Patients with major depressive disorder (MDD) often do not sufficiently benefit from treatment. That is, around 50% of patients with MDD do not respond to treatment and 20-30% only achieve partial remission. Future-oriented negative mental imagery (e.g., mental images of suicide or own funeral) is likely an important maintaining factor of depression. Initial studies in depression indicate that targeting mental imagery with ‘imagery rescripting’ could be a promising therapeutic technique to reduce depressive symptomatology by targeting these images directly that elicits strong affects/emotions and depressive symptomatology.

The PROFIT multicenter pilot RCT has a mixed factorial design with three time points: baseline, post-treatment, and follow-up of 3 months. This pilot study will test 50 patients with current MDD who have a future-oriented mental negative image. All patients in this pilot study receive ‘Treatment As Usual’, which involves a combination of pharmacological and psychological interventions. Half of the patients will also receive 3-5 sessions of future-oriented imagery rescripting (ImRes). In each ImRes session, patients identify an image of an autobiographic catastrophic future event. For example: catastrophic images of future suicide or the loss of work or a loved one. They are subsequently asked to “rescript” this image into a more benign one.

The primary aim of this pilot study is to determine the acceptability of the intervention. The secondary aims are to elucidate factors that may facilitate or hinder the feasibility of the follow-up RCT (e.g., recruitment process). And to estimate the variance of the effect on reduction of depressive symptomatology, which informs the sample size calculation of the follow-up RCT.

PROFIT is coordinated by the department of psychiatry of the Amsterdam UMC. This study is actively enrolling participants as of June 2024. PROFIT is supported by The Netherlands Organisation for Health Research and Development (ZonMW; grant number 10390052210057).