In one research study by Girgis et al. (92), 160 individuals with schizophrenia were randomized to clozapine or chlorpromazine treatment for up to 2 years. The adherence to clozapine was found to be higher than that of chlorpromazine. In another study conducted on 34 individuals with schizophrenia, it was found that there was no beneficial effect of clozapine over conventional antipsychotics (93). McEvoy et al. (94) found that a large percentage of individuals with schizophrenia discontinued treatment due to the inadequate efficacy of some antipsychotic drugs. An average daily dose of 523 and 600 mg/day of clozapine has been found to be effective in the treatment of positive and negative symptoms in individuals with schizophrenia (94). Sanz-Fuentenebro et al. (95) found that individuals with schizophrenia on clozapine continued their original treatment for a much longer period of time than patients on risperidone. Specifically, the retention rate for clozapine was 93 point 4% whereas the retention rate for risperidone was 82 point 8%. However, patients in the clozapine group normally have significant weight gain than those on risperidone (96).
In one study by Sahini et al. (97), a total of 63 patients were selected and randomly allocated to either clozapine or risperidone. The two groups were similar on sociodemographic variables including age, sex, education level, occupation, income, family type and marital status. The mean duration of illness was 19 point 39 months, in the clozapine group, and 18 point 63 months in the risperidone group. There was a significant reduction of positive symptoms in both drugs. It was found that both clozapine and risperidone equally reduced positive symptoms whereas clozapine was much superior compared to risperidone in reducing negative symptoms. Clozapine has been found to reduce suicidal ideation in individuals with schizophrenia (98); Along these lines, Hennen et al. (98) reported that with administration of clozapine in chronically psychotic patients has led to a reduced suicidal ideation. In fact, it was concluded that long-term treatment with clozapine resulted in a three-fold reduction of risk of suicidal behaviors. Further, patients on clozapine are often administered metformin (500 mg twice daily) to lose weight. Aripiprazole is sometime given along with clozapine to manage weight and improve metabolic parameters (99). In one study, Muscatello et al. (99), found that the administration of both aripiprazole and clozapine has led to a beneficial effect on the positive and general symptoms of individuals with schizophrenia, compared to clozapine alone.
McCreadie et al. (104) studied dietary habits of 102 individuals with schizophrenia with special emphasis on fruit and vegetable intake and smoking behavior. The study concluded that the patients (especially male patients) had poor dietary choices. Graham et al. (105) suggested that administering vitamin D to individuals with schizophrenia ameliorates their negative symptoms. In another study by Strassnig et al. (106), the dietary habits of a total of 146 adult community-dwelling individuals with schizophrenia were studied. It was observed that the patients consumed a higher quantity of food that includes protein, carbohydrate, and fat than that of a control group Such habits can lead to cardiovascular diseases, type II diabetes, and systemic inflammation in individuals with schizophrenia (107). These diseases are related to a short lifespan in individuals with schizophrenia (108). In a research study by Joseph et al. (109), it has been suggested that high-fiber diets can improve the immune and cardiovascular system, thereby, preventing premature mortality in schizophrenia.
There have been validation studies of CBT in schizophrenia over the last 15 years. In schizophrenia, CBT is one of the most commonly used therapy in the UK (generally in addition to medications) (51). In fact CBT has been recommended as first-line treatment by the UK national health service (NHS) for individuals with schizophrenia. Similarly, the American Psychiatric Association recommended CBT for individuals with schizophrenia (112). Recently the US Schizophrenia Patient Outcomes Research Team (PORT) has recommended CBT for patients who have persistent psychotic symptoms (112).
CBT was also found to be useful in reducing disorganized behavior which affects daily living in individuals with schizophrenia. In one research study by Wykes et al. (113) in the United States and United Kingdom, it has been found that CBT is more preferred than other behavioral therapies. This study show that CBT ameliorates positive symptoms, negative symptoms, mood and social anxiety. However, there was no effect on hopelessness. CBT sometimes includes the family of the patient in treatment session, which is why the patient and their carers usually welcome CBT. CBT brings the patient and their carers into a collaborative environment as a part of the treatment team and encourages them to participate actively in treatment. It has been found that hallucinations, delusions, negative symptoms and depression are also treated with CBT (38). CBT involves doing a homework which allows the patient and their carer to alleviate the distressing symptoms of schizophrenia. CBT encourages taking medications regularly and integrating with the community (51). CBT has also been found to have enhanced effect when combined with antipsychotic medication (114), as compared to the administration of medications alone.
Although most treatment studies focus on ameliorating positive and negative symptoms, other symptoms, such as homelessness and lack of education equally impact the quality of life in individuals with schizophrenia. Thus, targeting these symptoms is of paramount importance. By doing so, we will be able to provide an individualized treatment for schizophrenia as well as increase the patients' participation in society. Galletly et al. (7) provides a set of recommendations for the clinical management of schizophrenia. They adopt a somewhat holistic view of treating schizophrenia symptoms and problems the patients face such as unemployment. This guideline emphasizes early intervention, physical health, psychosocial treatments, cultural considerations and improving vocational outcomes as well as collaborative management and evidence-based treatment.
Cognitive behavioural therapy has been used for schizophrenia, but to which extent it is effective is still controversial. Results of existing meta-analyses are of difficult interpretation, because they mainly present effect sizes in the form of standardized mean differences between intervention and control groups based on rating scales, which are of unclear clinical meaning. No meta-analysis has considered the number of patients responding to treatment yet. Based on this ground, we present the first meta-analysis examining the response rates of patients with schizophrenia and positive symptoms to cognitive behavioural therapy.
We searched multiple databases for randomized controlled trials on psychological interventions of schizophrenia including patients with positive symptoms, and included for this analysis the studies on cognitive behavioural therapy (last search: January 2018). We applied a validated imputation method to calculate the number of responders from rating scales for the outcomes overall symptoms and positive symptoms, based on two criteria, at least 20% and at least 50% reduction from baseline on PANSS or BPRS total scores. Data were pooled in a single-group summary meta-analysis using R software. Additionally, several potential moderators of response to cognitive behavioural therapy were examined by subgroup and meta-regression analyses. The protocol has been registered in PROSPERO (CRD42017067795).
A possible strategy to deal with this issue was applied by Zhu and colleagues, who calculated response rates from continuous outcomes in the field of antipsychotic medication for patients with first episode schizophrenia . Thus, we decided to apply the same methodology to calculate response rates from studies on CBT that were included in the previous review , in order to provide an easy-to-interpret measure of treatment effect.
Goals for present meta-analysis are: i) calculating how well patients with schizophrenia and positive symptoms respond to cognitive behavioural therapy; ii) examining the determinants of response to cognitive behavioural therapy in this population.
The protocol of the original review was registered in PROSPERO (number CRD42017067795) and published . We included studies in adult individuals with a diagnosis of schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders), presenting current positive symptoms, as defined by inclusion criteria of the trial, with no restrictions on setting, gender or ethnicity. We excluded studies on patients with predominant negative symptoms or concomitant medical or psychiatric illness, and patients at different stages of illness (first episode, at risk of psychosis). Studies were included if at least 80% of the patients had schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders). Following the rules of the Cochrane Schizophrenia group we included trials regardless of the diagnostic criteria used , in order to increase representativeness and generalizability.
We searched Embase, MEDLINE, PsycINFO, PubMed, WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov and Cochrane Collaboration Controlled Trials Register for reports published up to January 2018 for randomized controlled trials that compared CBT with other psychological treatments or with a non-pharmacological control condition in patients with schizophrenia currently presenting positive symptoms. We applied no restrictions for language or publication period. Previous reviews on CBT were also inspected to determine if some studies met our inclusion criteria as well. 2b1af7f3a8