Adjunctive Raloxifene and Isradipine Improve Cognitive Functioning in Patients With Schizophrenia: A Pilot Study

Cognitive impairment is the most important feature of schizophrenia leading to severe functional disability. To identify pathways that improve pathophysiological neurocognition in schizophrenia is a current challenge for the development of goal-directed clinical interventions. In the present study, we investigated the effects of raloxifene (a selective estrogen modulator) and isradipine (a voltage-gated L-type calcium channel blocker) on cognitive deficits in patients with schizophrenia.

We designed a double-blind, randomized, parallel, placebo-controlled trial. We randomized 60 patients with schizophrenia into 3 groups including isradipine 5 mg, raloxifine 60 mg, and placebo for 6 consequent weeks, all in the same shape capsules, 2 times a day, along with treatment as usual. The initial and final results of blood tests, electrocardiograms, and cognitive tests in specific domains, such as attention, processing speed, executive function, and verbal memory were evaluated.

Our findings revealed a remarkable association between adjunctive raloxifene treatment and the alleviation of verbal memory deficits. Isradipine treatment significantly improved the verbal memory and attention dysfunction in some variables of the Stroop test, compared with the placebo. However, no effect was observed in processing speed and executive function deficits.

To the best of our knowledge, this study provides the first evidence that isradipine is a novel therapy option improving verbal memory and attention, both related to its activity in the hippocampus and the cerebellum. Further investigations are necessary to elucidate the mechanisms of action for both drugs in schizophrenia.