Modulation of the inflammatory response exerts beneficial effects on anger in treatment-resistant bipolar depression

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: Anger can worsen a person's emotions and increase the severity of an individual's mood state, notably depression. The State-Trait Anger Expression Inventory (STAXI) assessment tool is useful for assessing the experience, expression, and control of anger in normal individuals, and in evaluating anger experienced by patients with a variety of psychological and medical disorders. Since its creation, STAXI has been utilized in various studies involving substance abuse and major depressive disorder; however, anger has never been studied systematically in bipolar depression. Scientific evidence supports the hypothesis that immune system activation, reflected in its inflammatory response, contributes to the pathophysiology and phenomenology of bipolar disorder. However, there is limited research showing how the treatment of bipolar disorder is enhanced with an anti-inflammatory agent and how it affects anger, which prompted this investigation. The current clinical study tested the hypothesis that co-administration of a specific anti-inflammatory agent, Celecoxib, along with Escitalopram, a selective serotonin reuptake inhibitor, would be beneficial in patients with treatment resistant bipolar depression. In comparison to patients receiving Escitalopram monotherapy, it was hypothesized that the combination therapy would lead to an augmented response in alleviating bipolar depression. In addition, the combination therapy would result in a greater percentage of responders and remitters. It also was hypothesized that the combination therapy would reduce anger symptoms as assessed by STAXI from beginning to end of treatment. : In this double-blind, two-arm, placebo-controlled study, 65 consenting patients diagnosed with treatment resistant bipolar depression were randomized to receive either Escitalopram (10 mg twice/day) + Celecoxib (200 mg twice/day), or Escitalopram + placebo (twice/day). There were 47 completers: 27 in the Celecoxib, and 20 in the Placebo arm. The 17-item Hamilton Depression Rating Scale was used to assess response to treatment, with a 50% reduction from baseline indicating treatment response and a score < 7 indicating remission. The Beck Depression Index also was used as a self-report measure of depression. Levels of state and trait anger were assessed using the 57-item STAXI scale. Measures of depression, anger and perceived stress were collected at baseline and at week 8 of treatment. : A multiple regression analysis of baseline data indicated that the Hamilton depression score was significantly related to the feelings subscale of the state STAXI. However, the baseline Beck score was found to be predicted by perceived stress. To test treatment effects, an analysis of covariance revealed that the week 8 Hamilton depression score was significantly lower for patients receiving the combination therapy, controlling for baseline differences. The week 8 Beck score also was lower for those in the combination therapy group, but was not statistically significant. In comparison to the monotherapy group, those receiving the combination therapy showed a statistically higher proportion of responders and remitters. Significant differences in state or trait anger subscales were found only responders to the CBX add-on arm at week 8. : Limitations of the study include small sample size and short period of treatment. : An analysis of baseline data suggest that depression is associated with state feelings of anger and perceived stress. In comparison to receiving Escitalopram alone, the combination therapy was more effective in lowering Hamilton depression scores and was associated with greater proportions of responders and remitters. Anti-inflammatory combination therapy reduced state and trait anger by the end of treatment.

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