Acute Phase Of Schizophrenia Research Articles

Altered cerebellar effective connectivity in first-episode schizophrenia and long-term changes after treatment.

Cerebello-cortical functional dysconnectivity plays a key role in the pathology of schizophrenia (SZ). We aimed to investigate the changes in cerebello-cortical directional connectivity in patients with SZ. A total of 180 drug-naïve patients with first-episode SZ (54 reassessed after 1 year of treatment) and 166 healthy controls (HCs) were included. Resting-state functional magnetic resonance imaging was used to perform Granger causal analysis, in which each of the nine cerebellar functional systems was defined as a seed. The observed effective connectivity (EC) alterations at baseline were further assessed at follow-up and were associated with changes in psychotic symptom. We observed increased bottom-up EC in first-episode SZ from the cerebellum to the cerebrum (e.g. from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased top-down EC in the first-episode SZ was mainly from the cerebrum to the cerebellum (e.g. from the right inferior temporal gyrus, left middle temporal gyrus, left putamen, and right angular gyrus to the cerebellar language system). After 1 year of antipsychotic treatment, information projections from the cerebrum to the cerebellum were partly restored and positively related to symptom remission. These findings suggest that decreased top-down EC during the acute phase of SZ may be a state-dependent alteration related to symptoms and medication. However, increased bottom-up EC may reflect a persistent pathological trait.

Plasma concentrations of IL-8, IFN-γ and IL-1β in schizophrenia patients with subgroup analysis of first episode drug naïve patients

IntroductionIncreased plasma concentrations of proinflammatory cytokines are found in chronic schizophrenia patients, patients with first episode and in individuals with high risk for psychosis. The most replicated findings are increased concentrations of IL-6, TNF-α and IL-1β through different phases of the disorder while the results for two important proinflammatory cytokines IL8 and IFN-γ were not consistent.ObjectivesPrimary objective of this study was to assess differences in concentrations of IL-8, IFN-γ and IL-1β between schizophrenia patients and healthy controls, Secondary objective was to explore differences in first episode drug naïve patients.MethodsWe measured plasma concentrations of IL-8, IFN-γ and IL-1β in 64 healthy controls and 64 schizophrenia patients during acute exacerbation and remission phase. 25% were drug naive first episode schizophrenia patients. The patients were matched by age, sex and body mass index and exclusion criteria included obesity class 2 or higher, any concomitant organic mental or neurological disorder, acute or chronic inflammatory disease, and use of immunomodulatory drugs or psychoactive substances.Results Levels of IL-8 were significantly lower in patients with schizophrenia in acute phase and remission compared to healthy controls (p=0,009 for acute phase and p=0,020 for remission). There was no significant difference in the levels of INF-γ and IL-β between schizophrenia in acute phase and remission and healthy controls (p>0,05). In schizophrenia patients there was no difference in the levels of INF-γ, IL-β and IL-8 between acute phase, remission and healthy controls (p>0,05). There was no difference in plasma levels of IL-8, IFN-γ and IL-1β between first episode drug naïve and previously treated schizophrenia patients.Conclusions Our research did not find disturbance of plasma levels of IFN-γ and IL-1β in schizophrenia patients, although the increase of IL-1β was the most replicated finding up to date. Interestingly and contrary to expected the finding of significantly decreased levels of IL-8 in schizophrenia patients requires further research since IL-8 plays a vital role in the inflammatory pathway and may be implicated in cognitive dysfunction.Disclosure of InterestNone Declared

Evaluating the association of vitamin D3, parathyroid hormone, and C-reactive protein serum levels in patients with an acute psychotic episode: a cross-sectional study in tertiary centre in Iran

BackgroundThe high impact of vitamin D on brain development and its relationship with inflammatory markers in the clinical course of psychiatric disorders have compelled researchers to investigate the potential association between vitamin D levels, C-reactive protein (CRP) levels, and the incidence of mental disorders. In the present study, we aimed to compare the serum levels of vitamin D and its related markers, including calcium, phosphorus, and parathyroid hormone (PTH), along with CRP, in 3 groups of patients with acute psychotic episodes, including schizophrenia, bipolar disorder, and methamphetamine-induced psychosis, with a standard control group of the Iranian population.MethodsThis descriptive cross-sectional study was conducted at a psychiatric hospital in Tehran, Iran, and involved a total of 185 subjects. The subjects included four groups: acute phase of schizophrenia (n = 49), acute manic episodes of bipolar disorder (n = 43), methamphetamine-induced psychotic disorder (n = 46), and control group (n = 47). Among 138 patients in acute psychotic episodes, 33 patients were in their first episode of psychosis, while 105 patients were in acute exacerbation of their chronic psychotic disorders. The Brief Psychiatric Rating Scale (BPRS) was measured by an expert attending psychiatrist for all patients. Then, serum levels of calcium, phosphorus, parathormone, vitamin D, and CRP were assessed in all study groups.ResultsAmong our 185 study subjects, it was observed that individuals with higher education levels and those who were married had a lower prevalence of mental disorders. In all patient groups, the serum levels of CRP were significantly higher, and PTH levels were significantly lower than in the control group (p < 0.001). The serum levels of calcium, phosphorus, and vitamin D were not statistically significantly different between the patient and control groups of the study. In chronic psychotic patients, CRP levels were significantly higher (p < 0.031), and vitamin D levels were significantly lower (p < 0.044) compared to first-episode psychotic patients.ConclusionThis study suggests that CRP levels are significantly higher and PHT level is significantly lower in acute psychotic patients. Moreover, vitamin D levels were significantly lower in chronic psychotic patients compared to first-episode psychotic patients.

Thiol-disulphide Homeostasis in Patients with Schizophrenia: The Potential Biomarkers of Oxidative Stress in Acute Exacerbation of Schizophrenia.

: Recent evidence suggests that oxidative stress contributes to the pathophysiology of schizophrenia. This study aimed to compare thiol-disulphide homeostasis in acute and stable phases of schizophrenia for the first time. : Among the patients with schizophrenia, 61 in the acute-phase and 61 in the stable phase of their illness were enrolled in the study. Native thiol (NT), total thiol (TT), disulphide (SS), disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol for thiol-disulphide homeostasis were compared between the groups. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive/Negative Symptoms (SAPS/SANS), Clinical Global Impression-Severity Scale (CGI-S), Barnes Akathisia Rating Scale, and Simpson-Angus Scale were used to assess symptoms. : After controlling for age, sex, body mass index, and smoking status there were significant differences in NT, TT, SS/NT, SS/TT, and NT/TT, but not SS. Thiol/disulphide homeostasis has shifted in favour of the oxidative side in patients with acute-phase compared to that in stable schizophrenia. BPRS, SAPS, and CGI-S scores were significantly correlated with all six thiol-disulphide parameters, but not SANS, when controlling for age and sex. Significant receiver operating characteristic (ROC) curves were obtained for all thiol-disulphide homeostasis parameters. Discriminant analysis was found to be statistically significant in discriminating between groups. : These results show that oxidative status increases thiol-disulphide homeostasis in patients with acute-phase schizophrenia compared to those with stable schizophrenia. These findings suggest that thiol-disulphide parameters can be used as biomarkers for the acute exacerbation of schizophrenia.

A Medication Assessment Tool to Evaluate Prescribers’ Adherence to Practice Guidelines in Acute-Phase Schizophrenia Treatment: Development and Psychometric properties

Background: Studies showed that the adherence to practice guidelines is associated with a higher quality of care and better patient’s outcomes. In psychiatric practice, there is a quality gap between Practice guidelines (PGs) and routine clinical practice for the patients with schizophrenia which potentially hinders their recovery. One of the important reasons for this persistent gap is the lack of systematic methods to evaluate prescribers’ adherence to practice guidelines. Objectives: This study aimed to develop and validate a medication assessment tool (MAT) to evaluate prescribers’ adherence to pharmacotherapy recommendations in PGs during the acute phase of schizophrenia (APSCZ) in Iran (MATAPSCZ). Methods: This methodological cross-sectional study was conducted from August 2021 to April 2022. According to the literature review and discussions in the research group, an item pool of 91 items was developed. Then face and content validity of the scale were evaluated. Then, exploratory factor analysis (EFA) was used to specify the factor structure. At last, the reliability and responsiveness of the scale were assessed. The study sample consisted of 200 Iranian psychiatrists and final-year psychiatry residents. Results: Eleven items were merged in qualitative content validity. Then, sixteen and six items were excluded from the scale in terms of having low content validity ratios and corrected item-total correlation, respectively. In exploratory factor analysis, the remaining 48 items were classified into six factors, which included 50.1% of the total variance. Based on the results, Cronbach’s alpha, and McDonald’s omega of all factors were higher than 0.7, AIC was 0.2 to 0.4 for all factors, and the intraclass correlation coefficient for MATAPSCZ was 0.914. The standard error of measurement was ± 4.5, and the percentage of minimum detectable change for the tool was calculated to be 6.15%, which indicates its excellent responsiveness. Conclusions: The MATAPSCZ has acceptable psychometric properties and could be a useful tool to evaluate prescribers’ adherence to practice guidelines pharmacotherapy recommendations during the APSCZ.

The safety and efficacy of sequential intramuscular/oral ziprasidone treatment of acute episode in patients with schizophrenia: a multicenter, open-labeled study

BackgroundZiprasidone mesylate injection is an atypical antipsychotic drug which is recently approved in China. In combination with its oral formulation, sequential therapy with ziprasidone brings new interventions to patients with agitation in the acute phase of schizophrenia. The purpose of this 7-day multicenter study conducted in China was to evaluate the efficacy and safety of ziprasidone sequential treatment through intramuscular/oral routes in agitated patients with schizophrenia.MethodsA total of 95 patients were enrolled from three centers in this study. The study duration was 7 days. In the first 3 days, subjects were administered an intramuscular injection of ziprasidone 10–40 mg daily and started sequentially with oral ziprasidone 40–80 mg at dinner (or lunch) from the day of the last intramuscular injection. In the following 4 days, according to the severity of the symptoms and the drug response, 120–160 mg of ziprasidone was orally administered daily. In total, six visits were scheduled to assess the Positive and Negative Syndrome Scale (PANSS), the Behavioral Activity Rating Scale (BARS), the Clinical Global Impression of Severity (CGI-S), and Improvement (CGI-I) scores throughout the procedure. Lastly, adverse events were recorded during treatment.ResultsOut of the 95 patients that were enrolled, 83 cases were effectively completed. Visits 3, 4, 6, PANSS, and PANSS-excited component (PANSS-EC) subscale points, and Visit 2–Visit 6 viewpoints, BARS scale points, and baseline scores denote a progressive downward trend (P < 0.001). In this study, 62 adverse events were reported. The most common adverse events were extrapyramidal symptoms (EPS) (23 cases) and excessive sedation(10 cases), and 13 cases of prolonged QTc interval were reported.ConclusionsZiprasidone IM demonstrated significant and rapid reduction in agitation, and sequential oral formulation keep stability and continuation of the treatment can further ensure efficacy. Ziprasidone sequential therapy may provide a new approach to acute agitation in schizophrenic patients.Trial registrationThe Chinese Clinical Trials Registry; URL: https://www.chictr.org.cn: ChiCTR-OIC-16007970.

Source monitoring deficits in inpatients with schizophrenia and bipolar disorder in acute disorder phase

Source monitoring deficits in inpatients with schizophrenia and bipolar disorder in acute disorder phase

Impaired central set point of thyroid homeostasis during quetiapine treatment in the acute phase of schizophrenia

AimTo evaluate the impact of quetiapine treatment on central set point of thyroid homeostasis in patients with acute phase schizophrenia. MethodsDuring Jan. 2016 to Dec. 2018, we conducted a retrospective cohort study in “the Second Affiliated Hospital of Xinxiang Medical University”. All patients admitted for treatment of schizophrenia being euthyroid at admission and reevaluated for thyroid function during hospitalization were recruited and followed until discharge. Patients treated with mood stabilizers during hospitalization were excluded. Quetiapine use was the exposure measure. The primary outcomes were the parameters of central set point of thyroid homeostasis measured by “thyroid-stimulating hormone (TSH) index” and “thyroid feedback quantile-based index (TFQI)”. Multiple regression models were used to estimate the association between quetiapine exposure and outcomes. ResultsA total of 1302 patients were enrolled in this study. Quetiapine exposure was associated with a more significant decline in the TSH index and TFQI, and the adjusted β and 95% confidence interval (CI) were −0.12 (−0.22, −0.01) and −0.10 (−0.15, −0.05), respectively. A dose-response association between quetiapine exposure and decline in TSH index and TFQI was observed (P < 0.05). Sensitivity analyses restricting to patients under mono-atypical antipsychotic therapy, or selecting patients in the non-quetiapine group matched to quetiapine group yielded similar results. ConclusionQuetiapine was associated with TSH index and TFQI reduction in a dose-response pattern, suggesting that impaired central set point may be involved in the mechanism by which quetiapine affects hypothalamus-pituitary-thyroid axis in acute phase schizophrenia patients.

Preventing relapse in schizophrenia needs better evidence

Given the considerable contribution of schizophrenia spectrum disorders to the global burden of disease, implementing evidence-based treatments is a global health priority. 1 GBD 2017 Disease and Injury Incidence and Prevalence CollaboratorsGlobal, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392: 1789-1858 Google Scholar , 2 Patel V Saxena S Lund C et al. The Lancet Commission on global mental health and sustainable development. Lancet. 2018; 392: 1553-1598 Google Scholar Building on a previous network meta-analysis of randomised trials of antipsychotics for acute symptoms of schizophrenia, 3 Huhn M Nikolakopoulou A Schneider-Thoma J et al. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019; 394: 939-951 Google Scholar Johannes Schneider-Thoma and colleagues 4 Schneider-Thoma J Chalkou K Dörries C et al. Comparative efficacy and tolerability of 32 oral and long-acting injectable antipsychotics for the maintenance treatment of adults with schizophrenia: a systematic review and network meta-analysis. Lancet. 2022; 399: 824-836 Google Scholar assessed 32 oral and long-acting injectable antipsychotics for 14 different efficacy and tolerability outcomes in a systematic review and network meta-analysis published in The Lancet. The primary outcome was the number of participants who relapsed after clinical stabilisation. 4 Schneider-Thoma J Chalkou K Dörries C et al. Comparative efficacy and tolerability of 32 oral and long-acting injectable antipsychotics for the maintenance treatment of adults with schizophrenia: a systematic review and network meta-analysis. Lancet. 2022; 399: 824-836 Google Scholar The authors found that, for the prevention of relapse, most antipsychotics were superior to placebo, but there were no clinically relevant differences between antipsychotics, as most comparisons included a probability of no difference. Comparing side-effects between antipsychotics generally confirmed findings from trials of acute phase schizophrenia, showing the highest risk of extrapyramidal effects for first-generation antipsychotics, weight gain for second-generation antipsychotics, and hyperprolactinaemia for paliperidone and risperidone. However, for some important side-effects, such as tardive dyskinesia, imprecise results prevented clinical implications from being drawn. Comparative efficacy and tolerability of 32 oral and long-acting injectable antipsychotics for the maintenance treatment of adults with schizophrenia: a systematic review and network meta-analysisAs we found no clear differences between antipsychotics for relapse prevention, we conclude that the choice of antipsychotic for maintenance treatment should be guided mainly by their tolerability. Full-Text PDF

Cost-utility analysis of olanzapine versus combination of haloperidol-diazepam in patients with acute phase schizophrenia: An Indonesian context

Assessment of Quality of Life in Hypertensive PatientsSattanathan Kaliyaperumal, Sagarika Binitha Hari, Prasanth Kumar Siddela, Sara Yadala

Dose Adjustment Model of Paliperidone in Patients With Acute Schizophrenia: A post hoc Analysis of an Open-Label, Single-Arm Multicenter Study.

This study aimed to investigate the factors that influenced the clinicians to adjust the paliperidone dose in the acute phase of schizophrenia. This was a post hoc study of an 8-week, open-label, single-arm multicenter trial which evaluated the efficacy, safety, and tolerability of flexible doses of paliperidone ER (3–12 mg/day) in patients with acutely exacerbated schizophrenia. Patients were divided into groups according to the dose at week 8 (3, 6, and 9–12 mg). The responder was defined as the reduction percentage in the Positive and Negative Syndrome Scale (PANSS) total score of ≥30%. According to the chi-squared automatic interaction detection algorithm, decision tree models predicting an increase in the dose of paliperidone ER were established. A decision tree, based on 4-week Marder positive factor, Clinical Global Impression (CGI), and BMI, was established to guide the dose adjustments of paliperidone ER in the acute phase of schizophrenia. The multivariable logistic regression analysis showed that lower age at onset, higher baseline PANSS positive subscale score, and lower baseline Personal and Social Performance Scale (PSP) score were significant predictors of increased dose in responders. Patients with young-onset age, severe baseline symptoms, and poor function are more likely to benefit from high dosage.

Association between valproate treatment for acute phase schizophrenia and risk of new onset hypothyroidism

AimTo assess the association between acute phase treatment by valproate as an adjunctive drug and risk of new onset hypothyroidism in a large cohort of patients affected by schizophrenia. MethodsWe conducted a retrospective cohort study in a psychiatric hospital in China between January 2016 and December 2018. We obtained approval from the Ethics Committee of the study hospital prior to the commencement of the study. Patients who were diagnosed with schizophrenia and admitted to the study hospital during the study period with thyroid function tests at admission and during hospitalization were included. Patients with abnormal thyroid function at admission were excluded. Hypothyroidism, defined as TSH>4.2 mU/L or on L-thyroxine treatment, was the primary outcome. The primary exposure was adjunctive valproate plus atypical antipsychotics (AAPD), the secondary exposure was lithium plus AAPD and the comparison group was AAPD only. Adjusted relative risk (RR) and 95% confidence interval (CI) were estimated by log-binomial model to assess the independent association between valproate treatment and risk of hypothyroidism. ResultsA total of 1622 eligible patients were included the final analysis. Rate of new onset hypothyroidism was 10.7% and 20.9% in AAPD only and valproate plus AAPD groups, respectively. Adjusted RR (95% CI) for valproate plus AAPD was 1.85 (1.44–2.38), with AAPD only group as reference. Similarly, adjusted RR (95% CI) for lithium plus AAPD was 1.93 (1.32–2.69). ConclusionSimilar with lithium, valproate as adjunctive drug is associated with increased risk of new onset hypothyroidism during acute phase treatment for schizophrenia.

Assessment of the Minimum Clinically Important Difference in Symptoms and Functions of Patients With Acute Schizophrenia: A Post hoc Analysis of an Open-Label, Single-Arm Multicenter Study.

The purpose of this study was to evaluate the application of the minimum clinically important difference (MCID) concept to clinical results in Chinese patients with acutely exacerbated schizophrenia. The original study was an 8-week, open-label, single-arm, multicenter study of flexible doses of paliperidone-extended release (pali-ER) in Chinese patients with acutely exacerbated schizophrenia. This is a post hoc analysis to determine the MCID value of PANSS, PSP and evaluate the responsiveness of each outcome measurements in the acute phase of schizophrenia. The responsiveness of the four measurements (PANSS, PANSS reduction rate, PSP, CGI-S) was analyzed. Four hundred ninety nine patients completed the 8-week follow-up and were finally used for this post hoc analysis. The MCID calculated by different approaches varied from 14.02 to 31.50 for PANSS, 15.14 to 42.79% for PANSS reduction rate, and 7.62 to 13.13% for PSP. In addition, the improvement of the CGI-S owned the highest responsiveness of the four outcome measurements. The threshold value of MCID for schizophrenia patients was determined by choice of the assessment method to an extent. In addition, the CGI-S score appeared to be the most valid and responsive measure of effectiveness for the acute phase of schizophrenia when take the treatment satisfaction of patients as anchor.

The relationship of insight with psychopathological dimensions in patients with schizophrenia

Impaired insight in patients with schizophrenia results in less satisfactory clinical outcomes. This study was conducted to investigate the relationship between insight and individual psychopathological dimensions in inpatients with schizophrenia using a self-report questionnaire. In this study, 90 patients with schizophrenia aged 18–75 years admitted in the acute psychiatric ward of a medical center in Taiwan were enrolled. Patient insight was measured using the Self-Appraisal of Illness Questionnaire (SAIQ), and psychopathological dimensions were measured using the Positive and Negative Syndrome Scale (PANSS) and its five-factor structure model. A higher SAIQ score indicates greater insight. In bivariate correlation analyses, statistically significant correlations were observed between age, single marital status, educational level, and positive, excited, and depressed symptom factor of the PANSS and SAIQ score. In regression analyses, age and excited and depressed symptom factors were significantly associated with SAIQ score. No significant association was observed between insight and neurocognitive functions. Considering demographic characteristics, psychopathology, and neurocognition, in the acute phase of schizophrenia, younger patients with less severe excited symptoms and more severe depressive symptoms had greater insight.

Motivational differences in unipolar and bipolar depression, manic bipolar, acute and stable phase schizophrenia

Background: Motivational anhedonia has been observed in patients with a wide range of mental disorders. However, the similarity and uniqueness of this deficit across diagnostic groups has not been thoroughly investigated. Method: The study compared motivational deficits in 37 patients with major depressive disorder (MDD), 32 with bipolar depression, 33 with manic bipolar disorder (BD), 30 with acute phase and 33 with stable phase schizophrenia, as well as 47 healthy controls. Participants were administered the Effort-Expenditure for Reward Task which measures allocation of effort between a high-effort and a low-effort task for monetary rewards at varying magnitudes and probabilities. Results: Compared with healthy controls, BD manic, acute and stable phase schizophrenia patients were significantly less likely to choose the high-effort task in the high reward magnitude condition. BD manic and acute phase schizophrenia patients were significantly less likely to choose the high-effort task in the high probability condition. Acute and stable phase schizophrenia patients made less effort in the high estimated value condition. Bipolar manic patients made excessive effort in low estimated value but less effort in high estimated value. Contrary to expectations, both the unipolar and bipolar depression patients did not differ significantly from healthy controls in reward magnitude, probability, and estimated value conditions. Anhedonia and negative symptoms were associated with fewer high-effort task choices in schizophrenia patients. Conclusion: Motivation anhedonia showed distinct patterns across psychiatric patients: acute phase schizophrenia was the most severely affected, bipolar mania was similar to schizophrenia, but bipolar depression was similar to unipolar depression.

Dose-dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia

BackgroundAntipsychotics are a cornerstone of pharmacological treatment of schizophrenia. Improved understanding of the dose-response relationship of antipsychotics in terms of efficacy, adverse effects, and mortality can help to optimize the pharmacological treatment of schizophrenia. MethodsThis narrative literature review summarizes current evidence on the relationship of antipsychotic dose with efficacy, adverse effects, and mortality in patients with schizophrenia. ResultsThe efficacy of antipsychotics generally appeared to be highly dose-dependent in the acute phase of schizophrenia, with each antipsychotic having a specific dose-response curve. The presence or absence of dose-dependency and its extent varied according to the type of adverse effect. Parkinsonism, hyperprolactinemia, weight gain, and neurocognitive impairment appeared to be dose-related. The following adverse effects might be at least somewhat dose-dependent: akathisia, tardive dyskinesia, osteoporosis, sexual dysfunction, diabetes mellitus, myocardial infarction, stroke, thromboembolism, QT interval prolongation, anticholinergic adverse effects, somnolence, pneumonia, hip fracture, and neuroleptic malignant syndrome. In contrast, the relationships of antipsychotic dose with dyslipidemia, hypotension, seizure, sialorrhea, and neutropenia and agranulocytosis remained unclear due to mixed findings and/or limited data. Although a higher lifetime cumulative antipsychotic dose might contribute to higher mortality, it is still difficult to conclude whether mortality increases in a dose-dependent manner. ConclusionThese findings could help clinicians to optimize antipsychotic treatment in patients with schizophrenia by balancing risks and benefits in clinical practice. However, further investigations with larger sample sizes and more robust study designs that focus on each antipsychotic agent are needed.

Pharmacotherapy of Schizophrenia in Acute and Maintenance Phase.

Schizophrenia is one of the leading disorders causing impairment in society. Therefore, it is crucial to review evidence-based treatment approaches which are both effective and causing minimum side effects. In this paper, treatment recommendations for first episode schizophrenia, patients in acute phase with a history of multiple episodes, and patients in the maintenance phase will be discussed in light of the Psychiatric Association of Turkey Guideline for Treatment of Schizophrenia, other recent national and international guidelines as well as expert consensus reports in the literature. Finally, practical considerations will be suggested.

Antipsychotic Dose in Acute Schizophrenia: A Meta-analysis.

Little is known regarding optimal antipsychotic doses in the acute phase of schizophrenia. The aim of the present study was to employ the concept of minimum effective dose (MED) in examining efficacy and tolerability within this population. MED was identified for each antipsychotic through a previous systematic review. We then identified double-blind placebo-controlled randomized trials that involved fixed-dose antipsychotic monotherapy in acute schizophrenia and compared the identified MED vs higher doses of the same oral antipsychotic. Studies were selected from a recent meta-analysis examining dose-response relationship of second-generation antipsychotics and haloperidol. We extracted the data on study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events. For each antipsychotic, we conducted a meta-analysis to compare outcomes between MED and 2-fold MED, and MED and 3-fold MED. A total of 26 studies involving 5618 patients were included in the meta-analysis. In terms of study discontinuation, significant differences were found in study discontinuation due to lack of efficacy between MED and higher doses, in favor of 2-fold and 3-fold MEDs. Regarding psychopathology, both 2-fold and 3-fold MEDs were superior to MED for total and positive symptom scores. As for side effects, 2-fold MED proved inferior to MED for parkinsonism scores and diarrhea, whereas 3-fold MED was inferior for akathisia, somnolence, and vomiting. Findings suggest that clinicians can dose an antipsychotic at 2-fold or 3-fold MED for patients with acute schizophrenia but should closely monitor side effects.

Discerning undifferentiated anxiety from syndromal anxiety in acute-phase schizophrenia

BackgroundLiterature on anxiety in schizophrenia is confined to well-established diagnostic syndromes and the diagnostic category of unspecified anxiety disorder has not been quantitatively verified in this population. This study examined whether anxiety that is not differentiated into the well-established syndromes is empirically discernible from syndromal anxiety and no anxiety in acute-phase schizophrenia.MethodsAfter sampling 111 acute-phase schizophrenia patients, they were stratified into three groups: syndromal anxiety; undifferentiated anxiety; and without anxiety disorder. The groups were compared statistically in two data sets on measures for anxiety, psychotic severity, depressive features, akathisia and medication use.ResultsOn two measures of anxiety and for both data sets, the groups were significantly different without evidence of a confounding influence by akathisia, medication, or psychotic severity. The undifferentiated group was different from the syndromal group on the Staden Schizophrenia Anxiety Rating Scale (S-SARS) for both data sets (mean difference = 7.46, p < 0.001; mean difference = 7.69, p < 0.002) and on the Hamilton Anxiety Rating Scale for the one data set (mean difference = 14.68, p < 0.001) but not for the replicative data set (mean difference = 1.49, p = 0.494). The undifferentiated anxiety group was different from the no anxiety group for the respective data sets on both anxiety scales (S-SARS: mean difference = 8.67, p < 0.001; mean difference = 8.64, p < 0.001)(HAM-A: mean difference = 6.05, p < 0.001; mean difference = 8.67, p = 0.002). When depressive features had a confounding effect, it was small relative to the group differences.ConclusionsThe results suggest some patients in acute-phase schizophrenia present with undifferentiated anxiety that is discernible from both syndromal anxiety and those without an anxiety disorder. This finding may serve as empirical grounds for clinicians to recognise undifferentiated anxiety in acute-phase schizophrenia, and for further research into the clinical importance of undifferentiated anxiety in this population.

Feasibility and acceptability of cognitive rehabilitation during the acute phase of schizophrenia.

Although numerous studies have demonstrated promising results for the cognitive rehabilitation in subjects with schizophrenia, the efficacy of cognitive rehabilitation for everyday and social functioning is not yet sufficient. Although consideration of the contents and methods are vital, the timing for implementing cognitive rehabilitation also seems to be crucial. The aim of this study was to examine the feasibility and acceptability of cognitive rehabilitation during the acute phase of schizophrenia. Patients were recruited from consecutive acute admissions to the inpatient unit during a 15-month period and were evaluated to determine whether they could be enrolled in an 8-week cognitive rehabilitation program within 14 days of their hospital admission. Cognitive rehabilitation programs with a workbook style were adopted, taking the patients' conditions and burdens into consideration. Eighty-three patients were newly admitted during the entry period, and 49 patients (59.0%) were eligible for inclusion. Of them, 22 patients (44.9%) agreed to participate and started the program. Sixteen patients completed the program and underwent a second assessment. Thus, 32.7% (16/49) of all the eligible patients actually completed the study. The participants were quite satisfied with the program. This preliminary study yielded encouraging data demonstrating the feasibility and acceptability of cognitive remediation for patients with schizophrenia during the acute phase. The provision of cognitive rehabilitation during the acute phase of the first episode can reasonably be expected to lead to better functional outcomes.