Arthritis drug boosts effectiveness of anti-depressant medication

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Giving severely depressed patients the arthritis drug celecoxib (Celebrex®) dramatically boosted the effectiveness of their anti-depressant medication, a study has found.

Psychiatrist Dr Angelos Halaris, a professor in the department of psychiatry and behavioural neurosciences of Loyola University Chicago Stritch School of Medicine, presented the study at the Fifth International Congress on Psychiatry and the Neurosciences in Athens, Greece.

The eight-week study enrolled bipolar adults, aged 18 to 65, who were in the depressive phase of their disease and had not benefitted from an antidepressant. (Bipolar disorder is marked by alternating periods of elation and depression, with depression typically lasting longer.) Patients were randomly assigned to receive the antidepressant escitalopram (Lexapro®) plus celecoxib or Lexapro plus a placebo.

The study found 78% of the patients in the celecoxib group experienced at least a 50% reduction in their depression scores, with 63% reporting their depression had gone away completely. By comparison, only 45% of the placebo group recorded a 50% or more reduction in depression, with only 10% reporting their depression had lifted completely.

It typically takes four to six weeks before an antidepressant begins working. In the Loyola study, patients who took celecoxib began seeing a benefit from their antidepressant within a week – 55 patients completed the study: 31 in the Lexapro plus celecoxib group and 24 in the Lexapro plus placebo group.

Previous studies have found that depression revs up the immune system, resulting in chronic inflammation. This inflammatory response affects the normal balance of chemical messengers in the brain called neurotransmitters. Inflammation hinders the function of antidepressants that are designed to restore normal chemical balance. By fighting inflammation, celecoxib appears to make antidepressants more effective, Halaris said.

Celecoxib is used to treat pain, redness, swelling and inflammation from arthritis. It also can manage acute pain and menstrual cramps. By itself, it does not treat depression.
The study’s findings support the hypothesis that inflammation plays a critical role in depression. Reducing inflammation with a drug such as celecoxib “reverses treatment resistance and enhances overall antidepressant response,” Halaris wrote in the study. “Such an intervention, if implemented relatively early in the course of the disease, may arrest the neuro-progressive course of bipolar disorder.”

Abstract
Background: A pro-inflammatory state in unipolar and bipolar disorder has been described in the literature. A few clinical studies have referred to the beneficial effects of add-on celecoxib, aCOX-2 inhibitor, for a short period of time to reverse treatment resistance in unipolar depression. Although many pharmacological treatments exist for bipolar depression, none have included the use of a COX-2 inhibitor as adjunctive treatment option. Our study aimed to assess the outcome of treatment resistant bipolar depression following combined treatment of escitalopram plus celecoxib. We treated bipolar depressed patients, not previously fully responsive to antidepressant monotherapy, with escitalopram in combination with the anti-inflammatory agent, celecoxib. The primary hypothesis was that combination treatment will result in augmented treatment responses and a greater number of remitters compared to escitalopram monotherapy. Additionally, it was hypothesized that there would be an earlier response (earlier decline in HAM-D scores) in the escitalopram + celecoxib group vs. escitalopram alone. A secondary hypothesis was that there would be a reduction in pro-inflammatory biomarkers at end of treatment in patients randomized to receive the combination treatment.
Methods: This was a 10-week, randomized, double-blind, two-arm, placebo-controlled study. The study included a screening visit, a 1-week washout phase, a 1-week placebo run-in phase and an 8-week flexible dose phase. In addition to quantifying and qualifying symptoms of depression, we also considered the degree and intensity of perceived stress using the Perceived Stress Scale (PSS) before and after treatment.
Results: When comparing HAM-D mean scores pre- and post-treatment in the control group (escitalopram + placebo) vs. the active group (escitalopram + celecoxib), there was a statistically significant reduction in mean scores in the active group (p = 0.005), but not in the control group (p = 0.145). When comparing MADRS mean scores pre- and post-treatment in the control group vs. the active group, there was a statistically significant reduction in mean scores in the active group (p <0.001), but not in the control group (p = 0.172). When comparing HAM-A mean scores pre- and post-treatment in the control group vs. the active group, there was a statistically significant reduction in mean scores in the active group (p = 0.047), but not in the control group (p = 0.756).
Discussion: Depressive symptoms, as measured by HAM-D and MADRS scales, when patients were treated with the combination escitalopram and celecoxib, improved with high statistical significance post treatment when compared to baseline, while those in the escitalopram group alone did not. Anxiety scores in the combination group also decreased post-treatment with statistical significance, while those in the escitalopram group alone did not. PSS scores decreased significantly in the combination group while those in the escitalopram group did not. We ruled out pain perception as a possible confounding factor. Reversal of treatment resistance depression by modulation of the inflammatory response may arrest neuro-progression of affective illness.

Authors
A Halaris

Loyola University Chicago Stritch School of Medicine material
ICGP-ICPN 2016 Abstract Book S13.4 pg38-39


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