Adjunctive Antidepressant Therapy in Schizophrenia: Is It Beneficial?

Researchers investigated the efficacy of individual antidepressants in the treatment of depressive and negative symptoms associated with schizophrenia.

Approximately 25% of patients with schizophrenia experience depressive symptoms while 60% have at least one negative symptom. Patients with these symptoms not only suffer from functional impairment and a decreased quality of life, but also have an increased risk of suicide. Although the American Psychology Association recommends using antidepressants to treat both the depressive and negative symptoms associated with schizophrenia, other major guidelines and organizations do not offer this recommendation due to a lack of evidence for this use. Not only has treatment of these symptoms been challenging due to the uncertainty of which class of antidepressant is most effective, but also because it is also difficult to tell whether these medications actually increase the risk of psychosis, adverse events (AEs), and drop-out rates in schizophrenic patients.

A recent systematic review by Helfer et al evaluated the safety and efficacy of adjunctive antidepressant therapy in schizophrenic patients taking antipsychotic medications. A total of 3,608 participants from 82 randomized controlled trials were analyzed to compare antidepressant add-on therapy versus placebo or no intervention as a control group. Two primary outcomes were investigated: depressive symptoms and negative symptoms. Other outcomes studied were overall symptoms, positive symptoms, quality of life, adverse events, exacerbation of psychosis, responder rates, and AEs. Subgroup analysis of the primary outcomes was completed to determine the efficacy of antidepressants in specific groups of patients.

Results from the study found adjunctive antidepressants to be more effective than placebo or no intervention in treating depressive, negative, positive, and overall symptoms associated with schizophrenia. In the pooled analysis, it was found that use of antidepressants produced only a small reduction in these symptoms. However, a larger reduction in symptoms was seen in the subgroup analysis when only patients with more pronounced depressive or negative symptoms were included. This analysis found patients with more predominate negative or depressive symptoms to have larger reductions in these symptoms when treated with antidepressants. Data also showed an increase in quality of life and responder rate in the adjunctive antidepressant therapy group compared to the control group. This efficacy data is shown in Table 1.

The authors also investigated the efficacy of individual antidepressants in the treatment of depressive and negative symptoms associated with schizophrenia. The results indicated that monoamine oxidase inhibitors (MAOIs), trazodone, duloxetine, sertraline, and amitriptyline were more effective than no intervention at treating depressive symptoms. For patients with negative symptoms, selective serotonin reuptake inhibitors (SSRIs), tetracyclic antidepressants (TeCAs), selegiline, duloxetine, citalopram, fluvoxamine, and mirtazapine were found to be more efficacious compared to no therapy. The authors noted that because these results were obtained from small studies, it is difficult to determine the true efficacy of individual medications or classes. They did conclude, however, that they believe mirtazapine and SSRIs have the most potential at successfully treating negative and depressive symptoms in schizophrenic patients. The results of individual antidepressants with statistically significant data are summarized in Table 2.