How TCM Minimizes Antidepressants Side Effects – Depression and Chinese Medicine

In this article, we will be sharing about depression and Chinese medicine. One of the significant advantages of TCM is its potential for fewer side effects compared to conventional antidepressants.

Many patients taking standard medications, such as selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (Prozac) or sertraline (Zoloft), often experience adverse antidepressants side effects like nausea, weight gain, fatigue, and sexual dysfunction.

Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), often take as much as 8 weeks to reach their maximum effectiveness. 

In individuals with depression, certain proteins called G-proteins tend to cluster in specific areas of brain cell membranes known as lipid rafts. These rafts are rich in cholesterol and can inhibit the G-proteins’ ability to function properly, particularly affecting their interaction with a molecule called cyclic AMP (cAMP), which is crucial for signaling pathways related to mood regulation.

When SSRIs are administered, they also accumulate in these lipid rafts. As SSRIs accumulate up to a certain point, they end up moving the G-proteins out of the rafts, allowing them to access areas where they can function more effectively. This process contributes to the delayed therapeutic effects of the medication.

In a clinical trial involving 60 patients with mild to moderate depression, participants were randomly divided into two groups. One group received Xiaoyaosan (a formula containing Dang Gui, Chai Hu, Bai Shao and Gan Cao), while the other group was treated with a standard antidepressant. The results indicated that those treated with Xiaoyaosan experienced significant improvement in clinical symptoms within 6 weeks, with most patients returning to normal functioning. 

Moreover, Xiaoyaosan was noted to enhance the effects of sertraline (an SSRI), suggesting that it not only works quickly but can also complement traditional antidepressant therapy effectively without adverse reactions. 

While SSRIs accumulate in lipid rafts and gradually facilitate G-protein function by moving them out of these clusters, Xiaoyaosan appears to exert its effects through a broader range of mechanisms, including modulation of monoamine neurotransmitters and anti-inflammatory pathways. This may be a more effective approach than administering SSRIs to target G protein clusters in brain membranes.

Over time, prolonged exposure to elevated serotonin due to SSRIs can lead to downregulation of serotonin receptors. According to Harvard Health, this downregulation may cause cravings for carbohydrate-rich foods (e.g., bread, pasta, sweets), leading to increased caloric intake and subsequent weight gain.

Additionally, many antidepressants block histamine  H1 receptors in the brain. This interferes with a process in your body called thermogenesis – producing heat and creating energy from burning fat and calories. When you burn less fat, it accumulates. The more fat you have, the higher your body mass index. This explains why it’s so hard for people on antidepressants to lose weight even with exercise!

Some of the serotonin enhancing antidepressants are more weight gaining than others. For example, Paroxetine and mirtazapine are heavy hitters because they strongly block histamine receptors. 

TCM herbs, such as Bupleurum chinense (Chai Hu), are known to stimulate metabolic processes and increase thermogenesis, thereby improving energy expenditure. At the same time, Chai Hu also affects the release and reuptake of monoamines, which are critical for mood regulation. Specifically, it has been shown to enhance the synthesis and signaling of serotonin and norepinephrine, thereby alleviating depressive symptoms. It also reduces the activity of monoamine oxidase (MAO), an enzyme responsible for the breakdown of serotonin! This means a better mood and metabolism! 

Also read: Lose Belly Fat – 2 Effective Weight Loss Treatments!

Patients diagnosed with depression may also be prone to anxiety. If this is you, antidepressants may temporarily intensify feelings of anxiety, making it feel worse than before starting treatment.

Researchers at the University of North Carolina have discovered an additional pathway in the brain activated by serotonin. While serotonin is known to improve mood and reduce anxiety through one pathway, it also activates another pathway that increases levels of corticotropin-releasing factor (CRF), also known as corticotropin-releasing hormone (CRH). This hormone is typically released in response to stress or perceived environmental threats, triggering the body’s “fight or flight” response. However, when no real threat is present, this stress response manifests as heightened anxiety.

The study revealed that serotonin can inadvertently stimulate this stress pathway via CRH release, contributing to anxiety during the early stages of antidepressant treatment. 

To address this issue, conventional treatment typically begins with a low dose of the antidepressant, which is gradually increased to reach the therapeutic level—a process known as titration. In some cases, a benzodiazepine may be prescribed temporarily to manage heightened anxiety during the early phase of antidepressant treatment. Once the antidepressant has taken full effect and you are stabilised, your doctor will taper off the benzodiazepine, leaving the antidepressant as the primary treatment for your anxiety. 

However, this ends up taking lots of time, which is why some people take as much as 8 weeks before they start to feel better. 

TCM, on the other hand, may provide a solution to this. 

Quercetin, a flavonoid prevalent in many herbs, has exhibited anxiolytic and antidepressant-like effects in animal studies by antagonising CRH. Research indicates that quercetin administration significantly reduces plasma levels of corticosterone and adrenocorticotropic hormone, as well as CRH mRNA expression in the hypothalamus. 

Chaihu, also known as Bupleurum, contains quercetin as one of its bioactive compounds. Chaihu is commonly used for its effects on the liver, stress, and emotional balance. The presence of quercetin contributes to its anti-inflammatory, antioxidant, and potential anxiolytic properties.

In TCM, Chaihu is often included in herbal formulations like Xiao Yao San or Chaihu Shugan San, which are used to address conditions like stress, anxiety, and depression. The quercetin in Chaihu may partly explain the herb’s ability to modulate stress-related pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, which is often implicated in anxiety.

Many antidepressants, particularly tricyclic antidepressants (TCAs), block the action of acetylcholine, a neurotransmitter that plays a crucial role in stimulating muscle contractions in the intestines. This blockage reduces peristalsis, the wave-like muscle contractions that move food through the digestive tract, leading to slower bowel movements and constipation. 

Antidepressants that affect nerve endings in the brain also influence those in the gut. This interaction can disrupt normal GI function, causing symptoms such as constipation. Specifically, SSRIs (selective serotonin reuptake inhibitors) have been noted to cause constipation as well due to their complex effects on gut motility and fluid secretion.

A systematic review and meta-analysis assessed the effectiveness of Ma Zi Ren Wan (MZRW), a TCM formula, for functional constipation, including cases potentially exacerbated by medications like antidepressants. It showed that MZRW significantly improved complete spontaneous bowel movements (CSBM) compared to placebo and senna (a common constipation drug). 

Also read: TCM and Constipation in Parkinson’s Disease

Interestingly, Bai Shao, a herb commonly used in TCM formulae to treat depression, is also an ingredient in MZRW. This could mean better gastrointestinal health and mental well-being.

Moreover, we believe TCM could potentially be combined with conventional antidepressants to help “balance out” those common nasty side effects like gastrointestinal issues. A comprehensive review published in 2023 examined the clinical application of CHM for depression, noting that common antidepressants side effects include nausea, vomiting, and gastrointestinal disturbances.

The review concluded that combining CHM with mainstream antidepressants can improve response rates and reduce side effects compared to antidepressants alone. It emphasized that CHM might be more effective than placebo in treating depression and associated symptoms, including those related to gastrointestinal health.

Also read: Chi Nei Tsang Massage – Open up your Belly & Feel the Tremendous Relief

Medications that inhibit the reuptake of serotonin, such as selective serotonin reuptake inhibitors (SSRIs), are commonly associated with sexual dysfunction. Shockingly, around 60 to 80 percent of patients experience these adverse effects. For the majority, these issues tend to resolve after discontinuation of the medication; however, there are rare cases where individuals report persistent effects lasting months, years, or even indefinitely.

Serotonin is a key neurotransmitter that influences various aspects of sexual function. Increased serotonin levels can inhibit sexual desire and arousal through its action on specific serotonin receptors, particularly the 5-HT2A and 5-HT2C receptors. Activation of these receptors has been shown to suppress libido and impair erectile function.

So how can TCM help with this side effect of SSRIs? 

A clinical trial involving patients with mild to moderate depression compared the effects of Xiaoyaosan with standard antidepressants. Results indicated that those treated with Xiaoyaosan experienced significant improvements in clinical symptoms within six weeks, including enhancements in sexual function.

At our clinic. Xiaoyaosan is a base formula that we consider when treating depression. It is also useful to know that this formula may also complement sertraline (an SSRI) effectively —  it may enhance the clinical efficacy of sertraline while mitigating clinical symptoms lile anxiety and sexual dysfunction.

Additionally, another study revealed that Xiaoyaosan decoction is able to elevate brain BDNF levels even after they have fallen. Reduced BDNF levels are associated with waning sexual function, while increased levels of BDNF have been associated with improved sexual behavior and arousal. 

Who does this work? BDNF promotes the survival of neurons and supports synaptic plasticity, which may enhance sexual responsiveness and desire. XYS ability to improve sexual drive and function is most likely through the restoration of BDNF levels in the brain.

All in all, it appears that this TCM herbal formula has the potential to reduce the sexual dysfunction side effects that appear when using SSRIs.

The integration of TCM into the treatment of depression presents a promising alternative or complement to conventional antidepressants. As highlighted throughout this article, TCM offers several advantages, including a faster onset of symptom relief, fewer side effects, and a multifaceted approach to managing both mental health and associated physical ailments.

Herbal formulations like Xiaoyaosan and Mazirenwan demonstrate significant efficacy in alleviating symptoms of depression while simultaneously addressing common antidepressant side effects such as constipation, weight gain, anxiety and even sexual dysfunction.

Moreover, the potential for combining TCM with conventional treatments could lead to improved patient outcomes by mitigating adverse effects commonly experienced with antidepressants. 

Ultimately, embracing TCM as part of a comprehensive treatment strategy may offer patients a more balanced and effective path toward recovery from depression.