A Comparative Study of Benzodiazepine Hypnotics and Zopiclone in Schizophrenia: Effects on Polysomnograms and BPRS Scores

Abstract: Sleep variables and psychiatric symptoms during benzodiazepine (BZD) hypnotic therapy and during zopiclone (ZPC) treatment were investigated in 6 male chronic schizophrenics. The amount of stage 1 was smaller and that of stage 2 was larger during treatment with ZPC than BZDs. However, no significant difference was shown in the amount of slow-wave sleep (SWS) between the treatments. Both the total and negative-symptom scores in the Brief Psychiatric Rating Scale (BPRS) were lower, and the soundness of sleep in the subjective sleep assessments was better evaluated during treatment with ZPC than BZDs. These results suggest that ZPC may be more beneficial in treating schizophrenic insomnia than BZDs.     

Validity and reliability of the newly translated Hellenic Neuropsychiatric Inventory (H-NPI) applied to Greek outpatients with Alzheimer's disease: a study of disturbing behaviors among referrals to a memory clinic

CONTEXT: No rating scales of the neuropsychiatric symptoms of patients with dementia and Alzheimer's disease (AD) have previously been developed or translated. OBJECTIVES: To develop a Hellenic translation of the Neuropsychiatric Inventory (NPI), to evaluate it's reliability and validity, and to compare NPI results in Greek patients referred to a neuropsychiatry clinic for either of two reasons: disturbing behaviors evoking embarrassment and disturbing behaviors evoking fear in the caregiver. METHODS: The Hellenic translations of the NPI, Brief Psychiatric Rating Scale (BPRS), and Emotional Distress Scale (EDS) were compared in evaluating 29 consecutive referrals of patients with AD. RESULTS: The Hellenic NPI (H-NPI) demonstrated a high degree of internal consistency reliability, and of concurrent validity when compared to the BPRS or the EDS. Patients referred for behaviors evoking embarrassment presented with higher scores on NPI ratings of apathy. However, patients referred for behaviors evoking fear presented with higher scores on NPI ratings of aggression and irritability. CONCLUSIONS: These results indicate that the H-NPI is a reliable instrument, able to detect differences in clinically referred groups of AD patients.     

Multiple regression analysis of relationship between frontal lobe phosphorus metabolism and clinical symptoms in patients with schizophrenia

We investigated the differences among diagnostic types of 36 schizophrenic patients in the brain phosphorus metabolism in the frontal lobe. We performed phosphorus-31 magnetic resonance spectroscopy (³¹P-MRS) in the frontal region in patients with schizophrenia of the catatonic (n=4), disorganized (n=8), paranoid (n=10) and undifferentiated (n=14) types. In the disorganized type, the PME level was significantly decreased compared to those in the other three types, while the phosphodiester (PDE) level tended to be higher, although not significantly, than those in the other types. Using multiple regression analysis, we investigated whether or not the clinical symptoms were correlated with the brain phosphorus metabolism. An increased motor retardation factor score was significantly correlated with decreased PME level, whereas more severe emotional withdrawal and blunted affect were associated with increased PDE level. These results suggest that altered membrane phospholipid metabolism in the frontal region may be associated with negative symptoms and that schizophrenia of the disorganized type is associated with more severe negative symptoms and may present more severe brain abnormalities compared to the other types.     

Inter-rater reliability of the Brief Psychiatric Rating Scale and the Groningen Social Disabilities Schedule in a European multi-site randomized controlled trial on the effectiveness of acute psychiatric day hospitals

The objectives of this study were to report the inter-rater reliability of the Brief Psychiatric Rating Scale (BPRS 4.0) and the Groningen Social Disabilities Schedule (GSDS-II) as assessed in a randomized controlled trial on the effectiveness of psychiatric day hospitals spanning five sites in countries of Central and Western Europe. Following brief training sessions, videotaped BPRS-interviews and written GSDS-vignettes were rated by clinically experienced researchers from all participating sites. Inter-rater reliability often proved to be poor for items assessing the severity of both psychopathology and social dysfunction, but findings suggest that both instruments allow for the assessment of the presence or absence of specific psychopathological symptoms or social disabilities. Inter-rater reliability at subscale level proved to be good for both instruments. Results indicate that, with a brief training session and proper use of the instruments, psychopathology and social disabilities can be reliably assessed within cross-national research studies. The results are of particular interest given that the need to conduct cross-national multi-site studies including countries with different cultural backgrounds increases.     

A prospective case control study of psychiatric disorders in adults with epilepsy and intellectual disability

Purpose: No study to date has prospectively investigated the impact of epilepsy on psychiatric disorders among adults with an intellectual disability (ID). This study aimed to determine prospectively the influence of epilepsy on the development of psychiatric disorders in adults with ID. Method: Psychiatric symptoms were measured prospectively over a 1‐year period among 45 adults with ID and active epilepsy and 45 adults with ID without epilepsy, matched on level of ID. The 1‐year incidence rate (IR) of commonly occurring Axis 1 psychiatric disorders was compared with and without controlling for possible confounding factors. Total psychiatric symptom scores over the period were compared between the two groups using repeated‐measures analysis of covariance. Key Findings: Adults with epilepsy and ID had a more than seven times increased risk for developing psychiatric disorders, particularly depression and unspecified disorders of presumed organic origin, including dementia, over a 1‐year period compared to those with ID only. Comparison of the psychiatric scores showed the epilepsy group to have significantly higher unspecified disorder and depression symptom scores. Significance: The findings point to an increased risk of depression and unspecified disorders, including dementia, among adults with ID and epilepsy. Further exploration of the nature and treatment of these unspecified disorders may help the care of people with epilepsy and ID.     

Yi-gan san for the treatment of borderline personality disorder: an open-label study

BACKGROUND: Numerous medications have been tested on patients with borderline personality disorder (BPD). Although many of these medications have been demonstrated to be useful, no clear main treatment for BPD has emerged. Despite the efficacy of some of the medicines, acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Chinese herbal medicine yi-gan san (YGS, yokukan-san in Japanese) may be safe and useful in treating behavioral and psychological symptoms in dementia patients. We aimed at evaluating both efficacy and safety of yi-gan san in patients with well-defined BPD. METHODS: Twenty female outpatients diagnosed with BPD according to DSM-IV criteria and the revised Diagnostic Interview for Borderlines completed a 12-week open-label study with yi-gan san at an average daily dosage of 6.4+/-1.9 g (2.5-7.5 g). Psychometric instruments to assess efficacy included the Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scales for Depression (HAM-D), Global Assessment of Functioning (GAF), Clinical Global Impression Scale (CGI), and Aggression Questionnaire (AQ). RESULTS: Most psychometric scale scores exhibited a highly significant improvement (total BPRS; BPRS somatic concern, anxiety, tension, depressive mood, hostility, suspiciousness, motor retardation, uncooperativeness, and excitement subscale; CGI; GAF; AQ) over time. CONCLUSIONS: In this open-label pilot study, patients treated with YGS showed statistically significant reduction on self-rated and clinician-rated scales. The present findings suggest that yi-gan san might be effective for the treatment of a number of BPD symptoms, including low mood, impulsivity, and aggression.     

Evaluation of subjective treatment satisfaction with antipsychotics in schizophrenia patients

Adherence to antipsychotic treatment is particularly important in the long-term management of schizophrenia and other related psychotic disorders since poor adherence to medication is associated with poor health outcomes. Although the patients' subjective satisfaction with the medication is crucial for adherence to medication, few studies have examined the relationship between subjective satisfaction with antipsychotics and adherence. In this study, we investigated subjective satisfaction with antipsychotics in patients with schizophrenia by using the Treatment Satisfaction Questionnaire for Medication (TSQM), a self-reporting instrument to assess the major dimensions of patients' satisfaction with their medication. The subjects included 121 clinically stabilized outpatients who met the following criteria: 1) patients between 20 and 65 years of age, diagnosed with schizophrenia or other psychotic disorders as defined by DSM-IV, 2) patients undergoing oral antipsychotic monotherapy or taking only an antiparkinsonian agent as an adjuvant remedy, and 3) patients who had received a stable dose of an antipsychotic for more than four weeks. Patients were asked to answer the TSQM questions, and their clinical symptoms were also evaluated by the Brief Psychiatric Rating Scale (BPRS). Satisfaction with regard to side-effects (p=0.015) and global satisfaction (p=0.035) were significantly higher in patients taking second-generation antipsychotics (SGAs, n=111) than those taking first-generation antipsychotics (FGAs, n=10), whereas no significant difference was found between the two groups in clinical symptoms according to BPRS (p=0.637) or the Drug-induced Extrapyramidal Symptoms Scale (DIEPSS, p=0.209). In addition, correlations were not significant between the subjective satisfactions and clinician-rated objective measures of the symptoms. These findings suggest that SGAs have more favorable subjective satisfaction profiles than FGAs in the treatment of schizophrenia. Since it is often difficult to detect the difference by a traditional objective assessment of the patients, it is desirable that physicians pay attention to the patients' subjective satisfaction in conjunction with their own objective clinical assessment.     

Schizophrenia with prominent catatonic features ('catatonic schizophrenia'). II. Factor analysis of the catatonic syndrome

Previous factor analyses of catatonia have yielded conflicting results for several reasons including small and/or diagnostically heterogeneous samples and incomparability or lack of standardized assessment. This study examined the factor structure of catatonia in a large, diagnostically homogenous sample of patients with chronic schizophrenia using standardized rating instruments. A random sample of 225 Chinese inpatients diagnosed with schizophrenia according to DSM-IV criteria were selected from the long-stay wards of a psychiatric hospital. They were assessed with a battery of rating scales measuring psychopathology, extrapyramidal motor status, and level of functioning. Catatonia was rated using the Bush-Francis Catatonia Rating Scale. Factor analysis using principal component analysis and Varimax rotation with Kaiser normalization was performed. Four factors were identified with Eigenvalues of 3.27, 2.58, 2.28 and 1.88. The percentage of variance explained by each of the four factors was 15.9%, 12.0%, 11.8% and 10.2% respectively, and together they explained 49.9% of the total variance. Factor 1 loaded on "negative/withdrawn" phenomena, Factor 2 on "automatic" phenomena, Factor 3 on "repetitive/echo" phenomena and Factor 4 on "agitated/resistive" phenomena. In multivariate linear regression analysis negative symptoms and akinesia were associated with 'negative' catatonic symptoms, antipsychotic doses and atypical antipsychotics with 'automatic' symptoms, length of current admission, severity of psychopathology and younger age at onset with 'repetitive' symptoms and age, poor functioning and severity of psychopathology with 'agitated' catatonic symptom scores. The results support recent findings that four main factors underlie catatonic signs/symptoms in chronic schizophrenia.     

Minocycline as adjunctive therapy for patients with unipolar psychotic depression: an open-label study

Background

Approximately 25% of patients admitted to a hospital as a result of depression are actually suffering from psychotic depression. Psychotic symptoms can be present in patients with either unipolar depression or bipolar depression and can be difficult to treat. It was reported the second-generation tetracycline may exert potential antidepressant effects through its robust neuroprotective activities, which include neurogenesis, antioxidation, and anti-glutamate excitotoxicity, and may direct regulation of pro-inflammatory agents.

Methods

This was a 6-week, open-label study to evaluate the efficacy and safety of minocycline in combination with antidepressants in adult inpatients (n = 25) diagnosed with major depression with psychotic features (psychotic depression) according to DSM-IV-TR. The primary endpoint was the change from baseline in the Hamilton Depression Rating Scale (HAM-D-21) score from baseline to week 6. Secondary endpoints were changes in the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) Scale scores from baseline to week 6. Spontaneously reported adverse events were recorded.

Results

The patients' average age was 46.9 ± 10.2 years. Minocyline (150 mg/day) in combination with antidepressants (fulvoxamine, paroxetine, and sertraline) provided significant improvement in depression. Mean (± SD) HAM-D-21 was reduced to 6.7 ± 1.9 at week 6 from a baseline value of 40.4 ± 2.5. Significant improvement of psychotic symptoms (mean ± SD) was indicated by the decrease in BPRS scores from baseline (63.3 ± 8.7) to week 6 (4.6 ± 2.4). No serious adverse events occurred.

Conclusions

These preliminary data suggest that minocycline in combination with antidepressants is effective and well tolerated in the treatment of unipolar psychotic depression. Further studies using larger, double-blind, parallel-group design are warranted to confirm these findings.     

Combination therapy with amisulpride and antidepressants: clinical observations in case series of elderly patients with psychotic depression

Psychotic depression is classified as a clinical subtype of major depressive disorder. The combination of an antidepressant with an antipsychotic agent has been demonstrated to be efficacious for the treatment of psychotic depression. However, in elderly patients with psychotic depression, little information is available on the efficacy of such combinations. Therefore, we have evaluated combination treatment for 5 weeks with amisulpride and antidepressants in non-demented elderly patients with psychotic depression. Eleven patients were treated with either citalopram 20-40 mg/day (n=5) or mirtazapine 30-60 mg/day (n=6), and amisulpride 75-100 mg/day for 5 weeks. Clinical status was evaluated at baseline and after 3 and 5 weeks using the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale--17 items (HDRS) and the Clinical Global Impression Scale (CGI-S). In 5 of the 11 patients there was remission of depression, while in another 5 patients there was partial remission of depression and in one patient there was no remission. Finally, there was resolution of psychotic symptoms in all the patients involved. One patient developed tremor and rigidity but insisted on continuing with the drug since her psychopathology has improved considerably after the addition of amisulpride to antidepressant treatment. In conclusion, some of the elderly patients with psychotic depression may benefit from the combination of amisulpride and antidepressant pharmacotherapy.     

Reduced expression of apolipoprotein E receptor type 2 in peripheral blood lymphocytes from patients with major depressive disorder

We measured the mRNA levels of apolipoprotein E receptor type 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) in peripheral blood lymphocytes from 43 patients with major depressive disorder (27 drug-free patients and 16 medicated patients) and 43 age-matched healthy controls using a quantitative real-time RT-PCR method. The correlations between mRNA levels of both receptors and clinical variables in patients were also examined. The expression of ApoER2 mRNA, but not VLDLR, was significantly lower in patients as compared to controls, irrespective of the medication status. There was no statistically significant correlation between the reduction of ApoER2 mRNA levels and any of the clinical variables measured in patients. Results from this preliminary study suggest that the expression of ApoER2 may serve as a trait marker for major depressive disorder.     

Oxidative-antioxidative systems and their relation with serum S100 B levels in patients with schizophrenia: effects of short term antipsychotic treatment

Oxidative stress may be a contributing factor in the etiopathophysiology of schizophrenia, which may be exacerbated by the treatment with antipsychotics with pro-oxidant properties. Increased levels of S100 B are associated with neurodegenerative disorders, including schizophrenia. The aim of the present study was to investigate the role of oxidative cell damage in the pathogenesis of schizophrenia. Forty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia and 35 healthy control subjects were included in the study. Serum S100 B level was determined to investigate brain damage. Plasma malondialdehyde (MDA) levels and susceptibility of red blood cell (RBC) to oxidation were determined to investigate the oxidative status and plasma vitamin E, vitamin C, serum total carotenoid levels and total antioxidant capacity and RBC superoxide dismutase (SOD) and whole blood glutathione peroxidase activities were measured to investigate the antioxidative defence before and after 6 weeks of antipsychotic treatment. Plasma MDA and serum S100 B levels and RBC-SOD activity were significantly higher in the schizophrenia group than those of the control group. Treatment did not modify any of the oxidative-antioxidative system parameters or serum S100 B levels. S100 B level was significantly higher in patients with negative symptoms than the patients with positive symptoms and the control subjects. S100 B levels were significantly reduced after 6 weeks of treatment in patients with negative symptoms. The results of the present study might support the oxidative cell injury hypothesis of the schizophrenia. Furthermore, the underlying mechanisms of the subgroups of schizophrenia might be different as suggested by the increased S100 B levels and its decrement after treatment in patients with negative symptoms.     

Impaired MMN/P3a complex in first-episode psychosis: Cognitive and psychosocial associations

Mismatch negativity (MMN) is a neurophysiological indicator of the brain's ability to extract relevant information from an irrelevant background. The P3a orienting response often accompanies MMN in deviance detection paradigms. Both MMN and P3a have been described as reliable biomarkers of schizophrenia. MMN/P3a impairments are associated with deficits in verbal memory and attentional switching, reflecting dysfunctions in the temporal and frontal systems, respectively. It remains unresolved whether MMN/P3a are robust biomarkers of psychosis in first-episode patients. Thirty-four young people (18 to 30 years) were assessed in this study; 17 first-episode psychosis (FEP) patients were compared to 17 healthy controls. To elicit MMN/P3a, a two-tone passive auditory oddball paradigm with 8% duration deviants was used; event-related potentials were recorded at frontal, central and temporal (mastoid) sites. Neuropsychological assessments included processing speed, attentional switching, simple attention, and verbal learning and memory. Social functioning and quality of life measures were also obtained. The FEP group showed significantly reduced MMN amplitudes compared to controls. The FEP group also showed significantly reduced P3a amplitudes at frontal and central sites compared with controls. As expected, the FEP group also showed significant deficits in attention and verbal learning/memory. Correlational analyses found strong associations between fronto-central MMN/P3a peak amplitude and cognitive/psychosocial functioning. This study provides evidence of early neurobiological markers in young people with FEP. These findings suggest that MMN/P3a impairments are present at early stages of psychosis and that fundamental pre-attentive/deviance detection deficits may mark the beginning of progressive underlying changes with illness onset. Such deficits in FEP appear to have important links with higher-order cognitive and psychosocial functioning.     

Understanding the experiences and service needs of siblings of individuals with first-episode psychosis: a phenomenological study

Background: Despite recent focus on developing family‐inclusive services to meet the needs of young people with first‐episode psychosis, the needs of their siblings are often overlooked. Aims: This study explored the experiences and needs of siblings of young adults with first‐episode psychosis receiving support from two Early Intervention in Psychosis Services in South‐East England. Methods: Thirty‐one siblings aged 11–35 years, were given a semi‐structured interview to gather their perspectives and accounts of their lived experiences. The resultant rich qualitative data was analysed using responsive‐reader and framework methods. Results: Six themes were identified: siblings' roles and involvement; emotions; impact on relationships; coping patterns; resilience; and siblings' service needs. Conclusion: All participants had been greatly affected by the onset of the psychosis in their brother or sister. Most siblings did not identify themselves as carers, although most played a significant part in their brother's or sister's life. Participants wanted dynamic, robust and accessible services, especially information and peer support to meet their needs.     

Effect of the methylenetetrahydrofolate reductase gene polymorphisms on homocysteine, folate and vitamin B12 in patients with bipolar disorder and relatives

We investigated the effect of polymorphic variants of c.1298A>C (Glu429Ala) and c.677C>T (Ala222Val) in methylenetetrahydrofolate (MTHFR) gene on the total homocysteine (tHcy), folate and B12 levels in patients with bipolar disorder, first-degree relatives of patients, and controls. The c.677C>T and c.1298A>C polymorphisms in MTHFR were determined by polymerase chain reaction-restriction fragment length polymorphism in 197 bipolar patients, 278 relatives and 238 controls. tHcy and folate and vitamin B12 levels were measured by Fluorescence Polarization Immunoassay and Electrochemiluminescence, respectively. The tHcy was significantly increased in patients and relatives. In contrast, folate and B12 were significantly lower in patients and relatives. Gender was not considered as a significant determinant in the multivariate analysis. Genotypes of c.1298A>C and c.677C>T were correlated with tHcy, folate and B12. Patients and relatives carrying TT and/or AA and AC genotypes had elevated tHcy and reduced folate and B12 levels. High tHcy but low folate and vitamin B12 levels may be a risk factor for development of bipolar disorder.     

Cavum septum pellucidum in subjects at ultra-high risk for psychosis: compared with first-degree relatives of patients with schizophrenia and healthy volunteers

OBJECTIVE: The cavum septum pellucidum (CSP) is a space between the two leaflets of the septum pellucidum, and is a putative marker of disturbance in early brain development. We examined whether CSP was present more frequently in subjects at ultra-high risk (UHR) for psychosis compared to first-degree relatives of patients with schizophrenia (genetic high risk, GHR) and healthy controls (HC). METHODS: We evaluated CSP in 87 subjects (30 UHR, 23 GHR, and 34 HC) according to a published grading system using high-resolution magnetic resonance imaging (MRI) with 0.45-mm slice thickness. We also assessed two other criteria: presence of CSP on at least one MRI slice, and abnormally large CSP (i.e., > or =6 mm in length). Correlational analysis between CSP measures and clinical symptoms was also examined. RESULTS: Based on the grading scale, the UHR group exhibited a significantly higher incidence of abnormal CSP (grades 2, 3, and 4) compared to the HC group, but there were no significant differences in the incidence of abnormal CSP between the UHR and GHR or the GHR and HC groups. There were no significant differences among the groups in the presence of CSP on at least one MRI slice or abnormally large CSP based on the length of CSP. In addition, no significant correlations between CSP measures and clinical symptoms were found. CONCLUSION: These findings suggest that abnormal CSP might be associated with susceptibility to psychosis, although the CSP itself might be a normal anatomical variant. Further studies using a larger sample are needed to clarify issues on neurodevelopmental perspective in subjects at high risk for psychosis.     

Impact of panic attacks on quality of life among patients with schizophrenia

Objective

Schizophrenia patients had decreased levels of quality of life compared to normal population. The aim of this study was to investigate the impact of panic attacks on quality of life in patients with schizophrenia.

Methods

Eighty-eight patients with schizophrenia and 85 healthy subjects were included in the study.World Health Organization Quality of Life Instrument-Short Form (WHOQOL-Bref) was given to patients and healthy subjects to assess quality of life. Panic module of Structured Clinical Interview for DSM-IV (SCID) was administered to patients for diagnosis of panic attacks and panic disorder. Positive and Negative Syndrome Scale (PANSS) for symptom severity and Calgary Depression Scale (CDS) for depressive symptoms were administered to the patients.

Results

Patients with schizophrenia demonstrated significantly lower scores compared to healthy controls in all domains of WHOQOL-Bref. Twenty-five patients (28.4%) with schizophrenia had panic attacks (PA) and 10 patients (11.4%) met criteria for panic disorder (PD). Schizophrenia patients with PA had significantly lower scores on psychological domain of WHOQOL-Bref compared to the patients without PA. Schizophrenic patients with panic attacks had higher CDS scores than patients without PA.In the multivariate regression analyses the variance in psychological domain of WHOQOL-Bref was explained by depression rather than panic attack.

Conclusion

In patients with schizophrenia comorbid panic attacks may have a negative impact on quality of life, which is associated with depression significantly. Panic attacks and depressive symptomatology must be examined comprehensively in order to improve quality of life in patients with schizophrenia.     

Schizophrenia with auditory hallucinations: a voxel-based morphometry study

Many studies have shown widespread but subtle pathological changes in gray matter in patients with schizophrenia. Some of these studies have related specific alterations to the genesis of auditory hallucinations, particularly in the left superior temporal gyrus, but none has analysed the relationship between morphometric data and a specific scale for auditory hallucinations. The present study aims to define the presence and characteristics of structural abnormalities in relation with the intensity and phenomenology of auditory hallucinations by means of magnetic resonance voxel-based morphometry (MR-VBM) method applied on a highly homogeneous group of 18 persistent hallucinatory patients meeting DSM-IV criteria for schizophrenia compared to 19 healthy matched controls. Patients were evaluated using the PSYRATS scale for auditory hallucinations. Reductions of gray matter concentration in patients to controls were observed in bilateral insula, bilateral superior temporal gyri and left amygdala. In addition, specific relationships between left inferior frontal and right postcentral gyri reductions and the severity of auditory hallucinations were observed. All these areas might be implicated in the genesis and/or persistence of auditory hallucinations through specific mechanisms. Precise morphological abnormalities may help to define reliable MR-VBM biomarkers for the genesis and persistence of auditory hallucinations.     

Switching from conventional antipsychotics to ziprasidone: A randomized,open-label comparison of regimen strategies

In clinical psychopharmacology, the optimal method of switching from treatment A to treatment B with regard to efficacy and tolerability is an important area of study. We investigated the effects on efficacy and tolerability of switching patients from conventional antipsychotics to ziprasidone. This was a 6-week open-label, randomized study of 54 patients with persistent schizophrenia or schizoaffective disorder. Patients received ziprasidone 40 mg BID for 2 days, with titration up to 80 mg BID thereafter. The switch from conventional antipsychotics to ziprasidone was achieved using one of three discrete schedules: (1) abrupt discontinuation of conventional antipsychotics on day 1; (2) fast taper—50% of conventional antipsychotic dosage on days 1 through 7, followed by discontinuation and (3) slow taper—100% of conventional antipsychotic dosage on days 1 and 2, followed by 50% on days 3 through 7, then discontinuation. We found some evidence that the slow-taper strategy was associated with greater reductions in BPRS total scores early in the study compared to the other two strategies. However, these differences did not remain significant at endpoint, suggesting that there was no overall difference between the strategies.