Summary The response to antipsychotic treatment in schizophrenia appears to vary, and as such it has been proposed that different subtypes of schizophrenia exist, defined by treatment-response. This has not been formally examined using meta-analysis. Randomised controlled trials comparing placebo and antipsychotics in acute treatment of schizophrenia listed in PubMed, EMBASE and PsycINFO from inception until November 30, 2018 were examined. Relative variability of symptomatic improvement in antipsychotic-treated individuals compared to placebo-treated individuals was quantified using coefficient of variation ratio (CVR). Mean difference in symptom change was quantified using Hedges’ g. In addition, individual patient data from two clinical trials was examined in terms of both the distribution of total symptom change, and the variability of individual symptoms and symptom factors. 11,006 articles were identified. 66 met inclusion criteria, reporting on 17,202 patients. Compared with placebo, antipsychotic-treated patients demonstrated greater total symptom improvement (g=0.47, p<0.001) and reduced variability in symptomatic improvement for total (CVR=0.86, p<0.001), positive (CVR=0.89, p<0.001), and negative symptoms (CVR=0.86, p=0.001). Lower variability in antipsychotic-response was associated with studies published earlier (z=3.98, p<0.001), younger patients (z=3.07, p=0.002), higher dose treatments (z=-2.62, p=0.009), and greater mean-difference in symptom-change (z=-5.70, p<0.001). In the individual patient dataset (N=522 patients), antipsychotic treated patients did not show significantly increased variability for any individual symptom, and there was no evidence of a bimodal distribution of response. Compared to placebo, antipsychotic treatment shows greater improvement and lower variability of change in total, positive and negative symptoms. This is contrary to the hypothesis that there is a subtype of antipsychotic non-responsive schizophrenia. Instead our findings, provide evidence for a relatively homogeneous effect of antipsychotic treatment in improving symptoms of schizophrenia.

Background Antipsychotics are more effective than placebo in reducing symptoms in schizophrenia. However, response to treatment appears to vary, and as such it has been proposed that different subtypes of schizophrenia exist, defined by treatment-response. This has not been formally examined using meta-analysis. Methods Randomised controlled trials comparing placebo and antipsychotics for the acute treatment of schizophrenia published between January 1 1950 and November 30, 2018 were examined. Mean change and variance of change in symptoms were extracted from each study, alongside publication year, participant age and gender, baseline symptom severity, antipsychotic dose, and use of placebo lead-in. Relative variability of symptomatic improvement in antipsychotic-treated individuals compared to placebo-treated individuals was quantified using coefficient of variation ratio (CVR). Mean difference in symptom change was quantified using Hedges’ g. The significance of potential moderating factors was assessed using meta-regression and sensitivity analyses. In addition, individual patient data from two clinical trials (N=522) was examined in terms of both the distribution of total symptom change, and the variability of individual symptoms and symptom factors. Results 11,006 articles were identified. 66 met inclusion criteria, reporting on 17,202 participants. Compared with placebo, antipsychotic-treated patients demonstrated both greater symptomatic improvement (g=0.47, p&lt;0.001) and reduced variability in symptomatic improvement (CVR=0.86, p&lt;0.001). Lower variability in antipsychotic-response was associated with studies including younger patients (z=3.07, p=0.002), those published earlier (z=3.98, p&lt;0.001), with higher dose treatments (z=-2.62, p=0.009), and greater mean-difference in symptom-change (z=-5.70, p&lt;0.001). In the individual patient data antipsychotic treated patients did not show significantly increased variability for any individual symptom, and there was no evidence of a bimodal distribution of response. Discussion Compared to placebo, in addition to a greater mean change, antipsychotic treatment shows lower variability of change in total, positive, and negative symptoms. This is contrary to the hypothesis that there exists a subtype of antipsychotic non-responsive schizophrenia, instead providing evidence for a relatively homogeneous effect of antipsychotic treatment in improving symptoms of schizophrenia.

Treatment-resistant schizophrenia (TRS) poses a significant therapeutic challenge in psychiatric practice. Clozapine is recognized as a treatment of choice in TRS but is not always effective in alleviating patients' symptoms. Additionally, clozapine therapy is associated with multiple side effects and monitoring requirements that often limit its use and negatively affect patients' compliance with the treatment. Although clozapine augmentation options are available, there is currently no alternative monotherapy proven to be effective in TRS. We present a case of a young man with TRS who failed to respond to appropriate trials of risperidone, aripiprazole and also clozapine, and who experienced impairing adverse effects of clozapine that made further clozapine treatment not only futile but also detrimental to his health. He was successfully treated with cariprazine monotherapy, which culminated in the remission of his both positive and negative symptoms of psychosis as well as in the marked improvement in social functioning. Cariprazine, a newer atypical antipsychotic endowed with a D3-preferring mode of action, may offer a better tolerated and more acceptable treatment option for patients with difficult-to-treat psychotic symptoms.

Migration or mobility of individuals from one location to another is a frequent phenomenon and has been the case for millennia, although reasons for such movement of people have varied. Reasons for migration and the experiences an individual has when arriving at the new place are important, especially in terms of understanding the experiences and problems they may encounter. How well an individual adapts to the new country can be explained by factors of acculturation and how well this occurs may in turn affect the mental health of the person. Studies have shown that migration across the world is on the increase, as are the mental health problems amongst the migrant population; especially self-harm and suicide. Investigating the factors for this is important in order to develop strategies of prevention from a public health point of view. In this chapter we examine differences in the rates of suicide amongst the migrant groups across different countries and explore preventative methods from a public health perspective.