Citalopram Augmentation for Subsyndromal Symptoms of Depression in Middle-Aged and Older Outpatients With Schizophrenia and Schizoaffective Disorder: A Randomized Controlled Trial

Background: Subsyndromal symptoms of depression (SSD) in older outpatients with schizophrenia are common and clinically important. While many physicians prescribe antidepressants to patients with schizophrenia and schizoaffective disorder who have SSD, evidence for their effectiveness and safety has been meager. We describe a randomized placebo-controlled trial of citalopram in 198 patients.

Method: Participants in this 2-site study, conducted from September 1, 2001, to August 31, 2007, were men and women with DSM-IV schizophrenia or schizoaffective disorder who were 40 years of age or older and who met study criteria for SSD. Patients were randomly assigned to flexible-dose treatment with citalopram or placebo augmentation of their current antipsychotic medication. Analysis of covariance was used to compare improvement in scores on the Hamilton Rating Scale for Depression and Calgary Depression Rating Scale between treatment groups; secondary efficacy analyses compared improvement in several other dimensions of schizophrenia.

Results: Augmentation with citalopram was significantly more effective than with placebo in improving depressive (p=.002) and negative (p=.049) symptoms, mental functioning (p=.000), and quality of life (p=.046). There were no significant differences between citalopram and placebo in suicidal ideation, positive symptoms, cognition, general medical health, physical functioning, or symptoms of movement disorders. No adverse events were more frequent in participants receiving citalopram than in those receiving placebo, and only 4 participants from each treatment group terminated early because of side effects.

Conclusion: Subsyndromal symptoms of depression in middle aged and older patients with schizophrenia responded to treatment with citalopram with lessening of depressive symptoms and improved functioning and quality of life. It may be important for clinicians to identify and treat SSD in middle-aged and older patients with chronic schizophrenia.

Trial Registration: clinicaltrials.gov Identifier: NCT00047450