Treatment Outcome In Schizophrenia Research Articles

Pharmacologic treatment of schizophrenia

Despite pharmacologic advances, the treatment of schizophrenia remains a challenge, and suboptimal outcomes are still all too frequent. Although treatment goals of response, remission, and recovery have been defined more uniformly, a good "effectiveness" measure mapping onto functional outcomes is still lacking. Moreover, the field has to advance in transferring measurement-based approaches from research to clinical practice. There is an ongoing debate whether, and which, first- or second-generation antipsychotics should be used. However an individualized treatment approach needs to consider current symptoms, comorbid conditions, past therapeutic response, and adverse effects, as well as patient choice and expectations. Moreover acute and long-term goals and effects of medication treatment need to be balanced. While the acute response to appropriately dosed first-generation antipsychotics may not differ much from second-generation antipsychotics, advantages of lower rates of extrapyramidal side effects, tardive dyskinesia, and, possibly, relapse may favor second-generation antipsychotics. However when considering individual adverse effect profiles, the differentiation into first- and second-generation antipsychotics as unified classes can not be upheld, and a more differentiated view and treatment selection is required. To date, clozapine is the only evidence-based treatment for refractory patients, and the role of antipsychotic polypharmacy and other augmentation strategies remains unclear, at best. To improve the treatment outcomes in schizophrenia, research efforts are needed that elucidate biomarkers of the illness and of treatment response (both therapeutic and adverse effects). Moreover, new treatment options are needed that affect nondopaminergic targets with relevance for symptom reduction, relapse prevention, enhanced efficacy for nonresponders, and reduced key adverse effects.

The interactions between religion, religiosity, religious delusion/hallucination, and treatment-seeking behavior among schizophrenic patients in Taiwan

Religion could influence the psychopathology, treatment-seeking behavior, and treatment outcome in schizophrenia, but the associations between these factors have never been explored thoroughly, and the data in Han-Chinese society are scarcer still. The current study recruited 55 schizophrenic patients to explore the relationship between religion, psychopathology with religious content, treatment-seeking behavior, and outcome. Subjects with religious delusions/hallucinations had lower scores on functioning and higher scores on religiosity. The higher religiosity scores were correlated with older age, longer duration of illness, religious affiliation, lower preference of psychiatric treatment, lower functioning score, and delusion/hallucination. As to treatment-seeking behavior, patients with religious affiliation showed less preference toward psychiatric treatment. Individuals with religious delusion/hallucination were more likely to receive magico-religious healing and not to be satisfied with psychiatric treatment. A more positive view of psychiatric treatment was predicted by lower religiosity score, higher satisfaction with psychiatric treatment, and lower years of education. The religiosity level seems not directly related to clinical severity, but it seems to be a better predictor of religious delusions/hallucinations than religious affiliation status. Patients with religious delusions/hallucinations did not necessarily have more severe psychopathology. There are different profiles associated with religious affiliation/religiosity and religious delusions/hallucinations in relation to treatment-seeking behavior among schizophrenia patients in Han-Chinese society.

Progress in Defining Optimal Treatment Outcome in Schizophrenia

Historically, schizophrenia has been associated with early-onset, persistent symptoms, and progressive decline accompanied by poor functional recovery. The advent of effective drugs in the 1950s improved symptom control, at least from the standpoint of positive features (e.g. hallucinations, delusions). However, even here the response was limited and efficacy in other symptom domains (cognitive, deficit/negative) was minimal. With clozapine as the prototype, the second-generation antipsychotics arrived in the 1990s with claims of improved tolerability, as well as greater and broader clinical efficacy, all of which was to translate to gains in functional outcome and quality of life. The capacity of these drugs to effect such changes has since been tempered, but it remains that the research and hope generated served as an impetus to redefine outcomes. A medical-based model, centred on pharmacotherapy and symptom resolution, has given way to a re-conceptualization of schizophrenia and treatment goals. There is a clearer distinction between clinical and functional outcomes, and, with this, greater attention has been given to these other symptom domains that curtail improvement in the latter. At the same time, a concerted shift to shared decision making has underscored quality-of-life issues that benefit from, but cannot be guaranteed by, either clinical or functional improvement. To this end, the field has now embraced a recovery model that is seen as a process, multidimensional and individualized, rather than dichotomous and symptom driven.

Medication Nonadherence and Treatment Outcome in Patients With Schizophrenia or Schizoaffective Disorder With Suboptimal Prior Response

To examine the impact of medication nonadherence on treatment outcome in schizophrenia and potential risk factors for nonadherence. A post hoc analysis of a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10, 20, and 40 mg/day for patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) with suboptimal response to current treatment (N = 599) was conducted between September 12, 2003, and November 3, 2005, at 55 study centers in the United States. Nonadherence was defined as not taking medication as prescribed based on daily pill counts. Because there was no significant difference in nonadherence between dose groups, effects of nonadherence on efficacy and safety outcomes were examined using all 3 groups combined. Baseline demographics and symptom severity were investigated as potential risk factors for nonadherence. During the 8-week study, 34.5% of patients were nonadherent at least once. Nonadherent patients had significantly less improvement compared to adherent patients as measured by change in Positive and Negative Syndrome Scale total score (-22.57 vs. -26.84, p = .002). Longer duration of nonadherence was associated with reduced likelihood of treatment response (odds ratio = 0.94, 95% CI = 0.90 to 0.99, p = .008). The early treatment discontinuation rate was higher in nonadherent compared to adherent patients (40.8% vs. 24.5%, p < .001). Adherent and nonadherent patients had comparable outcomes in most safety measures, except for weight change, for which adherent patients had greater weight gain than nonadherent patients (2.63 kg vs. 1.96 kg, p = .02). Greater depression severity at baseline (p = .01) and greater hostility level during the study were significant risk factors for nonadherence (p = .02). Medication nonadherence had a significantly negative impact on treatment response, highlighting the importance of adherence to achieve satisfactory treatment outcome. Findings may also help clinicians identify patients at risk for nonadherence and utilize interventions to improve adherence. clinicaltrials.gov Identifier: NCT00100776.

P03-156 Oxcarbazepine as an adjunct of antipsychotic therapy in acute schizophrenia: A double-blind, randomised placebo-controlled clinical trial

The outcome in treatment of schizophrenia is still not satisfactorily, and using the adjunctive administration of various anticonvulsant drugs adjunctive to antipsychotics has become widely distributed. This study determines the efficacy of oxcarbazepine combined to olanzapine in treatment of schizophrenia in a double-blind, randomized, placebo-controlled, parallel-group, add-on therapy, 7 week study in 54 patients suffering schizophreniform disorder or schizophrenia. Patients were randomized to oxcarbazepine or placebo and titrated up to 1800 mg/ day in week 1 and maintained at that dose for another 6 weeks. Treatment of olanzapine started at week 2 with 5 mg/day. According to weekly improvement in Brief Psychiatric Rating Scale (BPRS), olanzapine dose was maintained constant or escalated in regular steps of 2.5 mg. Main outcome measure was the cumulative olanzapine dose from beginning administration of oxcarbazepine/placebo for a period of 42 days. Comparing treatment of oxcarbazepine and olanzapine with placebo and olanzapine, there was no difference in cumulative olanzapine doses in both groups. in the oxcarbazepine group was not significantly more rescue medication given. A mixed regression model was used to assess time trends in BPRS over the treatment period: the differences in the rate of change of BPRS in the two treatment groups suggested that the scores sank more rapidly in the oxcarbazepine group (p=0.063). Mean post-treatment aggression score also showed no significant difference. Results from this study do not support the use of OXC as an adjunct to atypical antipsychotics in patients with schizophrenia.

Cystamine prevents haloperidol‐induced decrease of BDNF/TrkB signaling in mouse frontal cortex

The role of brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology as well as treatment outcome of schizophrenia. Rodent studies indicate that several antipsychotic drugs have time-dependent (and differential) effects on BDNF levels in the brain. Earlier studies from our laboratory have indicated that long-term treatment with haloperidol (HAL) decreases BDNF, reduced GSH and anti-apoptotic marker, Bcl-xl protein levels and increases the expression of pro-apoptotic proteins in rat frontal cortex. Furthermore, findings from human as well as rodent studies suggest that treatment of schizophrenia must involve the neuroprotective strategies to improve the neuropathology and thereby clinical outcome. In the present study, we investigated the potential of cystamine (CYS), an anti-oxidant and anti-apoptotic compound, to prevent HAL-induced reduction in BDNF, GSH, and Bcl-xl protein levels in mice and the signaling mechanism(s) involved in the beneficial effects of CYS. The results indicated that CYS as well as cysteamine (the FDA-approved precursor of CYS) increased BDNF protein levels in mouse frontal cortex 7 days after treatment. CYS co-treatment prevented chronic HAL treatment-induced reduction in BDNF, GSH, and Bcl-xl protein levels. CYS treatment enhanced TrkB-tyrosine phosphorylation and activated Akt and extracellular signal-regulated kinase (ERK)1/2, downstream molecules of TrkB signaling. In addition, in vitro experiments with mouse cortical neurons showed that CYS prevented the HAL-induced reduction in neuronal cell viability and BDNF protein levels, and increase in apoptosis. BDNF-neutralizing antibody as well as K252a, a selective inhibitor of neurotrophin signaling blocked the CYS-mediated neuroprotection. Moreover, CYS-mediated neuroprotection is also blocked by LY294002, a phosphatidylinositol 3-kinase inhibitor or PD98059, a mitogen-activated protein kinase kinase (MEK) inhibitor. Thus, CYS protects cortical neurons through a mechanism involving TrkB receptor activation, and a signaling pathway involving phosphatidylinositol 3-kinase and MAPK. The findings from the present study may be helpful for the development of novel neuroprotective strategies to improve the treatment outcome of schizophrenia.

New Insights Into Clinical Response in Schizophrenia: From Dopamine D2Receptor Occupancy to Patients’ Quality of Life

New Insights Into Clinical Response in Schizophrenia: From Dopamine D₂Receptor Occupancy to Patients’ Quality of Life

Karon's Case of "Mr. X" and the "International Society for the Psychological Treatments of Schizophrenia and Other Psychoses" (ISPS)

This Commentary on the case study of Mr. X places Bertram Karon’s (2008) work in the contexts of (a) the current treatment of people suffering from psychotic disorders; (b) Karon’s historical connections with the ideas of such pioneering, humanistically oriented, psychodynamic psychiatrists as Frieda Fromm-Reichmann and Sándor Ferenczi; (c) the mission and work of the International Society for the Psychological Treatments of Schizophrenia and Other Psychoses (ISPS) and its U.S. chapter (ISPS-US); and (d) the ongoing struggle in psychiatry over the evidential legitimacy of the psychodynamic treatment of psychosis and schizophrenia. I conclude by pointing out that empirical details about process and outcome in the psychodynamic treatment of schizophrenia as documented in cases like Karon’s help to provide one source of such evidential legitimacy.

Peripheral Amino Acid Levels in Schizophrenia and Antipsychotic Treatment

Abnormal levels of amino acids have been reported in patients with schizophrenia and have also been investigated as a biomarker to monitor antipsychotic treatment, however results have been inconsistent. The purpose of the present review is to summarize the evidence in the literature of whether amino acid levels can be a biomarker and predict the treatment outcome in schizophrenia. The current review does not support amino acid concentration as a useful biomarker for monitoring antipsychotic response in patients with schizophrenia, although there is evidence that high levels of serum homocysteine and glutamate might be considered as a trait marker for schizophrenia. This review has also highlighted a considerable dearth of studies, specifically of studies evaluating antipsychotic side-effects.

The case for long‐acting antipsychotic agents in the post‐CATIE era

Long-acting antipsychotic agents were developed to promote treatment compliance in patients requiring maintenance treatment for schizophrenia. An analysis of the impact of non-compliance on treatment outcomes in schizophrenia and the advantages and disadvantages of long-acting antipsychotics. Partial or total non-compliance with oral antipsychotics remains widespread and is associated with significant increases in the risk of relapse, rehospitalization, progressive brain tissue loss and further functional deterioration. Long-acting agents have the potential to address issues of all-cause discontinuation and poor compliance. The development of the first long-acting atypical antipsychotic, which appears to be effective and well tolerated, should further improve the long-term management of schizophrenia. Long-acting agents represent a valuable tool for the management of schizophrenia and merit wider use, especially in light of emerging literature regarding the neuroprotective advantages of atypical antipsychotics over conventional agents in terms of regenerating brain tissue during maintenance therapy.

Remission in First-Episode Psychosis

Previous attempts to identify clinically useful predictors of treatment outcome in schizophrenia have been hampered by methodological inconsistencies, including a lack of standardized outcome measures. Recently proposed operationally defined criteria for remission provide an opportunity to readdress this topic. We applied the remission criteria to a sample of 57 subjects with first-episode psychosis (DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder), treated according to a fixed protocol in a prospective study. Subjects were recruited between April 1999 and January 2000 and were followed for 2 years. Various demographic, baseline clinical, and early-response variables were subjected to discriminant analysis for their ability to predict remission or nonremission. We also assessed the symptom improvement patterns over time and compared endpoint psychopathology in the remitters and nonremitters. A model incorporating neurologic soft signs, 6-week treatment response, duration of untreated psychosis, marital status, and Positive and Negative Syndrome Scale excited factor baseline score was able to correctly predict 89% of the remitters and 86% of the nonremitters. Symptom reduction at 6 weeks, including core psychotic symptoms, was significant in both groups (remitters, p < .0001; nonremitters, p < .0001), although reduction was substantially greater in the remission group (p = .004). Thereafter, the remission group continued to improve (p < .01), while the nonremitting group failed to do so (p = .55). Considerable overlap of endpoint symptoms was observed, and depressive symptom scores were similar in remitters and nonremitters. A combination of demographic, baseline clinical, and acute treatment response variables may accurately predict treatment outcome. Persistent noncore psychotic symptoms in subjects meeting proposed remission criteria require further investigation.

The relationship between patient satisfaction and treatment outcomes in schizophrenia

In recent years, the goals of treatment in schizophrenia have evolved from objective improvements in psychotic symptoms to encompass patient-related factors such as subjective response and quality of life. In order to examine factors that influence patient satisfaction with treatment, subjective quality of life and subjective response to treatment, two literature searches were performed using PubMed. The first searched for articles of any kind with no time limits using the search parameters 'schizophrenia AND satisfaction', 'antipsychotic AND satisfaction', 'schizophrenia AND subjective response', 'schizophrenia AND therapeutic alliance', 'schizophrenia AND psychosocial OR psychoeducation'. Secondly, PubMed was searched between January 1990 and December 2005 using the key words 'satisfaction', 'subjective response' and 'quality of life' in combination with an array of atypical agents. Results demonstrated that patient satisfaction with antipsychotic therapy is influenced by multiple factors. The most frequently reported reasons for dissatisfaction include drug side effects, lack of involvement in treatment planning or decision-making and lack of involvement of family members in the care plan. The majority of studies have demonstrated that the atypical antipsychotics are associated with significant improvements in quality of life, functional status and patient satisfaction compared with conventional agents. The therapeutic alliance is key to achieving optimal outcomes, by providing information and education to meet patients' needs, while facilitating compliance with drug therapy to ensure better clinical outcomes. A long-acting atypical antipsychotic that can ensure medication delivery will provide a platform for psychosocial interventions, and thus may further increase patient satisfaction and, ultimately, improve long-term outcomes in schizophrenia.

Effectiveness and tolerability of schizophrenia treatment in Central and Eastern Europe: results after 1 year from a prospective, observational study (IC-SOHO)

Objective. The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study is intended to complement smaller, shorter-term observational studies and randomised controlled clinical trials in providing information on the treatment of schizophrenia in various geographies that have not been well studied previously.Methods. Interim results after 12 months are presented for a subset of patients from eight Central and Eastern European (CEE) countries initiating or switching to olanzapine, risperidone, or typical antipsychotic monotherapy at Baseline (n=1387).Results. Patients initially prescribed olanzapine and risperidone experienced significantly greater improvements in a broad range of schizophrenia symptom domains compared with patients prescribed typicals. Furthermore, patients in the olanzapine group showed significantly greater improvements in overall and negative symptom domains compared with the risperidone group (all P≤0.05). While patients in the olanzapine group gained more weight than the other two groups, they had significantly lower odds of developing extrapyramidal symptoms, loss of libido, and sexual dysfunction. Patients initially prescribed olanzapine were also significantly less likely to have changed or added antipsychotics during 12 months of treatment compared with the risperidone and typicals groups.Conclusion. In this CEE sample, schizophrenia treatment outcomes after 12 months varied between patients initially prescribed different antipsychotics.

Condensed version of the Quality of Life Scale for schizophrenia for use in outcome studies

The Quality of Life Scale (QLS 21) is widely used in clinical trials involving schizophrenia patients. This study aimed to identify a core subset of QLS 21 items that maintains the validity and psychometric properties of the complete version. A parsimonious subset of items from the QLS 21 that can accurately predict the total scale score was sought and evaluated in 133 schizophrenia patients, using the heuristic algorithm for a regression model. Two additional data sets were used for model validation: a subset of 124 patients who participated in the model construction and who completed the QLS 21 1 year later as well as a new sample of 40 inpatients. Patients were examined with the Positive and Negative Syndrome Scale (PANSS), the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Talbieh Brief Distress Inventory (TBDI), the Extrapyramidal Symptom Rating Scale (ESRS) and the Global Assessment of Functioning Scale (GAF). Using only five QLS items (social initiatives, adequacy, acquaintances, motivation, and time utilization; QLS 5) as predictors, the correlation was 0.9805 between the predicted and true QLS totals. Two validation samples confirmed this finding. Additional analyses indicate that the QLS 5 exhibited similar performance to the QLS 21 regarding construct validity, test–retest reliability and responsiveness to changes over time. Thus, the five-item condensed Quality of Life Scale for schizophrenia maintains the validity of the full QLS, and has the advantage of shorter administration time. Utilization of the revised QLS 5 in routine care and clinical trials may potentially facilitate evaluation of treatment outcomes in schizophrenia.

P.2.034 Predictors of treatment outcome in schizophrenia — 1-year follow-up study of first-admitted patients

P.2.034 Predictors of treatment outcome in schizophrenia — 1-year follow-up study of first-admitted patients

Duration of untreated psychosis and treatment outcome in schizophrenia patients untreated for many years.

The duration of untreated psychosis (DUP) influences treatment outcome in schizophrenia but its relevance in untreated patients, ill for a very long duration, is not known. This study examined outcome and factors related to it after one year of treatment of schizophrenia patients who were ill for many years and not previously treated. Among 75 never-treated patients with schizophrenia detected in a community survey in Chennai, India, 49 took treatment and were followed up prospectively for one year. Evaluation at intake and outcome was carried out using standardized methods. A good clinical outcome in 29%, social outcome in 35%, occupational outcome in 51% and global outcome in 31% was observed at the end of one year. Patients with poor global outcome did not significantly differ from those with good outcome on demographic and clinical variables at intake but for the presence of delusions and formal thought disorder. The proportion with good outcome in clinical, work and global measures fell steadily with increasing DUP. This difference was significant for clinical and global outcomes after a DUP of 5 years. The relationship between DUP and response to treatment held good even in chronic stages of schizophrenia with longer DUP associated with poorer outcome.

Treatment outcome of schizophrenia co-morbid with obsessive-compulsive disorder.

To evaluate the pharmacological treatment outcome of schizophrenia, co-morbid with obsessive-compulsive disorder by comparing the effects of typical neuroleptic, atypical neuroleptic and a combination of typical with anti-obsessional drugs on positive and negative symptoms of schizophrenia and obsessional symptoms. A quasi-experimental study. The study was conducted at the Department of Psychiatry, Postgraduate Medical Institute and Services hospital, Lahore from September 2002 to July 2003. The sample consisted of 39 patients suffering from schizophrenia co-morbid with obsessive-compulsive disorder. They were divided in three groups according to the pharmacological treatment given by the treating psychiatrists. Sample was assessed at the start of treatment and twelve weeks later. Patients receiving typical neuroleptics and anti-obsessional drugs showed better outcome (p <.05) both in psychotic (pre-intervention mean scores of positive scale of PANSS 26.90 as compared to postinterventional mean scores 19.00) and obsessional symptoms (pre-intervention mean scores on Padua Inventory 165.00 compared to 84.00 postinterventional mean scores) than those receiving typical and atypical neuroleptics alone. Treatment outcome of schizophrenia co-morbid with obsessive-compulsive disorder shows better results if anti-obsessional drugs are added to the neuroleptics.

Validation of Polypharmacy Process Measures in Inpatient Schizophrenia Care

The influence of combining antipsychotics and different classes of psychotropic drugs on treatment outcome in schizophrenia remains unclear. As part of a comprehensive quality management program, we prospectively evaluated two schizophrenia polypharmacy performance measures in a cohort of 1,075 consecutively recruited individuals with schizophrenia in seven psychiatric hospitals. Multiple concurrent antipsychotic and overall psychotropic polypharmacy rates were noticeably high. In case-mix-adjustment models controlling for a variety of confounding baseline parameters, patients discharged with more than one antipsychotic had significantly poorer outcomes with respect to both mental state and social functioning. Prescription of more than three psychotropic agents did not adversely affect social functioning when patients taking more than three were compared to patients given fewer medications. Case-mix models suggest that antipsychotic polypharmacy, while used more often for individuals with chronic disease and more thought disturbance, is only partly a reaction to disease severity. The antipsychotic polypharmacy process measure may be used to identify treatment problems in order to find alternatives to polypharmacy. The measure can be easily assessed in a variety of settings and does not depend on the availability of case-mix data. The rising trend toward polypharmacy in schizophrenia care, which is not supported by current guideline recommendations, warrants critical appraisal.

Preferences for schizophrenia treatment outcomes among public policy makers, consumers, families, and providers.

This study measured state public policy makers' ratings of the importance of several key schizophrenia treatment outcomes and compared them with the ratings of primary stakeholders in schizophrenia treatment. Three groups of policy makers (40 administrative decision makers, 40 state legislators, and 20 legislative aides) and three groups of core stakeholders (20 persons with schizophrenia, 13 of their family members, and 20 of their mental health care providers) were recruited in Florida. Participants rated 12 descriptions of schizophrenia-related health states that reflected better and worse outcomes in six domains: psychotic symptoms, deficit symptoms, medication side effects, productive activity, daily activity, and social activity. All participants valued functional outcomes, such as improved productive and social activity, more than they valued improvements in symptoms. Public policy makers and primary stakeholders differed in the value they placed on two of the six outcomes. Compared with primary stakeholders, policy makers valued improvements in social functioning significantly more and improvements in medication side effects significantly less. Policy makers and primary stakeholders place similar value on some of the major goals of schizophrenia treatment, with both groups valuing functional outcomes most highly. However, the difference between groups in the importance placed on medication side effects may lead to conflicts in the allocation of resources to the provision of newer and more expensive medications, which are associated with fewer side effects. This initial examination of policy makers' views provides a starting point for developing consensus about schizophrenia treatment policies.

Paraphrase procedures for assessing comprehension of health outcome measures: an illustration from schizophrenia research.

Valid measurement of health outcomes require instruments that are meaningful to those who use them. Clinicians, patients, and others involved in health care have different perspectives on health conditions that are likely to lead to different interpretations of outcome measures and reductions in the accuracy and validity of outcome measurements. This study used paraphrase procedures, a systematic approach for evaluating respondent comprehension, to evaluate descriptions designed for use in studies of schizophrenia treatment outcomes. In four stakeholder groups directly and indirectly involved in schizophrenia treatment (clinicians, patients, patients' families, and the general public), the paraphrase procedures identified comprehension problems that could compromise measurement quality and yielded specific information to guide improvement of the outcome descriptions. The paraphrase procedures detected comprehension problems that were not identified by respondents. This study suggests that systematic assessment of comprehension can improve the quality of health outcome measurement.