Mononitrate Isosorbide as an Adjunctive Therapy in Schizophrenia: A Randomized Controlled Crossover Trial

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Schizophrenia is a disabling mental disorder with limited treatment responses.
• The glutamate/nitric oxide pathway is implicated in schizophrenia symptoms.
• Investigating novel therapeutic targets is crucial for improving patient outcomes.

Purpose of the Study:

• To evaluate the efficacy of isosorbide mononitrate (ISMN) as an adjunctive therapy for schizophrenia.
• To assess the impact of ISMN on positive and negative symptoms, cognitive function, and overall functioning.

Main Methods:

• A 2-month randomized, double-blind, placebo-controlled crossover trial involving 24 schizophrenia patients.
• Participants received ISMN 50 mg/day for one month, followed by placebo for one month.
• Symptom assessment included the Positive and Negative Syndrome Scale (PANSS) and cognitive testing; brain activation was measured using arterial spin labeling.

Main Results:

• Significant improvements were observed in total, general, and positive PANSS scores, Global Assessment of Functioning, and Clinical Global Impression during ISMN treatment compared to placebo.
• No significant differences were found in cognitive function (MATRICS Cognitive Consensual Battery) or negative PANSS subscale scores.
• Neuroimaging revealed reduced thalamic activity in patients with severe psychopathology during ISMN treatment.

Conclusions:

• Adjunctive treatment with ISMN 50 mg/day for 4 weeks demonstrated significant benefits for schizophrenia patients with persistent symptoms.
• ISMN enhanced antipsychotic treatment efficacy, particularly for positive symptoms and functional outcomes.
• Further research may explore ISMN's role in specific patient subgroups and its neurobiological underpinnings.