Discussion
schizophrenia, psychosis
This is the first study to investigate differential effects of antipsychotics on insight in a mixed sample of antipsychotic-naïve and previously medicated patients. All study drugs improved insight through the overall reduction in psychosis symptoms. For amisulpride and olanzapine, the improvements in insight exceeded this overall reduction in the analysis based on the first drug in the randomisation sequence. However, these differential effects were lost when only including the participants that chose the first drug in the randomisation sequence, and in the analysis based on the drugs that were chosen by the patient and their treating physician. We found no differences regarding effectiveness on insight among those being antipsychotic-naïve and those previously medicated with antipsychotics.We found that the level of insight was associated with symptom severity at baseline. This is in accordance with findings reported by Gharabawi et al. [Our findings are in line with the EUFEST study, as both studies detected an association between change in insight and decrease in other psychosis symptoms, as well as differential effects among antipsychotics [Our study also included participants without impaired insight in the analysis, in line with the 14 studies included in the paper by Mattila [The EUFEST study that investigated first-episode schizophrenia detected differential effects after 6 weeks [The differential effects were only detectable in analysis #1a. A possible reason may be that 24 participants chose a drug other than the first study drug in the random sequence. Consequently, we ran a sensitivity analysis focusing on the participants that chose the first drug in the sequence. Losing the differential effects when reducing the sample from 144 to 120 in analysis #1b indicate that our sample is too small to detect stable effects on insight that surpasses the effect of reduced total psychosis symptoms. Analysis #2 reflects the drugs that were chosen by the participants and their treating physicians. As the randomisation is no longer valid, these analyses are more prone to selection bias. Taken together, these results of all analyses would have been more solid if they were similar. This discrepancy does therefore not support a direct link between specific medications and changes in insight.
We had considerable attrition throughout the study. This was not surprising, as dropout is a known challenge in antipsychotic intervention studies [
Among the design limitations, we note that we did not include a placebo control group or an unmedicated group. This ruled out the investigation and comparison of natural fluctuations in insight, other symptoms, and their interaction. However, antipsychotic drug treatment is evidence-based and highly recommended in treatment guidelines [
Insight was only measured by item G12 from the PANSS, which is limited to evaluation by a clinician on a seven-point scale. Other more elaborate assessments of insight may have detected more detailed differential effects among the drugs. However, G12 correlates highly with more amplified assessments [