Research points to a selection of treatment modalities that have proven to be effective countermeasures against the effects of Sickness Syndrome depression, particularly for patients suffering from major depression. Currently no nutritional products or pharmaceuticals are marketed for the purpose of treating Sickness Syndrome depression, however there are specific strategies to aid the practitioner in reducing the inflammatory load on the brain that is causing depression in Sickness Syndrome depression patients.

Enhance Adrenal Function - Administering specific herbal, pharmaceutical and/or nutraceutical compounds regulates cortisol levels, maintains healthy adrenal gland activity, and increases alpha brain wave activity. The objective being to normalize the hypothalamic-pituitary-adrenal axis, thereby encouraging a healthy physical and psychological response to stress and supporting the health of the adrenal glands that are responsible for secreting normal levels of cortisol.

Regulate Insulin and Blood Sugar Levels - Administering specific herbal, pharmaceutical and/or nutraceutical compounds that normalize blood sugar levels and increase insulin sensitivity, ultimately regulating insulin and blood sugar levels.

Control Vagus Nerve Responses - The vagus nerve plays a central role in the pathophysiology of Sickness Syndrome depression, with research demonstrating that direct electrical stimulation of the vagus nerve increases expression of inflammatory cytokines in the brain. In fact, undergoing a vagotomy prevents Sickness Syndrome depression triggered by inflammatory cytokines.

Another component involved in the treatment of Sickness Syndrome depression is regulation of vagal output through the use of scientifically supported nutraceuticals, herbals, and/or pharmaceutical agents that regulate Vagal output, including but not limited to those compounds that modulate serotonin levels. Other lifestyle activities that are known to regulate vagal output, such as yoga exercises can also be employed as part of a larger treatment protocol.

Reduce Production of Series 2 Prostaglandins - Since the brain responds to inflammation associated with sickness behavior or Sickness Syndrome depression, one important process in the management of inflammation in the body is through modulation of the inflammatory cascade that leads to the production of Series 1, Series 2, and Series 3 prostaglandins. The Series 2 prostaglandins are pro-inflammatory while the Series 1 and Series 3 prostaglandins are anti-inflammatory.

Stress hormones and high insulin levels inhibit the production of Series 3 and Series 1 anti-inflammatory prostaglandins and favor the production of the pro-inflammatory series 2 prostaglandins. Specifically, stress hormones (including corticosteroids and catecholamines) that are released during the HPA response inhibit Delta 6 Desaturase activity —an enzyme required for the metabolic conversion of omega 3 fatty acids to the anti-inflammatory Series 3 prostaglandins that help reduce production of pro-inflammatory brain cytokines causing Sickness Syndrome depression.

Another step then, in the management of Sickness Syndrome depression, involves reducing the production of Series 2 Prostaglandins through the use of herbal, nutraceutical and/or pharmaceutical compounds that alter signal messaging substances involved in pro-inflammatory series 3 prostaglandin production including, but not limited to, cyclooxegenase inhibitors, lipoxegenase inhibitors, precursors to prostaglandin 1 and prostaglandin 3 production (e.g. Eicosapentaenoic acid and omega-3 fatty acids) and inhibitors of arachidonic acid and leukotriene synthesis.

Selectively Inhibit NF Kappa B activation - NF Kappa B (NFkB) is a ubiquitous family of transcription factors that initiate inflammation. Inhibiting of this family of transcription factors reduces the production of downstream pro-inflammatory prostaglandins and leukotrienes. However, because NFkB is essential to immune function, it is imperative to target only its pathologic manifestations. By precise inhibition of NFkB activation through the use of herbal and/or nutraceutical compounds known to weakly inhibit NFkB activation, inflammation will be reduced without compromising the essential role that NFkB plays in immune system function.

Utilize Antioxidants and Detoxification Therapies - Free radicals also stimulate NFkB activation to initiate the inflammatory response. As such, administering appropriate antioxidants that neutralize free radicals is another useful step in the method of addressing Sickness Syndrome depression.

Additionally, reducing toxins reduces the reactive oxygen species load which in turn causes pathogenic NFkB activity to selectively diminish. And, when toxins translocate across a weakened mucosal barrier into the blood stream, they stimulate the production of inflammatory cytokines via the HPA axis and increase glutaminase activity which lowers glutamine and glutathione levels. Glutathione levels contribute significantly to the human liver detoxification system, while glutamine is a primary source of fuel for intestinal enterocytes that help to maintain the integrity of another important detoxification system, the gastrointestinal tract.

Increase Levels Of Activated Estrogen Receptors - Activated estrogen receptors can decrease the production of pro-inflammatory cytokines. Speccally, activated estrogen receptors reduce levels of tumor necrosis factor alpha (TNF alpha) that bind to receptor cites on most cells in the body and trigger a chain of events that results in the genetic expression of pro-inflammatory cytokines that lead to Sickness Syndrome depression.  In addition, activated estrogen receptors keep NFkB bound to inhibitor Kappa B that prevents it from triggering the production of pro-inflammatory cytokines in the nucleus of the cell.

Individuals deficient in estrogen would benefit from administration of specific levels of herbal, nutraceutical and/or bio-identical hormone compounds that bind to and activate estrogen receptors, thereby increasing levels of activated estrogen receptors.

Treat Existing Infections - Sickness Syndrome depression is considered an adaptive response that permits survival following exposure to a variety of infectious organisms. This is an innate immune response designed to conserve energy, and limit the spread of infection to others. However, since infection also leads to the production of inflammatory cytokines which can increase the symptoms of Sickness Syndrome depression, a necessary step is to treat infection in the body when necessary with the use of select antimicrobial and/or antiviral herbal, nutraceutical and/or pharmaceutical compounds.

Many herbal and nutraceutical ingredients serve multiple purposes including offering antioxidant activity (e.g. one ingredient, like green tea, is a weak inhibitor of NFkB, and is an antioxidant and it increases alpha brain wave activity). As such, some components of nutraceutical formulations for Sickness Syndrome depression can address multiple steps in the treatment protocol.

Since the non-specific symptoms of Sickness Syndrome depression represent a facet of the inflammatory process, it becomes imperative to lower the levels of locally produced inflammatory brain cytokines and peripheral pro-inflammatory cytokines that cause the symptoms of sickness behavior. These symptoms are a major source of suffering for patients, often more so than the diseased organ itself.