Combining depot antipsychotic with an assertive monitoring programme for treating first-episode schizophrenia in a resource-constrained setting.

AIM: To assess the feasibility and effectiveness of depot antipsychotic (flupenthixol decanoate) combined with an assertive monitoring programme (AMP) in first-episode schizophrenia. METHODS: This was a prospective, non-comparative, longitudinal study conducted over 12 months assessing patient acceptance, adherence, outcome in domains of psychopathology, functionality and quality of life, and tolerability. RESULTS: Of 207 participants, 149 (72%) completed 12 months of treatment. Acceptance of and adherence to depot was good. Treatment response was achieved by 170 (82%) participants and remission by 124 (60%). Thirty-three (19%) responders relapsed and 10 (5%) participants met a priori criteria for treatment resistance. Treatment was generally well tolerated. CONCLUSIONS: Combination of depot antipsychotic with an AMP may be an effective and safe intervention in early phases of schizophrenia, and may be particularly suitable for resource-constrained settings.

Assessing the efficacy of a modified assertive community-based treatment programme in a developing country.

BACKGROUND: A number of recently published randomized controlled trials conducted in developed countries have reported no advantage for assertive interventions over standard care models. One possible explanation could be that so-called "standard care" has become more comprehensive in recent years, incorporating some of the salient aspects of assertive models in its modus operandi. Our study represents the first randomised controlled trial assessing the effect of a modified assertive treatment service on readmission rates and other measures of outcome in a developing country. METHODS: High frequency service users were randomized into an intervention (n = 34) and a control (n = 26) group. The control group received standard community care and the active group an assertive intervention based on a modified version of the international model of assertive community treatment. Study visits were conducted at baseline and 12 months with demographic and illness information collected at visit 1 and readmission rates documented at study end. Symptomatology and functioning were measured at both visits using the PANSS, CDSS, ESRS, WHO-QOL and SOFAS. RESULTS: At 12 month follow-up subjects receiving the assertive intervention had significantly lower total PANSS (p = 0.02) as well as positive (p < 0.01) and general psychopathology (p = 0.01) subscales' scores. The mean SOFAS score was also significantly higher (p = 0.02) and the mean number of psychiatric admissions significantly lower (p < 0.01) in the intervention group. CONCLUSIONS: Our results indicate that assertive interventions in a developing setting where standard community mental services are often under resourced can produce significant outcomes. Furthermore, these interventions need not be as expensive and comprehensive as international, first-world models in order to reduce inpatient days, improve psychopathology and overall levels of functioning in patients with severe mental illness.

Pathways to inpatient mental health care among people with schizophrenia spectrum disorders in South Africa.

OBJECTIVE: This study examined service utilization patterns and pathways to specialist mental health services among individuals with schizophrenia spectrum disorders in the Western Cape, South Africa, an area that has undergone deinstitutionalization since the mid-1990s. METHODS: Individuals who were consecutively admitted to any of the three psychiatric hospitals in the Western Cape from February 2007 to January 2008 were interviewed. Data on demographic characteristics, psychiatric history, service utilization, and pathways to care were gathered from service users, their relatives or associates, and hospital files. Univariate and multivariate analyses examined differences between high- and low-frequency service users. RESULTS: Of the total sample (N=152) most were first seen at the primary care level (62%). However, very few received treatment at this level (26%), and many (22%) were admitted directly to the psychiatric hospital, bypassing other treatment options. These service utilization patterns differ from the requirements listed in the recently adopted Mental Health Care Act (2002), which states that unless a patient has been recently discharged, he or she should be admitted for 72 hours of observation before referral to psychiatric hospitals. Compared with low-frequency service users, high-frequency users were younger, had lower income, tended to rely more on disability benefits, and were more likely to bypass other levels of care and be admitted directly to the psychiatric hospital. Poor medication adherence was the most likely precipitant for the episode of illness among all users. CONCLUSIONS: The study highlights the inadequacy of current community mental health services in providing for the needs of people with severe mental illness. In South Africa, as in many other middle-income countries, there is an urgent need to develop community-based care.

The revolving door phenomenon in psychiatry: comparing low-frequency and high-frequency users of psychiatric inpatient services in a developing country.

INTRODUCTION: Deinstitutionalization has led to a dramatic reduction of inpatient beds and subsequent increase in pressure on available beds. Another consequence of deinstitutionalization has been the phenomenon of the revolving door patient; high-frequency users (HFUs) admitted to hospital repeatedly, remaining well for only short periods of time. The purpose of the study was to determine factors that contribute to HFU of inpatient psychiatric services by schizophrenia and schizo-affective disorder subjects in a developing country with a view to understanding this phenomenon better. METHODS: Subjects were divided into HFU and low-frequency user (LFUs) groups for comparison with regard to selected variables. RESULTS: HFUs had higher PANSS scores (p < 0.01), were more likely to admit to lifetime substance use (p = 0.01), be on mood stabilizers (p < 0.01) and also to have been crisis (premature) discharges (p < 0.01). LFUs were more likely to have been treated with depot medication (p < 0.01). Multivariate analysis showed crisis discharge (p = 0.03) and depot use (p = 0.03) to be the only remaining significant predictors of HFU versus LFU status. DISCUSSION: Our findings suggest HFUs' characteristics to be similar across different settings, with under-utilization of depot antipsychotics and early discharge from hospital as particular contributors to high-frequency use of services in our sample. CONCLUSION: Results seem to indicate that HFU-specific interventions are vital to addressing these issues.

Changes in erythrocyte membrane fatty acids during a clinical trial of eicosapentaenoic acid (EPA) supplementation in schizophrenia.

In a previously reported double-blind, placebo-controlled trial of eicosapentaenoic acid (EPA) as supplemental treatment in 40 patients with schizophrenia, we found significant improvement in symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) compared to placebo (Emsley et al. 2002). Here we report changes in fatty acid composition of erythrocyte membranes in the same sample (n = 16 in each group). After 12 weeks of receiving EPA, levels of several saturated and mono-unsaturated fatty acids decreased significantly while levels of n-3 fatty acids increased significantly compared to the placebo group. Increases of n-3 and n-6 fatty acids in the erythrocyte membranes were greater in subjects who improved more than 20% on overall symptoms. Changes in fatty acids correlated significantly with improvement in PANSS sub-scale scores, more so in females than in males. Docosahexaenoic acid (DHA) (22:6n-3) levels increased less than expected, suggesting a possible defect in synthesis or incorporation of DHA into membranes in schizophrenia. Improvement in dyskinesia correlated significantly with an increase in alpha-linolenic acid (18:3n-3; p = 0.03), and a decrease in 20:1n-9 (p = 0.005).

Mass murders: implications for mental health professionals.

In this article, we attempt to uncover whether mass murders (the killing of multiple victims in single events) are preventable acts, the extent to which they are contributed to by biological and psychological factors, the notion that they are inextricably linked to mental illness, the role of the media, and what lessons can be learned by mental health professionals.

Crisis discharges and readmission risk in acute psychiatric male inpatients.

BACKGROUND: Severe pressures on beds in psychiatric services have led to the implementation of an early ("crisis") discharge policy in the Western Cape, South Africa. The study examined the effect of this policy and length of hospital stay (LOS) on readmission rates in one psychiatric hospital in South Africa. METHODS: Discharge summaries of adult male patients (n = 438) admitted to Stikland Psychiatric Hospital during 2004 were retrospectively examined. Each patient's clinical course was then analysed for the period between January 1st, 2004, and August 31st, 2006. RESULTS: Although shorter LOS was associated with decreased readmission rates, the effect of crisis discharges was far more powerful. Patients discharged as usual had a far lower risk of readmission than those discharged due to bed pressures (i.e. crisis discharge). CONCLUSION: Increased risks associated with the early discharge policy necessitate the urgent review of the current management of bed shortages in this inpatient facility. The strengthening of community initiatives, particularly assertive outreach could be a way forward.

Pathways to care and treatment delays in first and multi episode psychosis. Findings from a developing country.

BACKGROUND: In contrast to findings from the developed world where general practitioners and mental health professionals are central in first episode psychosis pathways, studies from Africa have found GPs to play a less prominent role with other help providers such as traditional healers being more important. METHODS: We compared pathways to care, treatment delays and gender differences in patients with first versus multi episode psychosis. RESULTS: Private sector GPs were first contacts in first episode patients in as many as 38% of patients and were significantly more likely to be the first contact (odds ratio = 4.5, 95% CI = 1.38-14.67) and final referring agent (odds ratio = 6.8, 95% CI = 1.56-25.12) in first episode patients. Female multi episode patients were significantly more likely to make first contact with primary care practitioners whereas male multi episode patients were more likely to first come into contact with the police (P = 0.003) and be admitted compulsorily (P = 0.009). Only 5.6% (n = 4) of patients contacted traditional healers at some point in their pathway to care. Treatment delays and DUP in first episode patients were longer and reached a median of 4.5 versus 2.5 months in multi episode patients. Treatment discontinuation of antipsychotics occurred in 82% of multi episode patients. Despite significantly longer overall treatment delays in first episode patients the distribution of treatment delays in multi episode patients followed a similar pattern to DUP in first episode patients with a subgroup having very long delays. CONCLUSIONS: Pathways to care in this treatment setting correspond more to findings from first world and newly industrialized countries. A subgroup of multi episode patients had very long periods of untreated illness. Limitations include small sample size and the retrospective nature of data collection.

First-episode psychosis: an update

Interest in the subject of first-episode psychosis has increased considerably in the last two decades. At present; a number of centres around the world focus on early identification and intervention in people with psychotic disorders. Researchers have focused particularly on people who are possibly experiencing the prodromal phase of the illness in the hope that; by instituting appropriate early intervention; the outcome of schizophrenia will be improved. Patients with first-episode psychosis present with different symptom domains that should be taken into account when planning treatment. Most patients initially respond to treatment; however; there is a high rate of relapse within a few years. It is therefore important that we continue to seek improved relapse prevention strategies. There has also been a resurgence of interest in psychosocial risk factors for the development of schizophrenia in the recent literature. We review the literature on first-episode psychosis and highlight the significant findings

Measuring anxiety in patients with schizophrenia.

This study describes the prevalence and distribution of anxiety symptomatology and anxiety disorders in a sample of hospitalized patients with schizophrenia, the estimated level of agreement between a clinician diagnostic measure and anxiety symptom status measures, and their internal consistency based on the average interitem correlations. Seventy inpatients receiving treatment for schizophrenia were assessed before discharge using a face-to-face diagnostic interview and structured questionnaires, namely the Mini International Neuropsychiatric Interview, the Hospital Anxiety and Depression Scale, the Hamilton Anxiety Scale, the Spielberger Anxiety Inventory, and the Stein Generalized Anxiety Disorder (GAD) Scale. About a quarter of patients met criteria for an anxiety disorder, with GAD and social phobia occurring most commonly. There was poor agreement between the Mini International Neuropsychiatric Interview and a diagnosis of anxiety based on symptom status measures. The Stein GAD scale demonstrated the highest internal consistency (0.85) followed by the Hamilton Anxiety Scale (0.76). Anxiety disorders and anxiety symptomatology are highly prevalent in schizophrenia. Accurate assessment is challenging yet important. More reliable measures of anxiety disorders in patients with schizophrenia and other psychotic disorders are clearly needed to allow for timely identification and treatment.

The relationships between depression and remission in first-episode psychosis.

This study assessed changes in depressive symptoms over time in 57 patients with first-episode psychosis, and investigated the relationships of these symptoms during the acute psychotic episode and the post-psychotic period with treatment outcome. Assessment instruments included the Calgary Depression Scale (CDS) and the Positive and Negative Syndrome Scale (PANSS). For the evaluation of treatment outcome, recently proposed operational remission criteria were used. PANSS factor analysis identified a depression/anxiety factor (PANSSD/ A) at baseline, which separated into "pure" depression (PANSS-D) and anxiety (PANSS-A) factors at 24 months. There were strong correlations between the CDS and the PANSS-D/A, PANSS-D and PANSS-A scores at baseline, but at 24 months significance was lost between CDS and PANSS-A. Compared to non-remitters, patients who achieved remission had significantly higher baseline CDS scores, but depressive symptoms resolved with antipsychotic treatment. Non-remitting patients had relatively low baseline CDS scores, but their depressive symptoms persisted throughout the study. These findings suggest that depressive symptoms in the acute psychotic episode differ from those in the post-psychotic period in terms of their phenomenology, temporal relationship to psychosis, and treatment response.

The effects of eicosapentaenoic acid in tardive dyskinesia: a randomized, placebo-controlled trial.

OBJECTIVE: Worldwide, conventional antipsychotic medication continues to be used extensively, and tardive dyskinesia (TD) remains a serious complication. The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD. METHOD: This was a 12-week, double-blinded, randomized study of ethyl-EPA 2g/day versus placebo as supplemental medication, in patients with schizophrenia or schizoaffective disorder, with established TD. RESULTS: Eighty-four subjects were randomized, of whom 77 were included in the analysis. Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores, but there were no significant between-group differences (p=0.4). Response rates (>or=30% improvement in TD symptoms) also did not differ significantly between EPA-treated subjects (45%) and placebo-treated subjects (32%) (p=0.6). However, a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD. The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially, although this was not sustained beyond 6 weeks. CONCLUSIONS: This trial failed to demonstrate an anti-dyskinetic effect for ethyl-EPA 2g/day on the primary efficacy measure. However, a modest and transient benefit is suggested in patients with more recent onset of TD. The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low, the study being underpowered, TD being too chronic in the majority of cases, differences in dietary fatty acid intake, or that EPA lacks an anti-dyskinetic action.

Remission in first-episode psychosis: predictor variables and symptom improvement patterns.

BACKGROUND: Previous attempts to identify clinically useful predictors of treatment outcome in schizophrenia have been hampered by methodological inconsistencies, including a lack of standardized outcome measures. Recently proposed operationally defined criteria for remission provide an opportunity to readdress this topic. METHOD: We applied the remission criteria to a sample of 57 subjects with first-episode psychosis (DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder), treated according to a fixed protocol in a prospective study. Subjects were recruited between April 1999 and January 2000 and were followed for 2 years. Various demographic, baseline clinical, and early-response variables were subjected to discriminant analysis for their ability to predict remission or nonremission. We also assessed the symptom improvement patterns over time and compared endpoint psychopathology in the remitters and nonremitters. RESULTS: A model incorporating neurologic soft signs, 6-week treatment response, duration of untreated psychosis, marital status, and Positive and Negative Syndrome Scale excited factor baseline score was able to correctly predict 89% of the remitters and 86% of the nonremitters. Symptom reduction at 6 weeks, including core psychotic symptoms, was significant in both groups (remitters, p < .0001; nonremitters, p < .0001), although reduction was substantially greater in the remission group (p = .004). Thereafter, the remission group continued to improve (p < .01), while the nonremitting group failed to do so (p = .55). Considerable overlap of endpoint symptoms was observed, and depressive symptom scores were similar in remitters and nonremitters. CONCLUSION: A combination of demographic, baseline clinical, and acute treatment response variables may accurately predict treatment outcome. Persistent noncore psychotic symptoms in subjects meeting proposed remission criteria require further investigation.

Neurological abnormalities in first-episode schizophrenia: temporal stability and clinical and outcome correlates.

OBJECTIVE: Neurological abnormalities in subjects with schizophrenia have been regarded as diagnostically non-specific and non-localising. This study assessed the temporal stability of neurological abnormalities in subjects with first-episode schizophrenia over the course of 12 months. We also examined their relationships with psychiatric symptoms, medication effects and treatment outcome. METHOD: The sample comprised 66 largely medication-naive subjects who were treated according to a fixed protocol. We performed a factor analysis of the Neurological Evaluation Scale (NES) items, and relationships between the NES factors and various clinical and outcome measures were explored. RESULTS: Five NES factors were identified, explaining 68.4% of the variance. While the NES total scores did not change significantly over time, poor performance on motor sequencing tests was related to longer duration of untreated psychosis, and showed a tendency to improve as psychiatric symptoms resolved. The most interesting finding was that high scores on the motor sequencing factor predicted the emergence of persistent dyskinesia at 24 months (ANCOVAR F(1, 20) = 19.287, p = 0.0002). CONCLUSIONS: Two NES factors (motor sequencing and attention) are reasonably replicable across samples, and have potential relevance for the further exploration of the pathogenesis of schizophrenia, as well as possible clinical applications.

Effects of quetiapine and haloperidol on body mass index and glycaemic control: a long-term, randomized, controlled trial.

The topic of antipsychotic-induced weight-gain and its relationship to glucose metabolism is under-studied. We evaluated the long-term effects of a new-generation antipsychotic, quetiapine and a conventional antipsychotic, haloperidol on body mass index (BMI) and glycaemic control in patients with schizophrenia previously treated with conventional antipsychotics. Forty-five clinically stable patients with schizophrenia participated in this randomized, investigator-blinded, parallel-group comparison of flexible doses of quetiapine and haloperidol treatment over 52 wk. Primary outcome measures were change from baseline in BMI and glycosylated haemoglobin (HBA1c) levels. There were no between-group differences at any of the time-points for BMI (F = 1.90, p = 0.1) and HBA1c (F = 1.17, p = 0.3) values, and there were no significant changes in BMI from baseline for either group. HBA1c levels decreased significantly at end-point for the haloperidol group (-1.5%, p = 0.04), but not for the quetiapine group (-0.3%, p = 0.5). Although the sample was not generally obese (mean baseline BMI 25.5 +/- 6.3 kg/m2), a large proportion exhibited evidence of abnormal glycaemic control prior to randomization (mean HBA1c 6.7 +/- 1.9%), with 48% having values that were at least mildly elevated (HBA1c > 6.1%) and 19% markedly elevated (HBA1c > 7%). The number of subjects with elevated HBA1c values decreased from baseline in both the haloperidol and quetiapine treatment groups. These findings suggest that switching treatment from a conventional antipsychotic to quetiapine is not associated with weight gain or worsening of glycaemic control, even in the long term. The study also highlights the high incidence of unrecognized glucose dysregulation in patients with schizophrenia receiving conventional antipsychotic treatment.

The neuropsychiatry of brain tumours

Every psychiatrist who has worked in the clinical field for some time will be able to relate a story of a patient who presented with psychiatric symptoms but eventually turned out to have a brain tumour. We all fear that someday we will misdiagnose a brain tumour and therefore fail to save a patient's life. The purpose of this article is to give a brief outline of the important clinical issues related to brain tumours and psychiatry

A single-blind, randomized trial comparing quetiapine and haloperidol in the treatment of tardive dyskinesia.

BACKGROUND: While the atypical antipsychotics should ultimately reduce the prevalence of tardive dyskinesia, it is likely to remain a significant clinical problem for a long time to come. No strategy has clearly emerged as the treatment of choice for tardive dyskinesia. Atypical antipsychotics have reduced propensities for producing acute extrapyramidal symptoms (EPS) and possibly tardive dyskinesia and may be effective in treating patients with established tardive dyskinesia. METHOD: This 12-month, randomized, investigator-blinded study compared the efficacy of quetiapine (N = 22) and haloperidol (N = 23) in treating patients with DSM-IV schizophrenia or schizoaffective disorder and established tardive dyskinesia. Dyskinesia was assessed using the Extrapyramidal Symptom Rating Scale (ESRS) dyskinesia subscale scores and the Clinical Global Impression (CGI) dyskinesia scores. Other EPS, weight, serum prolactin level, and glycosylated hemoglobin level were also assessed. Subjects were enrolled in the study between April 2000 and March 2002. RESULTS: Mean endpoint doses were 400 mg/day of quetiapine and 8.5 mg/day of haloperidol. Compared with the haloperidol group, the quetiapine group showed significantly greater improvements in ESRS dyskinesia (6 and 9 months [p or= 50% symptom reduction) was greater with quetiapine than haloperidol (64% [9/14] and 37% [6/16] at 6 months; 55% [6/11] and 28% [4/14] at 12 months). Other EPS decreased significantly with quetiapine at 3 (p =.01), 6 (p =.01), and 9 (p =.002) months. Serum prolactin levels decreased with quetiapine but increased with haloperidol, differing significantly between the groups at endpoint (p =.005). No significant changes in weight or glucose metabolism were recorded in either group. CONCLUSION: Quetiapine effectively reduces the severity of tardive dyskinesia and is well tolerated in patients with established tardive dyskinesia.

Evidence-based pharmacotherapy of schizophrenia.

The introduction of the new-generation antipsychotics has changed the way we treat patients with schizophrenia. This article reviews these agents, focusing mainly on the published randomized controlled trials and meta-analyses in which the new-generation antipsychotics are compared with placebo, conventional antipsychotics or with one another. Agents included are risperidone, olanzapine, quetiapine, ziprasidone, sertindole, amisulpride and aripiprazole. Acute-phase and maintenance studies are reviewed, as well as randomized trials for pre-psychotic, first-episode schizophrenia and refractory schizophrenia. Finally, specific areas of current clinical interest are dealt with. These are: conventional vs. new-generation antipsychotics, head-to-head comparisons of new-generation antipsychotics, and side-effect profiles.

A randomized, controlled comparison of the efficacy and tolerability of low and high doses of haloperidol in the treatment of first-episode psychosis.

While haloperidol is still widely used in the treatment of psychoses, the optimal daily dose remains a topic of controversy, particularly in first-episode psychosis. Previous studies have suggested that doses as low as 2 mg/d may be effective, whereas others have indicated superiority for higher over lower doses. This double-blinded, randomized controlled study compared the efficacy and tolerability of 2 vs. 8 mg/d of haloperidol over 6 wk in 40 subjects with first-episode psychosis. Both treatments were equally effective in reducing the PANSS Total and subscale scores. The low dose of haloperidol was better tolerated, with fewer extrapyramidal side-effects, less frequent use of anticholinergic medication and smaller elevations in prolactin levels. Using a low dose of haloperidol is at least as effective as, and better tolerated than a high dose of haloperidol in the treatment of first-episode psychosis.