Predictors of medication discontinuation by patients with first-episode schizophrenia and schizoaffective disorder

BACKGROUND: Enhancing medication adherence early in the course of schizophrenia and schizoaffective disorder may substantially improve long-term course. Although extensively studied in multi-episode patients, little data exist on medication adherence by first-episode patients. METHOD: Medication adherence was assessed during the first year of treatment and following recovery from the first relapse in patients treated by a standardized medication algorithm. RESULTS: During the first year of treatment, patients with poorer premorbid cognitive functioning were more likely to stop antipsychotics (t=-2.54, df=75, p=0.01). Parkinsonian side effects increased the likelihood (hazard ratio=41.22; 95% CI=2.30, 737.89; p=0.01), and better executive function decreased the likelihood (hazard ratio=0.40; 95% CI=0.18, 0.88; p=0.02) that patients discontinued maintenance medication after a first relapse. CONCLUSION: Interventions to ameliorate cognitive deficits and Parkinsonian side effects may enhance treatment adherence.     

ECT in medication resistant schizoaffective disorder

For the clinician, schizoaffective patients are a formidable challenge. They are usually the most disturbed, agitated, and difficult to control on the ward. Because they are often young, retain affect (though it may be bizarre) and may have functioned relatively well between episodes and/or prior to hospitalization, ECT is often considered a last resort or may not be given at all. This is unfortunate given the excellent response to ECT and Tsuang's³ finding that schizoaffective patients not treated with ECT had higher suicide and mortality rates compared with those who had received ECT.The present study and review concludes that: (1) ECT is a very effective acute treatment in schizoaffective disorder; (2) whether called schizoaffective or affective disorder with psychosis there appears to be a subgroup of young patients with prominent confusion and lack of response to medications for whom ECT is particularly effective; (3) lithium should be considered as a prophylactic treatment with these patients; and (4) patients with schizoaffective disorder (as described) should be considered as a separate group in future ECT and/or lithium treatment response studies.     

Depressive factors and their relationships with other symptom domains in schizophrenia, schizoaffective disorder, and psychotic depression

Relationships among different symptom domains were investigated in patients with acute exacerbation of schizophrenia with depressive symptoms, psychotic depression, or schizoaffective disorder, depressive subtype. Scores for depression and depressive factors were correlated with positive, negative, and extrapyramidal symptoms within diagnostic categories. No between-group differences in the relationship of different symptom domains could be found, and no substantial relationship between depression and positive symptoms could be revealed in any diagnostic subgroup. Only the retardation factor of depression showed a significant overlap with negative symptoms; depressive core symptoms did not. Core symptoms of depression were independent from other symptoms in all investigated diagnostic groups. Depression seems to represent a heterogeneous symptom domain with unique relationships of components to positive and negative symptoms across nosological borders. A more differentiated assessment, analysis, and treatment of depressive symptoms is therefore recommended for patients with combined depressive and psychotic symptoms.     

Suicidal behavior in schizophrenia and schizoaffective disorder

Individuals with schizophrenia and schizoaffective disorder are at increased risk for completed suicide and suicide attempts. Suicide risk is increased throughout the life span and most suicide attempters and completers make more than one attempt. Investigations show that individuals with these psychotic disorders are typically experiencing psychotic symptoms and in psychiatric treatment at the time of their attempts although frequently under-treated with respect to medication. We review the literature with regard to demographic and clinical risk factors for suicidal behavior among individuals with schizophrenia and schizoaffective disorder. Specifically the role of clinical symptoms, premorbid and current social functioning, depression, substance misuse and abuse and biological factors are presented. Future directions for research regarding assessment and intervention are discussed.     

Treatment adherence in schizophrenia and schizoaffective disorder

Medication nonadherence is common and difficult to detect in patients with schizoaffective disorder and schizophrenia. Roughly 50% of patients take less than 70% of prescribed doses. Many factors contribute to nonadherence, including poor illness insight, a negative attitude toward medication, substance abuse, and disorganization. Interventions to improve adherence consist of advising acceptance of illness, drawing analogies with treatment for chronic medical disease, and involving the patient in decision making. Clinicians must remain nonjudgmental, encouraging patients to disclose problems with adherence and anticipating that improvement in adherence may require a prolonged effort. Selection of medication is critical to avoid side effects and to provide a sense of well-being, which can result from improvement in insomnia, anxiety, or depression. Depot antipsychotics can improve adherence and provide the clinician with reliable information about the dosage of medication received for purposes of dose adjustments or to guide response to relapse.     

Thalamic morphology in schizophrenia and schizoaffective disorder

Background

Biomarkers are needed that can distinguish between schizophrenia and schizoaffective disorder to inform the ongoing debate over the diagnostic boundary between these two disorders. Neuromorphometric abnormalities of the thalamus have been reported in individuals with schizophrenia and linked to core features of the disorder, but have not been similarly investigated in individuals with schizoaffective disorder. In this study, we examine whether individuals with schizoaffective disorder have a pattern of thalamic deformation that is similar or different to the pattern found in individuals with schizophrenia.

Method

T1-weighted magnetic resonance images were collected from individuals with schizophrenia (n = 47), individuals with schizoaffective disorder (n = 15), and controls (n = 42). Large-deformation, high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. Multiple analyses of variance were used to test for group differences in volume and measures of surface shape.

Results

Individuals with schizophrenia or schizoaffective disorder have similar thalamic volumes. Thalamic surface shape deformation associated with schizophrenia suggests selective involvement of the anterior and posterior thalamus, while deformations in mediodorsal and ventrolateral regions were observed in both groups. Schizoaffective disorder had distinct deformations in medial and lateral thalamic regions.

Conclusions

Abnormalities distinct to schizoaffective disorder suggest involvement of the central and ventroposterior medial thalamus which may be involved in mood circuitry, dorsolateral nucleus which is involved in recall processing, and the lateral geniculate nucleus which is involved in visual processing.     

Antipsychotic medication,prolactin elevation,and ovarian function in women with schizophrenia and schizoaffective disorder

Some, but not all, antipsychotics elevate serum prolactin. Antipsychotic-induced hyperprolactinemia is thought to account for high rates of menstrual dysfunction and diminished estrogen levels in women with schizophrenia. However, few studies have directly assessed the relationships between prolactin, menstrual function, and ovarian hormone levels in this population. Sixteen premenopausal women with schizophrenia and schizoaffective disorder, eight treated with an antipsychotic with prolactin-elevating potential (five with typical antipsychotics and three with risperidone) and eight treated with an antipsychotic with prolactin-sparing potential (seven with olanzapine and one with clozapine), were studied for eight weeks. Data were collected on menstrual functioning and on serum prolactin, estradiol, and progesterone levels, and were compared between subjects who received an antipsychotic with prolactin-elevating potential and an antipsychotic with prolactin-sparing potential, and between subjects with hyperprolactinemia (N=6) and normoprolactinemia (N=10). Additionally, peak ovarian hormone levels were compared to normal values. While mean prolactin levels of subjects who received an antipsychotic with prolactin-elevating potential were significantly greater than those of subjects who received an antipsychotic with prolactin-sparing potential, there were no differences in rates of menstrual dysfunction or in ovarian hormone values between the two groups. Additionally, similar rates of menstrual dysfunction and ovarian hormone values were observed between the hyperprolactinemic and normoprolactinemic subjects. Moreover, irrespective of medication type or prolactin status, most subjects had peak estradiol levels below normal reference values for the periovulatory phase of the menstrual cycle. While our sample size is small, warranting the need for further investigation, the findings of this preliminary study suggest that antipsychotic-induced hyperprolactinemia, alone, may not adequately explain the observed ovarian dysfunction in women with schizophrenia.     

Strategies for improving treatment adherence in schizophrenia and schizoaffective disorder

Nonadherence with medication treatment is common but difficult to detect in patients with schizoaffective disorder and schizophrenia, almost half of whom take less than 70% of prescribed doses. Like patients in all areas of medicine, patients with schizoaffective disorder weigh the perceived benefits of medications against perceived disadvantages, but this process is complicated by their impaired insight, the stigma of the diagnosis, and the often troubling side effects of antipsychotic medication. Interventions to improve adherence include encouraging acceptance of the illness, drawing analogies with treatment for chronic medical disease, and involving the patient in decision making. Clinicians must remain nonjudgmental, encouraging patients to disclose problems with adherence and anticipating that improvement in adherence may require a prolonged effort. Selection of antipsychotic medication is critical to avoid adverse side effects, and some medications may provide a sense of well-being, such as improvement in insomnia, anxiety, or depression. Depot (rather than oral) antipsychotics can improve adherence and provide the clinician with reliable information about the dosage of medication received, which can be used for purposes of dose adjustments or to guide response to relapse.     

Combination of "atypical" antipsychotic medication in the management of treatment-resistant schizophrenia and schizoaffective disorder

BACKGROUND: This article reviews the published clinical data on treatment-resistant schizophrenic and schizoaffective patients managed with combinations of "atypical" antipsychotic medication. METHOD: A computerized MEDLINE literature search covering an 18-year period (1985-2003) was conducted. All pertinent papers on the subject of the use of combination "atypical" antipsychotic medication in the management of treatment-resistant schizophrenia and schizoaffective disorder were obtained with subsequent analysis and discussion of the retrieved data. RESULTS: The search identified 29 case reports and case series reports (172 patients) and one double-blind placebo-controlled trial (28 patients) describing the use of combination "atypical" antipsychotic medication (clozapine-risperidone; clozapine-sulpiride; clozapine-olanzapine; clozapine-quetiapine; olanzapine-sulpiride; olanzapine-quetiapine; risperidone-olanzapine; risperidone-quetiapine) in the treatment of resistant schizophrenic and schizoaffective patients. An overview of results suggests that the combinations were beneficial in the described patients with reduction of positive symptoms and occasionally negative symptoms. Significant adverse effects, while rare, were reported in a few cases and did not appear to different in nature from those managed on monotherapeutic regimens. CONCLUSION: Combinations of "atypical" antipsychotic medications are well tolerated and may be effective in the management of treatment refractory schizophrenia and schizoaffective disorder. However, further double-blind placebo-controlled trials are required in order to test and confirm these observations.     

Emotional awareness and delusions in schizophrenia and schizoaffective disorder

Background and objectivesEmotion plays a significant role in schizophrenia. Emotional awareness (i.e., attention to and clarity of emotions) is associated with a wide range of outcomes. Given that individuals with schizophrenia and schizoaffective disorder differ in the significance of their mood symptoms, the present research examined whether the association between emotional awareness and delusions differs for these two groups of patients.MethodsEmotional awareness (i.e., attention to and clarity of emotions) was measured with self-report in a sample of 44 individuals diagnosed with either schizophrenia or schizoaffective disorder. Clinical ratings of delusions were made using the Scale for the Assessment of Positive Symptoms.ResultsFor the sample as a whole, individuals with higher levels of attention to emotion tended to have more severe delusions. In addition, diagnostic group significantly moderated the relation between emotional clarity and delusions.LimitationsConclusions regarding causality cannot be drawn due to the cross-sectional design. Replication is particularly important given the small sample sizes.ConclusionsThe present research indicates that emotional awareness is associated with delusions. The results raise the possibility that the emotional factors that contribute to delusional beliefs among individuals with schizophrenia differ in at least some ways from the emotional factors that contribute to delusional beliefs among individuals with schizoaffective disorder.     

Physiology of schizophrenia, bipolar disorder, and schizoaffective disorder

OBJECTIVE: Endophenotypes have been proposed to identify the genetic and biological substrates of complex disorders. Three physiological inhibitory endophenotypes of large effect size in schizophrenia include suppression of P50 auditory evoked responses, inhibition of leading (small anticipatory) saccades during smooth pursuit eye movements, and cancellation of reflexive saccades in the antisaccade eye movement task. The aim of this study was to determine if the pattern of endophenotype abnormalities within individuals with schizophrenia differed from that within individuals with bipolar disorder. A second aim was to determine whether subjects with schizoaffective disorder, bipolar type, were neurophysiologically more similar to subjects with schizophrenia or subjects with bipolar disorder. METHOD: Endophenotypes were recorded for subjects diagnosed with schizophrenia (N=29), bipolar disorder (DSM-IV-TR) (N=40), and schizoaffective disorder, bipolar type (N=18). Data from normal comparison subjects were used to establish normal performance. RESULTS: Logistic regression determined that P50 ratio and frequency of leading saccades identified subjects with schizophrenia and bipolar disorder with a sensitivity of 95% and a specificity of 83%. The schizoaffective disorder group was split, with six subjects physiologically classified as schizophrenia-like and 12 subjects as bipolar-like. Those classified as schizophrenia-like were significantly younger at illness onset and had higher symptom ratings. CONCLUSION: A composite endophenotype of P50 ratio and frequency of leading saccades is consistent with the current clinical nosology of schizophrenia and bipolar disorder and parses patients with schizoaffective disorder, bipolar type, into two subgroups.     

Visual processing and neuropsychological function in schizophrenia and schizoaffective disorder

Persons with schizophrenia and schizoaffective disorder exhibit deficits in both visual processing and neuropsychological tasks. Little is known, however, about whether these deficits are related to one another. We administered psychophysical tests of visual discrimination and recognition, and neuropsychological tests of abstract flexibility, verbal learning, visual memory, working memory and attention to 42 outpatients with stable but chronic schizophrenia or schizoaffective disorder. Multiple regression analyses were performed to determine the relationship between these measures of neuropsychological function and visual psychophysical performance. Results indicated that motion perception was associated with working memory, and that the addition of a memory component to motion perception (motion recognition) was associated with both working memory and visual memory. Visual performance was not associated with symptom severity as measured by the PANSS. These results suggest that psychophysical tests of visual processing may contribute to deficits on neuropsychological tests of visual cognition, and may also reflect cross-modal disturbances of working memory function.     

Slow-wave sleep deficits and outcome in schizophrenia and schizoaffective disorder

Schizophrenia is associated with altered sleep architecture, particularly in regard to delta sleep. We examined the relation between the baseline polysomnographic measures in schizophrenic and schizoaffective patients and psychosocial outcome as measured by the Strauss & Carpenter scale at 1 (n = 20) and 2 (n = 7) years. The percentages of delta sleep at baseline were significantly correlated with total outcome scores at 1 and at 2 years. These preliminary findings suggest that delta sleep deficits may be associated with relatively poor outcome in this disorder.     

精神分裂症与分裂情感性障碍的核心特征与治疗

精神分裂症是一种严重的精神障碍,在普通人群中的患病率为0.5%~1.0%,在住院患者中,其比例更高。由于精神分裂症的不同亚型在治疗上并无区别,并且容易给临床诊断造成混乱,因此,DSM-5去除了精神分裂症的亚型。分裂情感性障碍的患病率约为精神分裂症的一半。其症状相当于既有精神分裂症的A组症状,同时又有心境症状,例如重性抑郁或躁狂。诊断此障碍必须符合两个关键标准:(1)在半数以上的病程中,除了存在精神分裂症诊断标准A的症状以外,还伴有重性抑郁发作或躁狂发作;(2)在没有心境发作至少2周(抑郁或躁狂)的情况下,存在持续的妄想或幻觉,即证明这些精神病性症状并非由心境发作所致。     

Predictors of risk for relapse in patients with schizophrenia or schizoaffective disorder during olanzapine drug therapy

PURPOSE: To evaluate the relationship of dose decrease, symptom worsening, and baseline covariates on subsequent relapse during olanzapine treatment in patients with schizophrenia or schizoaffective disorder. METHODS: In two 28-week, randomized, double-blind clinical trials, a Cox proportional hazards model was used to determine potential correlates of relapse (defined as > or =20% worsening on PANSS total and CGI-Severity 3) among patients (N=271) who responded to 8 weeks of olanzapine treatment (10-20mg/day). Variables examined included: demographics, illness characteristics, baseline symptoms, symptom change, dose, adverse events, and functioning. RESULTS: Patients with a lower last dose relative to the preceding visit interval were 4 times more likely to relapse during that visit interval than other patients (p<.001). A similar finding was observed for a decrease in interval modal dose, although this variable was more predictive of relapse in the visit interval immediately following dose decrease (p=.027). In a subgroup analysis by gender, there was a significantly greater incidence of relapse in men with a dose decrease, whereas a dose decrease in women did not correlate with relapse. Relapse was also correlated with the emergence or worsening of a psychiatric adverse event during the same (p<.001) and preceding (p=.007) visit intervals, and with increased rating scale measures of psychopathology. The occurrence of a non-psychiatric adverse event was not associated with relapse. CONCLUSION: Dose decrease is a significant predictor of relapse in male but not female patients. Psychiatric adverse events also predicted relapse. Patients should be periodically reassessed to determine the need for maintenance treatment with appropriate dose.