Treatment Of Schizophrenia Spectrum Disorders Research Articles

Soluble interleukin-2 receptor levels correlated with positive symptoms during quetiapine treatment in schizophrenia-spectrum disorders

Some but not all antipsychotics have been shown to modulate plasma cytokine levels in schizophrenia patients. Thus far, the most consistent finding has been the increase in plasma levels of soluble interleukin (IL)-2 receptor (sIL-2R) associated with clozapine treatment. Quetiapine is a second-generation antipsychotic with a pharmacological profile similar to that of clozapine, but its immunomodulatory effects have not been investigated in schizophrenia yet. The purpose of this exploratory study was to examine the changes in plasma levels of sIL-2R in schizophrenia during quetiapine treatment and association with psychopathology. Participants were 29 schizophrenia-spectrum disorder patients (DSM-IV criteria), and 28 healthy controls. Patients had a comorbid substance use disorder (cannabis>alcohol>cocaine), since quetiapine is increasingly used in this population of dual diagnosis. No participant suffered from infection or overt inflammatory diseases. On baseline, patients taking mostly second-generation antipsychotics were switched to quetiapine for a 12-week open-label trial. Five patients were drop-outs. Mean dose of quetiapine for trial completers (n=24) was 466.6mg±227.3. Psychiatric variables were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Plasma sIL-2R levels were assessed at baseline, weeks 6 and 12 in patients, and in healthy controls, using sandwich immunoassay. Plasma IL-6 and IL-1 receptor antagonist (IL-1RA) were measured for comparison purposes. On baseline, plasma sIL-2R, IL-6 and IL-1RA levels were higher in dual-diagnosis patients, compared to controls. Plasma sIL-2R further increased after quetiapine treatment (p=0.037), while plasma IL-6 and IL-1RA did not change. Clinical improvements were observed in positive, negative and depressive symptoms, and substance abuse severity (all p<0.01). Interestingly, changes in sIL-2R levels during treatment were inversely correlated with changes in positive symptoms (r=-0.524; p=0.009). That is, increases in sIL-2R levels were associated with reductions in positive symptoms. These data show that quetiapine elevates, like clozapine, sIL-2R levels in schizophrenia. Furthermore, the results suggest that sIL-2R alterations in schizophrenia rely on complex interplays between antipsychotics and the positive symptoms of the disorder. Future randomized controlled trials involving larger samples of schizophrenia patients are warranted to determine whether changes in plasma sIL-2R are quetiapine-related.

Clinical Experience Using Electroconvulsive Therapy in Adolescents with Schizophrenia Spectrum Disorders

The aim of this study was to evaluate the effectiveness and safety of electroconvulsive therapy (ECT) in adolescent patients diagnosed with schizophrenia spectrum disorders (SSD). All patients diagnosed with SSD who received ECT in the Child and Adolescent Psychiatry and Psychology Department in a general hospital in Barcelona, Spain, from January, 2003, to December, 2007, were identified retrospectively. As part of the usual evaluation protocol, Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) scales were administered before ECT, after the acute ECT phase (CGI), and at 6 months from baseline. Data related to characteristics of these patients such as demographics, pharmacological treatment, ECT parameters, and side effects were registered. Thirteen cases, ages 13-17 (mean age, 16.6 +/- 1.2 years), were included. Compared to pre-ECT scores, mean PANSS decreased significantly at 6-month assessment (t = 3.58, p = 0.004). Clinical response (20% or greater reduction in PANSS total scores at the 6-month end point) was achieved in 54% of patients. A significant improvement of mean CGI score was observed after the acute ECT phase (t = 11.88, p < 0.001) and at 6-month assessment (t = 12.48, p < 0.001). There were no severe incidents related to any session during the acute ECT phase, although 1 patient experienced a tardive seizure during the continuation ECT. Our clinical experience supports the assertion that ECT is a safe and effective treatment for SSD in adolescent patients.

The influence of baseline symptoms and insight on the therapeutic alliance early in the treatment of schizophrenia

Background The consistent association between therapeutic alliance and outcome underlines the importance of identifying factors which predict the development of a positive alliance. However, only few studies have examined the association between pretreatment characteristics and alliance formation in patients with schizophrenia. Objective The study examined whether symptoms and insight would predict the therapeutic alliance in psychotherapy of schizophrenia. Further, the associations and differences between patient and therapist alliance ratings were studied. Methods Eighty patients with schizophrenia spectrum disorders received manual-based psychotherapy. Assessment of symptoms and insight was conducted at baseline, and questionnaire-based alliance ratings were obtained three weeks into treatment. Patient and therapist alliance ratings were examined separately. Results Patient and therapist alliance ratings were not significantly correlated ( r = 0.17). Patient ratings of the alliance were significantly higher than the ratings of their therapists ( d = 0.73). More insight in psychosis significantly predicted higher patient ratings of the alliance. Less positive and negative symptoms were significant predictors of higher therapist alliance ratings. Conclusion The findings indicate that symptoms and insight have an influence on the therapeutic alliance in the treatment of schizophrenia spectrum disorders. Patients' and therapists' perceptions of the alliance do not seem to demonstrate much convergence.

Expert Canadian consensus suggestions on the rational, clinical use of ziprasidone in the treatment of schizophrenia and related psychotic disorders.

Many atypical antipsychotic medications are becoming available for clinical use. Ziprasidone is a recent addition to this group and is expected to become available for clinical use in Canada in 2005. Ziprasidone has some significant differences compared with other atypicals currently available in Canada. Clinicians need to understand the benefits and risks associated with each of the antipsychotic medications available for the treatment of schizophrenia and related psychotic disorders to ensure their most appropriate utilization. At the suggestion of Professor Stan Kutcher (chair) and as part of an ongoing commitment to provide independent education pertaining to the utility of new psychotropic compounds to health professionals, a panel of Canadian experts in the treatment of schizophrenia spectrum disorders was convened to provide consensus suggestions for the appropriate clinical use of ziprasidone. The consultations regarding the development of these recommendations were organized by Brainworks International (BWI) with arms-length funding from Pfizer Canada. This paper describes the experts' consensus views on the efficacy and safety of ziprasidone, their suggestions on which patients may be suitable for ziprasidone treatment, and how to initiate treatment (including how to switch from other antipsychotic medications), manage side effects, and monitor patients in long-term therapy. These suggestions are those of the authors only and are not endorsed by or necessarily reflect the opinions of BWI or Pfizer Canada.

Objective and subjective efficacy as well as tolerability of olanzapine in the acute treatment of 120 patients with schizophrenia spectrum disorders

The aim of the present study was to evaluate the objective and subjective efficacy as well as tolerability of olanzapine in acute treatment of schizophrenia spectrum disorders under naturalistic non-selective conditions. Inpatients with schizophrenia spectrum disorders, consecutively admitted over an 18-month period, treated with olanzapine, were included. Diagnoses were made according to ICD-10 criteria based on repeated clinical assessments. Efficacy and tolerability of olanzapine were assessed at baseline and at the end of inpatient acute treatment including Positive and Negative Symptom Scale (PANSS), Clinical Global Impression, subjective assessments, UKU and biological investigations. One hundred and twenty non-selected patients who met ICD-10 criteria for schizophrenia (73%), schizophreniform disorder (14%) or schizoaffective disorder (13%) were treated with olanzapine 15.3+/-5.2 mg/day. Baseline severity (PANSS total mean score 102.2) was higher compared to various admittance studies (PANSS total mean score 86-90). In 32% of patients (n=38), olanzapine treatment was discontinued, mainly because of inefficacy for positive (89%, n=34) and/or negative (95%, n=36) symptoms and/or because of adverse events (37%, n=14). Response rates as improvement in PANSS total score (after > or =3 weeks of treatment) of > or =20%, 30% or 40% were 68%, 55% and 35%, respectively. Response rates in post-hoc defined treatment resistant patients were not significantly different from non-refractory patients. Sedation (26%) was the most common side-effect, followed by weight gain (22%). With regards to subjective efficacy, 30% of the patients were not satisfied with the efficacy of olanzapine, while only 6% of the patients reported a not satisfying subjective tolerability. According to duration of olanzapine treatment, the results for patients, who remained in hospital, revealed a faster increase of weight compared to admittance studies (7 kg in 14 weeks versus 7 kg in 38 weeks). Olanzapine has been found to be effective and tolerable, also under naturalistic acute treatment conditions. Compared to previous double-blind admittance studies, patients had a higher severity of illness at entry and a lower > or =40% PANSS total score response rate. By contrast to previous results, mean dose of olanzapine was similar for multiple- and first-episode patients, and weight gain was more severe. The results underline the need of Phase IV studies for the assessment of clinical antipsychotic efficacy and tolerability.

Sex, ethnicity, and antipsychotic medication use in patients with psychosis

Previous studies suggested that African–American patients with psychotic disorders receive higher doses of antipsychotic medication than white patients, are more likely to receive depot antipsychotics, and are less likely to be prescribed second-generation antipsychotics. African–American men in particular may be most likely to receive excessive doses of antipsychotics and depot antipsychotics, although this is less clear. Few studies have examined how sex and ethnicity interactions affect treatment of psychotic disorders. In this study, we examined whether the interaction of sex and ethnicity predicted the use of depot antipsychotics and the dosing of antipsychotics in a sample of inpatients with psychotic disorders. The inpatient records of 167 patients with psychotic disorders were evaluated for type and dose of medication at discharge. African–American men received depot antipsychotic medication more frequently than African–American women and white patients. This difference persisted after controlling for sociodemographic and clinical variables. African–American men and women with psychotic mood disorders were also more likely to be discharged on high antipsychotic doses compared with white patients. There were no ethnic or sex differences in the dosing of antipsychotics for the treatment of schizophrenia spectrum disorders. There were also no ethnic or sex differences in the use of second-generation antipsychotics.

Duration of untreated psychosis, ethnicity and social isolation in the aesop (London) first onset psychosis study

Previous studies suggested that African–American patients with psychotic disorders receive higher doses of antipsychotic medication than white patients, are more likely to receive depot antipsychotics, and are less likely to be prescribed second-generation antipsychotics. African–American men in particular may be most likely to receive excessive doses of antipsychotics and depot antipsychotics, although this is less clear. Few studies have examined how sex and ethnicity interactions affect treatment of psychotic disorders. In this study, we examined whether the interaction of sex and ethnicity predicted the use of depot antipsychotics and the dosing of antipsychotics in a sample of inpatients with psychotic disorders. The inpatient records of 167 patients with psychotic disorders were evaluated for type and dose of medication at discharge. African–American men received depot antipsychotic medication more frequently than African–American women and white patients. This difference persisted after controlling for sociodemographic and clinical variables. African–American men and women with psychotic mood disorders were also more likely to be discharged on high antipsychotic doses compared with white patients. There were no ethnic or sex differences in the dosing of antipsychotics for the treatment of schizophrenia spectrum disorders. There were also no ethnic or sex differences in the use of second-generation antipsychotics.

Pre-onset detection and intervention research in schizophrenia psychoses: current estimates of benefit and risk.

Early detection and intervention is offering a compelling new perspective on the diagnosis and treatment of schizophrenia spectrum disorders. Relevant investigations include efforts to reduce the post-onset duration of untreated psychosis and efforts to identify and treat prodromally symptomatic high-risk patients in the pre-onset phase of the disorder. There appears to be consensus that the benefits outweigh the risks in studies aiming to treat first episode psychotic patients as soon as possible. In contrast, there is less consensus about pre-onset detection and intervention studies, the major concerns being the false positive rate of case identification, the evidence of benefit, the side effects of treatment, the potential harm from being informed that one is at risk for psychosis, the false negative rate of case identification, and the inclusion of adolescents. In this article, each of these issues is elaborated upon and discussed in terms of the existing evidence informing risk and benefit and in light of our own clinical experience conducting this research. It is concluded that we do not have enough data yet to justify pre-onset detection and intervention as standard practice, but we do have enough data concerning risk and benefit to justify pre-onset detection and intervention research.

Valproate and the symptomatic treatment of schizophrenia spectrum patients.

Valproate is currently one of the most frequently prescribed drugs in schizophrenia spectrum disorders. However, surprisingly little is known from controlled studies. Also, no review articles are available. Here, we summarize basic and clinical research on valproate and its application for treatment in schizophrenia spectrum disorders. The molecular and physiological effects of valproate are outlined. It is discussed how the effects of valproate on the cellular level involving serotonin, GABA, glutamate, sodium-channels, membrane fluidity and RNA-expression may account for its clinical effect in schizophrenia spectrum patients. The target symptoms are a reduction of psychomotor agitation and aggression, possibly reflecting a drug effect on temporal lobe pathology, which is considered to be involved in the etiology of schizophrenic illness.

Clozapine as a treatment tool: only in resistant schizophrenic patients?

Evidence indicates that clozapine is effective in the management of treatment-resistant schizophrenia and in affective psychoses. To examine whether affective components within the boundaries of the schizophrenia spectrum imply specific psychopathological characteristics of response to treatment, 60 patients with a treatment-resistant schizophrenia spectrum disorder who were treated with clozapine (75-600 mg/d) were evaluated in a naturalistic, open, follow-up study. The group comprised 41 patients with and 19 without bipolar features (43 men and 17 women, mean age 34.3 years). Patients were evaluated with the Brief Psychiatric Rating Scale (BPRS) during the first year of treatment. The results show a significant improvement in scores in both groups (P < 0.001) compared with the baseline evaluation. A higher percentage of responders was seen in the 'affective' group. No typical psychopathological characteristic or symptom cluster predicting the response to treatment was identified. During the study, 15 patients discontinued treatment: six for lack of efficacy, five for non-compliance and four for adverse events. The study confirms the efficacy of clozapine in the treatment of schizophrenia spectrum disorders, particularly in patients with bipolar features.

Racial differences in treatment of psychiatric inpatients.

The study examined several aspects of inpatient psychiatric treatment to determine if differences existed between treatment of African-American and white patients. Using a structured chart review, data were collected on 76 African-American and 88 white patients consecutively admitted to an acute inpatient setting with a principal axis I diagnosis of a major mood or psychotic disorder. Racial differences in treatment were examined using analysis of variance and logistic regression to assess the effects of diagnosis and socioeconomic status. Nonpsychotic African-American patients had shorter lengths of stay than white patients with similar disorders. White patients were more likely to be on one-to-one observational status. Clinicians were more likely to order urine drug screens for African-American patients with high socioeconomic status than for comparable white patients. African-American patients with schizophrenic disorders received higher neuroleptic dosages than white patients with similar diagnoses. Most racial differences cited in earlier studies of psychotic patients were not found or were not statistically significant once socio-economic status and diagnosis were accounted for. However, racial differences related to the detection, phenomenology, treatment, and course of psychotic disorders and the diagnosis and management of alcohol and drug use disorders and personality disorders were found.