Celecoxib, a selective COX-2 inhibitor, shows promise as an effective and safe adjunct treatment for major depression and mania, according to a new comprehensive systematic review.
The analysis also found celecoxib improved symptoms when used as a standalone antidepressant in patients with somatic disorders.
However, evidence for efficacy in bipolar depression remains unclear.
- Celecoxib at 400mg daily for 6 weeks improved symptoms in major depression and mania as add-on therapy.
- It was also effective as sole antidepressant treatment in depressed patients with somatic conditions.
- But results were inconclusive for bipolar depression due to limited quality data.
- The drug appears safe for short-term use up to 12 weeks at 400mg daily dose.
Source: Journal of Clinical Medicine 2023
Testing Celecoxib for Depression & Bipolar Mania
Depression and bipolar disorder are disabling mental illnesses affecting hundreds of millions of people worldwide.
While treatments exist, many patients fail to achieve remission with standard antidepressants and mood stabilizers.
This highlights the need for novel therapies, especially those targeting underlying disease mechanisms.
Inflammation is one such mechanism receiving increasing attention.
Markers of inflammation tend to be elevated in mood disorders.
Anti-inflammatory drugs like celecoxib may therefore hold promise as adjunctive treatments.
To comprehensively evaluate the potential of celecoxib, researchers conducted a systematic review of evidence from preclinical and clinical studies.
Their findings published in the Journal of Clinical Medicine offer new insights into the efficacy and safety of celecoxib for major depression, bipolar disorder, and comorbid somatic conditions.
Preclinical Evidence Supports Antidepressant Effects
First, authors analyzed 19 preclinical studies examining celecoxib in animal models.
All 17 studies using animal models of depression found celecoxib improved depressive-like behaviors.
It was also effective in combination with fluoxetine and bupropion.
The drug normalized elevated inflammatory markers like IL-1β, TNFα, and IFNγ in the brain.
Peripheral blood cytokine changes were less consistent.
Two studies further showed celecoxib with lithium abrogated mania-like behaviors induced by amphetamine.
It also reversed increases in frontal cortex IL-4 and serum IL-10.
No adverse effects occurred with varying administration routes and doses between 2-50 mg/kg/day.
The preclinical evidence thus demonstrates celecoxib’s antidepressant and anti-manic effects plus anti-inflammatory actions in animal models.
Major Depression: Adjunct Celecoxib Possibly Effective
Moving to human clinical trials, the authors identified 10 studies on celecoxib for major depression.
A meta-analysis of 4 high-quality RCTs found significant improvement with celecoxib 400mg daily for 6 weeks as an add-on therapy.
Studies used celecoxib alongside serotonin reuptake inhibitors (SSRIs) like sertraline and fluoxetine or norepinephrine reuptake inhibitor (NRI) reboxetine.
Celecoxib increased antidepressant response and depression remission rates.
One outlier study in treatment-resistant patients showed no benefits.
After exclusion, celecoxib augmentation had a large effect size of -1.12.
The drug was well-tolerated without serious adverse events.
Only IL-6 decreased significantly in one trial.
These results support celecoxib as a promising adjunct for major depression, but more research is needed in treatment resistance.
Bipolar Depression: Inconclusive due to Limited Quality Evidence
For bipolar depression, only 3 trials were found.
One high quality 10-week study showed greater improvement with celecoxib 400mg plus escitalopram versus placebo in treatment-resistant patients.
However, two other trials found no differences.
Given the limited evidence, no conclusions could be drawn about efficacy in bipolar depression.
Larger, high quality RCTs are warranted.
Bipolar Mania: Adjunct Celecoxib May Be Helpful
In contrast, 2 RCTs indicated celecoxib 400mg daily could improve mania symptoms as an add-on therapy.
It was used with sodium valproate or ECT.
The meta-analysis found a medium effect size of -0.82.
Adverse events did not differ from placebo.
The evidence suggests adjunctive celecoxib may benefit patients during manic episodes.
Further studies are still needed though to confirm efficacy.
Somatic Disorders: Clear Standalone Antidepressant Effect
Lastly, celecoxib used as sole antidepressant treatment consistently improved depressive symptoms in patients with somatic illnesses like cancer or brucellosis.
The large effect size of -1.35 supports its efficacy as monotherapy in this population.
Celecoxib’s Antidepressant Mechanisms (Anti-Inflammatory Effects)
Celecoxib’s mood enhancing effects are likely due in part to its anti-inflammatory COX-2 inhibitory activity.
By decreasing PGE2 and modulating cytokine balance, it may mitigate inflammation-induced depressive symptoms.
Preclinical studies support this.
However, clinical trials failed to confirm changes in most inflammatory markers like CRP, cytokines, and kynurenine metabolites.
Only single studies found reductions in IL-6 and TNF-alpha.
More research is needed to identify biomarkers and inflammatory phenotypes predictive of optimal treatment response.
Other mechanisms like serotonin system effects may also play a role.
Celecoxib didn’t alter antidepressant levels, ruling out pharmacokinetic interactions.
Should celecoxib be used to treat depression?
In summary, this comprehensive systematic review provides evidence that celecoxib exhibits antidepressant properties in major depression and somatic disorders, and antimanic effects in bipolar mania.
It appears safe and well-tolerated for short-term use.
Its efficacy in bipolar depression is uncertain.
Whether it could prevent recurrence or help treatment-resistant patients is unknown.
Optimal dosing hasn’t been defined. Predictive biomarkers need to be established.
Additional high quality randomized controlled trials (RCTs) addressing these gaps are warranted.
Longer term safety data would also be informative.
If future studies confirm its benefits, celecoxib could become a valuable new therapy for patients with mood disorders and somatic comorbidities.
- Paper: Celecoxib for Mood Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2023)
- Authors: Adam Gedek et al.