Undersogelser Side Effect Rating Scale Research Articles

Characterisation of medication side effects in patients with mostly resistant depression in a real-world setting

Objectives This study aimed to identify factors associated with side effects of psychotropic drugs in a real-world setting enriched with treatment-resistant depression (TRD) patients. Methods A total of 1410 depressed patients were treated in a naturalistic setting. Side effects were measured with the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU); the total score and UKU subscales were considered. Clinical-demographic variables were tested for association with side effects in univariate and then multivariate analyses. Results Total, psychic and neurological side effects were associated with depressive symptom severity, while autonomic side effects were higher in those with somatic comorbidities and other side effects were lower in patients receiving trazodone. In multivariate analyses, depressive symptom severity was associated with psychic and total side effects, while generalised anxiety disorder (GAD) with neurological side effects and somatic comorbidities remained associated with autonomic side effects. Trazodone was associated with lower side effects and with augmentation treatments. Augmentation therapies showed opposite effects depending on response status, i.e. increased or decreased the risk of side effects in responders and non-responders/resistant patients, respectively. Conclusions Psychic side effects may be difficult to distinguish from depressive symptoms and factors associated with different types of side effects are heterogeneous and likely interacting.

Impact of CYP2D6 Polymorphism on Equilibrium Concentration of Fluoxetine in Patients Diagnosed With Major Depressive Disorder and Comorbid Alcohol Use Disorders.

Fluoxetine is used in the treatment of patients with recurrent depressive disorder. Some of these patients do not achieve an adequate response to a treatment regimen containing fluoxetine, and many of these patients experience dose-dependent adverse drug reactions. The cytochrome P450 enzyme CYP2D6 is involved in the biotransformation of fluoxetine, the activity of which is quite dependent on the polymorphism of the gene encoding this enzyme. The objective of the study was to investigate the influence of the 1846G>A polymorphism of the CYP2D6 gene on the concentration/dose indicator of fluoxetine in patients diagnosed with major depressive disorder and comorbid alcohol use disorder. Our study included 101 patients with major depressive disorder and alcohol use disorder (average age: 41.3±14.5 y) who were treated with fluoxetine at an average dose of 26.1±8.7 mg/d. Treatment efficacy was assessed using validated psychometric scales, and the safety/tolerability of the therapy was assessed using the Udvalg for Kliniske Undersogelser Side-Effect Rating Scale. Genotyping was done using a real-time polymerase chain reaction. Therapeutic drug monitoring was performed using high-performance liquid chromatography-mass spectrometry. CYP2D6 genotyping by polymorphic marker 1846G>A (rs3892097) in the 101 patients found that there were 81 patients (80.2%) with the GG genotype ("wild-type," normal metabolism), 20 (19.8%) with the GA genotype (intermediate metabolism), and no subjects with the AA genotype (poor metabolism). Statistically significant results in treatment efficacy as evaluated by Hamilton Rating Scale for Depression scores at the end of the treatment course were found: GG 9.0 [confidence interval (CI): 6.0; 12.0] and GA 12.0 (CI: 9.5; 14.0), P=0.005. Statistically significant results were also obtained for the safety profile as measured by scores on the Udvalg for Kliniske Undersogelser Side-Effect Rating Scale: GG 3.0 (CI 2.0; 4.0) and GA 5.0 (CI: 4.0; 5.0), P<0.001. Finally, a statistically significant difference was found in concentration/dose indicators of fluoxetine in patients with the different genotypes: GG 4.831 (CI: 3.654; 6.204) and GA 7.011 (CI: 5.431; 8.252), P<0.001. The effect of the genetic polymorphism of the CYP2D6 gene on the efficacy and safety profiles of fluoxetine was demonstrated in a group of 101 patients with major depressive disorder and alcohol use disorder.

A Cross-sectional Study of Antipsychotic Drugs Induced Sexual Dysfunction Among Married Males with Remitted Schizophrenia Attending Tertiary Health Care Centre from Central India

Introduction: Schizophrenia is a chronic debilitating disease having a major impact on the sufferers’ lives. Antipsychotic drugs are the mainstay of the treatment of schizophrenia. But, antipsychotics can lead to a variety of sexual dysfunctions among the males with schizophrenia, which may affect their treatment compliance. Aim: To assess the prevalence and the types of sexual dysfunctions among married males with remitted schizophrenia who were on a single oral antipsychotic drug from either class (i.e., typical or atypical type). Materials and Methods: The present cross-sectional study was conducted in a tertiary health-care centre from Central India, with a sample size of 100 married males with schizophrenia who were in the remission phase on a single oral antipsychotic drug. Data were collected by using a convenient sampling method. Socio-demographic profile and clinical variables were recorded in a specific case report form prepared for the study using the Arizona Sexual Experiences (ASEX) scale and the Udvalg for Kliniske Undersogelser (UKU) side-effect rating scale to assess the prevalence and the types of oral antipsychotic drugs induced sexual dysfunctions among study participants. Results: The prevalence of antipsychotic drug induced sexual dysfunction was 54%. The most common type of sexual side-effect of oral antipsychotic treatment was Decreased Sexual Desire/Drive (DSD) as assessed by both ASEX (94.4%) and UKU (63.0%) scales. Sexual dysfunctions like DSD and Ejaculatory Dysfunction (EJD) were associated with the treatment of schizophrenia with typical antipsychotic drugs. Conclusion: The present study shows that the treatment with typical antipsychotics was significantly associated with sexual side-effects. So, routine inquiry during the follow-ups should be done regarding the evaluation of sexual side-effects of antipsychotic agents in order to improve treatment compliance and disease prognosis.

Premorbid Social Functioning and Affective Symptoms Predict Subjective Outcome Among Outpatients With Schizophrenia.

Improving the subjective outcome of patients is an important target in the treatment of schizophrenia. Accordingly, the aim of the present study was to examine the association of factors deemed relevant in this context, i.e., premorbid functioning, residual symptoms, and side effects of antipsychotic medication, with subjective outcome. To this end, 70 clinically stable outpatients with schizophrenia were included into a cross-sectional study. Premorbid functioning, psychopathology, and side effects were assessed by using the Premorbid Adjustment Scale, the Positive and Negative Syndrome Scale, and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale, respectively. Subjective outcome was measured in terms of life satisfaction (Life Satisfaction Questionnaire), self-esteem (Index of Self-Esteem), and needs for care (Berliner Bedürfnisinventar). Both premorbid social functioning and affective symptoms predicted life satisfaction, self-esteem, and patients’ basic needs, whereas positive and negative symptoms predicted needs in the health, social, and functional domains. Concerning side effects, parkinsonism and akathisia showed a significant negative correlation with self-esteem. These findings highlight the complex nature of subjective outcome in patients suffering from schizophrenia. Evidently, premorbid social functioning plays a prominent role in the experienced subjective outcome during the course of the illness. Furthermore, these preliminary findings underscore that constant efforts are essential to treat residual symptoms of the disorder and to avoid extrapyramidal motor side effects of antipsychotic medication. Longitudinal studies are needed to investigate this latter point in more detail.

T232. PREMORBID SOCIAL FUNTIONING AND AFFECTIVE SYMTPOMS ARE RELATED TO SUBJECTIVE OUTCOME AMONG OUTPATIENTS WITH SCHIZOPHRENIA

BackgroundImproving the subjective outcome of patients should be an important target in the treatment of schizophrenia. Accordingly, the aim of the present study was to examine the influence of determining factors, namely premorbid functioning, residual symptoms, and side effects of antipsychotic medication on subjective outcome.Methods70 outpatients with schizophrenia (ICD-10) who were clinically stable for a period of at least six months were included into a cross-sectional study. Premorbid functioning, psychopathology, and side effects were assessed by using the Premorbid Adjustment Scale, the Positive and Negative Syndrome Scale, and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale, respectively. Subjective outcome was measured in terms of life satisfaction (Life Satisfaction Questionnaire, LSQ), self-esteem (Index of Self-Esteem, ISE), and needs for care (Berliner Bedürfnisinventar, BeBI).ResultsBoth premorbid social functioning and affective symptoms correlated negatively with most life domains assessed by the LSQ as well as with self-esteem and were associated with less health, social, and functional needs. Concerning side effects, parkinsonism and akathisia showed a significant negative correlation with self-esteem.DiscussionOur results highlight the complex nature of subjective outcome in patients suffering from schizophrenia. Evidently, premorbid social functioning plays a prominent role in the experienced subjective outcome in the course of the illness. Furthermore, our findings underscore that constant efforts are essential to reduce depressive symptoms or anxiety in patients. Special attention should also be paid to extrapyramidal motor side effects of medication.

Genome-Wide Association Study of Sleep Disturbances in Depressive Disorders

Sleep disturbance affects about 75% of depressed individuals and is associated with poorer patient outcomes. The genetics in this field is an emerging area of research. Thus far, only core circadian genes have been examined in this context. We expanded on this by performing a genome-wide association study (GWAS) followed by a preplanned hypothesis-driven analysis with 27 genes associated with the biology of sleep. All participants were diagnosed by their referring physician, completed the Beck Depression Inventory (BDI), and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale at baseline. Our phenotype consisted of replies to 3 questions from these questionnaires. From standard GWAS chip data, imputations were performed. Baseline total BDI scores (n = 364) differed significantly between those with and those without sleep problems. We were unable to find any significant GWAS hits although our top hit was for changes in sleep and an intergenic marker near SNX18 (p = 1.06 × 10^–6). None of the markers in our hypothesis-driven analysis remained significant after applying Bonferroni corrections. Our top finding among these genes was for rs13019460 of Neuronal PAS Domain Protein 2 with changes in sleep (p = 0.0009). Overall, both analyses were unable to detect any significant associations in our modest sample though we did find some interesting preliminary associations worth further exploration.

An open-label randomised comparison of aripiprazole, olanzapine and risperidone for the acute treatment of first-episode schizophrenia: Eight-week outcomes

This study aimed to investigate the efficacy and tolerability of aripiprazole, olanzapine and risperidone in first-episode schizophrenia (FES). The eight-week, open, randomised study was conducted in six Chinese medical centres. Altogether, 498 FES subjects were randomised to aripiprazole (n = 165), olanzapine (n = 168) or risperidone (n = 165). Efficacy was measured with the Positive and Negative Syndrome Scale (PANSS), tolerability with the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU) and functioning with the Personal and Social Performance Scale (PSP). All three antipsychotics significantly improved the baseline to end-point PANSS total and each of the sub-scale scores (p < 0.001). Risperidone was superior to olanzapine and aripiprazole regarding PANSS total end-point scores (p < 0.05). Cumulative response (PANSS total score reduction ⩾30%) was similar between risperidone, olanzapine and aripiprazole (74.8%, 73.5% and 70.1%; p = 0.707), but risperidone was superior to aripiprazole regarding PANSS total score reduction ⩾50% (37.8% vs. 26.6%; p < 0.05). Olanzapine was associated with the largest weight gain at week 4 and 8 (p < 0.01), weight gain ⩾7% (olanzapine = 49.0% vs. risperidone = 32.5% vs. aripiprazole = 17.0%; p < 0.01), more psychic side effects at week 8 (p < 0.01 each) and more 'other' side effects at week 4 (p < 0.001) and week 8 (p < 0.05) but fewer neurological side effects at week 4 (p < 0.05) and week 8 (p < 0.01). PSP improved more with risperidone than with aripiprazole at week 4 and 8 (p < 0.05). For FES, risperidone might be a better choice than aripiprazole due to improved efficacy and functional improvement, without inferior tolerability. Aripiprazole is a better choice to avoid relevant short-term weight gain. Olanzapine could be chosen to avoid neurological adverse effects.

Effect size of lithium, carbamazepine, and sodium valproate in child and adolescent bipolar 1 disorder during manic phase: A prospective open-label study.

Aim:The aim was to evaluate the “effect size (ES),” tolerability, and acceptability of lithium, carbamazepine, and sodium valproate in the acute phase treatment of pediatric Bipolar 1 disorder patients during manic phase.Materials and Methods:This hospital-based, prospective, open-label study included 67 patients in manic phase of bipolar I disorder, aged 6–17 years, after informed consent by the caregivers. The patients were randomly assigned to the lithium group (n = 30), carbamazepine group (n = 20), and sodium valproate group (n = 17). They were assessed with the Schedule for Affective Disorders for School Age Children’s-Present and Life time version administered to the parent and child separately, Conner’s Abbreviated Rating Scale, and Cassidy Scale for Manic States (CSMS). Lithium was started in the dose of 30 mg per kg of body weight, carbamazepine in the dose of 10–20 mg/kg/day, and sodium valproate in the dose of 10–20 mg/kg body weight. Antipsychotic (chlorpromazine [CPZ] 100–500 mg per day or haloperidol up to 750 mg of CPZ equivalent) was allowed in the study. Injection haloperidol 10 mg and injection promethazine 50 mg intramuscular were allowed for initial 3–5 days to combat acute agitation. Rescue medication such as injection lorazepam 2–4 mg intramuscular was allowed throughout the study duration. The patients were rated weekly on CSMS, Bipolar Clinical Global Impression, Udvalg for kliniske Undersogelser Side Effect Rating Scale, and side effect checklist for lithium, sodium valproate, and carbamazepine, respectively. The serum level of concerned drug was obtained at weekly intervals and dose hiked, if needed to get target serum level.Results:The response rate was 90% in lithium group, 70% in carbamazepine group, and 88% in sodium valproate group on the basis of ≥33% reduction from baseline CSMS. The effects of change of CSMS over the 6 weeks across the three treatment group were found to be highly statistically significant.Conclusions:In the acute phase treatment of pediatric bipolar 1 disorder patients during manic phase, the ES for lithium was 0.85, for carbamazepine 0.71, and for sodium valproate 0.84. These agents are well tolerated in treating bipolar disorder in children.

Effect of Olanzapine on Clinical and Polysomnography Profiles in Patients with Schizophrenia.

Acute and short-term administration of olanzapine has a favorable effect on sleep in schizophrenia patients. This study aimed to clarify the effect of olanzapine on polysomnographic profiles of schizophrenia patients during the acute phase of illness after controlling for previous drug exposure. Twenty-five drug-naïve or drug-free schizophrenia patients were assessed at baseline and after six weeks of olanzapine treatment on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and Udvalg for Kliniske Undersogelser (UKU) side-effect rating scale and a whole-night polysomnography; fifteen patients completed the study. There was a significant reduction in all psychopathological variables with maximum reduction in PANSS total, BPRS total, and PANSS positive scores. A significant increase in total sleep time (TST), sleep efficiency (SE), nonrapid eye movement (NREM) stage 1 duration, stage 3 duration, stage 4 duration, and stage 4 percentage of TST, number of rapid eye movement (REM) periods, REM duration, and REM percentage of TST was observed. REM latency at baseline inversely predicted the reduction in BPRS total and PANSS total and positive scores. In summary, short-term treatment with olanzapine produced significant improvement in clinical and polysomnography profiles of patients with schizophrenia with shorter REM latency predicting a good clinical response.

The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction.

BackgroundIsoenzymes CYP2D6 and CYP3A4, the activity of which varies widely, are involved in metabolism of haloperidol and may influence its profile of efficacy and safety.ObjectiveThe primary aim of this study was to estimate the relationship between CYP3A5 gene polymorphism, activity of the CYP3A isoenzyme, and the risk of development of adverse drug reactions by haloperidol in patients with alcohol abuse.MethodsSixty-six male alcohol-addicted patients participated in the study. The safety of haloperidol was evaluated by Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU) and Simpson–Angus Scale for extrapyramidal symptoms (SAS). The activity of CYP3A was evaluated by determining the concentrations of an endogenous substrate of this isoenzyme (cortisol) and its urinary metabolite (6-beta-hydroxycortisol, 6-B-HC). Genotyping of CYP3A5*3 was performed by real-time polymerase chain reaction with allele-specific hybridization.ResultsThe frequency of A-allele occurrence in Russian population was very poor (2.27%). CYP3A5*3 polymorphism had no influence on safety profile indicators of haloperidol (UKU scale: p=0.55, SAS scale: p=0.64). In addition, there was no statistical significant difference between the values of indexes of the metabolic ratio (6-B-HC/cortisol) in groups with different genotypes of CYP3A5*3: GG 5.00 (3.36; 6.39) vs AG 5.26 (2.10; 6.78) (p=0.902).ConclusionThe frequency of A-allele occurrence of CYP3A5*3 in Russian population is very poor, and it has no high influence on the safety of haloperidol treatment; therefore, there are no reasons to take this polymorphism into account in patients with alcohol addiction who receive haloperidol.

Study of factors affecting drug compliance in schizophrenia- cross sectional survey

Introduction: Schizophrenia is a condition characterized by delusions, hallucinations, disorganized behavior, disorganized thought, and negative symptoms. There is overwhelming evidence that antipsychotics can be effective in treating the symptoms of schizophrenia. Approximately 75% of individuals relapse without drugs compared to 25% with drug. Patients who receive long-acting depot have lower relapse rates than patients who receive oral medications. The factors affecting drug compliance include side effects, psychopathology, social support, and insight. Indian studies are comparatively few in this area; knowledge of these factors can help in formulating strategies for enhancing drug compliance and outcome. Methods: This study was conducted at the Department of Psychiatry T D Medical College, Alleppey, a tertiary care teaching hospital. Patients who attended the Outpatient department were assessed with following instruments, Positive and negative symptom scale, Udvalg Klinske Undersogelser Side Effect Rating Scale, Multidimensional scale of perceived social support, Scale to assess Unawareness of Mental Disorder (SUMD), Compliance was assessed by using the criteria of fully compliant defined as those miss less than 20% of medication, partially compliant those who misses 20% to 80% of medication and noncompliant those who miss more than 80% of medicines. Data was analysed using Chi square test and regression analysis. Result: Sex, Education status, marital status, Occupation, and drugs administered had significant relationships with Compliance. Conclusion:, it is advisable to use minimum number of drugs for ensuring compliance.

The correlation between CYP2D6 isoenzyme activity and haloperidol efficacy and safety profile in patients with alcohol addiction during the exacerbation of the addiction.

BackgroundToday, it is proved that isoenzymes CYP2D6 and CYP3A4 are involved in metabolism of haloperidol. In our previous investigation, we found a medium correlation between the efficacy and safety of haloperidol and the activity of CYP3A4 in patients with alcohol abuse.ObjectiveThe aim of this study was to evaluate the correlation between the activity of CYP2D6 and the efficacy and safety of haloperidol in patients with diagnosed alcohol abuse.MethodsThe study involved 70 men (average age: 40.83±9.92 years) with alcohol addiction. A series of psychometric scales were used in the research. The activity of CYP2D6 was evaluated by high-performance liquid chromatography with mass spectrometry using the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline to pinoline. Genotyping of CYP2D6 (1846G>A) was performed using real-time polymerase chain reaction.ResultsAccording to results of correlation analysis, statistically significant values of Spearman correlation coefficient (rs) between the activity of CYP2D6 and the difference of points in psychometric scale were obtained in patients receiving haloperidol in injection form (Sheehan Clinical Anxiety Rating Scale =−0.721 [P<0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.692 [P<0.001]) and in those receiving haloperidol in tablet form (Covi Anxiety Scale =−0.851 [P<0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.797 [P<0.001]).ConclusionThis study demonstrated the correlations between the activity of CYP2D6 isozyme and the efficacy and safety of haloperidol in patients with alcohol addiction.

Treatment with antipsychotics and sexual dysfunction in a sample of schizophrenic inpatients

IntroductionPrevious studies show association between sexual dysfunction and antipsychotic treatment.ObjectivesTo study the prevalence and clinical correlates of sexual dysfunction in schizophrenic inpatients treated with antipsychotics. To analyze the influence of sexual complaints in treatment adherence.MethodsRetrospective descriptive study of psychiatric inpatients diagnosed of schizophrenia following DSM-IV-TR) criteria and treated in an acute care unit of Psychiatry in an university hospital in a 12-month period. Patients treated with combination of antipsychotics (typical and atypical) were excluded from the analysis (n = 60). Sexual side effects were evaluated with Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and evaluated in two treatment groups: conventional antipsychotics, and atypical antipsychotics. Patients were asked about subjective experience with other treatments.ResultsThe mean age of subjects was 32.4 (SD = 8.7). From the whole sample 38 (63.3%) were men and 22 (36.7%) women. Sexual dysfunction related to treatment was present in 78% of patients. Men were more affected than women and 69% of them related that sexual dysfunction had influenced the decision of treatment withdrawal previous to income. Amenorrhea was more common on risperidone and amisulpride. Analysis of different antipsychotics and its relationship with sexual dysfunction are presented.ConclusionsSexual dysfunction is a frequent side effect associated with antipsychotics in schizophrenic patients. The sexual side effects may reduce the quality of life and may increase non-compliance that is usually associated to readmissions and worse prognosis of severe mental illness.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Pain Affects Clinical Patterns and Treatment Outcomes for Patients With Major Depressive Disorder Taking Fluoxetine.

The aim of the study was to determine whether baseline pain was associated with discernible clinical features and treatment outcomes for patients with major depressive disorder (MDD) receiving 6-week fluoxetine treatment. A total of 131 inpatients with acutely ill MDD were enrolled to receive 20 mg of fluoxetine daily for 6 weeks. Pain was measured by the Short-Form 36 body pain index. Symptom severity, functional impairment, and severity of adverse events were assessed at baseline and again at weeks 1 to 4 and 6 using the 17-item Hamilton Depression Rating Scale, Modified Work and Social Adjustment Scale, and Utvalg for Kliniske Undersogelser Side Effect Rating Scale, respectively. Simple linear regression was employed to examine the clinical variables significantly associated with pain. The generalized estimating equations method was used to analyze the influence of pain on the 17-item Hamilton Depression Rating Scale, Modified Work and Social Adjustment Scale, and Utvalg for Kliniske Undersogelser Side Effect Rating Scale over time. Of the 131 participants, 119 (90.8%) who completed baseline pain measurements and had at least 1 postbaseline assessment were included in the analysis. Patients experiencing greater pain were more likely to have more severe depression, to be at greater risk of suicide, to have functional impairment, to experience stressful life events, and to have poor treatment outcomes. These findings suggest that pain was significantly associated with multiple aspects of patients with MDD. Patients with MDD with higher levels of pain were clinically useful in predicting poor outcomes after acute fluoxetine treatment.

Comparative study of sexual dysfunction and serum prolactin level associated with olanzapine, risperidone, and clozapine in patients with remitted schizophrenia.

Background:Sexual dysfunctions have been a major side effect of the second generation anti-psychotic drugs which often affects treatment compliance in patients with schizophrenia. There is no/few systematic review or research addressing sexual dysfunction and their effect on serum prolactin level among different atypical antipsychotics in India.Aims:To determine and compare the frequency of sexual dysfunction associated with olanzapine, risperidone, and clozapine and their effect on serum prolactin level in remitted patients with schizophrenia.Settings and Design:Cross-sectional hospital-based study. Recruitment by purposive sampling. Estimation of serum prolactin was done using enzyme-linked immunosorbent assay technique.Materials and Methods:The total sample size was 103, consisting of 31, 23, and 19 patients in olanzapine, risperidone, and clozapine groups, respectively and 30 controls. A Brief Psychiatric Rating Scale, Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and Sexual Functioning Questionnaire were administered. Analysis of variance was used to compare clinical variables. Chi-square test was used to identify the frequency of sexual dysfunction. Kruskal–Wallis test was used to compare UKU side effect, sexual dysfunction, and blood parameters across the study groups.Results and Conclusion:Eighty-six percentage reported sexual dysfunction in one or more domains of sexual functioning in risperidone group as compared to 48.3% in olanzapine and 31% in clozapine groups, respectively. Prolactin level elevation was statistically significant in risperidone group followed by clozapine and olanzapine groups, respectively.

P.3.c.059 Incidence, onset, and duration of treatment-emergent somnolence with asenapine in adult patients with schizophrenia or bipolar disorder

Background: The atypical antipsychotic olanzapine has been approved for the treatment of schizophrenia in Europe since 1996 but has been used primarily as a second-line treatment to the less expensive typical agents. However, similar to other atypical antipsychotic drugs, olanzapine has a lower risk of inducing extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, and sexual dysfunction compared with the typical antipsychotic drugs.Objective: The aim of this study was to determine whether patients with schizophrenia who have a poor response to their present antipsychotic therapy would show improvement when switched to olanzapine.Methods: This 13-week, multicenter, open-label, nonrandomized trial was conducted at 5 centers in Lithuania. Patients were started on oral olanzapine 10-mg tablets once daily, which could be adjusted by 5 mg/d in the dosing range of 5 to 20 mg/d. The primary efficacy measure was the total score on the Brief Psychiatric Rating Scale (BPRS), which was extracted from the Positive and Negative Syndrome Scale (PANSS). Efficacy response rate was defined a priori as the percentage of patients achieving ≥40% improvement in the BPRS total score. Secondary assessments included the PANSS total and BPRS and PANSS subscales and scores on the Clinical Global Impression-Severity of Illness (CGI-S), the CGI-Global Improvement (CGI-I), and the Patient Global Impression-Improvement (PGI-I) tests. Tolerability was primarily measured by assessing the incidence of treatment-emergent adverse events (AEs) according to the Udvalg fuer Kliniske Undersogelser (UKU) Side Effect Rating Scale and laboratory analyses.Results: Twenty-four patients (13 men [54.2%]; mean [SD] age, 32.4 [8.1] years) entered the study. Twenty-three (95.8%) of the 24 patients completed the study. The mean (SD) daily dosage of olanzapine was 11.40 (2.18) mg/d. The total mean (SD) BPRS score improved significantly from 37.8 (7.9) to 19.5 (13.7) (P < 0.001). The response rate was 58.3% (14/24 patients). The mean positive and negative BPRS scores and the mean total and subscale PANSS scores all improved significantly from baseline (P < 0.001). The mean (SD) CGI-S score improved significantly from 4.8 (0.8) at baseline to 3.5 (1.1) at end point (P < 0.001). Twenty-two patients (91.7%) showed improvement on the CGM scale. Similar improvement was found on the PGM scale. Treatment-emergent AEs occurred in 7 patients (29.2%). Improvement was found on 31 of the 48 UKU scale items; no change was shown on 15 items; and slight worsening was shown on 2 items. No clinical abnormalities were detected during the study.Conclusion: In this study of Lithuanian patients with schizophrenia, significant improvement was shown in all efficacy measures. In addition, olanzapine was well tolerated in these patients.

Actigraphic monitoring of activity and rest in schizophrenic patients treated with olanzapine or risperidone

Metabolic disturbances are a growing concern for the treatment of schizophrenia. As decreased activity and poor sleep quality are risk factors for metabolic disturbances, we investigated the activity and sleep patterns of schizophrenic patients using actigraphy. Seventy-three patients with schizophrenia spectrum disorder (mean age 29.2 ± 10.2 years, 27 females) treated with olanzapine (n = 54) or risperidone (n = 19) and 36 age- and sex-matched healthy controls were examined. Actigraphic recordings were obtained throughout seven consecutive days. The Athens Insomnia Scale (AIS) and Epworth Sleepiness Scale (ESS) were used to assess sleep and daytime sleepiness. Drug side effects were evaluated with the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and Barnes Akathisia Rating Scale (BARS). Mental status was rated with the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS). The patients had lower mean 24 h-activity (p < 0.001) and mean 10 h-daytime-activity (p < 0.001), and longer time in bed (p < 0.001). Higher PANSS scores, especially in the negative symptoms scale, were related to lower activity (rs = −0.508, p < 0.001). Higher depressive symptoms were related to lower mean 24 h-activity (rs = −0.233, p = 0.049), longer time in bed (rs = 0.315, p = 0.007) and higher AIS (rs = 0.377, p = 0.001) and ESS scores (rs = 0.321, p = 0.006). Healthy females presented higher activity than healthy males (p < 0.001). Similar but not significant gender differences were observed in the patients. These findings show that patients with schizophrenia treated with olanzapine or risperidone exhibit low physical activity and altered sleep pattern which may promote metabolic side effects. These changes are linked to negative and depressive symptoms.

Aripiprazole and Haloperidol in the Treatment of Delirium

To compare the efficacy and tolerability of aripiprazole and haloperidol in the amelioration of distressing symptoms of delirium and its motoric subtypes. At Memorial Sloan-Kettering Cancer Center, we prospectively collected sociodemographic and medical data and systematically rated all patients diagnosed with delirium with the Memorial Delirium Assessment Scale (MDAS), Karnofsky Performance Scale (KPS) and the abbreviated Udvalg Kliniske Undersogelser Side Effect Rating Scale (UKU) at the initial diagnosis of delirium (T1), after 48-72 h (T2) and 7 days later (T3). All collected information was entered into a delirium database. For our analysis, we subsequently extracted data on aripiprazole (ARI) treated patients to compare to case-matched haloperidol (HAL) treated patients. We retrieved 21 patients treated with aripiprazole and 21 case-matched patients treated with haloperidol. Initial MDAS scores did not significantly differ between the groups. Over the course of treatment (T1 to T3), MDAS scores improved from 18.1 to 8.3 for ARI and 19.9 to 6.8 for HAL. The delirium resolution rate was 76.2% for ARI and 76.2% for HAL. For patients with hypoactive delirium, the MDAS scores improved from 15.6 to 5.7 for ARI and 18.8 to 8.1 for HAL. Delirium resolution rates for patients with hypoactive delirium were 100% for ARI and 77.8% for HAL. For patients experiencing hyperactive delirium, the MDAS scores improved from 19.9 to 6.8 for ARI and 20.8 to 5.8 for HAL. Delirium resolution rates for patients with hyperactive delirium were 58.3% for ARI and 75% for HAL. There were no significant differences in treatment results between ARI and HAL. Treatment with HAL caused more extrapyramidal side effects. From our secondary analysis, aripiprazole may be as effective as haloperidol in the management of delirium and its subtypes. Treatment with haloperidol resulted in more side effects.

Outcome of suicidal patients with schizophrenia: results from a naturalistic study

Purpose was to assess suicidality before and at the time of admission in patients with schizophrenia and compare outcome differences. Biweekly PANSS (Positive and Negative Syndrome Scale), HAMD (Hamilton Depression Rating Scale) and UKU (Udvalg for Klinske Undersogelser Side Effect Rating Scale) ratings were evaluated in 339 in-patients with schizophrenic spectrum disorders. Response was defined as an initial 20% PANSS total score reduction at discharge, remission was defined according to the proposed consensus criteria by the Remission in Schizophrenia Working Group. Suicidal patients (22%) scored significantly higher on the PANSS negative subscore, PANSS insight item and HAMD total score at admission and at discharge. They developed significantly more side effects. No differences were found concerning response and remission between the two patient subgroups. Despite receiving significantly more antidepressants the suicidal patients suffered from significantly more depressive symptoms up to discharge, yet without differing regarding response and remission.

A 12-week, naturalistic switch study of the efficacy and tolerability of aripiprazole in stable outpatients with schizophrenia or schizoaffective disorder

The objectives of this 12-week multicenter open-label switching study were to evaluate the overall clinical efficacy, safety, and tolerability of aripiprazole in stable patients with schizophrenia or schizoaffective disorder, and to assess, in a naturalistic setting, whether such patients experience symptom worsening when switched from D2 receptor antagonists to aripiprazole (a D2 receptor partial agonist). Patients with schizophrenia or schizoaffective disorder in a symptomatically stable state were randomized to aripiprazole or standard-of-care antipsychotics. The Clinical Global Impression (CGI), Positive and Negative Syndrome Scale, and Investigator's Assessment Questionnaire were used monthly. The Udvalg for Kliniske Undersogelser side-effect rating scale scores and treatment emergent adverse events were recorded to assess the safety and tolerability of switching to aripiprazole from other antipsychotics. A total of 292 patients were randomly assigned to receive aripiprazole (N = 245) or non-aripiprazole antipsychotics (N = 47). Mean CGI-Improvement score at 12 weeks was 3.56+/-1.29 (95% confidence interval: 3.39-3.73) in the aripiprazole group, indicating that aripiprazole was effective in treating schizophrenic patients. Aripiprazole treatment resulted in improvement from baseline on all efficacy outcome measures, including Positive and Negative Syndrome Scale total, positive, negative, and general subscale, and CGI-Severity scores. In addition, after aripiprazole treatment, the remission rate was increased from 43.9% at baseline to 51.7% at 12 weeks. The proportion of patients with symptom worsening at 12 weeks was low (12.4%). Both Investigator's Assessment Questionnaire and Udvalg for Kliniske Undersogelser scores showed that there were fewer prolactin-related adverse events in the aripiprazole group than in the standard-of-care antipsychotics group (P<0.05). There were no significant between-group differences in time to failure to maintain remission and time to dropout. In the naturalistic setting, symptomatically stable outpatients with schizophrenia who were switched to aripiprazole showed clinically meaningful treatment benefits. The majority of patients was successfully switched from other antipsychotics without serious symptom exacerbation or adverse events over a course of 12 weeks.