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. 2025 Jul 10:48:101047.
doi: 10.1016/j.bbih.2025.101047. eCollection 2025 Oct.

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

Affiliations

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

Gunnhild E Hoprekstad et al. Brain Behav Immun Health. .

Abstract

Background: 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.

Methods: 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.

Outcomes: 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.

Interpretation: 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.

Keywords: Inflammation; PANSS general; PANSS total; Prednisolone; Psychosis; RCT; Schizophrenia; treatment.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gunnhild Hoprekstad and Erik Johnsen reports financial support was provided by Western Norway Regional Health Authority. Iris E. C. Sommer reports a relationship with Gabather that includes: consulting or advisory. Iris E. C. Sommer reports a relationship with Otsuka that includes: consulting or advisory. Iris E. C. Sommer reports a relationship with 10.13039/501100013327Lundbeck that includes: funding grants. Iris E. C. Sommer reports a relationship with Janssen that includes: funding grants. Petros Drosos reports a relationship with Western Norway Regional Health Authority that includes: funding grants. Rune A. Kroken reports a relationship with Western Norway Regional Health Authority that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Dosing scheme of study medication (prednisolone).
Fig. 2
Fig. 2
CONSORT flow diagram.
Fig. 3
Fig. 3
PANSS total score in the prednisolone group versus the placebo group (primary outcome) Figure legend. The vertical, dotted green lines indicate the start and end of prednisolone or placebo treatment.
Fig. 4
Fig. 4
The courses of the individual PANSS scores during the year of follow-up.
Fig. 5
Fig. 5
PANSS subscales (positive, negative, general) and CDSS for the prednisolone and placebo groups.

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