||BACKGROUND: In patients with depression, as well as in patients with schizophrenia, both mood and working memory performance are often impaired. Both issues can only be addressed and improved with medication to some extent. OBJECTIVE: This study investigates the mood and the working memory performance in patients with depression or schizophrenia and whether acupuncture can improve these. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A pragmatic clinical trial design was used. The study was conducted in a psychiatric clinic. Fifty patients with depression and 50 with schizophrenia were randomly divided into an experimental and a waiting-list group. Additionally, 25 healthy control participants were included. Twelve weeks of individualized acupuncture treatment was used as the clinical intervention. MAIN OUTCOME MEASURES: All patients were tested before (T1) and after (T2) acupuncture treatment on a mood scale (Beck Depression Inventory-II, BDI-II), a simple working memory task (digit span), and a complex working memory task (letter-number sequencing); the healthy controls were tested at T1 only. RESULTS: Patients with depression scored worse than the others on the BDI-II, and patients with schizophrenia scored worse than the healthy controls. On the digit span, patients with schizophrenia did not differ from healthy controls whereas they scored worse of all on the letter-number sequencing. With respect to the acupuncture findings, first, the present study showed that the use of acupuncture to treat patients with schizophrenia was both practical and safe. Moreover, acupuncture had a positive effect on the BDI-II for the depression group, but acupuncture had no effect on the digit span and on the letter-number sequencing performance for the two clinical groups. CONCLUSION: The clinical improvement in patients with depression after acupuncture treatment was not accompanied by any significant change in a simple working memory task or in a more complex working memory task; the same was true for the patients with schizophrenia. TRIAL REGISTRATION: Dutch Trial Register NTR3132.