High Baseline Levels Of C-Reactive Protein Predict Better Response To Lurasidone in Bipolar Depression
In a study presented at the 2017 meeting of the International Society for Affective Disorders, Charlies L. Raison and colleagues examined whether baseline levels of the inflammatory marker C-reactive protein (CRP) affected antidepressant response to the antipsychotic drug lurasidone in bipolar depression. The participants were divided into three double-blind groups: one received 20–60mg/day of lurasidone, another received 80–120 mg/day of lurasidone, and the third received placebo over a period of six weeks. The effect was dramatic—in people with CRP levels above 5 mg/L at the beginning of the study, lurasidone (at either dosage level) had a very large effect size (d=0.85), while in people with baseline CRP levels below 5 mg/L the effect size was smaller (d=0.35).
Interestingly, 118 of the participants (24.5%) had CRP levels above 5mg/L at baseline, indicating a substantial amount of inflammation was present in a quarter of the bipolar depressed patients. Higher levels of CRP at baseline were correlated with better improvement on specific items on the Montgomery–Åsberg Depression Rating Scale (MADRS): “lassitude” (or lack of energy), “apparent sadness,” “reported sadness,” and “pessimistic thoughts.” Raison and colleagues concluded: “These findings suggest that the efficacy of lurasidone in patients with bipolar depression may in part be linked to the inflammatory status of patients prior to treatment. If confirmed in prospective investigations, [the results of a wide-range CRP assay] may prove useful as a predictive biomarker that could help optimize the use of lurasidone for the treatment of patients with bipolar depression.”
Editor’s Note: In many instances, high levels of CRP predict a poor response to treatment (such as to selective serotonin reuptake inhibitor antidepressants (SSRIs) in unipolar depression), so these findings are of considerable interest. They also suggest the untested possibility that lurasidone has anti-inflammatory effects, as those with high levels of inflammation at baseline often respond better to drugs with direct anti-inflammatory effects such as celecoxib (Celebrex) or the antioxidant N-acetylcysteine (NAC).
Vitamin D3 Improves Depression in Older Adults
Researcher Negin Masoudi Alavi and colleagues reported in the journal Clinical Nutrition in 2018 that compared to placebo, 50,000 IU of vitamin D3 taken weekly for eight weeks improved depression in depressed patients over the age of 60.
Although the literature about vitamin D3’s effects on depression are mixed, a 2014 meta-analysis by Simon Spedding in the journal Nutrients found that in studies of vitamin D-deficient depressed participants whose vitamin D levels were restored to normal levels by the end of the study, vitamin D significantly improved depression. (Spedding attributed earlier mixed results to studies that did not clearly correct a vitamin D deficiency.) A 2013 study by Nayereh Khoraminya and colleagues in the Australian and New Zealand Journal of Psychiatry suggested that a 1500 IU dose of vitamin D3 combined with the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine improved depression more than fluoxetine plus placebo in depressed patients who were not necessarily deficient in vitamin D. Another study by Jacqueline A. Pettersen in the journal Experimental Gerontology found that in healthy adults, 4,000 IU of vitamin D3 improved cognitive functioning (namely visual memory) more than 400 IU.
Editor’s Note: Given these promising studies, the safety of D3, and fact that psychiatric patients are often deficient in vitamin D3, taking vitamin D3 supplements to improve depression might be worth trying.
