Question from a Member who is a psychiatrist in Greece. Asked during the coronavirus pandemic in April 2020:
I would like to get informed about reliable studies on the way psychiatric drugs affect the immune system. Here in Greece, we are trying to help colleagues treating COVID-infected patients who are on psychiatric drugs with relevant information.
The immune system is affected in several mental disorders and psychotropic medications affect the immune system. In fact, there is an entire field called psychoneuroimmunology or immunopsychiatry, which studies the mutual interactions between the brain and immune systems (Lancet Psychiatry 2015; Pariante, 2015).
On this page, I will focus on the interaction between psychotropic medications and the immune system.
Immune system abnormalities are predictors of response to treatment
A meta-analysis of studies found that patients with major depressive disorder whose depression responded to treatments antidepressant medications had lower serum interleukin 8 levels prior to treatment than those who did not respond to antidepressant treatment (Liu et al., 2020).
Regarding treatment, there is data supporting both of the following:
– Anti-inflammatory medications as potential future treatments for some patients with depressive disorders
– Antidepressants acting to optimize immune responses in patients with depressive disorders
Let’s look at both of these, one by one.
Anti-inflammatory medications as treatments for depressive disorders?
Due to considerable evidence of inflammation in patients with depressive disorders, it makes sense to research whether anti-inflammatory treatments can lead to an improvement in depression. A meta-analysis of clinical trials found that many different anti-inflammatory treatments have been found to be effective in some patients with depressive disorders (Köhler-Forsberg et al., 2019). The main ones among these are non-steroidal anti-inflammatory drugs (NSAIDs), cytokine inhibitors, and statins (Köhler-Forsberg et al., 2019). There is also some limited research suggesting the efficacy of minocycline, pioglitazone, and glucocorticoids (Köhler-Forsberg et al., 2019).
The cytokine inhibitors most studied for this purpose are anti-TNF-α agents including adalimumab, etanercept, infliximab, and tocilizumab (Kappelmann et al., 2018).
Effect of antidepressants on the immune system
In general, antidepressant medications tend to reduce the overactive inflammatory processes that are found in many patients with depressive disorders (Eyre et al., 2016; Hiles et al., 2012).
Some inflammatory markers decrease after antidepressant medication irrespective of whether or not the depression responds to treatment. For example, antidepressant medications are associated with a decrease in levels of interleukin 6 irrespective of whether or not the patients responded (Stawbridge et al., 2015).
Other inflammatory markers improve only in patients whose depression improves after antidepressant treatment. For example, in a meta-analysis of studies, treatment with antidepressant medications was associated with decreased levels of tumor necrosis factor–alpha (TNF-α), but only in those who responded to the treatment (Liu et al., 2020; Stawbridge et al., 2015).
Antidepressant medications and viral infections
Persons with mood disorders may be at higher risk of herpes zoster infection (Schmidt et al., 2018; Irwin et al., 2011) and of greater severity of the disease (Irwin et al., 2011).
Also, adolescents and adults with major depressive disorder, or even remitted major depressive disorder, have been found to be less likely to have anti-measles immunity despite having received childhood measles vaccination (Ford et al., 2019).
After receiving varicella-zoster vaccination, untreated patients with major depressive disorder had lower levels of cell-mediated immunity than persons who were not depressed and patients with major depressive disorder who had been treated with antidepressant medications (Irwin et al., 2013). Interestingly, this benefit of antidepressant medications was found whether or not the patients responded to the medication (Irwin et al., 2013). So, this study suggested that untreated major depressive disorder is associated with lower efficacy of varicella-zoster vaccination and that antidepressant medications normalized the response to the vaccine.
In another study, treatment with citalopram was found to reduce the susceptibility of immune cells to infection with HIV (Greeson et al., 2016).
Also, N-desmethylclozapine and fluoxetine have been found to inhibit the life cycle of the dengue virus (Medigeshi et al., 2016)
Effects of lithium on immune function
It has been suggested that lithium may have immunostimulating effects (Maddu and Raghavendra, 2015; Lieb, 2004, 2007).
In therapeutic doses, lithium may(Maddu and Raghavendra, 2015):
– Cause leucocytosis
– Increase the synthesis of antibodies by B-lymphocytes.[Optional to read: At higher than usual therapeutic doses, it may also stimulate the proliferation of T-lymphocytes, increase the phagocytic activity of macrophages, increase interleukin-2 production, and increase the activity of natural killer cells (Maddu and Raghavendra, 2015):
There are many published studies suggesting possible antiviral effects of lithium. For example, in vitro studies suggest that lithium can improve the immune response in patients with AIDS (Maddu and Raghavendra, 2015). Similarly, it has been suggested that lithium may inhibit the herpes simplex virus (Amsterdam et al., 1990, 1996). Lithium has also been found to improve the cell response to a coronavirus—avian coronavirus infectious bronchitis virus, which affects poultry (Harrison et al., 2007).
My point from this section is not at all that lithium should be used as an antiviral medication but that we don’t need to be concerned that lithium may impair the body’s response to coronavirus infection.
1. The brain and the immune system have complex mutual interactions. Several immune system abnormalities and evidence of systemic inflammation have been found in many patients with mood disorders.
2. Antidepressant medications seem to have a beneficial effect by tending to correct the immune system abnormalities present in depressive disorders.
3. Lithium also has immunostimulatory effects. Many in vitro and animal studies have suggested possible antiviral activity for lithium.
4. As of April 2020, standard psychotropic medications are not contraindicated in persons with viral infections.
5. In fact, In patients at risk of viral infections, effectively treating major depressive disorder may help to optimize recovery from the infection.
Next, please see these articles:
Optional to read
While most data support the Bottom Line discussed above, there is some data suggesting suppression of the immune system by psychotropic medications:
1. Second-generation antipsychotics were found to tone down the immune response in immune cells in healthy volunteers (Stapel et al., 2018).
2. Antidepressant medications inhibit an enzyme called sphingomyelinase that is involved in white blood cell function. In a study in mice that had been treated with amitriptyline, there was a significant decrease in sphingomyelinase activity (Johnson et al., 2016). When these mice were subjected to scald injury, those who had been treated with amitriptyline had greater reductions in immune response, e.g., lymphocyte precursors in the bone marrow and thymus, mature leukocytes in the spleen (Johnson et al., 2016). The authors hypothesized that “those taking antidepressants may be at a higher risk for complications following burn injury”.
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