRP/CT gene may be affected in dementia. In contrast, in depression, CT-LI but not CGRP-LI was decreased and the CGRP/CT concentration ratio was increased, which is consistent with a possibility of an altered splicing process favoring CGRP mRNA.

Adult↗
PubMedDate not supplied

Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism.

Extensive animal studies suggest neuropeptide Y (NPY) to be involved in coping with a wide range of stressors, and that impaired central NPY signalling could be involved in the pathophysiology of anxiety and depression. Human studies of central NPY levels in depression have, however, been inconclusive. Here, we examined levels of NPY-like immunoreactivity (NPY-LI) in the cerebrospinal fluid (CSF) of medication-free subjects with treatment refractory unipolar depression. Patients were admitted to a research inpatient unit, examined under standardized conditions, and compared with a sample of volunteers in whom psychiatric morbidity was excluded. A robust suppression of NPY levels in patient CSF was found, while other putative CSF markers (monoamine metabolites, somatostatin) did not differ between the groups. We then explored whether this finding might be related to a recently described T1128C coding polymorphism which results in a Leu7-> Pro7 substitution of the signal peptide, and a previously not described T -399C polymorphism in the promoter region of the preproNPY gene. Preliminary evidence was found for an association of both markers with a diagnosis of depression, indicating the possibility of an underlying haplotype influencing the vulnerability for developing depressive illness. Our present findings are in line with an extensive animal literature, and further support the notion that impaired NPY function could contribute to depressive illness.

Adult↗