Prednisolone add-on in early phase schizophrenia: A randomized, double-blind, placebo-controlled pilot study

New pharmacological treatment strategies are urgently needed for schizophrenia since current antipsychotic medications have limitations related to efficacy, tolerability, and disease course modification. Different lines of evidence converge on aberrant activity of the immune system, but translation into new treatment is still pending. Studies investigating the antipsychotic properties of less potent anti-inflammatory drugs have provided equivocal findings. A potent agent like prednisolone might be better suited for establishing proof-of-concept that dampening of inflammation may be beneficial in schizophrenia.

In this double-blind multicentre pilot study, 12 patients (aged 18-39) with schizophrenia maintained on stable antipsychotic regimens were randomized to prednisolone or placebo. Study medication was initiated with 40 mg/day and gradually tapered to zero over a period of 6 weeks. The primary outcome was difference in the Positive and Negative Syndrome Scale (PANSS) total score 6 weeks after baseline.

In patients randomized to prednisolone (N = 6), a clear trend towards more pronounced reduction of psychotic symptoms was observed compared to the placebo group (N = 6). Difference in symptom severity per the PANSS total score after 6 weeks of add-on treatment was 15·4 (SD = 8·5, p = 0·101). For the PANSS general score, we observed a statistically significant difference of 12·5 (SD = 4·6, p = 0·021) at week 6. Safety and tolerability were acceptable for the duration of prednisolone treatment.

These findings suggest beneficial effect of add-on prednisolone. However, this needs further replication in a larger sample for confirmation and to identify the mechanisms of action.