Online link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659301/

Meta-Analysis

Context: Despite lacking evidence for its safety and efficacy, antipsychotic cotreatment is common in schizophrenia.

Objective: To evaluate therapeutic and adverse effects of antipsychotic cotreatment vs monotherapy in schizophrenia.

Data Sources: Cochrane Schizophrenia Group register and hand searches of relevant journals/conference proceedings.

Study Selection: Randomized controlled trials comparing antipsychotic monotherapy to cotreatment with a second antipsychotic.

Data Extraction and Analysis: Two authors independently extracted data. For homogenous dichotomous data, we calculated random effects, relative risk (RR), 95% confidence intervals (CIs), and numbers needed to treat (NNT). For continuous data, weighted mean differences were calculated.

Results: In 19 studies (1229 patients) with 28 monotherapy and 19 cotreatment arms, antipsychotic cotreatment was superior to monotherapy regarding 2 a priori defined coprimary outcomes: less study-specific defined inefficacy (N = 22, n = 1202, RR = 0.76, CI = 0.63–0.90, P = .002, NNT = 7, CI = 4–17, P = .0008, I2 = 78.9%) and all-cause discontinuation (N = 20, n = 1052, RR = 0.65, CI = 0.54–0.78, P < .00001). Results were consistent using Clinical Global Impressions thresholds of less than much (P = .006) and less than minimally (P = .01) improved. Specific psychopathology and adverse event data were insufficient to yield meaningful results. In sensitivity analyses, 5 efficacy moderators emerged: concurrent polypharmacy initiation, clozapine combinations, trial duration >10 weeks, Chinese trials, and second-generation + first-generation antipsychotics. In a meta-regression, similar dose combinations, second-generation + first-generation antipsychotics and concurrent polypharmacy initiation remained significant.

Conclusions: In certain clinical situations, antipsychotic cotreatment may be superior to monotherapy. However, the database is subject to possible publication bias and too heterogeneous to derive firm clinical recommendations, underscoring the need for future research.

Keywords: antipsychotics, polypharmacy, combination, monotherapy, schizophrenia, efficacy, all-cause discontinuation, side effects, trial methodology

–  In this meta-analysis, 19 studies are included with a total population size of 1229 patients. All participating patients in this meta-analysis were 18 years old or older, except in 4 Chinese studies, where they included a few patients who were 16 years old or older.

–    The studies included in this meta-analysis come from several different countries such as: Turkey, U.S, Canada, China, Israel and Japan.

–          Fifteen studies were double blind, the others were single blind.

–     Almost all studies included in this meta-analysis used the PANSS (positive and negative syndrome scale) or the BPRS (brief psychiatric rating scale) to determine the efficiency of schizophrenia treatment with either monotherapy or combination therapy.

–       Out of 19 studies, 10 of them compared 1 antipsychotic combination treatment with only one antipsychotic monotherapy.

–        In the other 9 studies, 1 antipsychotic combination treatment was compared with 2 different antipsychotic monotherapies.

–     Most participating patients (1054 patients) were suffering from chronic schizophrenia while the rest of the participating patients (162 patients) were acutely exacerbated patients.

–     From the 19 studies in this meta-analysis, 28 antipsychotic monotherapies used either first generation antipsychotic or a second-generation antipsychotic. The most commonly used first generation antipsychotic drug that was used in monotherapy was Chlorpromazine and the most commonly used second generation antipsychotic in monotherapy was Clozapine.

– Combination therapies used either 2 first generation antipsychotic, 2 second generation antipsychotic or a combination of first and second antipsychotic. Just like in monotherapies, the most commonly used antipsychotics were Chlorpromazine and Clozapine.

–    Positive effects for the antipsychotic polypharmacy treatment were apparent the most in patients who acutely exacerbated schizophrenia than those with chronic schizophrenia.

–  Antipsychotic co-treatment proved to be more superior than antipsychotic monotherapy in those studies that lasted more than 10 weeks or longer.

–     In the studies that lasted less than 10 weeks, the effectiveness of antipsychotic co-treatment over antipsychotic monotherapy was not clear.

–      In all the analysis done by this meta-analysis, co-treatment with both a first and  second-generation antipsychotic proved to be more superior than monotherapy with either first- or second-generation antipsychotic.

–    Co-treatment that is initiated at the beginning of treatment shows a much higher efficiency in controlling positive and negative symptoms in schizophrenia patients than co-treatment that is added later on.

–      When it came to adverse effects, there was no significant difference between the group that received monotherapy or co-treatment.

–          I chose this article because it has the highest level of evidence being a meta-analysis. It involves 19 studies with a total population size of 1229 which makes the data more reliable. I also selected this article because it’s very relevant to my PICO question because it looks at data from 19 studies that compare the effectiveness of monotherapy antipsychotic treatment vs combination treatment of antipsychotic for people suffering from schizophrenia. All the studies in this meta-analysis were randomized controlled trials and from different countries which leaves little to no room for bias. The overwhelming majority of the population in this meta-analysis are adults with schizophrenia which is the population of my interest for this PICO assignment.