Treatment response in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission

Background

Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission.

Method

A naturalistic, cross-sectional study was performed using patient interviews and information from patient files. The new classification method CANSEPT, which combines the Camberwell Assessment of Need rating scale, the Udvalg for Kliniske Undersøgelser side effect rating scale (SE), and the patient's previous treatment history (PT), was used to group the patients according to treatment response. CANSEPT was evaluated by comparison of expected and observed results.

Results

In the patient population (n = 123), the patients in functional remission, as defined by CANSEPT, had higher quality of life, fewer hospitalizations, fewer psychotic symptoms, and higher rate of workers than those with the worst treatment outcome.

Conclusion

In the evaluation, CANSEPT showed validity in discriminating the patients of interest and was well tolerated by the patients. CANSEPT could secure inclusion of correct patients in the clinic or in research.     

Predictors of symptomatic remission in patients with first-episode schizophrenia: A 16 years follow-up study

Objective

Recent views on schizophrenia outcome and treatment suggest that symptomatic remission is possible, and a definition of remission has been proposed by the Remission in Schizophrenia Working Group (RSWG).This study evaluated whether patients who achieved remission after several years of illness (R) showed psychopathological differences at the onset of their disorder compared to non-remitted (NR) patients.

Method

Forty-eight patients with first-episode schizophrenia were evaluated with the Positive and Negative Symptoms Scale (PANSS) both at the onset of illness and after a mean period of 16 years. Patients were defined as R or NR according to the RSWG criteria.

Results

Eighteen patients (37.5%) were classified as R at follow-up. At onset, R patients showed a lower illness severity, less severe negative and general psychopathology symptoms compared to NR. Furthermore, they underwent fewer psychotic episodes than NR over the course of follow-up. Remission was predicted by lower severity of negative and general psychopathology symptoms at onset and by lesser number of psychotic episodes during follow-up.

Conclusions

The symptomatic remission may be a viable outcome in schizophrenia, particularly for patients with a mild illness and less severe negative symptoms at onset and with few psychotic episodes over time.     

Seventeen-year clinical outcome of schizophrenia in Bali

Objective

To examine the 17-year clinical outcome of schizophrenia and its predictors in Bali.

Methods

Subjects were 59 consecutively admitted first-episode schizophrenia patients. Their clinical outcome was evaluated by standardized symptomatic remission criteria based on Positive and Negative Syndrome Scale (PANSS) scores and operational functional remission criteria at 17-year follow-up. The standardized mortality ratio (SMR) over 17 years was also calculated as another index of clinical outcome.

Results

Among these 59 patients, 43 (72.9%) could be followed-up, 15 (25.4%) had died, and one (1.7%) was alive but refused to participate in the study. Combined remission (i.e. symptomatic and functional remission) was achieved in 14 patients (23.7% of original sample). Duration of untreated psychosis (DUP) was a significant baseline predictor of combined remission. Mean age at death of deceased subjects was 35.7, and SMR was 4.85 (95% CI: 2.4-7.3), indicating that deaths were premature. Longer DUP was associated with excess mortality.

Conclusions

The long-term outcome of schizophrenia in Bali was heterogeneous, demonstrating that a quarter achieved combined remission, half were in nonremission, and a quarter had died at 17-year follow-up. DUP was a significant predictor both for combined remission and mortality.     

Response and remission of subjective well-being in patients suffering from schizophrenia spectrum disorders

Background

Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being.

Method

The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome.

Results

Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission.

Conclusions

Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.     

Psychosocial remission in schizophrenia: developing a clinician-rated scale

Background

There is a growing awareness of the importance of psychosocial factors incorporated in treatment goals in schizophrenic patients. Remission, both symptomatic and psychosocial, is now an achievable goal in a substantial proportion of patients. Thus, the development of handy tools to quantify outcomes is called for.

Objective

To develop a brief, clinician-rated scale for the assessment of psychosocial remission in schizophrenia (the Psychosocial Remission in Schizophrenia [PSRS] Scale). The scale is to match the quantification of symptomatic remission as delineated by the American Psychiatric Association task force.

Method

A “bank” of 124 questions pertaining to psychosocial remission was derived from published scales reflecting 2 domains: quality of life and activities of daily living. Psychiatrists, residents, psychiatric nurses, and community nurses were presented with the questions. All were asked to choose the 8 items they considered as reflecting the essence of psychosocial remission. Interrater reliability of the final scale version was assessed among psychiatrists.

Results

The questions' bank was reviewed by 429 mental health professionals. The 4 items found to be most frequently sanctioned in the quality-of-life domain were (a) familial relations (endorsed by 78% of participants), (b) understanding and self-awareness (46%), (c) energy (58%), and (d) interest in everyday life (38%). The 4 items sanctioned in the instrumental activities of daily living domain were (a) self-care (86%), (b) activism (65%), (c) responsibility for medications (54%), and (d) use of community services (32%). Interrater reliability among 70 psychiatrists ranged from 0.67 to 0.83.

Conclusion

The PSRS is an 8-item scale quantifying psychosocial remission in schizophrenia in a manner that complements symptomatic assessment of remission. The PSRS may be useful for both research and clinical evaluation.     

Psychopathologic, neuropsychological and functional outcome measures during cognitive rehabilitation in schizophrenia: A prospective controlled study in a real-world setting

Background

Cognitive dysfunction has been demonstrated in patients with schizophrenia, and this may affect patients’ functional outcome. The improvement of such dysfunction by means of cognitive remediation interventions has become a relevant target in the care of schizophrenia.

Objective

To assess the effectiveness of the cognitive subprograms of Integrated Psychological Therapy (IPT) on symptomatological, neuropsychological and functional outcome variables and to analyze the relationships between cognitive and functional outcome changes in schizophrenia.

Methods

Thirty-two patients with schizophrenia were assigned to cognitive remediation (IPT-cog) or usual rehabilitative interventions in a naturalistic setting of care. Clinical, neuropsychological and functional outcome variables were assessed at baseline and after 24 weeks of treatment.

Results

The IPT-cog group improved significantly more than the comparison group with respect to psychopathological and functional outcome variables. Moreover, only the IPT-cog group improved significantly in the neuropsychological domains of verbal and working memory, with specific significant correlations between neurocognitive performance and functional outcome changes.

Conclusions

The results of the study confirm the effectiveness of the cognitive remediation component of IPT in schizophrenia, and indicate that some of the changes in functional outcome may be mediated by improvement in specific cognitive domains.     

Does personality disorder decrease the likelihood of remission in early-onset chronic depression?

Background

The impact of personality disorders (PD) on the course of depression has been gaining interest among clinical researchers over the past decade. Recent observational studies have found that PD was associated with impaired social functioning and reduced likelihood of depression recovery. Elevated rates of PD have been noted in early-onset and chronic forms subtypes of depression. However, scant data exist regarding the link between PD and outcome for this depression subtype.

Methods

The National Epidemiological Survey on Alcohol and Related Conditions database was analyzed. This survey included 43 093 respondents, 18 years and older, conducted in 2001 through 2002. Logistic regression was used to identify demographic and clinical predictors of remission in early-onset chronic depression.

Results

The absence of PD, having more years of education, and being married considerably improved the likelihood of remission. Paranoid personality disorder and obsessive-compulsive disorder were the only specific PD found to be associated with a reduced probability of remission.

Limitations

Depression remission status may have biased the recollection of PD symptoms. Borderline personality disorder, narcissistic personality disorder, and schizotypal personality disorder were not assessed.

Conclusions

This study suggests that PD are significant predictors of remission in early-onset chronic depression.     

Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder

Objective

Lower serotonin transporter (5-HTT) binding (BP_P = f_PB_avail/K_D) is reported during a major depressive episode (MDE) compared to healthy controls. Higher 5-HTT binding in the diencephalon has previously been associated with acute response to antidepressant treatment. We assessed baseline 5-HTT binding as a predictor of one-year remission from a MDE, examining binding in brain regions implicated in the pathophysiology of major depressive disorder (MDD).

Methods

5-HTT binding was quantified using positron emission tomography (PET) with [¹¹C]McN5652 in 19 currently depressed subjects with MDD and 41 healthy controls. Depressed subjects received open, naturalistic antidepressant treatment. Remission status was determined one year after PET scan and treatment initiation.

Results

Significant differences in 5-HTT binding among the three groups (healthy controls, remitters, and non-remitters) were observed in a linear mixed-effects model. Post hoc, non-remitters had lower 5-HTT binding than controls in midbrain, amygdala, and anterior cingulate. Remitters did not differ significantly from controls or non-remitters in 5-HTT binding. Remitters did not differ from non-remitters in clinical characteristics apart from greater family history of depression among non-remitters. A logistic regression model fit to determine the capacity of baseline 5-HTT binding to predict remission status at one year yielded a coefficient that was suggestive but not significant (p = 0.057).

Limitations

The small sample size and heterogeneous treatments received reduced statistical power to detect differences in binding based on clinical outcome.

Conclusions

Lower pretreatment 5-HTT binding may be predictive of non-remission from major depression following one year of naturalistic antidepressant treatment. Future studies using standardized treatment are warranted.     

Toward a more comprehensive assessment of depression remission: the Remission Evaluation and Mood Inventory Tool (REMIT)

Objective

Depression remission continues to be defined in terms of resolution of the Diagnostic and Statistical Manual of Mental Disorders criteria symptoms. However, it may be useful to assess additional symptoms as part of a more complete evaluation of remission. We sought to develop an adjunct self-report measure that can be used with commonly used depression measures when assessing remission.

Methods

Secondary data analysis and expert input were used to develop candidate items that were evaluated cross-sectionally in 1003 primary care clinician-identified depressed patients from two practice-based research networks. Multivariable regression analysis, with self-assessed recovery as the dependent variable, identified five symptoms that contributed significantly beyond the Patient Health Questionnaire (PHQ)-8. Further analysis was performed in selected subsamples.

Results

Emotional control, contentedness, future seeming dark, ability to bounce back and happiness yielded an 11% increase in R² beyond 60% yielded by the PHQ-8. The summed Remission Evaluation and Mood Inventory Tool (REMIT) 5 items have a mean=9.6 (S.D.=4.5), range 0-20 and reliability of 0.86. Subsample analysis showed incremental R² ranging from 9% in men to 15% in African-Americans.

Conclusion

Depression remission is a multidimensional concept that includes important nondepressive symptom dimensions. These important dimensions can be measured using a self-report instrument feasible for routine primary care. Pending longitudinal validation, REMIT5 is a promising tool for depression management.     

Acknowledging illness and treatment needs in first-time admitted psychiatric patients

Purpose

Help-seeking and service utilization depends on the patients’ interpretation of their illness and treatment needs. Worry, denial of illness, need for treatment and need for hospitalization in first-time admitted patients was studied.

Subjects

New patients in two mental hospitals were consecutively recruited. Three hundred and thirty-four satisfied the inclusion criteria and 251 gave informed consent. One hundred and ninety-six had complete datasets (56% of those eligible).

Methods

Demography was recorded with the Minimal Basic Dataset by Ruud et al. (1993) [45]. Experiences of hospitalisation were measured with the Patient's Experience of Hospitalisation Questionnaire by Carskey et al. (1992) [9]. MINI was used for diagnosing and SCL-90-R by Derogatis (1997) [13] for subjective symptoms. Standard multiple regressions were performed with the PEH subscales (Denial, Worry, Need for treatment and Need for hospitalisation) as dependents and demography, diagnosis and SCL-90-R subscales as explanatory variables.

Results

(a) Psychoticism and the diagnosis of schizophrenia were associated with little worrying, denial of illness, of treatment needs and of need for hospitalisation. (b) Anxiety and affective disorders were related to worries, acknowledgement of illness, need for treatment and for hospitalisation.

Conclusions

In contrast to patients with mainly anxiety and affective disorders, psychotic patient tended to deny illness-related worries, that they had an illness and that they needed treatment and hospitalisation. An affective disorder together with suicidal thoughts (not attempts) was a strong drive towards hospital admission.     

Long-term effects of transference interpretation in dynamic psychotherapy of personality disorders

Background

Only a few treatment studies of personality disorders (PD) patients are on longer-term psychotherapy, general outcome measures are used, and follow-up periods are usually short. More studies of long-term therapies, using outcome measures of core psychopathology, are needed.

Method

This study is a dismantling randomized controlled clinical trial, specifically designed to study long-term effects of transference interpretation. Forty-six patients with mainly cluster C personality disorders were randomly assigned to 1 year of dynamic psychotherapy with or without transference interpretations. The outcome measures were remission from PD, improvement in interpersonal functioning, and use of mental health resources in the 3-year period after treatment termination.

Results

After therapy with transference interpretation PD-patients improved significantly more in core psychopathology and interpersonal functioning, the drop-out rate was reduced to zero, and use of health services was reduced to 50%, compared to therapy without this ingredient. Three years after treatment termination, 73% no longer met diagnostic criteria for any PD in the transference group, compared to 44% in the comparison group.

Conclusions

PD-patients with co-morbid disorders improved in both treatment arms in this study. However, transference interpretation improved outcome substantially more. Long-term psychotherapy that includes transference interpretation is an effective treatment for cluster C personality disorders and milder cluster B personality disorders.     

Personality traits and medical outcome of cardiac illness

Objective

Our goal was to examine the empirical literature on the effect of personality traits on the medical outcome of cardiac illness.

Method

Pub Med and Psychological Abstracts were searched for the years 1990 to September 2009 using the terms personality, personality traits, personality disorder, health, recovery from illness, cardiac illness and surgical recovery. Articles were then selected that were prospective, had a peer review published measure of personality, a standardized measure of outcome of physical illness and at least one year follow up.

Results

Seven articles were identified that met our criteria. All seven had a significant finding that personality traits predicted medical outcomes. Of these seven articles six had similar enough measures of personality to be included in a meta analysis. (All used Type D personality.) Meta analysis found an odds ratio of 3.76 for Type D personality traits predicting poorer medical outcome. This indicated that patients with Type D personality had a 276% increase in the odds of a poor medical outcome compared to patients without Type D personality.

Conclusions

These findings indicate that personality traits are a strong predictor of medical outcome of cardiac disease.     

Complex personality disorder in bulimia nervosa

Objective

Recent research has suggested a move toward a dimensional system for the classification of personality disorders (PDs). Tyrer's dimensional model using severity as a form of categorizing PDs was used to compare eating disorder outcome in women with bulimia nervosa (BN) over 3 years.

Method

One hundred thirty-four women with BN were divided into 4 groups based on PD severity: no PD (n = 32), personality difficulty (n = 27), simple PD (n = 29), and complex PD (n = 46). Eating disorder symptoms and attitudes, general psychosocial functioning, and depressive symptoms were examined at pretreatment and at 1-year and 3-year follow-up (posttreatment).

Results

The complex PD group had greater Axis I comorbidity and psychopathology than the remaining 3 groups at pretreatment. At 1-year and 3-year follow-up, there were no differences in eating disorder outcome, general psychosocial functioning, and depressive symptoms across the 4 groups.

Conclusion

These results suggest that having an increased number of PDs comorbid with BN does not influence eating disorder outcome up to 3 years after treatment.     

Cognitive behavioral therapy versus paroxetine in the treatment of hypochondriasis: An 18-month naturalistic follow-up

Background

The present maintenance study investigated whether the reduction in hypochondriacal complaints after initial treatment with CBT or paroxetine sustained during a follow-up period and whether psychiatric severity at pretest predicted the course of hypochondriacal symptoms.

Method

A naturalistic follow-up period of 18 months after a 16-week RCT consisting of 33 patients initially allocated to a CBT condition and 29 patients to a paroxetine condition. The main outcome measure was the Whiteley Index.

Results

The initial treatment effect of CBT and paroxetine sustained during the follow-up period. No significant differences between CBT and paroxetine were found. Treatment course could not be predicted by psychiatric comorbidity.

Conclusion

CBT and paroxetine are both effective treatments for hypochondriasis in the long term.     

A longitudinal study of obsessive-compulsive disorder in individuals at ultra-high risk for psychosis

Background

We evaluated whether (1) a diagnosis of obsessive-compulsive disorder (OCD) at baseline, or (2) the persistence, remission or emergence of de novo OCD at follow-up, were associated with the development of different psychotic disorders in a cohort of individuals at ultra-high risk (UHR) for psychosis.

Methods

Patients were assessed for OCD at baseline and after a mean of 7.4 years follow-up and classified into: (i) Non-OCD group - patients without OCD both at baseline and follow-up (n = 269; 86.2%), (ii) Incident OCD group - patients without OCD at baseline but with OCD at follow-up (n = 17; 5.4%), (iii) Remitting OCD group - patients with OCD at baseline but without OCD at follow-up (n = 20; 6.4%), (iv) Persistent OCD group - patients with OCD both at baseline and at follow-up (n = 6; 1.9%). Rates of different DSM-IV psychotic disorders at follow-up were compared across these groups.

Results

Patients who displayed remitting OCD were not related to the development of any DSM-IV psychotic disorder. A diagnosis of incident OCD was associated with greater rates of psychotic disorders at follow-up, particularly mood disorders with psychotic features and psychotic disorders not otherwise specified (PDNOS), and greater baseline severity of general psychopathology, alogia, and avolition-apathy. Two of the six patients (40%) with persistent OCD developed schizophrenia, while only 12.5%, 5.0%, and 9.7% of incident, remitting, and non-OCD groups, respectively, exhibited the same condition at follow-up. Rates of antipsychotic use in the previous two years were not significantly different between the groups.

Conclusions

Our findings suggest that, in a cohort of individuals at UHR for psychosis, remission of OCD does not increase the risk of psychosis, while de novo OCD was associated with development of mood disorders with psychotic features and PDNOS.     

Rapid antipsychotic response with ziprasidone predicts subsequent acute manic/mixed episode remission

Objective

To assess rapid antipsychotic efficacy with oral ziprasidone monotherapy in bipolar acute manic/mixed episodes with psychotic features, and predictive value of rapid antipsychotic response for subsequent acute manic/mixed episode remission.

Methods

Pooled analysis of two 3-week, randomized, double-blind, placebo-controlled trials of ziprasidone (40-160 mg/d) in inpatients with bipolar I disorder, and a current manic or mixed episode, with (n = 152) or without (n = 246) psychotic features. Psychosis improvement was evaluated by change in SADS-C psychosis score (sum of delusions, hallucinations, and suspiciousness items). Rapid antipsychotic response (?50% decrease in SADS-C psychosis score by Day 4) and acute manic episode response and remission (endpoint ?50% MRS decrease, and a MRS score ? 12, respectively) were analyzed.

Results

Significantly greater antipsychotic effects were observed by Day 4 with ziprasidone treatment (vs. placebo) and the magnitude of improvement increased significantly with time, in all subjects, in the subgroup of all psychotic subjects, and psychotic subjects with low baseline agitation (p < 0.05). Rapid antipsychotic response predicted subsequent acute manic episode remission independent of ziprasidone or placebo treatment received (p < 0.001, ROC AUC = 0.71) with significant improvement in accuracy of MRS remission prediction when compared to models using early changes in MRS score alone (p = 0.01).

Limitations

Post hoc analysis, use of 3 SADS-C psychosis items to assess psychosis.

Conclusions

The predictive value of rapid (Day 4) improvement in psychotic symptoms for subsequent (Day 21) remission of acute manic/mixed symptoms may facilitate enhanced therapeutics, in view of the current practice of brief hospitalization for patients with acute manic/mixed episodes with psychotic features.     

Cognitive abilities and clinical variables in bipolar I depressed and euthymic patients and controls

Background

While studies demonstrated that bipolar patients (BP) display cognitive deficits during mood episodes and remission, little is known about the clinical influences underlying these deficits. The aim of this study was to compare the performance of euthymic and depressed BPs and non-affective/psychotic disorder controls at several cognitive tasks, exploring which clinical variables influenced the performance of these subtests. It is hypothesized that the cognitive deficits in rank order are: depressed BPs > euthymic BPs > controls.

Methods

Sixty-five bipolar-I outpatients and thirty-four controls were assessed by the Brazilian version of the Wechsler Adult Intelligence Scale, Third Edition (WAIS-III). BPs were divided into depressed and euthymics, and these two groups were then compared to non-affective/psychotic disorder controls.

Results

For 12 of 14 subtest scores, comparisons yielded statistically significant (p < 0.05) between-group differences, including three subtests of attention and working memory (Digit Span and its two subtests) with both depressed and euthymic BPs, compared to controls, displaying significantly worse performance, and six subtests of visual and working memory with depressed (but not euthymic) BPs performing worse than controls. For all subtests, comparisons of depressed and euthymic patients’ scores were non-significant. Performance on several subtests was negatively predicted by the severity of the disorder in both patient groups.

Limitations

The cross-sectional design of the study, as well as confounding effects of medications and co-morbidities.

Conclusions

The fact that the impairment of cognitive performance of both groups of patients is influenced by the severity of the illness is consistent with the literature.     

Posttraumatic stress disorder and depression in heart transplantation recipients: the relationship with outcome and adherence to medical treatment

Objective

There is growing evidence of the importance of psychiatric risk factors for predicting the outcome of heart transplantation (HT) recipients. The aim of our study was to investigate the role of major depression and posttraumatic stress disorder (PTSD) in the prediction of the outcome of HT in a consecutive sample of 107 recipients.

Method

All subjects of the study underwent a structured diagnostic interview for assessing the presence of pretransplant and posttransplant major depression and transplantation-related PTSD 1 to 5 years after HT. The adherence to medical treatment was assessed some months after the structured interview. The medical outcome (acute rejections, cancer, mortality) was followed up for 8 years on average after the interview, using a prospective design.

Results

Estimated frequency of psychiatric diagnoses after HT was 12% for transplantation-related PTSD and 41% for major depression. The presence of an episode of major depression prior to HT is a significant independent risk factor for posttransplant malignancies. Age, posttransplant malignancies and poor adherence are significant predictors of mortality in the survival analyses.

Conclusions

The present study highlights the importance of the assessment of psychosocial variables and psychiatric diagnoses before and after transplantation in HT recipients. Our findings have important clinical implications and require replication with larger samples.