Antipsychotic drug treatment in first-episode mania: a 6-month longitudinal study

OBJECTIVE: To determine the use of antipsychotics during and following inpatient treatment of patients with a first-episode of mania. METHOD: The 198 subjects available for analysis were 129 consecutively hospitalized first-episode manic patients and 69 nonaffective psychotic patients assessed at admission and at 6-month follow-up postdischarge. Comparisons between the groups were made on frequency, type, and doses of antipsychotics prescribed during and after hospitalization in relation to clinical status. RESULTS: First-episode manic patients were given lower mean +/- SD daily doses of antipsychotics than nonaffective psychotic patients at discharge (163 +/- 132 mg chlorpromazine equivalents [CPZe] vs. 224 +/- 167 mg CPZe, p = .0102), at 6-month follow-up (109 +/- 167 mg CPZe vs. 260 +/- 178 mg CPZe; p = .0001), and if recovered (110 +/- 174 mg CPZe vs. 265 +/- 207 mg CPZe, p = .0014). At 6-month follow-up, 31 (24%) of 129 manic and 24 (35%) of 69 nonaffective psychotic patients continued to receive antipsychotics (NS). There was no difference between the groups in the time to discontinuation of antipsychotic agents. The mean time to drug discontinuation in manic patients was 98 days. CONCLUSION: (1) Antipsychotic doses at discharge and at 6-month follow-up were much lower in manic than in nonaffective psychotic patients, although there was no significant difference in the proportion of patients who continued to receive them 6 months after discharge. (2) The time to discontinuation was independent of clinical outcome. In those who discontinued the antipsychotic agent, the time to discontinuation was more rapid in the manic group than in the nonaffective psychotic patients.     

Hopelessness and first-episode psychosis: a longitudinal study

Hopelessness has not been adequately studied in first-episode psychotic patients, although it is already present at the early stages, especially in schizophrenic patients. We have studied 96 neuroleptic-naive psychotic patients (49 schizophrenic patients and 47 other non-affective psychotic patients) over a period of 12 months after their first admission. The total score on the Hopelessness Scale (HS) at first admission was higher in the schizophrenic patients, and correlated with younger age and with negative symptoms. High HS scores at baseline predicted poor short-term outcome in schizophrenic patients, as evidenced by worse global functioning at the 12-month follow-up. These correlations were not observed in the other psychoses group. Our results suggest that young, severely affected schizophrenic patients who experience hopelessness might be at higher risk of poor outcome.     

The child and adolescent first-episode psychosis study (CAFEPS): design and baseline results

OBJECTIVE: The child and adolescent first-episode psychosis study (CAFEPS) is a multicenter, two-year, longitudinal project aiming to evaluate different clinical, neuropsychological, neuroimaging, biochemical, immunological, and genetic variables and treatment and prognostic factors in these patients. This paper describes the methods and rationale behind the study and the general characteristics of the sample. METHOD: At six different centers, from March 2003 through November 2005, we consecutively recruited 110 patients, ages 9-17 years, who presented with a first psychotic episode. Controls were recruited from the same geographic areas and were matched for gender and age. RESULTS: Patients had lower socioeconomic status (SES) (p=0.018) and parental years of education (p<0.001) than controls. The percentage of patients recruited increased with age (p<0.001) and there was a higher percentage of males (p<0.001). The total mean PANSS score was 89.03+/-20.1, the positive score 23.8+/-6.5 and the negative score 20.02+/-8.8. There were no significant differences between the genders with respect to age, parental years of education, SES, or scores in premorbid adjustment or general functioning. There were statistically significant positive correlations between age and positive symptoms and between all PANSS subscales and the Disability Assessment Schedule, and negative correlations between positive symptoms and global functioning. Diagnoses after the baseline evaluation were: psychotic disorder not otherwise specified (NOS) 35.5%, schizophreniform disorder 24.5%, mood disorder with psychotic symptoms 22.7%, schizophrenia 10%, schizoaffective disorder 2.7%, and other psychotic disorders 4.5%. Patients had worse premorbid adjustment (p<0.001) and global functioning (p<0.001) than controls after controlling for SES. CONCLUSIONS: Infancy and adolescence adjustment and global functioning are lower in children and adolescents with psychotic disorders than in controls, severity of symptoms are related to general disability, and the most frequent diagnoses are psychotic disorders NOS.     

A multi-dimensional approach to insight and its evolution in first-episode psychosis: A 1-year outcome naturalistic study

The aim of the study was to describe the evolution of the different dimensions of insight at 1 year and its associations with psychopathology and symptomatic remission. Participants included 55 patients hospitalized for a first psychosis episode and followed up at 6 and 12 months after discharge. Measures included the Scale to Assess Unawareness of Mental Disorder and the Positive and Negative Syndrome Scale (PANSS). Six dimensions of insight were evaluated, for current episode at hospital discharge and at 6 and 12 month FUs and past episode (at 6 and 12 month follow-ups). Our results show that concerning the current episode, only awareness of the social consequences and of the positive symptoms significantly improved during follow-up. Insight into the past episode improved for awareness of having a mental disorder, the social consequences and the positive symptoms of mental illness. Cross-sectional associations between insight and PANSS show weak to moderate, albeit significant, associations. Most of the dimensions of insight are positively and significantly associated with remission. Our findings suggest that the main underlying dimensions of insight evolve differently over time, which could suggest different inherent processes. This could be useful for developing psychotherapeutic programmes acting upon the different aspects of insight.     

Risperidone in first-episode psychosis: a longitudinal, exploratory voxel-based morphometric study

Previous studies have provided evidence supporting a neuroplastic effect of atypical antipsychotics. The present investigation explores the short-term effects of risperidone on brain parenchyma by performing voxel-based morphometry on baseline and 6-week follow-up MRI scans obtained from 15 neuroleptic-na?ve individuals with first-episode psychosis treated with risperidone and 15 healthy controls. The risperidone-treated subjects demonstrated changes in grey matter and white matter in several brain regions, including superior temporal gyrus. No areas of change were found in controls. The results of this exploratory investigation support the possibility that risperidone has short-term effects on brain parenchyma in individuals with first-episode psychosis.     

Duration of untreated psychosis and 12-month outcome in first-episode psychosis: the impact of treatment approach

Carbone S, Harrigan S, McGorry PD, Curry C, Elkins K. Duration of untreated psychosis and 12-month outcome in first-episode psychosis: the impact of treatment approach. Acta Psychiatr Scand 1999: 100 : 96–104. © Munksgaard 1999. Objective: Early intervention research is examining whether reducing the duration of untreated psychosis (DUP) leads to improved outcome from first-episode psychosis. Another key influence may be the quality of treatment after initiation of care. This study examined the effect of phase-specific treatment on 12-month outcome for different categories of DUP. Method: A total of 250 first-episode psychosis cases were followed up 12 months after stabilization. The sample consisted of two historically sequential cohorts treated in the same region within different service models, one of which was more intensive and phase-specific. Outcome was compared according to four predefined categories of DUP. Results: Only patients with a mid-range DUP of 1–6 months who were treated within the phase-specific model experienced significantly better outcomes than patients treated within the previous model. Conclusion: These data suggest that there may be a limited window of opportunity in which to influence outcome. However, the complexity of this relationship is emphasized.     

Neocortical gray matter volume in first-episode schizophrenia and first-episode affective psychosis: a cross-sectional and longitudinal MRI study.

BACKGROUND: Overall neocortical gray matter (NCGM) volume has not been studied in first-episode schizophrenia (FESZ) at first hospitalization or longitudinally to evaluate progression, nor has it been compared with first-episode affective psychosis (FEAFF). METHODS: Expectation-maximization/atlas-based magnetic resonance imaging (MRI) tissue segmentation into gray matter, white matter (WM), or cerebrospinal fluid (CSF) at first hospitalization of 29 FESZ and 34 FEAFF, plus 36 matched healthy control subjects (HC), and, longitudinally approximately 1.5 years later, of 17 FESZ, 21 FEAFF, and 26 HC was done. Manual editing separated NCGM and its lobar parcellation, cerebral WM (CWM), lateral ventricles (LV), and sulcal CSF (SCSF). RESULTS: At first hospitalization, FESZ and FEAFF showed smaller NCGM volumes and larger SCSF and LV than HC. Longitudinally, FESZ showed NCGM volume reduction (-1.7%), localized to frontal (-2.4%) and temporal (-2.6%) regions, and enlargement of SCSF (7.2%) and LV (10.4%). Poorer outcome was associated with these LV and NCGM changes. FEAFF showed longitudinal NCGM volume increases (3.6%) associated with lithium or valproate administration but without clinical correlations and regional localization. CONCLUSIONS: Longitudinal NCGM volume reduction and CSF component enlargement in FESZ are compatible with post-onset progression. Longitudinal NCGM volume increase in FEAFF may reflect neurotrophic effects of mood stabilizers.     

Psychosocial treatment for first-episode psychosis: a research update

OBJECTIVE: This article reviews research on psychosocial treatment for first-episode psychosis. METHOD: PsycINFO and MEDLINE were systematically searched for studies that evaluated psychosocial interventions for first-episode psychosis. RESULTS: Comprehensive (i.e., multielement) treatment approaches show promise in reducing symptoms and hospital readmissions, as well as improving functional outcomes, although few rigorously controlled trials have been conducted. Individual cognitive behavior therapy has shown modest efficacy in reducing symptoms, assisting individuals in adjusting to their illness, and improving subjective quality of life, but it has shown minimal efficacy in reducing relapse. Some controlled research supports the benefits of family interventions, while less controlled research has evaluated group interventions. CONCLUSIONS: Adjunctive psychosocial interventions early in psychosis may be beneficial across a variety of domains and can assist with symptomatic and functional recovery. More randomized, controlled trials are needed to evaluate the effectiveness of these interventions, particularly for multielement, group, and family treatments.     

Stigma and treatment delay in first-episode psychosis: a grounded theory study

Aim: A longer duration of untreated psychosis (DUP) is associated with greater morbidity in the early course of schizophrenia. This formative, hypothesis-generating study explored the effects of stigma, as perceived by family members, on DUP. Methods: Qualitative interviews were conducted with 12 African American family members directly involved in treatment initiation for a relative with first-episode psychosis. Data analysis relied on a grounded theory approach. A testable model informed by constructs of Link's modified labelling theory was developed. Results: Four main themes were identified, including: (i) society's beliefs about mental illnesses; (ii) families' beliefs about mental illnesses; (iii) fear of the label of a mental illness; and (iv) a raised threshold for the initiation of treatment. A grounded theory model was developed as a schematic representation of the themes and subthemes uncovered in the family members' narratives. Conclusions: The findings suggest that due to fear of the official label of a mental illness, certain coping mechanisms may be adopted by families, which may result in a raised threshold for treatment initiation, and ultimately treatment delay. If the relationships within the grounded theory model are confirmed by further qualitative and quantitative research, public educational programs could be developed with the aim of reducing this threshold, ultimately decreasing DUP.     

Economic impact of services for first-episode psychosis: a decision model approach

Aim: To assess the impact of early intervention (EI) services on service costs for people with first‐episode psychosis. Methods: A decision model was constructed to map the care pathways following input from EI services and from standard care. A Markov process was used to run the model over 18 2‐month cycles. Probabilities and costs for the model of admissions, readmissions and use of community services were obtained from the literature, routine sources and expert opinion. One‐way and probabilistic sensitivity analyses were conducted to address uncertainty around the parameter estimates. Results: The model estimated 1 year costs to be £9422 for EI and £14 394 for standard care. The respective figures over 3 years were £26 568 and £40 816. One‐way sensitivity analyses revealed that the results were robust to changes in most parameters with the exception of the readmission rate. A relatively small decrease in the readmission rate for standard care patients would eliminate the cost saving. The probabilistic sensitivity analyses also showed that the results were robust to parameter changes. Conclusions: This study suggests cost savings associated with EI. However, caution is required as the model is relatively simple and relies on a number of assumptions.     

Patient satisfaction with treatment in first-episode psychosis

Purpose: To examine first-episode psychotic patients' satisfaction with elements of a comprehensive 2-year treatment program. Subjects and method: The TIPS (Early Treatment and Intervention in Psychosis) project provided a 2-year treatment program consisting of milieu therapy (inpatient), individual psychotherapy, family intervention and medication. Of 140 patients at baseline, 112 were included at 2-year follow-up. Eighty-four participants were interviewed using a questionnaire eliciting levels of satisfaction with different treatment elements at two of the four sites. Results: Participants and non-participants did not differ on demographic or clinical data at baseline. Of those participating, 75% were satisfied with treatment in general. Individual and milieu therapy received higher rating than medication or family intervention. No predictors of general satisfaction with treatment were found, but continuously psychotic patients were the least satisfied with medication treatment. Discussion: As in most patient satisfaction studies within mental health treatment networks, there was high level of general satisfaction with the total package of treatment but considerable variation in satisfaction for specific interventions. In this sample of first-episode psychosis patients, there was general satisfaction with treatments based on one-to-one relationships while multi-family group intervention was consistently valued less enthusiastically.     

Early intervention with second-generation antipsychotics in first-episode psychosis: results of an 8-week naturalistic study

Objective: The objective was to compare short-term effectiveness of aripiprazole with three other second-generation antipsychotics (SGAs) in the treatment of first-episode psychosis. Method: In a naturalistic, ‘single-blind’ design, 60 subjects experiencing their first psychotic episode were treated for 8 weeks with aripiprazole (n = 19), risperidone (n = 16), olanzapine (n = 14) or quetiapine (n = 11). Medication and dosing decisions were made by treating psychiatrists, constrained to once-a-day dosing, low initial doses and no clozapine. Weekly ratings were obtained using the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Rating Scale and Barnes Akathasia Rating Scale. Weight and vital signs were also collected weekly. Results: The group presented with severe psychotic symptoms (mean baseline PANSS total score of 105.2), which were reduced rapidly (P < 0.0005). The between-group and group by time interaction terms were non-significant. Similar reductions were seen across all PANSS sub-scales. At Week 1 the mean PANSS Activation Scale score was reduced more with olanzapine than in the other groups (P < 0.002). Few instances of extrapyramidal symptoms occurred; all were sporadic and did not require treatment. Group body weight increased by 7.3% over the study. Vital signs remained unchanged. Conclusions: Early intervention with low doses of four SGAs led to rapid symptom reduction in first-episode psychotic patients with severe psychopathology. Although no clear medication advantages were observed in the short term, longer duration studies with larger samples will be required for determining efficacy, rates of compliance, relapse prevention and diminished incidence of extrapyramidal signs and symptoms.     

Steroid-induced psychosis in a child: treatment with risperidone

Steroid-induced psychosis is one of the most serious adverse effects of steroid therapy but is a little-known complication in children. There is no clear mechanism model for steroid-induced behavioral disturbance, but it may be related with dose or level of free fraction of steroids. Our case is a 12-year-old boy diagnosed with steroid-induced psychosis and treated with risperidone, an atypical antipsychotic, due to distinct psychotic symptoms. Pediatricians should be aware of this rare complication when administering corticosteroids for various medical illnesses.     

Aggressive behaviour and psychosis in a clinically referred child and adolescent sample

Background

Despite evidence of an increased risk of violence among adults suffering from psychosis, very little is currently known about the relationship between early onset psychosis and aggressive behaviour. We aimed to identify and examine overlaps between aggressive behaviour and psychosis in a referred child and adolescent sample to assess whether potential risk factors and other associated features of this co-occurring pattern can be identified at a young age.

Methods

Standardised item sheet data on young people referred to the Child and Adolescent Department of the Maudsley Hospital between 1973 and 2004 were used to contrast three groups: (1) aggressive-only (n?=?1,346), (2) psychosis-only (n?=?173), and (3) co-occurring aggression and psychosis (n?=?39) on a range of comorbid symptoms and potential risk factors.

Results

Co-occurring cases presented with elevated rates of depersonalisation/derealisation, intrusive thoughts and restlessness, and were more likely to have received past treatment compared with both psychosis-only and aggressive-only cases. Although co-occurring cases resembled the psychosis-only group in many domains, including socio-demographic background and rates of emotional symptoms, they differed from ‘pure’ psychosis cases in having high levels of special educational needs, irritability, non-aggressive antisocial behaviours, as well as being more likely to be from a low social class and have increased contact with police and child care authorities.

Conclusions

Our findings suggest that it is possible to identify early risk factors for aggression in individuals with psychosis.