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Pain 01/2013; · 5.78 Impact Factor
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ABSTRACT: While the role of neurocognitive impairment in predicting functional outcome in chronic schizophrenia is now widely accepted, the results that have examined this relationship in the early phase of psychosis are surprisingly rather mixed. The predictive role of cognitive impairment early in the illness is of particular interest because interventions during this initial period may help to prevent the development of chronic disability. In a University of California, Los Angeles (UCLA) longitudinal study, we assessed schizophrenia patients with a recent first episode of psychosis using a neurocognitive battery at an initial clinically stabilized outpatient point and then followed them during continuous treatment over the next 9 months. Three orthogonal cognitive factors were derived through principal components analysis: working memory, attention and early perceptual processing, and verbal memory and processing speed. All patients were provided a combination of maintenance antipsychotic medication, case management, group skills training, and family education in a UCLA research clinic. A modified version of the Social Adjustment Scale was used to assess work outcome. Multiple regression analyses indicate that the combination of the 3 neurocognitive factors predicts 52% of the variance in return to work or school by 9 months after outpatient clinical stabilization. These data strongly support the critical role of neurocognitive factors in recovery of work functioning after an onset of schizophrenia. Cognitive remediation and other interventions targeting these early cognitive deficits are of major importance to attempts to prevent chronic disability.
Schizophrenia Bulletin 09/2011; 37 Suppl 2:S33-40. · 8.80 Impact Factor
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ABSTRACT: Although in the early course of schizophrenia relapse prevention is of paramount importance, there is an increasing emphasis on establishing and maintaining sustained periods of symptom remission. Recovery in the early course of illness is also possible, although the rates of recovery are lower than for symptom remission. Symptom remission and recovery rates vary considerably across recent-onset schizophrenia studies because of a lack of consistency in treatment interventions and in applying operational outcome criteria.
Patients who were within two years of their first psychotic episode (N=77) that were treated with continuous antipsychotic medication in conjunction with psychosocial interventions (without targeted work rehabilitation) were assessed during the first outpatient year after hospital discharge. Published operational criteria were used to classify symptom remission and recovery.
The rate of full symptom remission maintained for 6 months was 36%, while the rate of recovery for 6 months was 10%. When the same criteria were applied for a continuous period of one year, 22% of patients were found to achieve symptom remission but only 1% of patients met recovery criteria. Using multivariate prediction, the WAIS Comprehension score was a significant predictor of 6 months of good functional outcome.
Although some schizophrenia patients can achieve both symptom remission and recovery in the early course of illness, the overall rate of symptom remission during the first post-hospitalization year is much higher than the rate of recovery. This suggests that interventions targeting work and social functioning are likely necessary to raise the chances of recovery. Cognitive factors can be predictive of good functional outcome even in the early course of schizophrenia.
Biological Psychiatry 07/2011; 132(1):18-23. · 8.28 Impact Factor
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ABSTRACT: This study examined whether the presence of subsyndromal depressive symptoms predicted functional recovery after an acute manic episode.
Subjects with bipolar I disorder (according to the Structured Clinical Interview for DSM-IV) who, at the time of symptomatic recovery from an acute manic or hypomanic episode, had a concomitant functional recovery (n = 52) were compared on demographic variables and mood symptoms to those who had symptomatically recovered but not functionally recovered (n = 33). Demographic and mood variables were examined in the nonfunctionally recovered group to assess predictors of time to functional recovery. The primary functional outcome measure used was the Life Functioning Questionnaire, a 5-minute, gender-neutral self-report scale to measure role function in 4 domains: workplace, duties at home, leisure time with family, and leisure time with friends. Participants in the study were recruited from July 2000 through February 2005.
Depressive symptoms, even at a subsyndromal level, were significantly associated with persisting functional impairment after symptomatic recovery from a manic episode (P < .02). Subsyndromal depressive symptoms also significantly predicted a slower time to functional recovery over the next 9 months (P = .006).
The presence of even mild subsyndromal depressive symptoms may interfere with functional recovery in patients with bipolar disorder after symptomatic recovery from a manic or hypomanic episode.
The Journal of Clinical Psychiatry 05/2011; 72(5):692-7. · 5.80 Impact Factor
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ABSTRACT: This study examined the effect of medication nonadherence on the return of positive symptoms among recent-onset schizophrenia patients.
Three sets of operational criteria for medication nonadherence with differing levels of severity were compared for their ability to predict relapse. Explicit operational criteria are provided with the hope that they will be adopted by others. Psychotic symptoms were prospectively rated on a frequent basis, and systematic criteria were applied using a computer scoring program to identify periods of psychotic symptom return. In addition, a specialized statistical survival analysis method, optimal for examining risk periods and outcomes that can recur during the follow-up assessment, was used.
As hypothesized, medication nonadherence robustly predicted a return of psychotic symptoms during the early phase of schizophrenia (hazard ratios=3.7-28.5, depending on the severity of nonadherence).
Even brief periods of partial nonadherence lead to greater risk of relapse than what is commonly assumed. Patients in the early phase of schizophrenia should be cautioned about the possible consequences of partial or relatively brief periods of antipsychotic medication nonadherence.
American Journal of Psychiatry 01/2011; 168(3):286-92. · 12.54 Impact Factor
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Journal of clinical psychopharmacology 08/2010; 30(4):470-1. · 5.09 Impact Factor
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ABSTRACT: In contrast to the trial design of acute mania studies, there is no standard design for bipolar maintenance studies. Over the past 15 years, the design of monotherapy maintenance studies in bipolar disorder has evolved significantly, but recent study designs continue to differ in important ways.
We reviewed the design of recent controlled bipolar maintenance studies, using PubMed, from August 2006 to August 2009, examining the strengths and weaknesses of different study design features.
Design differences are sufficiently important that the disparate results across maintenance studies may reflect either true differences in medication efficacy or the effects of these design differences on outcome. Design elements such as recent episode polarity, stabilization criteria, using enriched versus nonenriched samples, length of stabilization before randomization, length of experimental phase, and recurrence outcome criteria are critical factors that differ widely across studies and likely play a role in study outcome.
As consensus for trial designs for bipolar maintenance therapy is developed, it will be easier to develop algorithms for maintenance treatment based on results from studies as opposed to clinical opinions.
Current Medical Research and Opinion 08/2010; 26(8):1835-42. · 2.38 Impact Factor
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George Bartzokis,
Po H Lu,
Stephanie B Stewart,
Bolanle Oluwadara,
Andrew J Lucas,
Joanna Pantages,
Erika Pratt,
Jonathan E Sherin,
Lori L Altshuler,
Jim Mintz, Michael J Gitlin,
Kenneth L Subotnik,
Keith H Nuechterlein
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ABSTRACT: Imaging and post-mortem studies provide converging evidence that patients with schizophrenia have a dysregulated developmental trajectory of frontal lobe myelination. The hypothesis that typical and atypical medications may differentially impact brain myelination in adults with schizophrenia was previously assessed with inversion recovery (IR) images. Increased white matter (WM) volume suggestive of increased myelination was detected in the patient group treated with an atypical antipsychotic compared to a typical one.
In a follow-up reanalysis of MRI images from the original study, we used a novel method to assess whether the difference in WM volumes could be caused by a differential effect of medications on the intracortical myelination process.
Two different male cohorts of healthy controls ranging in age from 18-35 years were compared to cohorts of subjects with schizophrenia who were treated with either oral risperidone (Ris) or fluphenazine decanoate (Fd).
A novel MRI method that combines the distinct tissue contrasts provided by IR and proton density (PD) images was used to estimate intracortical myelin (ICM) volume.
When compared with their pooled healthy control comparison group, the two groups of schizophrenic patients differed in the frontal lobe ICM measure with the Ris group having significantly higher volume.
The data suggest that in adults with schizophrenia antipsychotic treatment choice may be specifically and differentially impacting later-myelinating intracortical circuitry. In vivo MRI can be used to dissect subtle differences in brain tissue characteristics and thus help clarify the effect of pharmacologic treatments on developmental and pathologic processes.
Biological Psychiatry 08/2009; 113(2-3):322-31. · 8.28 Impact Factor
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Michael J Gitlin
CNS spectrums 01/2008; 12(12 Suppl 22):13-5. · 2.20 Impact Factor
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The Journal of Clinical Psychiatry 07/2007; 68(6):973-4. · 5.80 Impact Factor
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ABSTRACT: Objective. This retrospective study was done to assess the impact of concurrent alcohol use on the illness presentation of patients hospitalized for mania.Design. Retrospective demographic and clinical data were systematically collected from the hospital records of 122 patients hospitalized for an index episode of mania between 1988 and 1995. Comorbid alcoholism was defined as alcohol abuse/dependence, based on DSM-IV criteria. Blind to alcohol use and treatment intervention, a retrospective clinical assessment of illness severity was made by the Clinical Global Impression (CGI) at the end point of hospital discharge. Demographic and clinical differences between the alcoholic and nonalcoholic manic subjects were analyzed by chi-square and independent t-tests. Survival analyses with hospital length of stay as the dependent variable were conducted on the two groups.Setting. Tertiary care university hospital.Participants. Patients with bipolar disorder hospitalized for mania.Measurements. Clinical Global Impression (CGI), clinical variables (suicidality, polysubstance abuse, hospital length of stay).Results. Alcoholic manic and nonalcoholic manic patients differed significantly in two categorical measures: suicidality on admission (36.7 vs. 18.5%) and current polysubstance abuse/dependence (46.6 vs. 7.6%). There was no significant difference in length of hospitalization between the two groups.Conclusions. The results of this study are consistent with previous studies that have found an association between alcoholism and increased suicidality and polysubstance abuse in bipolar disorder.
Psychiatry 04/2007; 4(4):34-9.
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ABSTRACT: Research on predicting and preventing episodes of schizophrenia and mood disorder lacks consistent, specific definitions of episodes. We present an operational system for identifying relapse, exacerbation, and remission of schizophrenia and bipolar disorder within longitudinal studies that involve repeated symptom assessments. Three major classes of episodic outcome are defined: relapse or significant exacerbation, nonrelapse, and stable, severe persisting symptoms. These major classes are further subdivided to distinguish nine categories of episodic outcome. To examine ease of use, interrater reliability, and validity, the classification system was applied to recent-onset samples of schizophrenia patients (N=77) and bipolar mood disorder patients (N=23) followed on medication for 9- to 12-month periods. A range of episodic outcomes were distinguished with high interrater reliability. Despite being prescribed continuous medication, 21% of the recent-onset schizophrenia patients and 61% of bipolar patients met criteria for relapse or significant exacerbation during this follow-up period. Predictive relationships support the validity of this system for classifying episodes. A computer program is available to facilitate its use. Use of these explicit definitions of episodes may help to clarify the relationship between episodic outcome and other fundamental domains of illness outcome, particularly other symptom dimensions, work functioning, and social functioning.
Psychiatry Research 12/2006; 144(2-3):153-66. · 2.52 Impact Factor
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ABSTRACT: This article reviews studies of the placebo response in antidepressant clinical trials, describes methods that have been attempted to decrease it, and discusses implications of the placebo response in depression for research on treatments for neuropathic pain. Literature reviews and research studies examining the placebo response in clinical trials of treatments for depression were reviewed. Existing data suggest that the placebo response in antidepressant clinical trials is substantial and that a high placebo response in a clinical trial is associated with a reduced likelihood of demonstrating the statistical superiority of antidepressant treatment vs. placebo. Attempts to decrease the placebo response in antidepressant clinical trials have generally not been effective. In addition, there is little evidence that decreasing the placebo response rate makes it more likely that superiority of active vs. placebo treatment will be demonstrated. Analyses of neuropathic pain clinical trial databases should be conducted to examine factors associated with trial outcomes. Aspects of neuropathic pain clinical trials that require further consideration or investigation include the following: (a) exclusion of patients with mild pain severity; (b) exclusion of patients with short episode duration; (c) maximizing reliability, validity, and responsiveness of outcome measures; (d) minimizing extraneous contact with investigative staff and other sources of nonspecific therapeutic effects; (e) trial duration; (f) minimizing the number of treatment groups; (g) flexible vs. fixed dose designs; (h) strategies for identifying patients and accelerating enrollment; (i) identification of run-in periods that reduce the placebo response rate; and (j) registration of clinical trials and publication of negative studies.
Neurology 01/2006; 65(12 Suppl 4):S7-19. · 8.31 Impact Factor
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ABSTRACT: Despite a high prevalence rate, patients with bipolar disorder and active alcohol use are routinely excluded from controlled clinical trials leaving clinicians with little evidence-based medicine to guide treatment. This report evaluates preliminary data of alcohol consumption patterns utilizing the Alcohol Timeline Followback (TLFB) method in actively drinking patients with bipolar disorder.
A sample of 30 patients underwent a Structured Diagnostic Interview for DSM-IV (SCID-IV) as well as completing various measures of alcohol use and associated morbidity.
In the month prior to study entry, the TLFB reported 18.4/30+/-9.12 drinking days, 9.9+/-4.73 drinks per drinking day and 169.4+/-101.71 total standard drinks for this study group. There was a significant difference in the number of drinks per drinking day between those diagnosed with rapid cycling than non-rapid cycling bipolar disorder and those with a new diagnosis versus established diagnosis of bipolar disorder.
This study highlights heavy alcohol use in patients with bipolar disorder and alcohol comorbidity. The TLFB method provides 'real world' quantification of use. Further studies are encouraged to elucidate implications of heavy drinking patterns as found in our rapid cycling and newly diagnosed cohorts.
Bipolar Disorders 09/2005; 7(4):377-81. · 5.29 Impact Factor
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ABSTRACT: The ability of electrodermal variables to predict negative symptoms and functional outcome over a 1-year period in schizophrenia was investigated in 78 young, recent-onset outpatients. Patients were stabilized on standardized medication and largely free of psychotic symptoms. Higher levels of both tonic (skin conductance level, nonspecific skin conductance response rate) and phasic (number of skin conductance orienting responses) activity were associated with more negative symptoms and with a combination of poorer social and occupational outcome at 1-year follow-up. This pattern was seen in both male and female patients, and in older and younger patients. Results are interpreted as suggesting that high levels of arousal and overreactivity to the environment may interfere with efficient cognitive processing in schizophrenia, contributing to poor outcome, and that negative symptoms might partially serve as a means of coping with overarousal.
Psychophysiology 08/2005; 42(4):483-92. · 3.29 Impact Factor
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ABSTRACT: Although stressful life events can trigger psychotic and depressive symptom exacerbation in schizophrenia, many patients who experience stressful events do not subsequently relapse. Models of vulnerability, stress, and protective factors in schizophrenia suggest that effective coping responses may serve as protective factors. Coping behavior, in turn, may be influenced by a schizophrenia patient's level of self-efficacy and neurocognitive functioning. Using the Coping Responses Inventory, we examined how 29 recent-onset schizophrenia outpatients and 24 demographically matched normal comparison subjects responded to a negative interpersonal life event. Approach oriented coping responses, such as "Think of different ways to deal with the problem" and "Make a plan of action and follow it," were used significantly more often by normal subjects (M=2.27) than by schizophrenia patients (M=1.89; p < 0.02). Among schizophrenia patients, greater use of approach, problem-focused coping strategies was associated with high self-efficacy (r=0.55, p < 0.01) and better performance on a measure of sustained attention emphasizing perceptual processing (r=0.42, p < 0.05). Multiple regression indicated that self-efficacy and sustained attention accounted for 56% of the variance in the use of problem-focused coping, strategies by schizophrenia patients.
Schizophrenia Research 08/2004; 69(2-3):343-52. · 4.75 Impact Factor
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ABSTRACT: Bipolar disorders, particularly bipolar spectrum disorders, frequently go unrecognized and undiagnosed by clinicians and thus remain untreated or inappropriately treated. Although the symptoms of bipolar I disorder are widely acknowledged and recognized among clinicians, epidemiology sampling studies over the past several years have found that bipolar II disorder and bipolar spectrum disorders are likely to be more prevalent and more challenging to diagnose, particularly as depressive presentations are far more common in these groups. Bipolar disorder is associated with increased morbidity and mortality, as well as higher healthcare costs, but it is unclear how much of the consequences of bipolar disorder are unrecognized in the face of poor recognition of bipolar II and bipolar spectrum disorders. This article addresses challenges in diagnosing and treating bipolar disorder in the face of a depressive episode, and offers guidelines for recognizing and appropriately managing these patients. Studies with the newer anticonvulsant mood stabilizer lamotrigine have shown antidepressant effects in bipolar disorder, and may fill an unmet need for treatment options in patients who present with depression in the context of bipolar disorder. Depression and Anxiety 19:199–208, 2004. © 2004 Wiley-Liss, Inc.
Depression and Anxiety 12/2003; 19(4):199 - 208. · 4.18 Impact Factor
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ABSTRACT: The intra- and interindividual variability in apparent steady-state plasma levels of risperidone (RSP) and its metabolite 9-hydroxyrisperidone (9-OHRSP) in schizophrenic patients was investigated. Patients (n = 46, age 26.4 +/- 5.3 years) with diagnosed schizophrenia were treated with a fixed daily oral dose of RSP (1-12 mg/d). The steady-state plasma samples from these patients were collected over a period of 5 years and a total of 549 visits. Plasma concentrations of RSP and 9-OHRSP were determined using a highly sensitive and specific LC-MS-MS method with a detection limit of 0.1 ng/mL. All plasma samples had measurable amounts of 9-OHRSP; however, RSP was nondetectable (<0.1 ng/mL) in 18% of the plasma samples. 9-OHRSP levels were, on average, approximately 22 times higher than those of RSP. The plasma levels of RSP and 9-OHRSP varied widely among patients receiving similar doses of RSP, and the intra- and interindividual variations of RSP and 9-OHRSP plasma levels were found to be large. The data indicated that there was no significant change in the steady-state levels of either RSP or 9-OHRSP during the treatment period. Similarly, the dose-normalized concentration did not vary significantly during the treatment period or with the administered dose. The absence of RSP in many plasma samples (<0.1 ng/mL) and presence of 9-OHRSP at severalfold higher concentrations than RSP indicate that measuring plasma levels of RSP alone may lead to erroneous interpretation in plasma level monitoring studies. The current data support the fact that it is important to measure steady-state levels of total active moiety by analyzing both RSP and 9-OHRSP for plasma drug monitoring.
Therapeutic Drug Monitoring 12/2003; 25(6):657-64. · 2.49 Impact Factor
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ABSTRACT: Despite the prevalence and morbidity of bipolar depression, few randomized treatment trials have been conducted to assess clinical efficacy. Even fewer studies have assessed approaches that optimize treatment response for bipolar depression. This review will define three types of common combination strategies--adjunctive, acceleration and augmentation--and discuss the limited literature of controlled studies reported on acceleration and augmentation approaches.
Biological Psychiatry 05/2003; 53(8):691-700. · 8.28 Impact Factor
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The Journal of family practice 04/2003; Suppl:S10-3. · 0.61 Impact Factor
