Implications for future research of "medication-free research in early episode schizophrenia".
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Antipsychotic Agents↗
Biomedical subjects
Nina R Schooler
Publications and source records attributed to Nina R Schooler.
Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes.
OBJECTIVE: The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders. METHOD: One hundred twelve subjects (70% male; mean age=23.3 years [SD = 5.1]) with first-episode schizophrenia (75%), schizophreniform disorder (17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2.5-20 mg/day) or risperidone (1-6 mg/day). RESULTS: Response rates did not significantly differ between olanzapine (43.7%, 95% CI=28.8%-58.6%) and risperidone (54.3%, 95% CI=39.9%-68.7%). Among those responding to treatment, more subjects in the olanzapine group (40.9%, 95% CI=16.8%-65.0%) than in the risperidone group (18.9%, 95% CI=0%-39.2%) had subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications. Extrapyramidal symptom severity scores were 1.4 (95% CI=1.2-1.6) with risperidone and 1.2 (95% CI=1.0-1.4) with olanzapine. Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was 17.3% (95% CI=14.2%-20.5%) with olanzapine and 11.3% (95% CI=8.4%-14.3%) with risperidone. Body mass index at baseline and at 4 months was 24.3 (95% CI=22.8-25.7) versus 28.2 (95% CI=26.7-29.7) with olanzapine and 23.9 (95% CI=22.5-25.3) versus 26.7 (95% CI=25.2-28.2) with risperidone. CONCLUSIONS: Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.
Adult↗
Lipid monitoring in patients with schizophrenia prescribed second-generation antipsychotics.
OBJECTIVES: Treatment with second-generation antipsychotic (SGA) medications has been linked with increased rates of the metabolic syndrome (i.e., dyslipidemia, obesity, and hyperglycemia). Several sets of published recommendations now provide clinicians with guidelines for monitoring metabolic parameters in individuals with schizophrenia treated with SGAs. However, few data are available regarding actual metabolic monitoring practices in this patient population. The objectives of the study were to determine baseline lipid monitoring rates for individuals with schizophrenia prescribed SGAs during the period prior to the publication of monitoring guidelines and to determine whether individuals with abnormal lipid levels received follow-up monitoring sooner than individuals with normal levels. METHOD: Lipid monitoring rates for 408 individuals with schizophrenia who were prescribed SGAs from October 1999 to October 2003 were examined using administrative data from a Veterans Affairs facility. Survival analysis was used to examine time to follow-up lipid measurement and to compare time to follow-up measure for individuals with normal initial lipid levels versus those with elevated initial lipid levels. RESULTS: Eighty-five percent of individuals had at least 1 measurement for total cholesterol or triglycerides in a 4-year period. Abnormal initial measurements predicted significantly earlier follow-up monitoring (p < .005 for total cholesterol, p < .05 for triglycerides, p < .001 for low-density lipoprotein cholesterol). However, median time to follow-up measure was 304 days (approximately 10 months) for individuals with elevated total cholesterol levels, which is too long for optimal clinical follow-up. CONCLUSION: Program managers and clinicians should assess adequacy of monitoring and support quality improvement initiatives in this area.
Antipsychotic Agents↗
Relapse prevention and recovery in the treatment of schizophrenia.
Nonadherence to medication is a predictor of relapse in patients diagnosed with schizophrenia, and preventing relapse is crucial to achieving the goal of recovery. Long-term treatment with antipsychotics can be effective, although long-term patient response to medication may be difficult to predict from trials that measure response, remission, and relapse rates because they are often too short. Longer trials are needed to fully understand the implications of adherence and symptom remission in patient outcome. Recovery, however, is contingent on the stabilization of the symptoms of schizophrenia and the acquisition of the skills necessary to function in society. Psychosocial interventions, such as family psychoeducation, social skills training, and cognitive-behavioral therapy, used in conjunction with pharmacotherapy are effective in helping to prevent symptom relapse and promote functional recovery in patients with schizophrenia.
Antipsychotic Agents↗
Optimizing treatment of schizophrenia. Enhancing affective/cognitive and depressive functioning.
Recognition and treatment of schizophrenia has largely focused on positive symptoms of the disorder, such as delusions, hallucinations, and disorganization. However, other important symptoms, such as depression, cognition, and social functioning, have not received comparable attention. Fifty percent of schizophrenic patients suffer from comorbid depression, which is a major risk factor for suicide in this population, while 10% to 25% suffer from comorbid obsessive-compulsive disorder. Cognitive deficits commonly observed in patients with schizophrenia include problems with concentration, attention, and memory, as well as problem-solving and verbal skills. These deficits are observed at early stages of the illness and can predict deficits in functional capabilities, such as occupational and social skills, educational attainment, and the ability to live independently. The severity of such impairments affects all patient in this population, including up to 10% of patients working full time and up to one third of those working part time. In light of the debilitating effects of depression, cognitive impairment, and other aspects of affective functioning on the quality of life of patients with schizophrenia, physicians need to partner with their patients to address these concerns and determine an appropriate treatment regimen. This can be done with simple functional-based cognitive questioning, the use of evidence-based psychosocial practices, and psychoeducation on the many pharmacotherapeutic options. It is recommended that depressive or suicidal symptoms of schizophrenia be treated with an antidepressant or mood stabilizer only if the symptoms have not subsided after treatment of the psychosis with an atypical antipsychotic. Additionally, relative to older medications, atypicals have demonstrated benefit in improving some of the cognitive impairments.
Affective Symptoms↗
Personality dimensions in first-episode psychoses.
OBJECTIVE: The authors compared the patterns and specificity of premorbid personality dimensions in first-episode schizophrenia patients with those in patients with first-episode nonschizophrenia psychoses and healthy comparison subjects. METHOD: A series of 63 patients with first-episode schizophrenia and related psychotic disorders, 34 patients with first-episode nonschizophrenia psychoses, and 77 healthy comparison subjects were assessed with the Personality Disorder Evaluation, a semistructured interview schedule that measures personality dimensions. RESULTS: Cluster A as well as cluster C dimensional scores-in particular, the avoidant personality score-were higher for the schizophrenia patients, and cluster B dimensional scores were higher for the patients with nonschizophrenia psychoses. Cluster C dimensional scores, particularly the avoidant personality score, were highly intercorrelated with all cluster A dimensional scores. CONCLUSIONS: The observed association between avoidant personality and schizophrenia supports the recent literature on the comorbidity of nonspectrum personality disorders in schizophrenia. This association may be related to shared neurodevelopmentally mediated impairments in social cognition in schizophrenia and some cluster C personality dimensions.
Adult↗
Duration of untreated psychosis and time to treatment response for delusions and hallucinations.
OBJECTIVE: Duration of untreated psychosis is associated with time to treatment response among patients with schizophrenia. However, individual psychotic symptoms have not been investigated in this context. The authors examined the relationship between duration of untreated psychosis and time to response for hallucinations and delusions. METHOD: Data were available for 118 patients with first-episode schizophrenia in a longitudinal treatment study. Patients received open-label treatment with conventional antipsychotics and were followed for up to 5 years. Duration of untreated psychosis was correlated with time to response for delusions and hallucinations, and predictors of time to response were examined. RESULTS: Time to response for delusions was significantly longer than that for hallucinations. Duration of untreated psychosis was significantly correlated with time to response for delusions but not for hallucinations. In regression analyses, duration of untreated psychosis was the only predictor for time to response for delusions; it was not a predictor for hallucinations. CONCLUSIONS: The results suggest that duration of untreated psychosis may be specifically associated with time to response for delusions. This association may have clinical implications.
Adult↗
The effects of clozapine and risperidone on spatial working memory in schizophrenia.
OBJECTIVE: The purpose of this investigation was to evaluate the effects of clozapine and risperidone on spatial working memory in patients with schizophrenia. METHOD: Spatial working memory performance was evaluated at baseline and after 17 and 29 weeks in 97 patients with schizophrenia participating in a multisite trial. RESULTS: Compared with baseline performance while receiving conventional antipsychotic medication, risperidone improved, and clozapine worsened, spatial working memory performance. CONCLUSIONS: The differential effects of these medications on spatial working memory may be due to the anticholinergic effects of clozapine and prefrontal dopamine-enhancing effects of risperidone.
Adult↗
Double-blind, placebo-controlled study of modafinil for fatigue and cognition in schizophrenia patients treated with psychotropic medications.
OBJECTIVE: To assess the effects of modafinil on fatigue, symptoms, attention, working memory, and executive functioning in schizophrenia patients treated with psychotropic medications. METHOD: Twenty-four patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder (10 men and 14 women) were randomly assigned to modafinil up to 200 mg a day (N = 13) or placebo (N = 11) as an adjunct therapy in an 8-week, double-blind, placebo-controlled study. Data were collected from May 18, 2001 to September 11, 2003. RESULTS: Four subjects terminated the study early, including one because of worsening of psychosis during the first week taking modafinil. In the modafinil (N = 10) and placebo (N = 10) groups, fatigue improved significantly over time (p < .01), but there were no differences between groups on changes in fatigue, positive and negative symptoms, or cognition. CONCLUSION: Fatigue improved in both groups, and there were no differences between groups on changes in fatigue, symptoms, attention, working memory, or executive functioning. Lack of differences between groups may be due to small sample size or possible regression to the mean in the placebo group.
Adult↗
Do clozapine and risperidone affect social competence and problem solving?
OBJECTIVE: The purpose of this investigation was to evaluate the effects of clozapine and risperidone on social skill and problem solving in patients with schizophrenia. METHOD: The Wisconsin Card Sorting Test and the Maryland Assessment of Social Competence were administered at baseline, week 17, and week 29 of a multisite clinical trial. RESULTS: Despite evidence of clinical improvement with both medications, there was virtually no medication effect on either social competence or problem solving. CONCLUSIONS: These findings underscore the circumscribed nature of symptomatic improvement in the broader spectrum of clinical outcomes and suggest that new-generation medications may not be expected to produce substantial changes in social role functioning or social problem-solving capacity in the community. The generalizability of the findings should be viewed cautiously because of the low power of this trial, and replication is warranted.
Adult↗
Physical health monitoring of patients with schizophrenia.
OBJECTIVE: Schizophrenia is associated with several chronic physical illnesses and a shorter life expectancy, compared with life expectancy in the general population. One approach to improving the health of patients with schizophrenia is to improve the monitoring of physical health that occurs in psychiatric settings. The authors discuss a consensus panel's recommendations for improving the physical health monitoring of patients with schizophrenia who are treated in outpatient settings. METHOD: A consensus meeting including psychiatric and other medical experts assembled on October 17-18, 2002, to evaluate the existing literature and to develop recommendations for physical health monitoring of patients with schizophrenia. Conference participants reviewed the literature in the following areas: 1) weight gain and obesity; 2) diabetes; 3) hyperlipidemia; 4) prolongation of the QT interval on the ECG; 5) prolactin elevation and related sexual side effects; 6) extrapyramidal side effects, akathisia, and tardive dyskinesia; 7) cataracts; and 8) myocarditis. Experts for each topic area formulated monitoring recommendations that were discussed by all of the participants until a consensus was reached. RESULTS: Consensus recommendations included regular monitoring of body mass index, plasma glucose level, lipid profiles, and signs of prolactin elevation or sexual dysfunction. Information from monitoring should guide the selection of antipsychotic agents. Specific recommendations were made for cardiac monitoring of patients who receive medications associated with QT interval prolongation, including thioridazine, mesoridazine, and ziprasidone, and for monitoring for signs of myocarditis in patients treated with clozapine. Patients who receive both first- and second-generation antipsychotic medications should be examined for extrapyramidal symptoms and tardive dyskinesia. Patients with schizophrenia should receive regular visual examinations. CONCLUSIONS: The conference participants recommended that mental health care providers perform physical health monitoring that typically occurs in primary care settings for their patients who do not receive physical health monitoring in those settings. This change in usual practice is recommended on the basis of the conference participants' belief that this additional monitoring will result in the earlier detection of common, serious risk factors that could, without detection and intervention, contribute to impaired health of patients with schizophrenia.
Adult↗
The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2003 update.
BACKGROUND: The Texas Medication Algorithm Project (TMAP) has been a public-academic collaboration in which guidelines for medication treatment of schizophrenia, bipolar disorder, and major depressive disorder were used in selected public outpatient clinics in Texas. Subsequently, these algorithms were implemented throughout Texas and are being used in other states. Guidelines require updating when significant new evidence emerges; the antipsychotic algorithm for schizophrenia was last updated in 1999. This article reports the recommendations developed in 2002 and 2003 by a group of experts, clinicians, and administrators. METHOD: A conference in January 2002 began the update process. Before the conference, experts in the pharmacologic treatment of schizophrenia, clinicians, and administrators reviewed literature topics and prepared presentations. Topics included ziprasidone's inclusion in the algorithm, the number of antipsychotics tried before clozapine, and the role of first generation antipsychotics. Data were rated according to Agency for Healthcare Research and Quality criteria. After discussing the presentations, conference attendees arrived at consensus recommendations. Consideration of aripiprazole's inclusion was subsequently handled by electronic communications. RESULTS: The antipsychotic algorithm for schizophrenia was updated to include ziprasidone and aripiprazole among the first-line agents. Relative to the prior algorithm, the number of stages before clozapine was reduced. First generation antipsychotics were included but not as first-line choices. For patients refusing or not responding to clozapine and clozapine augmentation, preference was given to trying monotherapy with another antipsychotic before resorting to antipsychotic combinations. CONCLUSION: Consensus on algorithm revisions was achieved, but only further well-controlled research will answer many key questions about sequence and type of medication treatments of schizophrenia.
Algorithms↗
Relationship between costs and symptoms in schizophrenia patients treated with antipsychotic medication: a review.
BACKGROUND: The purpose of this review is to understand how changes in costs of illness are related to the effects of antipsychotic medications on symptoms in schizophrenia patients. METHOD: A search of the MEDLINE database was performed using the keywords costs, symptoms, and schizophrenia. Studies published between 1965 and 2003 in English, French, German, or Spanish that assessed costs, symptoms, and relationships between costs and symptoms were reviewed. RESULTS: Twenty studies were identified. Most of the reviewed clinical trials of antipsychotic medications reported a decrease in mean costs of illness and an improvement in symptoms. However, many of the studies did not examine the relationship between changes in costs and symptoms. CONCLUSION: There is little evidence that changes in costs of illness are directly related to the effects of antipsychotic medications on symptoms. This review emphasizes the need for standardizing the assessment of costs and clinical outcomes, looking more specifically at the relationship between types of costs and specific aspects of psychopathology and developing new statistical models relating changes in costs and clinical outcomes.
Antipsychotic Agents↗
Penultimate observation carried forward (POCF): a new approach to analysis of long-term symptom change in chronic relapsing conditions.
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Antipsychotic Agents↗
Prolonged untreated illness duration from prodromal onset predicts outcome in first episode psychoses.
Several, although not all, studies suggest that prolonged duration of untreated illness (DUI) predicts poor outcome in psychotic disorders such as schizophrenia. It is unclear whether this association can be explained by factors such as baseline deficits or poor premorbid adjustment. First episode psychotic patients were evaluated at 1 and 2 years following baseline evaluations. Predictive measures showing significant correlations with outcome were entered in multiple regression analyses with Strauss-Carpenter scale (SC) and Global Assessment of Functioning scale (GAF) outcome scores as dependent variables. Illness duration computed from the onset of the prodrome (DUI-pro), used both as a dichotomous and as a continuous measure, highly significantly predicted both GAF and SC scores at 2 years. On the other hand, baseline functioning significantly predicted the 1-year but not the 2-year outcome. When Premorbid Adjustment Scale (PAS) scores were additionally entered into the analyses in a smaller subset, the relation between DUI-pro and the 2-year outcome scores remained significant. Significant associations were also seen between outcome and baseline neuropsychological deficits involving attention and memory. Further research is needed to examine whether prolonged untreated illness is simply associated with poor outcome or plays a causal role in relation to outcome. The latter, if true, would strongly support therapeutic intervention efforts in the prodromal and early psychotic phases of schizophrenia.
Adolescent↗
Diagnostic specificity and neuroanatomical validity of neurological abnormalities in first-episode psychoses.
OBJECTIVE: Neurological abnormalities are frequently seen in patients with first-episode psychotic disorders but are generally considered to be diagnostically nonspecific, neurologically nonlocalizing, and, hence, "soft." This study examined the neuroanatomical correlates and diagnostic specificity of abnormal findings on the neurological examination in first-episode schizophrenia and other psychotic disorders. METHOD: Neuroleptic-naive patients with schizophrenia (N=90) and with nonschizophrenia psychoses (N=39) and carefully matched healthy subjects (N=93) were compared on total and factor scores for a reliable subset of Neurological Evaluation Scale items. The relationship between neurological examination abnormalities and alterations in the relevant brain structures as assessed by magnetic resonance imaging was examined in a subset of subjects. RESULTS: Factor scores for repetitive motor task abnormalities were higher in both patient groups, relative to the healthy group, and did not distinguish between the patient groups. Factor scores for abnormalities in cognitively demanding and perceptual tasks were markedly higher in the schizophrenia group, relative to both comparison groups, and were not different between the nonschizophrenia psychoses group and the healthy comparison group. Higher scores for the cognitive/perceptual abnormalities factor were correlated with smaller volumes of the left heteromodal association cortex. CONCLUSIONS: Neurological signs may serve as expedient bedside measures that are potentially useful in the assessment of idiopathic psychoses, and cognitive/perceptual neurological signs may have a measure of diagnostic specificity. These findings provide neurobiological validation of abnormal findings on the neurological examination. These abnormalities may reflect discrete neuroanatomical alterations in schizophrenia and may have a localizing value.
Adult↗
Relapse and rehospitalization: comparing oral and depot antipsychotics.
A review of studies that compared conventional oral and depot antipsychotic medications highlighted the following points. Mirror-image studies in which patients served as their own controls provided evidence of substantial benefit for depot injectable medications. The randomized clinical trials did not, in general, support the findings of significant decrease in relapse rates between these 2 routes of administration. Across the studies reviewed, the 1-year relapse rate for long-acting depot medication was 27% compared with 42% for patients who received oral medication. The 27% risk of relapse in patients who received guaranteed depot medication suggests that relapse is not always driven by noncompliance. In the only study that lasted for 2 years, the risk of relapse decreased substantially in the depot-treated patients, suggesting that risk of noncompliance may be a more important factor in relapse over extended periods of time. A recent formal meta-analytic review of depot medications concluded that this route of administration resulted in clinical advantages in terms of global outcome.
Administration, Oral↗
Maintaining symptom control: review of ziprasidone long-term efficacy data.
Reducing the risk of relapse and maintaining symptom control are core goals in the long-term treatment of patients with schizophrenia or schizoaffective disorder because symptom control can allow patients and clinicians to focus on functional improvement. The atypical antipsychotic agents have gained widespread acceptance in this setting because they are at least as effective as the conventional antipsychotic agents, may offer an advantage in relapse prevention, and offer safety advantages, primarily a reduced liability for movement disorders. However, there are differences among the atypical agents that may affect both clinician choice and patient adherence to long-term therapy. Ziprasidone has shown long-term antipsychotic efficacy in comparisons with haloperidol, olanzapine, and risperidone, as well as efficacy in patients switched from another antipsychotic agent. This review examines symptom efficacy data for ziprasidone in long-term trials that lasted between 28 and 52 weeks. Antipsychotic medication is the foundation of long-term treatment of schizophrenia. Optimization of treatment for the individual patient requires consideration of symptom control, prevention of relapse, and possible long-term health consequences. Clinical trial data on ziprasidone's long-term efficacy provide a firm basis for selection of this agent.
Antipsychotic Agents↗