Antonio Ciudad

Recovery from schizophrenia: Results from a 1-year follow-up observational study of patients in symptomatic remission

OBJECTIVES This report presents the results of an observational empirical clinical investigation about the prevalence and correlates of a proposed definition of recovery from schizophrenia in outpatients in Spain. METHODS Of 1010 outpatients with schizophrenia (DSM-IV-TR), a subgroup of 452 patients in symptomatic remission (SR) was followed for 1 year. SR was defined according to Andreasens severity criteria based on the Scales for the Assessment of Positive (SAPS) and Negative (SANS) Symptoms. A Global Assessment of Functioning scale score of >80 was considered to be indicative of adequate functioning (AF). Correlates of recovery were identified by logistic regression. RESULTS At baseline, 103 (22.8%; N=452) patients fulfilled the recovery definition (SR + AF). After 1 year, 338 patients (89.9%; N=376) maintained SR. Among these, the proportion of patients in recovery increased to 27.1% (102 out of 376). Better premorbid adjustment (PA) and improved social cognition correlated with recovery at baseline. After 1 year, PA, duration of untreated psychosis (DUP), type of pharmacotherapy, attitudes toward medication, and variation of depressive symptoms and social cognition determined the likelihood of recovery. CONCLUSIONS The proportion of patients in recovery increased among those fulfilling SR criteria. After 1 year, in addition to known factors like shorter DUP and better PA, social cognitive abilities and depressive symptoms were found to correlate with recovery.

A randomized, 1-year follow-up study of olanzapine and risperidone in the treatment of negative symptoms in outpatients with schizophrenia.

Objective: To evaluate the efficacy of olanzapine compared with risperidone in negative symptoms, after 1 year of treatment, in schizophrenic outpatients with prominent negative symptoms. Methods: This was a multicenter, randomized, monitored, open-label, parallel, dose-flexible, 1-year study of outpatients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) with prominent negative symptoms (Scale for the Assessment of Negative Symptoms [SANS] summary score >10) previously treated with conventional antipsychotics. Patients were randomly assigned to treatment with an initial dose of olanzapine 10 mg/d or more (n = 120) or risperidone 3 mg/d or more (n = 115). The primary efficacy measure was the SANS summary score. Secondary efficacy measures included Scale for the Assessment of Positive Symptoms, Clinical Global Impression of Severity Scale, Calgary Depression Scale, and Social Functioning Scale. The response rate was defined as 30% or more of improvement in the SANS summary score. Results: The mean dose throughout the study was 12.2 mg/d (±5.8 mg/d) for olanzapine and 4.9 mg/d (±2.0 mg/d) for risperidone. At 1 year, olanzapine patients showed significantly higher improvement than risperidone patients on the SANS summary (P = 0.015) and on the affective flattening (P = 0.007) and avolition/apathy (P = 0.028) SANS subscales. There were also significant improvements in favor of olanzapine in the Scale for the Assessment of Positive Symptoms summary (P = 0.021), Clinical Global Impression of Severity (P = 0.008), and Social Functioning Scale total (P < 0.001) scores. The response rate was greater (P = 0.001) in the olanzapine cohort (69.2%) than in the risperidone cohort (48.7%). Olanzapine patients reported less extrapyramidal side effects but a higher incidence of clinically important body weight increase than risperidone patients. Conclusions: Long-term treatment with olanzapine was associated with significantly better improvement in negative symptoms as compared with risperidone-treated schizophrenic outpatients with prominent negative symptoms.

Remission in schizophrenia: Results from a 1-year follow-up observational study

OBJECTIVES This study used the Remission in Schizophrenia Working Group operational-severity criteria to, a) provide descriptive data on prevalence and stability of symptomatic remission, b) attempt a criterion (concurrent) validation of this measure of remission, and c) explore correlates of remission stability. METHODS From an unselected sample of 1010 stable outpatients with schizophrenia (DSM-IV-TR), a subgroup of 452 (44.8%) in symptomatic remission was followed for 1 year. Of these, 376 were re-evaluated in a research diagnostic assessment. In addition to relevant sociodemographic and clinical data, measures included symptoms, depression, functioning, social cognition, attitudes towards medication, and quality of life. Estimates of point prevalence are provided. Correlates of remission were identified by logistic regression. RESULTS Symptomatic remission at baseline correlated with better premorbid adjustment, better social cognition, good treatment compliance, younger age, the absence of comorbid substance abuse, current or past participation in psychotherapy, and a lack of past participation in rehabilitation. After 1 year, 338 out of the 376 (89.9%) patients re-evaluated were found again in remission. In this assessment, better premorbid adjustment, good treatment compliance, and improvement of depressive symptoms and social cognition during follow-up again correlated with remission. CONCLUSIONS The results of this study suggest that symptomatic remission (as defined above) has considerable criterion validity and is a realistic goal in the treatment of schizophrenia. Attaining and sustaining remission may warrant better clinical and functional outcomes for patients.

Systematic review of the economic aspects of nonadherence to antipsychotic medication in patients with schizophrenia

Purpose There is strong evidence supporting the link between nonadherence to antipsychotic medication and relapse of schizophrenia. However, less obvious are the economic consequences of nonadherence. The systematic review reported here evaluated the economic aspects of nonadherence to antipsychotic medication. Methods A systematic review of scientific papers in the PubMed MEDLINE, Embase, PsychINFO, BIOSIS, and Evidence-Based Medicine Reviews databases was undertaken. Studies that measured adherence to antipsychotic medication and that provided comparative information on health care costs were included. Results Eight studies met the inclusion criteria. All were observational. Despite the differences between the studies in terms of design, adherence measures, and cost components analyzed, the results of this systematic review indicate that nonadherence to antipsychotic medication is associated with increased hospitalization rates and resource utilization, resulting in increased direct health care costs. Conclusion Nonadherence to antipsychotic medication results in poor health and economic outcomes; therefore, the authors suggest endorsing interventions aimed at improving adherence because they can improve patient health without substantially increasing costs.

Safety and effectiveness of olanzapine versus conventional antipsychotics in the acute treatment of first-episode schizophrenic inpatients.

OBJECTIVE To assess the safety and effectiveness of olanzapine compared to typical antipsychotics in the treatment of first-episode schizophrenics in acute psychiatric inpatient wards. METHODS Data were collected from a prospective, comparative, nonrandomized, open, observational study of 904 inpatients with schizophrenia. One hundred and fifty-eight patients fulfilled the criteria for first-episode schizophrenia, defined as (1) the International Classification of Diseases: Mental and Behavioral Disorders, 10th ed. (ICD-10) diagnosis of schizophrenia, (2) antipsychotic nai;ve, and (3) a course of illness of less than 5 years. Eighty-nine (56.3%) of these patients were assigned to the olanzapine treatment group (OLZ) and 69 (43.7%) to the control group that received treatment with conventional antipsychotics (CON). Safety was evaluated in terms of the spontaneous adverse events reported and a specific questionnaire for extrapyramidal symptoms (EPS). Clinical status was measured by means of the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression of Severity (CGI-S). Clinical response was defined as the baseline-endpoint decrease in BPRS>40% plus an endpoint BPRS<18 or an endpoint CGI</=3. RESULTS The rate of clinical response to treatment in the OLZ was 76.7%, compared to 54.4% in the CON (chi(2)=8.48; P=.003). Olanzapine was significantly more effective than conventional antipsychotics in lowering the total BPRS score (P=.0003), as well as each of the following BPRS subscales: positive symptoms (P=.0019), negative symptoms (P<.0001), depression (P=.018), and agitation (P=.007), even after mean scores were adjusted for their baseline value and disease duration. Olanzapine also proved to be significantly superior to conventional antipsychotics in lowering mean CGI scores (P=.013). The frequency with which new EPS appeared, or previously existing ones worsened, was significantly greater in the CON than in the OLZ (55.1% vs. 13.5%; P<.001). Anticholinergics were needed more frequently in the CON than in the OLZ (58.0% vs. 6.7%; P<.0001). CONCLUSIONS The results of this observational, naturalistic study show that olanzapine is safe and effective in a nonselected sample of acute, first-episode schizophrenic inpatients.

Residual symptoms and functioning in depression, does the type of residual symptom matter? A post-hoc analysis

BackgroundThe degrees to which residual symptoms in major depressive disorder (MDD) adversely affect patient functioning is not known. This post-hoc analysis explored the association between different residual symptoms and patient functioning.MethodsPatients with MDD who responded (≥50% on the 17-item Hamilton Rating Scale for Depression; HAMD-17) after 3 months of treatment (624/930) were included. Residual core mood-symptoms (HAMD-17 core symptom subscale ≥1), residual insomnia-symptoms (HAMD-17 sleep subscale ≥1), residual anxiety-symptoms (HAMD-17-anxiety subscale ≥1), residual somatic-symptoms (HAMD-17 Item 13 ≥1), pain (Visual Analogue Scale ≥30), and functioning were assessed after 3 months treatment. A stepwise logistic regression model with normal functioning (Social and Occupational Functioning Assessment Scale ≥80) as the dependent variable was used.ResultsAfter 3 months, 59.5% of patients (371/624) achieved normal functioning and 66.0% (412/624) were in remission. Residual symptom prevalence was: core mood symptoms 72%; insomnia 63%; anxiety 78%; and somatic symptoms 41%. Pain reported in 18%. Factors associated with normal functioning were absence of core mood symptoms (odds ratio [OR] 8.7; 95% confidence interval [CI], 4.6–16.7), absence of insomnia symptoms (OR 1.8; 95% CI, 1.2–2.7), episode length (4–24 weeks vs. ≥24 weeks [OR 2.0; 95% CI, 1.1–3.6]) and better baseline functioning (OR 1.0; 95% CI, 1.0–1.1). A significant interaction between residual anxiety symptoms and pain was found (p = 0.0080).ConclusionsDifferent residual symptoms are associated to different degrees with patient functioning. To achieve normal functioning, specific residual symptoms domains might be targeted for treatment.

Olanzapine Orally Disintegrating Tablet: A Review of Efficacy and Compliance

Medication nonadherence, especially in psychiatric disorders, has been associated with treatment failure and other negative outcomes. Orally disintegrating formulations have been developed as an alternative to improve medication adherence. This report reviews the properties, efficacy, and safety profile of olanzapine as an orally disintegrating tablet, and explores their association with medication compliance compared with standard oral formulation. Medical literature, published on orally disintegrating formulation of olanzapine identified using Pubmed and EMBASE, was used. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug. Studies evaluating the biostability, biodisposability, pharmacokinetics, efficacy, and safety of orally disintegrating olanzapine as treatment of patients with psychiatric disorders were reviewed. Measurement tools included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions‐Severity (CGI‐S), Simpson‐Angus Scale (SAS), Abnormal Involuntary Movement Scale, and Nursing Assessment of Medication Acceptance (NAMA). Orally disintegrating olanzapine, an effective atypical antipsychotic with an acceptable safety profile, can facilitate the burden of treatment on patients and caregivers due to its ease of administration. This is especially important in diseases such as schizophrenia and bipolar disorder, which can be chronic and require long‐term treatment.

Early Response and Remission as Predictors of a Good Outcome of a Major Depressive Episode at 12-Month Follow-Up: A Prospective, Longitudinal, Observational Study

OBJECTIVE The goal of treating major depressive disorder (MDD) should be not only achieving remission in a particular episode but also avoiding relapses and attaining long-term recovery. The current study was designed to evaluate whether response and remission achieved within the first 6 weeks of antidepressant treatment are associated with a 12-month good outcome (achieving remission by 6 months and remaining in remission until the end of follow-up). METHOD This prospective, longitudinal, multicenter study included adult outpatients who had a DSM-IV diagnosis of MDD, baseline scores ≥ 15 on the 17-item Hamilton Depression Rating Scale (HDRS(17)), Clinical Global Impressions-Severity of Illness scores ≥ 4, and a minimum remission period of 12 weeks between the index episode and the immediately prior episode (or who were in their first MDD episode). The primary efficacy measure was early response (a 50% decrease from baseline in HDRS(17) score by week 6). The secondary efficacy measure was early remission (HDRS(17) score ≤ 7 by week 6). RESULTS Among the total of 930 patients included from December 2006 to June 2007, 38.2% showed early response, and 20.5% showed early remission. Of the early responders, 76.1% had a 12-month good outcome as compared to 81.1% of early remitters. Logistic regression showed that factors associated with a good outcome included early response (odds ratio [OR] = 4.14), being employed, and the absence of physical comorbidities. Early remission was also strongly associated with a good outcome (OR = 4.72). CONCLUSIONS Either response or remission achieved by week 6 is the strongest prognostic factor for the 12-month good outcome of an episode of MDD.

Improvement in social functioning in outpatients with schizophrenia with prominent negative symptoms treated with olanzapine or risperidone in a 1 year randomized, open-label trial

UNLABELLED GENERAL PURPOSE: To evaluate the social functioning of schizophrenic outpatients after switching to second-generation antipsychotics. METHODOLOGY Multi-center, randomized, open-label, parallel, flexible-dose, 1-year study of schizophrenic outpatients with prominent negative symptoms (defined as a SANS Global score > or =10), previously treated with conventional antipsychotics. Patients were randomly assigned (1:1 ratio) to treatment with an initial dose of at least 10 mg/day olanzapine (N = 120) or at least 3 mg/day risperidone (N = 115). Dosage could be modified during the study according to clinical criteria. Social functioning was evaluated using the total and subscales scores of the Social Functioning Scale (SFS) (validated Spanish version). Other efficacy measures included the SANS, SAPS, and CGI-S scales. Response was defined in advance as a 30% improvement in the SANS Global score. RESULTS The mean doses during the trial were 12.2 mg/day (S.D. = 5.8) of olanzapine and 4.9 mg/day (S.D. = 2) of risperidone. There were no significant baseline differences in SFS total scores or other relevant clinical variables. At 1 year, olanzapine-treated patients presented a mean improvement in SFS total scores (7.75) that were significantly higher (p = 0.0028) than for risperidone-treated patients (-0.92). Treatment with olanzapine resulted in a greater numerical improvement than risperidone in all SFS domains and reached statistical significance in such categories as social engagement or withdrawal (p = 0.01), independence (performance) (p = 0.0098), independence (competence) (p = 0.04), recreational activities (p = 0.0391), and occupation/employment (p = 0.0024) in which the greatest difference between the olanzapine and risperidone groups was found (0.86 vs. -3.06). Significantly more patients treated with olanzapine reached or surpassed the SFS typified total scores corresponding to a functional level that is representative of a sample of stabilized Spanish outpatients with schizophrenia without prominent negative symptoms (p = 0.0009). Associated factors were treatment with olanzapine and a 30% improvement or more in SANS global score or SAPS global score. CONCLUSIONS Long-term treatment with olanzapine was associated with overall greater improvement in social functioning (as measured by SFS) compared to risperidone-treated patients.

Effect of olanzapine or risperidone treatment on some cognitive functions in a one-year follow-up of schizophrenia outpatients with prominent negative symptoms

AIMS To compare olanzapine and risperidone outcome on some neurocognitive dimensions in chronic schizophrenia patients with prominent negative symptoms. METHOD We randomised and followed for 1 year 235 chronic schizophrenia outpatients with a SANS global score > or =10 to open-label flexible-dose treatment with olanzapine or risperidone. Clinical, functional and cognitive assessments [including the COGLAB battery reaction time, vigilance-span of apprehension (VSA) and a card-sorting task] were done periodically. RESULTS There were no significant differences between olanzapine (n=120) and risperidone (n=115) treatments in the neurocognitive dimensions tested. Mean+/-SD doses were 12.2+/-5.8 mg/day of olanzapine and 4.9+/-2.0 mg/day of risperidone. Patients in the olanzapine group showed a significant improvement in the VSA total score, but the within-group change was modest (effect size of 0.26); the difference with the risperidone group was not significant (p=0.207). Patients in both groups showed a significant improvement in a composite measure of executive efficiency based on the card-sorting task, with within-group effect size of 0.21 (risperidone) and 0.35 (olanzapine); the between-group difference was not significant (p=0.164). At baseline, better functional status correlated with VSA. Patients scoring lower on VSA or executive efficiency at baseline improved more on these respective measures. CONCLUSION Modest pro-cognitive effects can also be found in chronic schizophrenia outpatients with prominent negative symptoms when treated with olanzapine or risperidone.