Thursday, November 13, 2025
Issue #253
Green Mountain National Forest, Vermont
Hello there!
Three months. (No, I'm not referring to how long it has been since my last article!) Often, that's when withdrawal symptoms such as stress, insomnia, and anxiety suddenly worsen even after a prolonged, smooth withdrawal process.
During my 20+ years of holistic psychiatric practice, I have considered this three-month milestone as a significant sign of long-term resilience. But why three months?
I believe I've found greater clarity on this question. Read on for more insights. Hope you're enjoying this beautiful autumn season.
SSRI Withdrawal's Effects
on Stress Resilience and Sleep
The Interconnection Between
Neurotransmitters and Hormones
Today's article is different because I'm going to share how SSRIs, and likely many other psychiatric medications, influence not just the neurotransmitter system but simultaneously undermine the hormonal system directly and indirectly.
As a psychiatrist, my 10 years of medical training lacked attention to the effects of stress and medication withdrawal on patients. If I had dozed off or forgotten the bit of information that had been provided, I apologize for my lack of giving credit where it's due. However, this neglect in medical training might be one reason why training programs are notoriously stressful and why the focus is on how to prescribe, without knowing how to withdraw psychiatric medications.
In this article, I want to clarify how SSRI withdrawal can undermine hormonal function and reverse well-being, and more importantly, how to treat this withdrawal problem.
San Juan Range of the Rocky Mountains, Colorado
"Why do I wake up in the morning with anxiety?" the patient asked.
He had smoothly come off 60 mg of Prozac with ease, but now, nearly three months after stopping Prozac, he was experiencing gradually increasing fatigue, insomnia, anxiety, and stress.
Energy testing indicated that this patient didn't need to make more serotonin support using 5-HTP. If he didn't need more serotonin, then what was he missing?
Energy medicine techniques had been extremely helpful in immediately mitigating his symptoms, but not permanently. His withdrawal symptoms resurfaced after two to three days.
Although not every patient experienced this pattern, I have seen enough patients to recognize that there was something significant about the three-month milestone. A pattern. Something I was missing.
Researching this question, I discovered that SSRI withdrawal undermines hypothalamic function and the hypothalamic-pituitary-adrenal and gonadal (HPA and HPG) axes.
I had supported the hormones in many ways to treat underlying problems, insomnia, reproductive hormonal function, and even low stress resilience, but I did not know that SSRI withdrawal undermined the HPA and HPG axes directly through its effects on the hypothalamus.
What happens when the HPA and HPG axes are undermined during SSRI withdrawal? And how can this problem be reversed naturally? Read on to find out.
(Citations at the end of this article)
When the HPA or HPG axes are undermined during SSRI withdrawal, the effects may not be evident until months after the patient has stopped taking the medication. Symptoms that arise are similar in nature to the psychiatric disorder or withdrawal symptoms: waking up with anxiety, increasing depression, intrusive worries, and fatigue.
It's tempting to add more serotonin support such as 5-HTP and its cofactors in response to the SSRI withdrawal process, but if you do, the patient may experience symptoms such as vivid dreams, more "gurgling" in the GI system, and other side effects associated with a higher-than-optimal serotonin level.
What else can one do at this point in the withdrawal?
Looking for a missing piece of the puzzle led me to the connection between SSRIs and their direct effects on the hypothalamus and the HPA and HPG axes. Lowering the SSRIs will theoretically lead to a weakened HPA and HPG axes.
How can one support the HPA and HPG axes? Here is helpful and readily available information that I was able to find quickly online (thanks to AI):
Adaptogenic herbs
Ashwagandha: An adaptogen used in Ayurvedic medicine that supports adrenal health and function.
Rhodiola: Helps the body adapt to stress and supports healthy stress hormone balance.
Holy Basil: Used in traditional Chinese medicine to support the HPA axis and manage stress.
Eleuthero (Siberian ginseng): Helps maintain a healthy stress response and supports HPA axis function.
Maca: Supports stress hormone balance through the HPA axis.
Vitamins and minerals
B Vitamins: Essential for the synthesis of adrenal hormones and neurotransmitters; levels can be depleted during stress.
Vitamin C: Supports adrenal function and can help manage cortisol levels.
Magnesium: A crucial mineral for HPA axis function that can increase anxiety when deficient; supplementation may help normalize function.
Selenium: Supports the function of the hypothalamus and pituitary glands.
Other supplements
5-HTP: A precursor to serotonin that supports sleep regulation, which can be affected by stress.
Licorice Root: Can influence cortisol levels by inhibiting the enzyme that converts cortisol to cortisone; should be used with caution and is not recommended for long-term use.
Magnolia Bark Extract: Contains compounds that can calm the nervous system and reduce stress-induced cortisol levels.
Kava: A plant with sedative and anxiolytic properties that can help with anxiety and sleep quality.
My patients were already on many of the nutritional supplements, but among the ones listed above that they would benefit from adding were: Ashwagandha and magnolia. I have used these supplements before, and now I know one more reason why they can be helpful for my patients.
To combine both into one supplement, I chose to start my patients on Cortisol Manager by Integrative Therapeutics. It has both Ashwagandha and Magnolia bark in each tablet. Integrative Therapeutics is a trustworthy company. I have used their products for decades and found them quite effective. You may find other companies that may be even better.
With the addition of Cortisol Manager, episodes of awakening with anxiety subsided and stress resilience improved.
I thought my battle with withdrawal challenges was over. Everything that needed attention had been addressed. However, not so fast. New challenges arose that led to new insights.
Read my next article on "The Hidden Neurotransmitter System" to learn more about my battle to support my patients' withdrawal process, and why many patients are put on SSRIs and antipsychotic medications without realizing that another hidden neurotransmitter system is the underlying culprit behind their depression, anxiety, and obsessive-compulsive (OCD) symptoms.
I hope you've found this article helpful and insightful. Have a great week!
Citations:
Hengartner, M.P. (2020). Protracted withdrawal syndrome after stopping antidepressants. Journal: Therapeutic Advances in Psychopharmacology. (Open access: PMC). This analysis of 69 individual reports documents prolonged withdrawal symptoms lasting months to years after stopping antidepressants. The report highlights persistent affective and autonomic symptoms (anxiety, depression, agitation) consistent with long-term central nervous system adaptations; findings support the plausibility that hypothalamic and stress-regulatory circuits (including HPA mechanisms) remain dysregulated in some individuals post-discontinuation. Open-access / more info: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768871/
Antonioli, M., et al. (2012). Neuroimmune–endocrine effects of antidepressants. (Open access: PMC). This review synthesizes evidence that antidepressants modulate neuroimmune and endocrine systems, including effects on HPA axis activity and glucocorticoid receptor signaling. The authors describe how chronic antidepressant exposure can alter HPA feedback sensitivity and immune-endocrine interactions, providing mechanistic pathways by which withdrawal could unmask HPA dysregulation. Open-access / more info: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280108/
David, D.J., et al. (2009). Behavioral effects of fluoxetine in an animal model (includes HPA findings). (Open access: PMC). Preclinical work showing that chronic fluoxetine modifies stress-responses and corticosterone dynamics in rodents. These animal findings demonstrate that SSRIs alter hypothalamic–pituitary–adrenal signaling, offering a mechanistic bridge to explain human withdrawal-associated HPA axis perturbations. Open-access / more info: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759281/
Michelson, D., et al. (2000). Hormonal markers of stress response following interruption of fluoxetine/paroxetine/sertraline. (PubMed abstract). A clinical endocrine study that measured physiological markers during substitution/interruptions of SSRI treatment. The study observed increases in some stress-related markers and heart rate following interruption of paroxetine, consistent with reactivation of stress-response systems during antidepressant cessation. Open-access / more info: https://pubmed.ncbi.nlm.nih.gov/10674280/
Spandidos Publications / Review (2024). Effects of selective serotonin reuptake inhibitors on the endocrine system. A recent review summarizing evidence that SSRIs can disrupt endocrine function — including impacts on the HPA axis, gonadal function, thyroid, and metabolic regulation. The paper emphasizes clinical implications given long-term SSRI prescribing and recommendsmonitoring endocrine function when clinically indicated. Open-access / more info: https://pubmed.ncbi.nlm.nih.gov/39070109/
Henssler, J., et al. (2024). Incidence of antidepressant discontinuation symptoms. The Lancet Psychiatry. A large systematic analysis estimating incidence and severity of discontinuation symptoms across antidepressant classes. The work quantifies population risk and highlights that a meaningful minority experience severe discontinuation effects, reinforcing the clinical relevance of physiological mechanisms such as HPA/HPG perturbations during withdrawal. Open-access / more info: https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(24)00133-0/fulltext
Jha, M.K., et al. (2018). When discontinuing SSRI antidepressants is a challenge. American Journal of Psychiatry. A practical clinical review discussing discontinuation phenomenology, management strategies, and potential biological underpinnings. The review notes that discontinuation symptoms can reflect both serotonergic readjustment and downstream endocrine/autonomic dysregulation (including HPA axis involvement). Open-access / more info: https://pubmed.ncbi.nlm.nih.gov/30501420/
Review: Progress in the study of the effects of selective serotonin reuptake inhibitors on reproductive toxicity and HPG (2025 / 2024 review - open access). A recent review addressing reproductive toxicity and HPG-related effects of SSRIs, covering impacts on germ cells, reproductive hormones, sexual dysfunction, and potential mechanisms. It consolidates animal and human findings tying SSRI exposure to HPG perturbation — relevant for post-discontinuation sexual and gonadal dysfunction reports. Open-access / more info: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078316/
Be sure to subscribe to my podcasts and updates!
To sustain my work as a holistic psychiatrist and support my efforts to improve psychiatric treatment for all through my podcasts, articles, website, and YouTube channel, please show your appreciation and help champion holistic psychiatry by clicking HERE to contribute!
Click here to listen to all of The Holistic Psychiatrist Podcast episodes
Contact here to email Dr. Lee directly.
If you like this podcast, please give it a 5-star rating and share this with others! Thank you!
For more about Dr. Alice W. Lee, please visit:
Website: www.holisticpsychiatrist.com
More stories and insights: Holistic Articles
YouTube: The Holistic Psychiatrist
To schedule consultations or appointments, call Dr. Lee's office at 240-437-7600
Dr. Lee is located in downtown Salt Lake City, Utah.
The content provided by this podcast is for informational purposes only and has not been approved by the U.S. FDA. This podcast is not intended to provide personal medical advice, which should be obtained from a medical professional.