Plasma oxytocin and personality traits in psychiatric outpatients.

The oxytocin system is regarded as being of relevance for social interaction. In spite of this, very few studies have investigated the relationship between oxytocin and personality traits in clinical psychiatric populations. We assessed the relationship between personality traits and plasma oxytocin levels in a population of 101 medication-free psychiatric outpatients (men = 37, women = 64). We used the Karolinska Scale of Personality (KSP) and diagnostic and symptomatic testing. Plasma oxytocin levels were analysed with a specific radioimmunoassay at inclusion and after one month for testing of stability. Plasma oxytocin levels were stable over time and did not differ between patients with or without personality disorders, nor were they related to severity of depressive or anxiety symptoms. The KSP factors Impulsiveness and Negative Emotionality were significant independent predictors of plasma oxytocin. A subscale analysis of these personality factors showed significant positive correlations between baseline plasma oxytocin and the KSP subscales monotony avoidance and psychic anxiety. The significant association between the KSP factor Impulsiveness and oxytocin levels observed at baseline was observed also one month later in men. These findings suggest that personality traits such as Impulsiveness and Negative emotionality which are linked to social functioning in several psychiatric disorders seem to be associated with endogenous plasma oxytocin levels. These variations in oxytocin levels might have an impact on social sensitivity or social motivation with possible gender differences.

Early switch strategy in patients with major depressive disorder: a double-blind, randomized study.

OBJECTIVE: Antidepressant switch is a commonly used strategy in the absence of an adequate response, but optimum timing is not well established. We compared the efficacy of an early and a conventional antidepressant switch strategy in patients with major depressive disorder. METHODS: Patients with no or minimal improvement (<30% reduction in baseline 17-item Hamilton Depression Rating Scale [HAMD17] score) after 4 weeks on escitalopram 10 mg/d were randomized to either early switch strategy with duloxetine 60 to 120 mg/d for 12 weeks (arm A) or conventional switch strategy (arm B): 4 further weeks on escitalopram 10 to 20 mg/d; then, in case of nonresponse (response, ≥ 50% reduction in HAMD17), switch to duloxetine 60 to 120 mg/d for 8 weeks, or continued escitalopram in responders. Co-primary end points were time to confirmed response and remission (HAMD17, ≤ 7). Strategies were compared using Kaplan-Meier, logistic regression, and repeated-measures analyses. RESULTS: Sixty-seven percent (566 of 840) of patients showed no or minimal improvement and were randomized to arm A (282 patients) or arm B (284 patients). No between-strategy differences in time to confirmed response (25% Kaplan-Meier estimates, 3.9 vs 4.0 weeks, P = 0.213) or remission (6.0 vs 7.9 weeks, P = 0.075) were found. Rates of confirmed responders were similar (64.9% vs 64.1%); however, more patients randomized to early switch achieved confirmed remission (43.3% vs 35.6%; P = 0.048). CONCLUSIONS: Although no differences in the primary end points were found, a higher remission rate was seen with the early switch strategy. Our findings suggest that further investigations to reevaluate the conventional approach to antidepressant switch strategy would be worthwhile.

The Scandinavian Solutions for Wellness study - a two-arm observational study on the effectiveness of lifestyle intervention on subjective well-being and weight among persons with psychiatric disorders.

BACKGROUND: Solutions for Wellness (SfW) is an educational 3-month program concerning nutrition and exercise for persons with psychiatric disorders on psychotropic medication, who have weight problems. This observational study assessed the impact of SfW on subjective well-being, weight and waist circumference (WC). METHODS: Data was collected at 49 psychiatric clinics. Where the SfW program was offered patients could enter the intervention group; where not, the control group. Subjective well-being was measured by the Subjective Well-being under Neuroleptics scale (SWN), at baseline, at the end of SfW participation, and at a follow-up 6 months after baseline. Demographic, disease and treatment data was also collected. RESULTS: 314 patients enrolled in the SfW group, 59 in the control group. 54% of the patients had schizophrenia, 67% received atypical antipsychotics, 56% were female. They averaged 41 +/- 12.06 years and had a BMI of 31.4 +/- 6.35. There were significant differences at baseline between groups for weight, SWN total score and other factors. Stepwise logistic models controlling for baseline covariates yielded an adjusted non-significant association between SfW program participation and response in subjective well-being (SWN increase). However, statistically significant associations were found between program participation and weight-response (weight loss or gain < 1 kg) OR = 2; 95% CI [1.1; 3.7] and between program participation and WC-response (WC decrease or increase < 2 cm) OR = 5; 95% CI [2.4; 10.3]), at 3 months after baseline. CONCLUSIONS: SfW program participation was associated with maintaining or decreasing weight and WC but not with improved subjective well-being as measured with the SWN scale.

Atomoxetine's effect on societal costs in Sweden.

OBJECTIVE: To compare societal costs between patients treated with atomoxetine and placebo in Sweden. METHOD: Ninety-nine pediatric ADHD patients were randomized to a 10-week double-blind treatment with atomoxetine (n = 49) or placebo (n = 50). All parents received four sessions of psycho-education. Parents filled out a resource utilization questionnaire covering the 10 weeks prior to treatment and the 10-week on-treatment period. Published unit costs/prices were used to calculate costs. RESULTS: Mean on-treatment costs in the atomoxetine group (SEK [Swedish Krona] 4,558) were significantly lower compared with placebo (SEK 7,684) after adjusting for baseline costs and site (p = .007). All 99 patients entered an open atomoxetine extension phase. Both groups had numerical reductions in direct and indirect costs while on atomoxetine treatment during the extension phase. The atomoxetine medication costs were offset by the reductions in direct nonmedical and indirect costs. CONCLUSIONS: These data provide preliminary evidence that atomoxetine together with parental psycho education reduces nonmedication costs associated with ADHD in Sweden.

Atomoxetine improves patient and family coping in attention deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled study in Swedish children and adolescents.

This 10-week study assessed the efficacy of atomoxetine in combination with psychoeducation compared to placebo and psychoeducation in the improvement of Quality of Life in Swedish stimulant-naive children and adolescents with attention deficit/hyperactivity disorder. A total of 99 patients were treated with atomoxetine (49 patients) or placebo (50 patients) for 10 weeks and assessed regarding broader areas of functioning using the Quality of Life measures Child Health and Illness Profile-Child Edition (CHIP-CE), Family Strain Index [FSI; equivalent to the Family Burden of Illness Module used in the study], Appraisal of Stress in Child-Rearing (ASCR), Five to fifteen (FTF), "I think I am" ("Jag tycker jag är"), and Children's Depression Rating Scale-Revised (CDRS-R) before and after the active treatment phase. Simultaneously, the patients' parents participated in a 4-session psychoeducation program. A statistically significant difference in favor of atomoxetine was seen in the improvement from baseline to study endpoint for the CHIP-CE domains "Achievement" and "Risk avoidance", for the FSI total score, for the ASCR section (I) domain "Child as a burden", for all FTF domains except for "Language and Speech", and for the CDRS-R total score. No difference between treatment groups was observed in the patient-assessed evaluation of self-esteem using the "I think I am" scale. Atomoxetine combined with psychoeducation had a positive effect on various everyday coping abilities of the patients as well as their families during 10 weeks of treatment, whereas the patients' self-image and the parents' image of the climate in the family were not significantly improved.

Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled study in stimulant-naïve Swedish children and adolescents.

OBJECTIVE: The primary objective of this study was to assess the impact of atomoxetine in combination with psychoeducation, compared with placebo and psychoeducation, on health-related quality of life (HRQL) in Swedish stimulant-naïve pediatric patients with attention deficit/hyperactivity disorder (ADHD). HRQL results will be presented elsewhere. Here, psychoeducation as well as efficacy and safety of the treatment are described. PATIENTS AND METHODS: A total of 99 pediatric ADHD patients were randomized to a 10-week double-blind treatment with atomoxetine (49 patients) or placebo (50 patients). Parents of all patients received four sessions of psychoeducation. Atomoxetine was dosed up to approximately 1.2 mg/kg day (< or = 70 kg) or 80 mg/day (> 70 kg). Improvement of ADHD symptoms was evaluated using the ADHD rating scale (ADHD-RS) and clinical global impression (CGI) rating scales. Safety was assessed based on adverse events (AEs). RESULTS: The study population was predominantly male (80.8%) and diagnosed with the combined ADHD subtype (77.8%). The least square mean (lsmean) change from baseline to endpoint in total ADHD-RS score was -19.0 for atomoxetine patients and -6.3 for placebo patients, resulting in an effect size (ES) of 1.3 at endpoint. Treatment response (reduction in ADHD-RS score of > or = 25 or > or = 40%) was achieved in 71.4 or 63.3% of atomoxetine patients and 28.6 or 14.3% of placebo patients. The lsmean change from baseline to endpoint in CGI-Severity was -1.8 in the atomoxetine group compared with -0.3 in the placebo group. The difference between treatments in CGI-Improvement at endpoint was -1.4 in favor of atomoxetine. No serious AEs occurred. The safety profile of atomoxetine was in line with the current label. CONCLUSIONS: Atomoxetine combined with psychoeducation was superior to placebo and psychoeducation in ADHD core symptoms improvement. The large ES might be a result of including stimulant-naïve patients only, but also may indicate a positive interaction between atomoxetine treatment and psychoeducation, possibly by increased compliance.

Capsulotomy for obsessive-compulsive disorder: long-term follow-up of 25 patients.

CONTEXT: Capsulotomy is sometimes used as a treatment of last resort in severe and treatment-refractory cases of obsessive-compulsive disorder (OCD). OBJECTIVE: To evaluate the long-term efficacy and safety of capsulotomy in OCD. DESIGN: Noncontrolled, long-term follow-up trial (mean of 10.9 years after surgery). SETTING: University hospital referral center. PATIENTS: Twenty-five consecutive patients with OCD who underwent capsulotomy from 1988 to 2000. INTERVENTION: Unilateral or bilateral capsulotomy. Lesions were created by means of radiofrequency heating (thermocapsulotomy) or gamma radiation (radiosurgery, gammacapsulotomy). MAIN OUTCOME MEASURE: Yale-Brown Obsessive-Compulsive Rating Scale (Y-BOCS) score. RESULTS: The mean Y-BOCS score was 34 preoperatively and 18 at long-term follow-up (P < .001). Response (defined as > or = 35% reduction at long-term follow-up compared with baseline) was seen in 12 patients at long-term follow-up. Nine patients were in remission (Y-BOCS score, < 16) at long-term follow-up. Only 3 patients were in remission without adverse effects at long-term follow-up. Response rates did not differ significantly between surgical methods. A mean weight gain of 6 kg was reported in the first postoperative year. Ten patients were considered to have significant problems with executive functioning, apathy, or disinhibition. Six of these 10 patients had received high doses of radiation or had undergone multiple surgical procedures. Results of our magnetic resonance imaging analysis in 11 patients suggest that the OCD symptom reduction may be increased by reducing the lateral extension of the lesions, and a reduction in the medial and posterior extension may limit the risk of adverse effects (ie, smaller lesions may produce better results). CONCLUSIONS: Capsulotomy is effective in reducing OCD symptoms. There is a substantial risk of adverse effects, and the risk may vary between surgical methods. Our findings suggest that smaller lesions are safer and that high radiation doses and multiple procedures should be avoided.

Long-term outcome of patients with dysthymia and panic disorder: a naturalistic 9-year follow-up study.

The highly prevalent psychiatric disorders dysthymia and panic disorder have often a chronic or recurrent course with superimposed major depression. The prominent comorbidity between these diagnoses constitutes a confounding factor in the study of long-term outcome. We performed a 9-year follow-up of 38 patients with "pure" diagnoses, i.e. without comorbid dysthymia and panic disorder, selected from two 2-year naturalistic treatment studies with psychotherapy and antidepressant medication. The aims of the present study were to investigate 1) the stability of change, and 2) the impact of comorbid personality disorders (PDs) on long-term outcome. Patients were reassessed with SCID-I and SCID-II interviews, SCL-90/BSI and a detailed, modified life-charting interview, investigating course and treatment over time. About 50% of patients showed substantial improvement, of whom about half were in remission. Comorbid PD was a negative prognostic factor independently of Axis I diagnosis. Although patients with panic disorder had a lower frequency of comorbid PD, later onset, shorter duration of illness and better outcome after the original studies, there was no difference in the long-term outcome. The less stable outcome among panic patients suggests that standard treatments are not resulting in enduring remission. In order to achieve remission, it is necessary to 1) address comorbid PDs, 2) perform careful assessments of all comorbid diagnoses, and 3) build routines for the follow-up and augmentation of treatments.

Long-term changes in self-reported personality following capsulotomy in anxiety patients.

The objective of the study was to describe changes in self-reported personality in anxiety patients undergoing capsulotomy. Sixteen patients with anxiety diagnoses undergoing capsulotomy were included. Ratings of personality characteristics with the Karolinska Scales of Personality (KSP), anxiety symptoms and adverse effects such as apathy and dysexecution were performed at baseline, at 1 year and 8-18 years post-operatively. Twelve patients had an anxiety reduction of at least 50%. Patients were significantly less anxiety prone at long-term follow-up as measured by KSP. Four patients suffered from adverse effects indicating frontal lobe dysfunction. There was no significant correlation between the reduction in BSA score and the KSP change from pre-operatively to long term in any of the KSP scales. In line with previous studies, high anxiety proneness normalizes after capsulotomy in anxiety patients. Adverse effects were more frequent than expected. The conclusion based on previous KSP findings that the incidence of adverse personality changes following capsulotomy is low and does not increase with time is challenged by the present study.

Lesion topography in capsulotomy for refractory anxiety--is the right side the right side?

OBJECTIVE: A previous report on bilateral capsulotomy in obsessive-compulsive disorder showed common topographic features of lesions in the right-sided internal capsule in all patients responding to the treatment. The aims of the present study were to test if the same region was involved in anxiety patients responding to surgery and to examine whether lesion area and site correlated with adverse events and effect on target symptoms. METHOD: Eleven anxiety patients who had undergone bilateral thermocapsulotomy were examined after 8-23 years. A quantitative MRI evaluation of the lesions within the internal capsule was conducted in three axial planes. RESULTS: None of the eight responders had lesions that corresponded to the earlier reported right-sided anatomical denominator. Four patients out of 11 were rated as having significant clinical symptoms indicating frontal lobe dysfunction. The total sum of the lesion area determined in each of the three anatomical levels did not correlate with the degree of anxiety reduction. However, the lesion area appeared to be related to a rating of executive dysfunctioning, apathy and disinhibition.

Self-assessment of DSM-IV criteria for major depression in psychiatric out- and inpatients.

The Depression Self-Rating Scale (DSRS) is a self-report inventory based on the DSM-IV criteria for major depression. This study aimed to investigate diagnostic concordance of a major depressive disorder (MDD) using the DSRS and the Structured Clinical Interview for DSM-IV, axis I disorders (SCID-I). An additional aim was to investigate whether concordance could be improved by adding different cut-off scores for the Beck Depression Inventory (BDI) or the self-report version of the Montgomery-Asberg Depression Rating Scale (MADRS-S). MDD was determined by means of the SCID-I interview and the DSRS in 83 psychiatric in- and outpatients. Depressive severity was assessed using the BDI and the MADRS-S. A DSRS-version including the A- and C-criteria for an MDD had a sensitivity and a specificity for an expert-rated diagnosis of 86% and 75%, respectively. By using cut-off scores for the BDI or the MADRS-S, specificity could be raised to 85% without loss of sensitivity. The DSRS appears to be a useful instrument in the diagnostic process involving MDD, particularly when used in combination with the BDI or the MADRS-S. The DSRS is thought to be of value in psychiatric outpatient departments, where treatment of patients is often delegated to paramedical staff or nurses. The scale might also be used as an independent diagnostic tool in epidemiological studies in order to achieve an estimate of the prevalence of MDD in different population settings.

Capsulotomy for refractory anxiety disorders: long-term follow-up of 26 patients.

OBJECTIVE: The objective of the present study was to evaluate the long-term efficacy and safety of capsulotomy in patients with anxiety disorders. METHOD: Twenty-six patients who had undergone bilateral thermocapsulotomy were followed up 1 year after the procedure and after a mean of 13 years. Primary diagnoses were generalized anxiety disorder (N=13), panic disorder (N=8), and social phobia (N=5). Measures of psychiatric status included symptom rating scales and neuropsychological testing. Ratings were done by psychiatrists not involved in patient selection or postoperative treatment. A quantitative magnetic resonance imaging (MRI) evaluation was conducted to search for common anatomic denominators. Seventeen of the 23 patients who were alive at long-term follow-up were followed up in person, and one was interviewed by telephone; the relatives of these 18 patients were interviewed. RESULTS: The reduction in anxiety ratings was significant both at 1-year and long-term follow-up. Seven patients, however, were rated as having substantial adverse symptoms; the most prominent adverse symptoms were apathy and dysexecutive behavior. Neuropsychological performance was significantly worse in the patients with adverse symptoms. No common anatomic denominator could be found in responders in the analysis of MRI scans. CONCLUSIONS: Thermocapsulotomy is an effective treatment for selected cases of nonobsessive anxiety but may carry a significant risk of adverse symptoms indicating impairment of frontal lobe functioning. These findings underscore the importance of face-to-face assessments of adverse symptoms.

Pentagastrin test for anxiety--psychophysiology and personality.

RATIONALE: CCK(B) receptor agonists such as pentagastrin or CCK(4) have anxiogenic panic-like effects in humans. Our previous findings are in agreement with a relationship between C-peptide plasma levels (as a measure of insulin release) and sensitivity to psychotropic activation by CCK(B) receptor stimulation. OBJECTIVES: Our present aim was to study the transient humoral, physiological and psychotropic effects of pentagastrin bolus injection and whether personality might affect the outcome. METHODS: Pentagastrin was given in bolus i.v. injections to healthy volunteers at increasing doses (0.003, 0.012, 0.05 and 0.2 microg/kg). Physiological parameters were recorded before and during each pentagastrin challenge and humoral variables described previously were included in the analyzes. Subjects rated the discomfort following pentagastrin administration on the state anxiety and discomfort scale (SADS). The Karolinska scale of personality (KSP), anxiety sensitivity index (ASI) and Hamilton anxiety scale (HAS) were used to characterize the subjects before the test. RESULTS: Galvanic skin response (GSR) and heart rate (HR) were significantly increased within 1 min following 0.2 microg/kg pentagastrin, the GSR increase correlating negatively to the C-peptide increase and positively to ratings on SADS. Even the lower dose (0.05 microg/kg pentagastrin) induced a significant increase in GSR. ASI measures correlated weakly to the increase in ratings on SADS following 0.05 microg/kg and 0.2 microg/kg pentagastrin. CONCLUSIONS: We found correlations between psychophysiology, humoral response and subjective ratings following pentagastrin administration. CCK(B) receptor stimulation might reveal phenotype properties predictive of anxiety-related traits, measurable through serum levels of C-peptide. Furthermore, our results support the predictive value of ASI for fearfulness.

Anxiogenic effects of the CCK(B) agonist pentagastrin in humans and dose-dependent increase in plasma C-peptide levels.

RATIONALE: Cholecystokinin type B (CCK(B)) receptor agonists such as pentagastrin or CCK-4 have panic-like anxiogenic effects in humans. It has also been shown that CCK-4 can stimulate insulin release and thus C-peptide release from pancreatic islet cells. Combined, these mechanisms may provide a basis for a bioassay. OBJECTIVES: Our aim was to study if a pentagastrin bolus injection evokes insulin release (as measured by C-peptide) and if the levels of C-peptide correlate to the anxiogenic effect of pentagastrin. METHODS: Pentagastrin was given in bolus IV injections to healthy volunteers at increasing doses (0.003, 0.012, 0.05 and 0.2 microg/kg). RESULTS: A significant increase in the plasma level of C-peptide was observed 2-4 min after the highest dose of pentagastrin. This increase was accompanied by a transient panic-like anxiety within 2 min following pentagastrin, measured using a state anxiety scale. Also, 0.05 microg/kg pentagastrin gave a minor but significant subjective discomfort at the same time interval. The basal plasma level of C-peptide preceding the pentagastrin injection showed a positive correlation to the intensity of the subsequent pentagastrin-induced panic-like anxiety as rated on the state anxiety scale. In addition, basal plasma levels of cortisol were positively correlated to the subsequent pentagastrin-induced increase in plasma C-peptide levels. CONCLUSIONS: Our results imply a possible relationship between insulin/C-peptide release and sensitivity to psychotropic activation by CCK(B) receptor stimulation. Furthermore, we postulate that both basal and pentagastrin-induced plasma levels of C-peptide may possess characteristic phenotype properties for anxiety related traits.