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2015 Volume 27 Issue 4
In this issue
Systematic review and meta-analysis
Efficacy and safety of treating patients with refractory schizophrenia with antipsychotic medication and adjunctive electroconvulsive therapy: a systematic review and meta-analysis Wenzheng WANG, Chengcheng PU, Jiangling JIANG, Xinyi CAO, Jijun WANG, Min ZHAO, Chunbo LI Background: The efficacy and safety of the combined treatment of refractory schizophrenia with antipsychotic medications and electroconvulsive therapy (ECT) remain uncertain. 
Aim: Conduct systematic review and meta-analysis of available literature in English and Chinese about ECT in the treatment of refractory schizophrenia. 
Methods: English and Chinese databases were searched for studies published prior to May 20, 2015 regarding the efficacy and safety of the combined treatment of refractory schizophrenia with antipsychotic medications and ECT. Two researchers selected and evaluated studies independently using pre-defined criteria. Review Manager 5.3 software was used for data analysis. 
Results: A total of 22 randomized control studies, 18 of which were conducted in mainland China, were included in the analysis. Meta-analysis of data from 18 of the 22 studies with a pooled sample of 1394 individuals found that compared to treatment with antipsychotic medications alone, combined treatment with antipsychotic medications and ECT had significantly higher rates of achieving study-specific criteria of‘clinical improvement’ (RR=1.25, 95%CI=1.14-1.37). Based on the Grades of Recommendation, Assessment,Development, and Evaluation (GRADE) criteria, the quality of evidence for this assessment of efficacy was‘moderate’. However, the proportion of participants who experienced headache during the treatment was significantly higher in the combined treatment group (RR=9.10, 95%CI=3.97-20.86, based on a pooled sample of 517 from 8 studies) and the proportion who experienced memory impairment was also higher in the combined treatment group (RR=6.48, 95%CI=3.54-11.87, based on a pooled sample of 577 from 7 studies). The quality of evidence about these adverse events was rated as ‘very low’. 
Conclusions: There are very few high quality randomized controlled clinical trials about the combination of antipsychotic medications and ECT in the treatment of refractory schizophrenia. This meta-analysis found that the combination of antipsychotic medications and ECT could improve psychiatric symptoms in patients with refractory schizophrenia, but the incomplete methodological information provided for most of the studies, publication bias (favoring studies with better outcomes in the combined treatment group), and the low quality of evidence about adverse outcomes, cognitive impairment, and overall functioning raise questions about the validity of the results. 
Key words: electroconvulsive therapy; antipsychotic medication; refractory schizophreinia; systematic review; meta-analysis
Original research article
Comparison of the effectiveness of duloxetine in depressed patients with and without a family history of affective disorders in first-degree relatives Shiliang WANG, Mincai QIAN, Hua ZHONG, Guohua SONG, Meijuan LU, Rui FENG, Lei ZHANG, Jianliang NI, W Background: It remains unclear whether or not a positive family history of affective disorders predicts the effectiveness of antidepressant treatment of depression. 
Aim: Assess the relationship of a family history of affective disorders to the efficacy of duloxetine in the treatment of depressive disorder. 
Methods: Seventy-seven patients with depressive disorder (as defined by the 10th edition of the International Classification of Diseases, ICD-10) were enrolled in the study and treated with standard doses of duloxetine for 12 weeks. Among these patients 37 had a family history of affective disorder in first-degree relatives and 40 did not. The Hamilton Depression rating scale (HAMD-17), Hamilton Anxiety rating scale (HAMA), Side Effects Rating Scale (SERS), Snaith-Hamilton Pleasure Scale (SHAPS), and Beck Depression Inventory (BDI) were assessed at baseline and at the end of the 2nd, 4th, 6th, 8th, and 12th week after enrollment. Repeated measures analysis of variance and logistic regression were used to analyze the association between a family history of affective disorders and the efficacy of duloxetine. 
Results: Patients with a positive family history of affective disorders had an earlier age of onset, a longer duration of illness, a higher level of psychic anxiety, and more prominent anhedonia. Repeated measures analysis of variance showed a significant improvement in the severity of depression over the 12 weeks but no differences in the magnitude or speed of improvement between the two groups. Treatment was considered effective (i.e., drop in baseline HAMD-17 total score of >50%) in 75.7% of those with a family history of affective disorders and in 77.5% of those without a family history (X2=0.04, p=0.850).
Conclusion: Family history of affective disorders is not associated with the effectiveness of duloxetine in the acute treatment of depressive disorder. 
Key words: family history; depressive disorders; duloxetine; China
Treatment of major depressive disorders with generic duloxetine and paroxetine: a multi-centered, double-blind,double-dummy, randomized controlled clinical trial Zhiyang WANG, Xiufeng XU, Qingrong TAN, Keqing LI, Cui MA, Shiping XIE, Chengge GAO, Gang WANG, Huaf Background: This study is a pre-registration trial of generic duloxetine that was approved by the China Food and Drug Administration (approval number: 2006L01603). 
Aim: Compare the treatment efficacy and safety of generic duloxetine to that of paroxetine in patients with major depressive disorders (MDD). 
Methods: This was a double-dummy, double-blind, multicenter, positive drug (paroxetine), parallel randomized controlled clinical trial. The 299 patients with MDD recruited for the study were randomly assigned to use duloxetine (n=149; 40–60 mg/d) or paroxetine (n=150; 20 mg/d) for 8 weeks. The Hamilton Depression rating scale (HAMD-17) was administered at baseline and 1, 2, 4, 6, and 8 weeks after starting treatment. Remission was defined as a HAMD-17 score below 8 at the end of the trial, and treatment effectiveness was defined as a decrease in baseline HAMD-17 score of at least 50% by the end of the trial.Safety was assessed based on the reported prevalence and severity of side effects and changes in laboratory and electrocardiographic findings. Three patients in the duloxetine group dropped out before starting medication, so results were analyzed using a modified intention-to-treat (ITT) method with 146 in the experimental group and 150 in the control group. 
Results: Both groups experienced 29 dropouts during the 8-week trial. HAMD-17 scores decreased significantly from baseline throughout the trial in both groups. Based on the ITT analysis, at the end of the trial there was no significant difference between the duloxetine group and the paroxetine group in effectiveness (67.1% v. 71.3%, X2=0.62 p=0.433), remission rate (41.1% v. 51.3%, X2=3.12, p=0.077), or in the incidence of side effects (56.8% v. 54.7%, X2=0.14, p=0.705). 
Conclusion: Generic duloxetine is as effective and safe as paroxetine in the acute treatment of patients with MDD who seek care at psychiatric outpatient departments in China. 
Key words: duloxetine; paroxetine; efficacy; safety; major depressive disorder; randomized controlled trial;China
Single-blind, randomized controlled trial of effectiveness of Naikan therapy as an adjunctive treatment for schizophrenia over a one-year follow-up period Hong ZHANG, Chenhu LI, Liyu ZHAO, Guilai ZHAN Background: Current treatments for schizophrenia are often only partially effective. 
Aim: Assess the possible benefit of using adjunctive Naikan therapy, a cognitive approach based on selfreflection that originated in Japan for the treatment of schizophrenia. 
Methods: After resolution of acute psychotic symptoms, 235 psychiatric inpatients with schizophrenia who had a middle school education or higher were randomly assigned to a control group (n=112) that received routine medication and inpatient rehabilitative treatment or an intervention group (n=123) that also received adjunctive Naikan therapy for 2 hours daily, 5 days a week for 4 weeks. The patients were then discharged and followed up for 12 months. The Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance scale (PSP), and Insight and Attitude Questionnaire (ITAQ) were used to assess patients at enrollment, after the 1-month intervention, and after the 12-month follow-up. Evaluators were blind to the group assignment of patients. 
Results: Only 13(10.6%) of the intervention group participants relapsed over the 12-month follow-up, but 23(20.5%) control group participants relapsed (X2=4.50, p=0.034). Using a modified intention-to-treat analysis and a repeated measure analysis of variance, the PANSS, PSP, and ITAQ total scores all showed significantly greater improvement over the 12-month follow-up in the Naikan group than in the control group. The drop in mean chlorpromazine-equivalent dosage from enrollment to the end of follow-up was significantly different in the intervention group but not in the control group, though the change in dosage over time between groups was not statistically significant. 
Conclusions: This study provides robust support for the effectiveness of Naikan therapy as an adjunctive treatment during the recovery period of schizophrenia. Compared to treatment as usually, adjunctive Naikan therapy can sustain the improvement in psychotic symptoms achieved during acute treatment, improve insight about the illness, enhance social functioning, and reduce relapse over a one-year follow-up period.Further research of this treatment with larger and more diverse samples of patients with schizophrenia is merited. 
Keywords: Naikan therapy; schizophrenia; relapse; social functioning; randomized controlled trial; China
Forum
Comorbid bipolar disorder and obsessive-compulsive disorder Daihui PENG, Kaida JIANG Summary: Obsessive-compulsive symptoms are common in patients with bipolar disorders. This comorbid condition complicates the clinical treatment of the two disorders, so identifying these individuals is important. We discuss the comorbid occurrence of obsessive-compulsive disorder and bipolar disorder,introduce possible etiological mechanisms that could result in this common comorbid condition, discuss recent research advances in the area, and propose some clinical principles for managing such patients. 
Key words: obsessive-compulsive disorder; bipolar disorder; comorbidity
Obsessive compulsive symptoms in bipolar disorder patients: a comorbid disorder or a subtype of bipolar disorder? Shenxun SHI Summary: Over the last decade increasing attention has been focused on individuals that simultaneously meet the criteria of two or more mental disorders. One of these comorbid conditions, comorbid bipolar disorder and obsessive compulsive disorder, is relatively common among patients with a primary diagnosis of bipolar disorder. But there is little research about the diagnosis and treatment of this comorbid condition, particularly in China. The available studies are primarily cross-sectional studies with small samples, so they are of limited use in understanding the etiology and course of this combined condition.A review of the limited literature suggests that this is a relatively severe, refractory subtype of bipolar disorder that only occasionally merits being considered a comorbid disorder. Larger prospective studies are needed to clarify the etiology, prognosis, and appropriate treatment for this comorbid condition. 
Keywords: bipolar disorder; obsessive compulsive disorder; comorbid mental disorders
Commentary
Challenges to the uniqueness of psychotic experience in psychosis: insights on research methodology and intervention Linda CW LAM Summary: Paul Bebbington’s recent Special Article on the value of psychosocial epidemiology as a tool for understanding the symptomatology of psychosis provides a fresh perspective on understanding the etiology of schizophrenia and related psychotic conditions. Assessment of psychotic-like experiences in non-clinical populations may help to clarify the role of non-psychotic symptoms such as anxiety and depression in the onset and course of psychotic disorders. This approach may also make it possible to expand the repertoire of interventions for preventing the onset or ameliorating the course of psychotic conditions. There is, however,a long road to travel before the mapping of the relationships between brain pathology,psychological symptoms, environmental stressors, and clinical diagnoses are sufficiently detailed to merit the creation of anew psychiatric nosology. 
Keywords: psychosocial epidemiology; psychosis; non-psychotic symptoms; psychosocial stressors; prodromal psychosis
Case report
Case report of comorbid schizophrenia and obsessive-compulsive disorder in a patient who was tube-fed for four years by family members because of his refusal to eat Ankur SACHDEVA, Mina CHANDRA, Ankit SAXENA, RP BENIWAL, Manish KANDPAL, Arvind KUMAR Summary: Refusal to eat is a common presentation in many psychiatric disorders including obsessive compulsive disorder and schizophrenia. In the acute situation it may be a medical emergency; when it becomes chronic it can become an ingrained behavior that is difficult to change. The diagnosis of individuals who refuse to eat may be difficult, particularly in persons with comorbid medical problems, impaired intelligence, or lack of insight into their condition. Tube-feeding is an effective short-term intervention that can be discontinued when the patient re-starts oral intake. However, in some situations patients may become dependent on the use of tube-feeding. We present a case report of a patient with schizophrenia,obsessive compulsive disorder, borderline intelligence, and seizure disorder who was tube-fed by his family members for more than three years because he refused to eat orally. 
Keywords: refusal to eat; comorbid psychiatric disorders; schizophrenia; obsessive-compulsive disorder; borderline intelligence; seizure disorder; case report; India
Biostatistics in psychiatry
Introduction to longitudinal data analysis in psychiatric research Xian LIU Summary: The onset, course, and management of mental health problems typically occur over relatively long periods of time, so a substantial proportion of psychiatric researc–particularly the research that can provide clear answers about the complex interaction of biological, psychological, and social factors–requires multiple assessments of individuals and the environments in which they live over time. However,many psychiatric researchers use incorrect statistical methods to analyze this type of longitudinal data,a problem that can result in unrecognized bias in analytic results and, thus, incorrect conclusions. This paper provides an introduction to the topic of longitudinal data analysis. It discusses the different dataset structures used in the analysis of longitudinal data, the classification and management of missing data, and methods of adjusting for intra-individual correlation when developing multivariate regression models using longitudinal data. 
Key words: Intra-individual correlation; longitudinal data; missing data; multivariate and univariate data structures; repeated measurements