Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 29, 2026 1 hour, 8 minutes ago
Medical News: A new review has suggested that the antidepressant drug mirtazapine could become a promising treatment option for people struggling with Long COVID, particularly those suffering from persistent fatigue, brain fog, poor sleep, anxiety and depression. The review was conducted by Dr. Marcos Altable from the Department of Neurology, Neuroceuta (Virgen de África Clinic), Ceuta, Spain, and highlights how the drug's unique effects on serotonin, inflammation and brain repair could potentially target several of the biological problems believed to drive Long COVID.
Researchers suggest the antidepressant mirtazapine could potentially target multiple biological mechanisms responsible
for Long COVID symptom
Why Serotonin Matters in Long COVID
Long COVID continues to affect millions worldwide, with symptoms lasting for months or even years after the initial infection. Researchers increasingly believe that one of the major biological changes involves a sharp disruption of the body's serotonin system.
Serotonin is far more than a "feel-good" chemical. It helps regulate sleep, memory, mood, energy levels, pain perception and communication between the brain and immune system. The review explains that SARS-CoV-2 infection may lower serotonin through several pathways. These include reduced absorption of tryptophan—the amino acid needed to produce serotonin—gut microbiome disturbances, chronic inflammation, increased breakdown of serotonin, platelet dysfunction and diversion of tryptophan into inflammatory metabolic pathways instead of serotonin production.
The combined effect may help explain why so many Long COVID patients experience exhaustion, poor concentration, insomnia and emotional disturbances.
Why Mirtazapine Is Different
Unlike conventional antidepressants that mainly prevent serotonin reabsorption, mirtazapine works by blocking specific serotonin receptors while increasing the release of both serotonin and norepinephrine. According to the review, this distinctive mechanism may offer broader benefits for Long COVID patients.
The drug may improve deep restorative sleep, enhance brain plasticity, reduce harmful neuroinflammation and help normalize stress hormone activity.
Researchers also note that increased norepinephrine activity could improve motivation and reduce persistent fatigue.
This
Medical News report highlights that the review proposes mirtazapine as a multi-target therapy capable of addressing several biological abnormalities simultaneously rather than focusing on only one symptom.
Potential Benefits Beyond Mood
One of the review's most interesting findings is that mirtazapine could help repair brain function by increasing brain-derived neurotrophic factor (BDNF), a protein essential for forming new neural connections and repairing damaged brain circuits.
The review also discusses evidence sugg
esting that mirtazapine reduces activation of microglia, the immune cells of the brain that become overactive during chronic inflammation. Lowering this inflammatory activity may help reduce production of inflammatory molecules such as IL-6 and TNF-alpha that have repeatedly been linked to Long COVID.
Improved sleep represents another important advantage. Deep sleep allows the brain and body to recover, and mirtazapine has previously been shown to shorten the time needed to fall asleep while increasing restorative sleep stages. Better sleep may in turn improve daytime energy, memory and overall quality of life.
The review further suggests that by reducing inflammation and supporting healthier neurotransmitter function, the drug may also lessen anxiety, depression and the cognitive difficulties commonly described as brain fog.
More Research Is Still Needed
Despite the encouraging biological evidence, the author emphasizes that no randomized clinical trials have yet tested mirtazapine specifically in Long COVID patients. Important questions remain regarding the most effective dose, treatment duration, long-term safety and which groups of patients are most likely to benefit.
Future studies should evaluate improvements in fatigue, cognition, sleep quality, inflammatory markers and quality of life while carefully monitoring side effects such as drowsiness and weight gain.
Conclusion
Although the evidence remains preliminary, this comprehensive review presents a compelling scientific case that mirtazapine deserves serious investigation as a potential Long COVID therapy. By simultaneously targeting serotonin dysfunction, chronic inflammation, impaired neuroplasticity and sleep disturbances, the medication could address several of the condition's underlying biological mechanisms rather than simply masking individual symptoms. Carefully designed clinical trials will now be essential to determine whether these promising theoretical benefits can translate into meaningful improvements for patients living with this debilitating condition.
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.preprints.org/manuscript/202502.0885
For the latest on Long COVID, keep on logging to Thailand
Medical News.
Read Also:
https://www.thailandmedical.news/articles/long-covid
https://www.thailandmedical.news/news/the-antidepressant-drug-mirtazapine-may-help-the-brain-clear-toxic-waste
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