Does atomoxetine improve executive function, inhibitory control, and hyperactivity? Results from a placebo-controlled trial using quantitative measurement technology.

The primary objective of this study was to evaluate the efficacy of atomoxetine (ATX) on attention-deficit/hyperactivity disorder (ADHD)-related symptoms assessed as standard variables of a computer-based continuous performance test (cb-CPT) combined with a motion-tracking (MT) device. This was a 2-arm, 8-week, randomized, double-blind, placebo-controlled study in patients with ADHD (6-12 years). Therapy with ATX started with 0.5 mg/kg per day for 1 week, followed by 7 weeks on the target dosage of 1.2 mg/kg per day. Primary outcomes were cb-CPT/MT standard scores after 8 weeks using mixed models for repeated measurements. In addition, investigator-rated ADHD Rating Scale (ADHD-RS), Weekly Ratings of Evening and Morning Behavior (WREMB), and Clinical Global Impression - Severity-ADHD (CGI-S-ADHD) scores were assessed. Of 128 patients randomized, 125 were evaluated (ATX/placebo: 63/62). Baseline characteristics were comparable in both groups (overall, 80.2% boys; mean [SD] age, 9.0 [1.79] years; comorbid Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis, 40.0% oppositional defiant disorder/conduct disorder; prior stimulant treatment, 24.8%; ADHD-RS total score, 36.99 [11.56]). At week 8, all cb-CPT/MT q-scores were significantly reduced versus placebo (all P < 0.001) with effect sizes (ESs) of reaction time (RT) variation (ES = 0.71), mean RT (ES = 0.41), number of microevents (ES = 1.00), commission error rate (ES = 0.50), distance of movement (ES = 0.90), area of movement (ES = 1.08), omission error rate (ES = 0.70), time active (ES = 0.69), motion simplicity (ES = 0.38), and normalized variance of RT (ES = 0.50). Secondary end points also improved significantly in favor of ATX: ADHD-RS (total score ES = 1.30, P < 0.001; hyperactivity/impulsivity subscore ES = 1.37, P < 0.001; inattention subscore ES = 1.07, P < 0.001), WREMB (total score ES = 1.00, P < 0.001; morning subscore ES = 0.59, P = 0.002; evening subscore ES = 1.02, P < 0.001), CGI-S-ADHD (ES = 1.11, P < 0.001). The results of this study show that ATX for 8 weeks significantly reduced ADHD-related symptoms as measured by the cb-CPT/MT.

Differential 3-year effects of first- versus second-generation antipsychotics on subjective well-being in schizophrenia using marginal structural models.

OBJECTIVE: This study examined the differential effects of first- (FGAs) versus second-generation antipsychotics (SGAs) on subjective well-being in patients with schizophrenia. METHOD: Data were collected in an observational 3-year follow-up study of 2224 patients with schizophrenia. Subjective well-being was assessed with the Subjective Well-being under Neuroleptic Treatment Scale (SWN-K). Differential effects of FGAs versus SGAs were analyzed using marginal structural models in those patients taking antipsychotic monotherapy. RESULTS: The marginal structural model, which analyzed the differential effect on the SWN-K total score, revealed that patients on SGAs had significantly higher SWN-K total scores, starting at 6 months (3.02 points; P = 0.0061, d = 0.20) and remaining significant thereafter (end point: 5.35 points; P = 0.0074, d = 0.36). CONCLUSIONS: Results of this large observational study are consistent with a small but clinically relevant superiority of SGAs over FGAs in subjective well-being extending previous positive findings of differential effects on quality of life.

Effect of atomoxetine on quality of life and family burden: results from a randomized, placebo-controlled, double-blind study in children and adolescents with ADHD and comorbid oppositional defiant or conduct disorder.

PURPOSE: To evaluate the effect of atomoxetine on quality of life (QoL) and family burden in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant (ODD) or conduct disorder (CD). METHODS: This secondary analysis was based on a randomized, double-blind, 9-week study of atomoxetine (target dose 1.2 mg/kg body weight) versus placebo. The study included 180 patients (atomoxetine 121, placebo 59), aged 6-17 years. QoL was measured using the KINDL-R questionnaire. The total score encompasses six dimensions (or subscales) measuring QoL in terms of "physical well-being", "emotional well-being", "self-esteem", "friends", "family", and "school". Family burden of illness was measured using the FaBel questionnaire. RESULTS: With atomoxetine, the KINDL-R total score improved significantly (P = 0.021) more than with placebo. This improvement also applied to the subscales except for "physical well-being" (opposite effect) and "school" (no effect). No significant treatment group differences were seen on the FaBel questionnaire. No differences were found between the fast and slow titration groups in terms of ADHD, ODD, and disruptive behavior severity. Furthermore, no such differences were observed for QoL and family burden. CONCLUSIONS: This study suggests positive effects of atomoxetine on quality of life, as measured by the KINDL-R scores on emotional well-being, self-esteem, friends and family, in children and adolescents with ADHD and comorbid ODD/CD. No significant treatment effects were seen on family burden, as measured by FaBel total score.

Quality of life and attention-deficit/hyperactivity disorder core symptoms: a pooled analysis of 5 non-US atomoxetine clinical trials.

The objective of this pooled analysis was to correlate parameters related to quality of life with attention-deficit/hyperactivity disorder (ADHD) core symptoms analyzing data of 5 atomoxetine clinical trials in children and adolescents with ADHD. Data from 5 clinical trials (4 from Europe and 1 from Canada) with similar inclusion/exclusion criteria and similar duration (8-12 weeks' follow-up) were included. All studies used the Child Health and Illness Profile, Child Edition (CHIP-CE), parent rating form at baseline and end point. Correlation coefficients and effect sizes to ADHD-Rating Scale (ADHD-RS) scores were calculated. A total of 794 patients aged 6 to 15 years (mean, 9.7 years), with mean (SD) baseline Clinical Global Impression of Severity of 4.8 (0.89) and ADHD-RS of 41.8 (8.04), were included. Baseline total CHIP-CE mean t score (standard, 50 [10]) was 28.9 (11.76), and the strongest impairments were seen in risk avoidance (30.2 [14.62]) and achievement (30.5 [10.4]) domains. At baseline, CHIP-CE versus ADHD-RS correlation was low (total, -0.345) except for the risk avoidance domain (total, -0.517). For changes from baseline to end point, a low correlation between the scales was found (total, -0.364; placebo-controlled studies only, n = 372). Quality of life impairment in ADHD was found in CHIP-CE total score and several domains. Correlations between CHIP-CE and ADHD-RS at baseline, end point, and for change from baseline to end point were low to moderate. These findings suggest that measuring quality of life adds clinically relevant insight beyond core symptom evaluation in children and adolescents with ADHD.

Development and Validation of a Brief Measure of Self-Management Competence: The Self-Management Self-Test (SMST).

BACKGROUND: Self-management can be considered a way of dealing with oneself and relates to actions undertaken to create order, discipline, and control. The concept is closely linked to concepts of self-efficacy and self-regulation but can be distinguished from these. The Self-Management Self-Test (SMST) is a 5-item assessment scale designed to measure self-management competence in individuals with or without a psychiatric disorder (as screened using PHQ). The aim of this study was to validate the SMST in terms of convergent validity, the ability to differentiate, criterion validity, internal consistency, and test-retest reliability. METHODS: Eighty-seven adults hospitalized for treatment of major depression (clinical sample) and 595 individuals from the general population (population sample) filled out the SMST and 5 other stress-related psychometric instruments measuring similar constructs. All instruments were repeated 4 to 6 weeks later. Convergent validity, internal consistency, and test-retest reliability were tested based on data from the population sample. Convergent validity was determined by correlations with other stress-related psychometric instruments. Correlations in the range of r = -0.4 to -0.6 were expected. To test for criterion validity, the clinical sample was matched with a subsample from the population sample, consisting only of individuals without a psychiatric disorder as screened using PHQ (nonclinical subsample, n = 87). The ability to differentiate was based on receiver operating characteristic (ROC) curve analysis. RESULTS: Correlations between the SMST and the other stress-related tests were significant and in the expected direction and predominantly within the expected range (Pearson r = - 0.40 to -0.64). The correlation with the Multidimensional Fatigue Inventory-20, measuring fatigue, and with the dimensional scale for depression in the PHQ was higher than expected and referred to very similar items. Thus, convergent validity mainly lay within the expected range. Internal consistency was high (Cronbach α = 0.80), and test-retest reliability was fairly low (r = 0.71). The SMST showed a significant difference, t(157) = 7.97, P < .001, between the clinical sample (M = 9.36, SD = 3.39) and the nonclinical subsample (M = 12.94, SD = 2.47) with a large effect size (d = 1.3). The area under the ROC curve (AUC) was excellent (AUC = 0.81, SE = 0.034, P < .001), suggesting that the SMST can distinguish between the clinical and nonclinical samples. CONCLUSIONS: The SMST can be considered an effective self-rating test to assess self-management competence in individuals from the general population as well as in people with major depression. It may also be useful to detect treatment outcomes in people with major depression. The high internal consistency indicates that all 5 items are important for the test as a whole. The low test-retest reliability suggests sensitivity to change. The SMST is likely to differentiate particularly well at low levels of self-management competence, suggesting it may be a useful tool in studies investigating people with depression or other psychiatric disorders such as post-traumatic stress disorder. Furthermore, the SMST could be useful in assessing the effect of treatment interventions over time and evaluating patient-reported outcomes.

Effects of clozapine and olanzapine on cytokine systems are closely linked to weight gain and drug-induced fever.

The second generation antipsychotics clozapine and olanzapine are known to cause weight gain. However, only clozapine is associated with drug-induced fever. Cytokines have been linked to the induction of both weight gain and drug-induced fever. We investigated these potential side effects of clozapine and olanzapine and studied their differential effects on cytokine secretion. Thirty patients suffering from schizophrenia, schizophreniform disorder or schizoaffective disorder were treated with either clozapine (mean modal dose: 266.7+/-77.9mg) or olanzapine (21.2+/-2.5mg) in a randomized, double-blind, 6-week study. Body mass index (BMI), tympanic temperature, and plasma levels of leptin and cytokines (tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 and 2 (sTNFR-1/2), soluble interleukin-2 receptors (sIL-2R), interleukin-6) were determined weekly. BMI, leptin and cytokines significantly increased over time, except interleukin-6 and sTNFR-1 in the olanzapine group. All cytokines numerically increased compared to baseline already during the first week of treatment in both groups. Leptin, TNF-alpha, sTNFR-1, sTNFR-2 and sIL-2R levels correlated with the BMI. Five patients who received clozapine (33%) developed drug-induced fever (>/=38 degrees C). In these, interleukin-6 peak levels were significantly (p<0.01) higher than in those patients treated with clozapine who did not develop fever. In conclusion, increase of BMI appears to be related to clozapine's and olanzapine's similar effects on cytokine systems, whilst drug-induced fever appears to be related to clozapine's differential effects on interleukin-6.

Long-term patterns of subjective wellbeing in schizophrenia: cluster, predictors of cluster affiliation, and their relation to recovery criteria in 2842 patients followed over 3 years.

OBJECTIVE: To study the longitudinal patterns of subjective wellbeing in schizophrenia using cluster analysis and their relation to recovery criteria, further to examine predictors for cluster affiliation, and to evaluate the sensitivity and specificity of baseline subjective wellbeing cut-offs for cluster affiliation. METHODS: Data was collected in an observational 36-month follow-up study of 2842 patients with schizophrenia in Germany. Subjective wellbeing was assessed using the SWN-K scale. Cluster analyses were applied based on Ward's procedure. Predictors were analyzed using logistic regression models. Optimal SWN-K total score cut-off points for cluster affiliation were analyzed using Cohen's kappa. RESULTS: 4 distinct clusters were identified: a stable low (33%), a stable moderate (31%), a stable high (16%), and a cluster with distinct initial improvement and then stable high subjective wellbeing (20%). Highly concordant patterns were also observed for symptoms, social functioning, and quality of life. Sensitivity and specificity of SWN-K total score cut-offs at baseline were 82.8% and 63.8% for or=80 points for the stable high cluster. Affiliation to the stable low cluster was related to a 0.6% chance of being in recovery at 3-year endpoint. CONCLUSIONS: Long-term patterns of subjective wellbeing are stable and highly concordant with course of symptoms, functioning level, and quality of life. Baseline subjective wellbeing cut-off points were found to be sufficient predictors of outcome, which, particularly in case of impaired subjective wellbeing and low baseline functioning level, make early treatment adaptations mandatory.

Development and Validation of a Brief Measure of Self-Management Competence: The Self-Management Self-Test (SMST).

BACKGROUND: Self-management can be considered a way of dealing with oneself and relates to actions undertaken to create order, discipline, and control. The concept is closely linked to concepts of self-efficacy and self-regulation but can be distinguished from these. The Self-Management Self-Test (SMST) is a 5-item assessment scale designed to measure self-management competence in individuals with or without a psychiatric disorder (as screened using PHQ). The aim of this study was to validate the SMST in terms of convergent validity, the ability to differentiate, criterion validity, internal consistency, and test-retest reliability. METHODS: Eighty-seven adults hospitalized for treatment of major depression (clinical sample) and 595 individuals from the general population (population sample) filled out the SMST and 5 other stress-related psychometric instruments measuring similar constructs. All instruments were repeated 4 to 6 weeks later. Convergent validity, internal consistency, and test-retest reliability were tested based on data from the population sample. Convergent validity was determined by correlations with other stress-related psychometric instruments. Correlations in the range of r = -0.4 to -0.6 were expected. To test for criterion validity, the clinical sample was matched with a subsample from the population sample, consisting only of individuals without a psychiatric disorder as screened using PHQ (nonclinical subsample, n = 87). The ability to differentiate was based on receiver operating characteristic (ROC) curve analysis. RESULTS: Correlations between the SMST and the other stress-related tests were significant and in the expected direction and predominantly within the expected range (Pearson r = -0.40 to -0.64). The correlation with the Multidimensional Fatigue Inventory-20, measuring fatigue, and with the dimensional scale for depression in the PHQ was higher than expected and referred to very similar items. Thus, convergent validity mainly lay within the expected range. Internal consistency was high (Cronbach α = 0.80), and test-retest reliability was fairly low (r = 0.71). The SMST showed a significant difference, t(157) = 7.97, P < .001, between the clinical sample (M = 9.36, SD = 3.39) and the nonclinical subsample (M = 12.94, SD = 2.47) with a large effect size (d = 1.3). The area under the ROC curve (AUC) was excellent (AUC = 0.81, SE = 0.034, P < .001), suggesting that the SMST can distinguish between the clinical and nonclinical samples. CONCLUSIONS: The SMST can be considered an effective self-rating test to assess self-management competence in individuals from the general population as well as in people with major depression. It may also be useful to detect treatment outcomes in people with major depression. The high internal consistency indicates that all 5 items are important for the test as a whole. The low test-retest reliability suggests sensitivity to change. The SMST is likely to differentiate particularly well at low levels of self-management competence, suggesting it may be a useful tool in studies investigating people with depression or other psychiatric disorders such as post-traumatic stress disorder. Furthermore, the SMST could be useful in assessing the effect of treatment interventions over time and evaluating patient-reported outcomes.

Patterns of physician and patient rated quality of life during antipsychotic treatment in outpatients with schizophrenia.

Quality of life (QoL) in patients with schizophrenia has been assessed both from physician and patient perspectives, but little is known about agreement between these perspectives and predictors of agreement. The aim of this study was to analyze a large sample of patients with schizophrenia to discover patterns of physician and patient-rated QoL in patients with schizophrenia and identify predictors for these patterns. This study (EASE) was designed to investigate the QoL and subjective well-being in out-patients with schizophrenia during antipsychotic treatment in a naturalistic setting. Assessments were carried out at baseline and at 3, 6, 9 and 12 months, using the quality of life scale (QLS) and the subjective well-being on neuroleptics scale (SWN-K). A hierarchical cluster analysis was used to define groups of patients based on the SWN-K and QLS total scores at all visits. 1174 patients were included in the cluster analyses that were based on SWN-K and QLS total scores over time. Four distinct clusters were identified: patients with: (1) continuously high QoL (23.2%), (2) continuously moderate QoL (45.8%), (3) continuously low QoL (11.2%), and (4) improving QoL (19.9%). Clusters 1-3 were stable in terms of QoL, whilst cluster 4 changed towards improvement. Various predictors for the four clusters were identified. In the cluster with improving QoL, the absence of treatment with an oral conventional antipsychotic pre-study and no medication change due to lack of efficacy at baseline were predictors for improvement. In the cluster with continuously high QoL, no medication change due to lack of efficacy and lowest CGI-S scores at baseline were predictors. Oral conventional antipsychotic treatment pre-study was predictive for the cluster with continuously moderate QoL. In the cluster with continuously low QoL, medication change due to lack of efficacy and highest CGI-S scores were predictors. These findings suggest that various factors may predict whether a patient with schizophrenia experiences a continuously high QoL, a continuously moderate QoL, a continuously low QoL, or improving QoL whilst on antipsychotic treatment.

Effectiveness and tolerability of olanzapine in the treatment of adolescents with schizophrenia and related psychotic disorders: results from a large, prospective, open-label study.

OBJECTIVE: The aim of this study was to assess effectiveness and tolerability of oral olanzapine treatment of adolescents with schizophrenic disorders. METHOD: Adolescent patients (12-19 years) with schizophrenia, schizoaffective, or schizophreniform disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) were enrolled in a multicenter, prospective, open-label study. Following a 2- to 9-day washout period, patients initially received 10 mg/day olanzapine. Dose modification was allowed during week 2 (dose range 5-15 mg/day) and during weeks 3-6 (dose range, 5-20 mg/day). Responders (improvement > or =30% on the Brief Psychiatric Rating Scale, BPRS) continued olanzapine for additional 18 weeks. Psychopathology was assessed using BPRS and Clinical Global Impressions (CGI) scales; side effects were assessed by adverse event reporting. RESULTS: Out of 96 patients enrolled at 10 sites, 60 (62.5%) met response criteria at week 6. Mean BPRS total scores decreased significantly (p < 0.001) from baseline (39.2 +/- 13.4) to week 6 last observation carried forward (LOCF) (22.2 +/- 14.7). The rate of patients considered markedly ill or worse (CGI-S) decreased from 83.3% (baseline) to 37.5% (week 6, LOCF). The most common reported adverse event was weight gain (30.2%, 29/96). Three patients (3.1%) discontinued due to adverse events. CONCLUSIONS: In this study of young patients with schizophrenia, schizoaffective, or schizophreniform disorders, olanzapine treatment was associated with marked symptom improvement. As changes in weight and prolactin levels may be greater in adolescent than in adult patients, potential risks and benefits of olanzapine treatment in adolescents should be considered carefully.

The effects of music therapy on the interaction of the self and emotions-An interim analysis.

OBJECTIVES: Music therapy is a well-established non-verbal treatment method in psychiatry and psychosomatic medicine. However, empirical data of its impact on emotion modulation processes and personality dimensions are still sparce. An interesting concept is the use of music for emotion modulation in everyday life. The purpose of this interim study was to assess the interplay of personality dimensions and emotion modulation strategies in patients treated with music therapy versus patients without music therapy. DESIGN: A cross-sectional design was used. SETTING: The study was conducted during the course of inpatient treatment in a general psychiatric hospital. Data from n = 137 patients was included in the analysis. MAIN OUTCOME MEASURES: According to the mediator model a regression analysis was performed using personality variables as potential predictors and emotion modulation variables as outcome criteria. RESULTS: In the music therapy group, insecurity predicted the use of music for both cognitive problem solving and positive stimulation in everyday life. In the non-music therapy group, cooperation and insouciance predicted the use of music for reduction of negative activation. CONCLUSIONS: Specific personality dimensions predict greater targeted emotion modulation strategies if music therapy is applied than without it. That is, music therapy helps patients acquire more conscious (i.e. cognitive-related strategies) emotion modulation techniques by means of including their individual personality, whereas patients without music therapy simply "vent" their negative emotions (i.e. non-cognitive strategies). Conversely, the data suggest that music therapy can contribute to modify personality dimensions through the development of these emotion modulation strategies. This could be a plausible explanation for beneficial long-term effects of music therapy.

Correlation of physician and patient rated quality of life during antipsychotic treatment in outpatients with schizophrenia.

Perception of quality of life (QOL) may differ depending on the perspective. This 12-month, prospective, naturalistic study compared QOL ratings in outpatients on antipsychotic treatment for schizophrenia both from a "subjective" patient rated and an "objective" physician rated perspective. Included were 1462 patients. Two scales were used to assess patient and physician perspectives: the Subjective Well-being on Neuroleptics (SWN) scale and the Quality of Life Scale (QLS). Linear correlation was found between both ratings: 10 points on the SWN corresponded to 9.35 points on the QLS. Spearman's correlation coefficients increased over time up to r=0.71 at Month 12. Patients were grouped into four cohorts depending on the degree of concordance between SWN and QLS ratings. Several factors affecting the concordance of both ratings were identified. Compared to the cohort with QLS=SWN, higher QOL ratings by the physician (QLS>>SWN) were more likely in females than in males (OR=1.36; 95% CI 1.00 - 1.85) and in older than in younger patients (50 years: OR=0.58, 95% CI 0.34 - 0.998), but less likely in patients with high baseline CGI-severity (CGI >4; OR=0.63; 95% CI 0.47 - 0.86) or treatment with oral typicals before baseline (OR=0.53; 95% CI 0.31 - 0.91). Higher QOL ratings by the patient (SWN>>QLS) were less likely in patients with psychotherapy before baseline (OR=0.54; 95% CI 0.36 - 0.81), medication intolerability before baseline (OR=0.53; 95% CI 0.36 - 0.78) or patient request of treatment change at baseline (OR=0.64; 95% CI 0.42 - 0.96). The combination of several factors predicted concordant ratings, including male sex, young age, high CGI at baseline, and psychotherapy prior to the study.

Quality of life and subjective well-being during treatment with antipsychotics in out-patients with schizophrenia.

OBJECTIVE: To assess the Quality of Life (QOL) in outpatients with schizophrenia under antipsychotics from two perspectives: a "subjective" perspective as rated by the patient and an "objective" perspective as rated by the physician. METHOD: EASE (External Assessment of Quality of Life in Out-patients with Schizophrenia) is a 12-month, prospective, naturalistic study of the QOL in patients on antipsychotic treatment for schizophrenia in an out-patient setting in Germany. The study included 1462 patients who were initiated on a new antipsychotic or switched to another antipsychotic. The Subjective Well-being under Neuroleptics scale (SWN) and the Quality of Life Scale (QLS) were used to assess the QOL in these patients. The Clinical Global Impression (CGI) scale was used to assess overall symptom severity. Four cohorts were identified and evaluated: (a) patients treated with olanzapine monotherapy (N=1007), (b) another atypical antipsychotic as monotherapy (N=335), (c) a typical antipsychotic as monotherapy (N=32) and (d) combination therapy with more than one antipsychotic (N=88). RESULTS: QOL as assessed by both SWN and QLS improved in all treatment cohorts. SWN responses in the respective cohorts were (a) 52.3%, (b) 38.8%, (c) 31.3% and (d) 44.3%, whilst the QLS responses were (a) 58.2%, (b) 45.1%, (c) 59.4% and (c) 40.9%. Symptom severity as assessed by the CGI also improved over time regardless of the type of antipsychotic. An increase of one point on the CGI corresponded to a change in SWN total score of -9.67 points and a change in QLS total score of -13.36 points. CONCLUSIONS: Both QOL and symptom severity improved over the 12-month study period, regardless of the type of antipsychotic taken. QOL improvement as perceived both from a "subjective" and an "objective" perspective was greatest in the cohort on olanzapine monotherapy.

Effectiveness of atomoxetine and quality of life in children with attention-deficit/hyperactivity disorder as perceived by patients, parents, and physicians in an open-label study.

OBJECTIVES: Health-related quality of life in children with attention-deficit/hyperactivity disorder (ADHD) may improve with atomoxetine treatment. However, the degree of improvement may be perceived differently by patients, parents, and physicians. The primary aim of this study was to investigate ADHD-related difficulties as perceived from these three perspectives and to compare the perspectives. The degree of perceived difficulties was taken to reflect the health-related quality of life of patients in the study. A second objective was to assess the effectiveness of atomoxetine in children with ADHD in an open-label setting. METHODS: Children aged 6-11 years with ADHD were treated for 24 weeks with atomoxetine at a target dose of 0.5-1.2 mg/kg per day. ADHD-related difficulties were assessed after 8 and 24 weeks of treatment using the newly devised Global Impression of Perceived Difficulties (GIPD) scale. This instrument, that has not yet been psychometrically validated, reflects patient quality of life from the three perspectives. Agreement among the perspectives was determined using Cohen's kappa. RESULTS: A total of 262 patients was treated with atomoxetine. The mean dose for the respective visit intervals ranged between 1.15 and 1.17 mg/kg per day. Quality of life as reflected by the degree of perceived difficulties improved over time. Change in GIPD scores was greatest within the first 2 weeks. The course of the mean GIPD total scores over time showed a similar pattern among the three different rater perspectives. However, patients perceived the degree of difficulties as significantly less compared to parents and physicians. Agreement of ratings was highest between physicians and parents. CONCLUSIONS: Results from the GIPD suggest that patient quality of life improves with time on atomoxetine. The effectiveness of atomoxetine in an open-label study was very similar to the effectiveness shown in placebo-controlled trials.

Clozapine-induced weight gain: a study in monozygotic twins and same-sex sib pairs.

To assess the relative contribution of genetic factors in antipsychotic-induced weight gain, we explored the similarity in body mass index (BMI) (kg/m(2)) change under clozapine only (clozapine DeltaBMI) and upon additional inclusion of BMI change under prior antipsychotic medication (total DeltaBMI) of five monozygotic twins in comparison with seven same-sex sibs. Twin and sib pairs were identified by a telephone screening of 786 office-based psychiatrists. Measured data on weight and other clinical variables were obtained cross-sectionally and retrospectively from medical records. We found greater similarity in total DeltaBMI in monozygotic twins (intrapair difference 2.78+/-3.41 kg/m(2)) than in same-sex sibs (5.55+/-4.35 kg/m(2)), resulting in heritability estimates of h(2)=0.8 and A=0.45 (ACE twin model). However, intrapair differences in clozapine DeltaBMI were similar between twins (4.18+/-4.27 kg/m(2)) and sibs (4.68+/-4.88 kg/m(2)). We hypothesize that the weight plateau achieved under clozapine is influenced by genetic factors. The weight gain achieved during pretreatment with other antipsychotics seems to limit clozapine-induced weight gain, thus presumably explaining why heritability/similarity in monozygotic twins in comparison with same-sex sibs is greater for total DeltaBMI than for clozapine DeltaBMI. An important caveat is that, owing to the sample size, the heritability estimates have a large standard error and thus have to be interpreted with caution.

Clozapine: weight gain in a pair of monozygotic twins concordant for schizophrenia and mild mental retardation.

Clozapine is an atypical antipsychotic known to cause considerable weight gain. The extent to which genetic factors determine weight gain is unknown. Here we report on a pair of female monozygotic twins concordant for schizophrenia and mild mental retardation who were treated with clozapine over 5.5 years. One twin gained a total of 53.1 kg and had a weight of 107.5 kg (BMI=38.1 kg/m2) at the end of the observation period. The other twin gained a total of 48.2 kg and finally had a weight of 100.4 kg (BMI=33.8 kg/m2). Because both patients experienced considerable weight gain during treatment, our observation suggests that the antipsychotic-induced weight gain is under strong genetic control.

Treatment compliance or medication adherence in children and adolescents on ADHD medication in clinical practice: results from the COMPLY observational study.

Although the efficacy and tolerability of ADHD medications have been investigated fairly extensively, there are very few data comparing the different types of medication (e.g. psychostimulants, non-stimulants) in terms of medication adherence. The primary research objective of the COMPLY observational study was to evaluate medication adherence (i.e. compliance) over 1 year in children and adolescents with ADHD in a routine clinical setting. COMPLY was a prospective 12-month, observational, open-label study that included children and adolescents, aged 6-17 years, with ADHD. Medication adherence (i.e. compliance) was measured using the Pediatric Compliance Self-Rating (PCSR) instrument and using items 1-4 of the Medication Adherence Rating Scale (MARS). A total of 504 patients were enrolled. At baseline, 252 patients (50.0 %) were prescribed non-stimulant (atomoxetine) medication and 247 patients (49.0 %) were prescribed psychostimulant medication. Both types of medication were prescribed concomitantly in five patients (1.0 %). After 12 months, 123 patients (48.8 %) were taking atomoxetine and 176 patients (71.3 %) were taking psychostimulants. Adherence (PCSR score ≥ 5) was present in both groups (atomoxetine: 67.5 %; psychostimulant: 74.2 %) throughout the observation period. MARS scores declined over time in both groups (atomoxetine: from 3.7 to 2.9; psychostimulant: from 3.6 to 3.1), indicating a deterioration in adherence. There was no statistically significant difference in terms of medication adherence between the two groups.

Does Comorbid Disruptive Behavior Modify the Effects of Atomoxetine on ADHD Symptoms as Measured by a Continuous Performance Test and a Motion Tracking Device?

OBJECTIVE: To compare the reduction of ADHD symptoms under atomoxetine in patients with and without comorbid oppositional defiant disorder (ODD) or conduct disorder (CD) using a computer-based continuous performance test (cb-CPT) combined with an infrared motion tracking (MT) device. METHOD: Secondary analysis of a placebo-controlled study in ADHD patients (6-12 years old) treated with atomoxetine (target dose: 1.2 mg/kg per day). Cb-CPT/MT scores were analyzed using ANCOVA (last observation carried forward [LOCF]). RESULTS: The data (N = 125) suggested a more pronounced atomoxetine effect in the group with comorbid ODD/CD as measured by all cb-CPT/MT parameters except for "normalized variation of reaction time" (nVRT). CONCLUSION: The results showed that atomoxetine reduced ADHD severity as measured by cb-CPT and MT parameters regardless of whether comorbid ODD/CD was present. The treatment effect of atomoxetine on hyperactivity appears to be more pronounced in the subgroup of patients with comorbid ODD/CD than in the subgroup without this comorbidity.

Chart review for potential features of myocarditis, pericarditis, and cardiomyopathy in children and adolescents treated with clozapine.

Clozapine is known to cause cardiac side effects, including myocarditis, pericarditis, and cardiomyopathy. Prompted by a case of clozapine-related pericarditis in an adolescent, we undertook a retrospective chart review to discover whether any unrecognized cases of myocarditis, pericarditis, or cardiomyopathy were among the children, adolescents, and young adults we had treated with clozapine. The sample comprised a total of 36 patients, who were monitored regularly over a period ranging from 2.5 to 79 months. The average observation period was 7.5 months. Patients were assessed for potential indicators of myocarditis, pericarditis, or cardiomyopathy. In more than 66% of all patients, at least one of several parameters potentially indicative of pericarditis, myocarditis, or cardiomyopathy was abnormal in at least one instance during the observation period. In all cases in which abnormalities were discovered, the abnormalities were found to be unspecific for myocarditis, pericarditis, or cardiomyopathy. With the exception of the case which prompted our study, none of the patients were found to have developed any such disorder in the course of further treatment with clozapine.