Cognitive changes in alcohol-induced psychotic disorder.

AIMS: This study aimed to explore the neuro-cognitive deficits of alcohol-induced psychotic disorder as compared to the cognitive deficits of uncomplicated alcohol dependence. METHODS: Participants were recruited from the acute psychiatric admission wards of the Department of Psychiatry, University of Stellenbosch and Stikland and Tygerberg Academic Hospitals in the Western-Cape, South Africa. Participants who met DSM IV TR criteria (American Psychiatric Association. Diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington, DC, 2000) for Alcohol Dependence and for alcohol-induced psychotic disorder, respectively, were included. Participants who met criteria for another current DSM IV TR Axis I disorder were excluded. A structured interview was done prior to neuropsychological assessment to ascertain current mental state and to obtain relevant demographic detail and history. Neuropsychological assessments were performed and supervised by clinical psychologists at either Tygerberg or Stikland Hospital. RESULTS: The groups were matched demographically with similar period of abstinence prior to assessment. The alcohol-induced psychotic disorder group experienced first psychotic symptoms at age 35. The results reflected statistically significant differences on tasks measuring immediate memory; recall upon delay; exaggeration of memory difficulty and abstract thinking. CONCLUSION: This study concurs with earlier literature that some cognitive deficits are greater in alcohol-induced psychotic disorder compared to uncomplicated alcohol dependence.

Comparative risk of major cardiovascular events associated with second-line antidiabetic treatments: a retrospective cohort study using UK primary care data linked to hospitalization and mortality records.

AIMS: To examine the risk of major cardiovascular events associated with second-line diabetes therapies, in patients with type 2 diabetes, after adjusting for known cardiovascular risk factors. METHODS: This was a retrospective cohort study of patients prescribed second-line regimens between 1998 and 2011 after first-line metformin. The UK Clinical Practice Research Datalink, with linked national hospitalization and mortality data, for the period up to December 2013, was used. Inverse probability of treatment-weighted time-varying Cox regression models was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing a major cardiovascular event (cardiovascular death, myocardial infarction, stroke, acute coronary syndrome, unstable angina, or coronary revascularization) associated with second-line therapies. Analyses adjusted for patient demographic characteristics, comorbidities, glycated haemoglobin, socio-economic status, ethnicity, smoking status and concurrent medications. RESULTS: A total of 10 118 initiators of a second-line add-on to metformin of either a sulphonylurea (n = 6740), dipeptidyl peptidase-4 (DPP-4) inhibitor (n = 1030) or thiazolidinedione (n = 2348) were identified. After a mean (standard deviation) of 2.4 (1.9) years of follow-up, 386, 36 and 95 major cardiovascular events occurred in sulphonylurea-, DPP-4 inhibitor- and thiazolidinedione-initiators, respectively. In comparison with the metformin-sulphonylurea regimen, adjusted HRs were 0.78 (95% CI 0.55; 1.11) for the metformin-DPP-4 inhibitor regimen and 0.68 (95% CI 0.54; 0.85) for the metformin-thiazolidinedione regimen. CONCLUSIONS: Thiazolidinedione add-on treatments to metformin were associated with lower risks of major cardiovascular disease or cardiovascular death compared with sulphonylurea add-on treatment to metformin. Lower, but non-statistically significant, risks were also found with DPP-4 inhibitor add-on therapies.

The effects of sub-chronic clozapine and haloperidol administration on isolation rearing induced changes in frontal cortical N-methyl-D-aspartate and D1 receptor binding in rats.

Glutamate and dopamine disturbances are implicated in frontal cortical dysfunction in schizophrenia. Little, however, is known about the nature of dopamine D(1) and N-methyl-D-aspartate (NMDA) receptor interactions in the illness, nor of the extent of their co-involvement in antipsychotic drug response. It is well known that early life adversity may pre-date the development of schizophrenia. Using a neurodevelopmental model of schizophrenia, namely post weaning social isolation rearing (SIR), we studied the effect of SIR (post natal day 21-61) on frontal cortical NMDA and D(1) receptor binding characteristics with/without chronic haloperidol (0.1 mg/kg/day i.p.) or clozapine (5 mg/kg/day i.p.) treatment, undertaken from post-natal day 50-60. SIR increased frontal cortical NMDA-density, with decreased affinity (decreased pK(D)), but reduced D(1) receptor density (without effects on pK(D)). In socially reared animals, clozapine but not haloperidol increased NMDA receptor density without effects on pK(D.) Neither drug markedly affected D(1) receptor density, although clozapine increased D(1) affinity. Increased NMDA density in SIR animals was unaffected by haloperidol, but further increased by clozapine. However, SIR-associated decrease in NMDA affinity remained unaltered despite drug treatment. Reduced D(1) receptor density in SIR animals was exacerbated by haloperidol, but unaltered by clozapine, without changes in pK(D). SIR thus induces opposing effects on frontal cortical NMDA and D(1) radio-receptor binding characteristics, which has direct bearing on the mutual interplay of these receptors in schizophrenia. The ability of SIR to affect NMDA receptor affinity warrants deeper study. Furthermore, at the doses examined, in contrast to haloperidol, clozapine bolsters frontal cortical glutamatergic but stabilizes D(1) dopaminergic pathways in a neurodevelopmental animal model of schizophrenia, possibly explaining the atypical clinical characteristics of this drug.

Psychiatric disorders and general medical conditions: implications for the clinician.

Patients with severe mental illness have higher than expected prevalence rates of co-morbid general medical conditions, particularly metabolic and cardiovascular disease. They are also at increased risk of contracting HIV. Conversely, these and other medical disorders also increase the risk of developing mental disorders. Mental illness and general medical conditions have mutually adverse effects on long-term outcome. This interaction of diseases contributes significantly to the excess morbidity in and higher than expected standard mortality ratios for patients with mental illness. As medical practice becomes more specialized and arguably compartmentalized it may increasingly fail to integrate health care for patients with severe mental illness. In this paper we discuss the high co-morbidity of mental illness with other medical disorders as well some of the potential mechanisms involved. We furthermore argue that the bidirectional relationship between mental and medical disorders should be considered in the planning of treatment for either group of disorders. The central role of the psychiatrist in co-ordinating and integrating the health care of patients with severe mental illness is emphasized.

Mental health literacy: focus on developing countries.

Mental health literacy refers to knowledge and beliefs about mental disorders which aid their recognition, management and prevention. This is a non-systematic review of published articles on mental health literacy in the general population and among primary healthcare workers, in particular, in developing countries, sourced from Medline, PsychInfo and African Healthline databases (1990-2006). Our review of the literature suggests that public knowledge about mental disorders as medical conditions, and their evidence based treatment strategies, in developing countries may be generally poorly or inaccurately understood. The review also reveals that improving the mental health literacy among primary health care professionals is imperative. Poor mental health literacy can be an obstacle to providing treatment for those in need, and is of particular concern in low and middle-income countries where mental health services are already scarce. It is likely that strategies for improvement will need to be comprehensive and innovative, taking advantage of opportunities and meeting challenges faced in the developing world.

HIV/AIDS risk behaviour in South African schizophrenia patients.

BACKGROUND: Initially the risk of HIV in people with severe mental illness (SMI) was grossly underestimated, but comparisons with the general population have in fact revealed higher infection rates in this particular group. Not only are patients with SMI sexually active but it has also been demonstrated that this group and especially patients with schizophrenia are less knowledgeable about HIV risk behaviours than the general population. Currently no data concerning the participation in and knowledge of HIV/AIDS risk behaviours by South African schizophrenic patients is available. METHODS: Patients with schizophrenia and a control-group were recruited from community clinics in the Western Cape, South Africa, whereafter 43 from each group were matched (race, age, sex). The patient group was subjected to a structured clinical interview and both groups completed the AIDS Risk Behaviour Assessment (ARBAQ) and Knowledge (ARBKQ) Questionnaires. RESULTS: Comparatively, significant knowledge deficits could be demonstrated for the patient group in overall terms (p<0.001) as well as for five specific items (all p<0.05) on the ARBKQ. Furthermore, 10% of the patients believed that the depot antipsychotic injection placed individuals at risk for contracting HIV. Both groups also admitted participation in various high risk sexual behaviours. CONCLUSION: Our results suggest that patients with schizophrenia should be a target group when developing AIDS prevention programmes. In order to identify particularly at risk individuals, a comprehensive risk behaviour assessment should form part of the psychiatric interview.

Oral zinc augmentation with vitamins A and D increases plasma zinc concentration: implications for burden of disease.

A study evaluating zinc supplementation in patients with Alzheimer's disease yielded variable zinc plasma levels in spite of positive cognitive and physiological results. In an attempt to raise and sustain plasma zinc levels, a single patient was given 15 mg zinc/day with various combinations of vitamins. A sustained raise in plasma zinc concentration (and therefore its potential bioavailability) was obtained only when the zinc was augmented with both vitamins A and D (in RDA concentrations). In order to verify these results, a follow-up study was conducted in 70 volunteers. Seven groups of 10 healthy subjects received various combinations of zinc and the two vitamins A and D, namely: zinc, vitamin A, vitamin D, zinc plus vitamin A, zinc plus vitamin D, vitamins A and D, and zinc plus vitamins A and D. Plasma zinc levels were determined at baseline, 3 weeks and 6 weeks. Plasma zinc levels increased significantly (p < 0.02) from 11.82 (+/-2.60) to 13.32 (+/-3.04) mum/L only in the group receiving the combination of zinc and vitamins A and D. This novel method of increasing plasma zinc levels by the augmentation of vitamins A and D may have implications for the reduction of burden of disease.

Duration of untreated psychosis and outcome in first-episode psychosis. Perspective from a developing country.

OBJECTIVE: To investigate the association between duration of untreated psychosis (DUP) and treatment outcome in a sample of subjects from a developing country. METHOD: Forty-eight subjects with a first episode of psychosis were evaluated prior to treatment and at 3-month intervals over a period of 24 months. We first examined correlations between DUP and symptom improvement as measured on the Positive and Negative Symptom Scale (PANSS), and then performed multivariate analysis to determine the validity of DUP as a predictor of outcome. RESULTS: DUP was significantly correlated with improvement in PANSS total and negative subscale scores as well as the PANSS depression factor at 21 and 24 months. Multivariate analysis found DUP to be the only significant predictor of improvement in negative symptoms at 24 months. CONCLUSION: DUP was a significant predictor of outcome in a cohort form a developing country. This study provides support for early detection and intervention strategies.

A culture-bound syndrome 'amafufunyana' and a culture-specific event 'ukuthwasa': differentiated by a family history of schizophrenia and other psychiatric disorders.

BACKGROUND: 'Amafufunyana' and 'ukuthwasa' are two culture-specific descriptive terms used by Xhosa traditional healers to explain aberrant behavioral and psychological phenomena. Some overlap between these conditions and schizophrenia (DSM-IV) is apparent. The aim of this study was to determine the extent to which amafufunyana and ukuthwasa were used as cultural explanatory models by traditional healers for DSM-IV-defined schizophrenia and whether there were significant phenomenological differences in schizophrenia symptoms in patients with the diagnosis of amafufunyana rather than ukuthwasa. SAMPLING AND METHODS: Xhosa patients with schizophrenia underwent a structured clinical diagnostic interview (Diagnostic Interview for Genetic Studies). The use of traditional diagnostic and treatment methods was assessed by structured open-ended interviewer-rated questions. The sample was then stratified for the presence/absence of a past/current diagnosis of amafufunyana and/or ukuthwasa. The clinical parameters were compared across groups by means of the chi2 or Student t tests. RESULTS: 247 adult subjects participated in the study. 106 (53%) patients reported a previous diagnosis of amafufunyana, and 9 (4.5%) reported a diagnosis of ukuthwasa. A family history of schizophrenia (p = 0.004) or any psychiatric disorder (p = 0.008) was more common in the ukuthwasa group. Subjects with a primary diagnosis other than amafufunyana or ukuthwasa were more likely to be married (p = 0.004), to have a history of stressor(s) prior to illness onset (p = 0.026), to be from a rural environment (p = 0.007) or to have a history of cannabis abuse/dependency (p = 0.015). CONCLUSION: The culture-bound syndrome amafufunyana and the culture-specific phenomenon of ukuthwasa are both used to explain symptoms in patients with schizophrenia (DSM-IV). Identification of cases as amafufunyana and ukuthwasa may correlate with a distinction between familial and sporadic cases of schizophrenia. Whether the positive connotations associated with ukuthwasa, as opposed to the more negative connotations associated with amafufunyana, hold any implications for the treatment or prognosis of schizophrenia remains to be clarified.

Violence in male patients with schizophrenia: risk markers in a South African population.

OBJECTIVE: We investigate the role of functional variants in the catecholamine-O-methyl transferase gene (COMT) and the monoamine oxidase-A gene (MOA-A), as well as previously identified non-genetic risk factors in the manifestation of violent behaviour in South African male schizophrenia patients. METHOD: A cohort of 70 acutely relapsed male schizophrenia patients was stratified into violent and non-violent subsets, based on the presence or absence of previous or current violent behaviour. Standardized violence rating scales were also applied and the COMT/NlaIII and MAO-A promoter region variable number of tandem repeats (VNTR) polymorphisms were genotyped. RESULTS: A multiple logistic regression model based on the clinical, genetic and socio-demographic variables indicated that delusions of control (OR = 3.7, 95% CI = 1.21-11.61) and the combined use of cannabis and alcohol (OR = 6.89, 95% CI = 1.28-37.05) were two significant predictors of violent behaviour in this schizophrenia population. No association was found between the tested polymorphisms and violent behaviour. CONCLUSIONS: Although the sample size may have limited power to exclude a minor role for these specific gene variants, such a small contribution would have limited clinical relevance given the strong significance of the non-genetic markers. These findings suggest that currently proactive management of violent behaviour in this schizophrenia population should continue to be based on clinical predictors of violence.

Management of violent behaviour in acutely relapsed schizophrenics.

The management of aggressive behaviour has always been a critical issue in psychiatry. Finding measures that can be used to accurately predict the likelihood of assaultative behaviour and thus ensure timeous appropriate pharmacological management remains a dilemma. The study objective was to investigate the naturalistic, pharmacological management of inpatient aggressive behaviour in a group of 50 schizophrenic subjects with a view to determine: (1) whether a presenting history of recent violence lead to altered pharmacological management and (2) whether the NOSIE could be regarded as a useful assessment tool with regards to inpatient behaviour management. No significant difference could be demonstrated between the 2 subsets of subjects (history of violence vs none) with respect to total doses of medication administered. No statistical correlation could be found between the total NOSIE score and the dose of psychotropic medication used. The relationship between a subset of NOSIE-items and the total dose of medication was more complex and a clear linear relationship could be demonstrated for a total score of 0 to 5. In this particular ward setting a presenting history of recent violent behaviour did not influence the administration of medication and neither could the clinical judgement employed by the nursing staff to manage inpatient behaviour be captured by the NOSIE. However, a five-item subset of the NOSIE with questions relating to aggression and irritability warrants further scrutiny in this regard.

Attitudes towards and beliefs about schizophrenia in Xhosa families with affected probands.

OBJECTIVE: The development of effective psychoeducational programs for the management of schizophrenia requires an understanding of attitudes towards and beliefs about the disorder in families of affected probands. In order to establish the need for adaptation of Western psychoeducational programs, these variables were investigated in Xhosa speaking families in South Africa. DESIGN: Xhosa speaking family members of patients with DSM-IV schizophrenia were recruited on a voluntary basis, and interviewed with a structured belief and attitudes questionnaire adapted from previous studies in the West. SETTING: The study population was drawn from both urban and rural Xhosa communities in South Africa. SUBJECTS: 100 Xhosa speaking family members participated in the study. RESULTS: Family members most often recommended treatment with psychotropic medications (88%) and traditional healers (32%), and least often recommended psychotherapy (4%) and meditation (1%). Of the respondents who recommended traditional healing methods, 92% also recommended simultaneous use of allopathic treatment. CONCLUSION: Attitudes towards and beliefs about schizophrenia in family members of patients with schizophrenia may differ substantially from those described in previous work in the West. An understanding of local attitudes and beliefs is crucial for the successful development of local psychoeducational programs.

Quetiapine augmentation of serotonin reuptake inhibitors in obsessive-compulsive disorder.

The augmentation of serotonin reuptake inhibitors (SRIs) with atypical antipsychotics for the management of treatment-resistant obsessive-compulsive disorder (OCD) is gaining increasing acceptance. Quetiapine is a novel antipsychotic which is well tolerated, and which may therefore be particularly useful in this context. Charts of all patients treated in our OCD clinic with the combination of an SRI and quetiapine were reviewed. Demographic details and clinical symptoms on the Yale-Brown Obsessive-Compulsive Scale and the Clinical Global Impressions Scale (CGI) were tabulated before and after augmentation. Eight OCD patients who had proven resistance to treatment with SRIs had received quetiapine augmentation. Four of these eight patients were responders (CGI of 1 or 2) within 4 weeks. In the treatment-responders, the medication was well tolerated. Although limited by the retrospective design and lack of controls, these data are consistent with the growing literature suggesting that approximately one-half of OCD patients resistant to treatment with SRIs may respond to augmentation with an atypical antipsychotic. Quetiapine, a relatively well tolerated agent, deserves further controlled study in this context.

Serum concentrations of some metals and steroids in patients with chronic fatigue syndrome with reference to neurological and cognitive abnormalities.

Chronic fatigue syndrome is defined by the Atlanta Centers for Disease Control (Atlanta, GA, USA) as debilitating fatigue lasting for longer than 6 months. Symptoms include disturbances of cognition. Certain factors have in the past been shown to influence cognition, including metals such as aluminum, iron, and zinc; and steroids such as dehydroepiandrosterone. In the present study, concentrations of these factors were determined in the serum and plasma of patients and their age- and gender-matched healthy controls (10 women and 5 men in each group). In addition, copper, dehydroepiandrosterone sulphate, cortisol, cholesterol, hemoglobin, ferritin and transferrin concentrations, as well as transferrin genetic subtypes were determined in both groups. The results indicate that patients had significantly increased serum aluminum and decreased iron compared to controls. In the females, serum iron and dehydroepiandrosterone sulphate were significantly decreased and correlated. Total cholesterol was significantly increased, and significantly negatively correlated with dehydroepiandrosterone sulphate. There were no differences in zinc, copper, cortisol, hemoglobin, transferrin and ferritin concentrations, or in transferrin genetic subtypes.

Association between a catechol-o-methyltransferase polymorphism and obsessive-compulsive disorder in the Afrikaner population.

BACKGROUND: It has been proposed that the catechol-o-methyl transferase gene (COMT) may play a role in the pathogenesis of obsessive-compulsive disorder (OCD). Whereas studies in a North American population showed that the low activity (L) allele of a functional polymorphism in COMT was associated with OCD in male patients, this result was not supported by studies in a Japanese population. The present association study assessed the risk for OCD conferred by this COMT polymorphism in a geographically different patient group, namely, the relatively genetically homogeneous Afrikaner population of South Africa. METHODS: Fifty-four unrelated OCD patients and fifty-four sex-matched controls were recruited from the same Afrikaner community. Patients and controls were phenotyped (DSM-IV) and genotyped for a NlaIII polymorphism with H (high activity) or L (low activity) alleles in the COMT gene. RESULTS: The H/L genotype was significantly more common than expected in the OCD patient group (P = 0.0017). LIMITATIONS: Replication studies with related individuals may be useful in discovering factors underpinning the H/L genotype abundance in the Afrikaner population. CONCLUSIONS: These results emphasise the need for further studies in genetically homogeneous populations to help define the complex etiology of this disease.

The factor structure for positive and negative symptoms in South African Xhosa patients with schizophrenia.

Most studies investigating the symptom dimensions of schizophrenia utilising the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) favour a three factor model. This study sought to investigate the factor structure of both the global and individual items of the SANS and SAPS in a large sample of South African Xhosa patients with schizophrenia. A total of 422 subjects participated. Both principal components and factor analytical procedures were applied. For the global items, a two-factor solution representing positive and negative symptoms accounted for 59.9% of the variance. Alternatively, the three-dimensional model of negative, psychotic and disorganisation factors was supported by a five-factor solution if the more heterogeneous items of attention and alogia were ignored. Analysis of the individual items yielded a five-factor solution with the negative symptoms splitting into diminished expression and disordered relating, and the positive symptoms separating into factors for psychosis, thought disorder and bizarre behaviour. Our findings are very similar to those from other parts of the world, providing evidence that the factor structure for the symptoms of schizophrenia is relatively resistant to cultural influences. This is particularly true for negative symptoms.

Determining the optimal dose of haloperidol in first-episode psychosis.

Uncertainty exists as to the most appropriate dose of haloperidol in first-episode psychosis. This study set out to determine whether ultra-low doses of haloperidol could successfully treat patients with first-episode psychosis. Thirty-five patients with a first episode of psychosis were treated with haloperidol in an open label, fixed protocol over a 12-week period with doses restricted to 1 mg per day for the first 4 weeks. Twenty-nine (83%) remained on haloperidol after 12 weeks at a mean dose of 1.78 mg per day, 16 (55%) had stabilized on 1 mg/day or less. The mean percentage reduction in Positive and Negative Symptom Scale score between baseline and 6 and 12 weeks was 30.3% (SD 20.9%) and 41.4% (SD 16.6%), respectively. There were no significant differences in mean extrapyramidal symptom ratings between baseline and 12 weeks. Ultra-low doses of haloperidol are effective and well tolerated in first-episode psychosis. Initial doses should be maintained for a sufficient period of time to allow for the medication to take full effect.

Psychiatric research in South Africa: a systematic review of Medline publications.

BACKGROUND: There is debate about the future path that medical and psychiatric research in South Africa should take. In particular, there have been calls to make research more relevant to the needs of the population. There is, however, little systematically collected data on the nature, strengths, and flaws of past psychiatric research in this country. METHODS: We undertook a MEDLINE search to gather all manuscripts that fell under the umbrella of psychiatric research and published by South Africa-based authors during the years 1966-1997. Several kinds of data were collated from each of the articles, including information about the authors and the journal, as well as information on the focus and type of article. RESULTS: While publications from South Africa continue to grow in number, relatively few involve collaborative research groups and few authors write more than one paper. Many papers relevant to psychiatry were published in general medical journals and many were from general medical departments. While blacks and females have been included in research, a number of important areas have received little attention. CONCLUSIONS: Psychiatry research in South Africa requires additional fostering, including additional resources for research training and arguably additional development of subspecialty focuses. Given the limited resources, and the nature of modern research, increased emphasis on collaboration seems advisable. A number of areas in psychiatry deserve particular attention from future researchers.

A comparison of the effects of quetiapine ('seroquel') and haloperidol in schizophrenic patients with a history of and a demonstrated, partial response to conventional antipsychotic treatment. PRIZE Study Group.

Quetiapine ('Seroquel') is a well-tolerated, novel, atypical antipsychotic with consistent efficacy in the treatment of schizophrenia. To date, no clinical studies have evaluated the effect of quetiapine in patients who only partially respond to conventional antipsychotics, yet this type of patient is most frequently seen by psychiatrists. Therefore, this international, multicentre, double-blind study was conducted to compare the efficacy and tolerability of 8 weeks' treatment of quetiapine 600 mg/day with haloperidol 20 mg/day in 288 patients who had a history of partial response to conventional antipsychotics and displayed a partial or no response to 1 month of fluphenazine (20 mg/day) treatment. Patients on quetiapine tended to have greater improvement than those on haloperidol in the primary efficacy measure, mean Positive and Negative Symptom Scale (PANSS) score, after 4 weeks' treatment (-9.05, -5.82, respectively, P = 0.061) and at study end (-11.50, -8.87, respectively, P = 0.234). Similarly, there was a trend towards patients on quetiapine demonstrating greater improvements in the secondary efficacy measures (Clinical Global Impression, PANSS subscale and Brief Psychiatric Rating Scale scores) [week 4 (baseline) to week 12 (end)], but the difference between treatments did not reach significance. Significantly more patients on quetiapine than on haloperidol showed a clinical response-patient response rates, defined as > 20% reduction in PANSS total score between weeks 4 and 12, were 52.2% for quetiapine and 38.0% for haloperidol (P = 0.043). Patients receiving quetiapine required less anticholinergic medication (P < 0.011), had greater reduction in extrapyramidal symptoms (EPS) (P = 0.005) and fewer treatment-emergent EPS-related adverse events compared to those on haloperidol (P < 0.001). Serum prolactin concentrations were elevated at the end of fluphenazine treatment in 73% of patients. Between weeks 4 and 12, elevated serum prolactin concentrations significantly decreased in quetiapine-treated patients compared to those receiving haloperidol (P < 0.001). At the end of quetiapine treatment, 83% of patients had normal prolactin levels while only 21% of patients receiving haloperidol were within the normal range. These results suggest that quetiapine may make a valuable contribution to the management of patients with a history of partial response to conventional antipsychotics.