Initial Presentation

Pam was a 62-year-old physician with a past psychiatric history of depression. She had been successfully treated with sertraline (Zoloft) for the past 20 years. Despite consulting with several psychiatrists and naturopathic doctors over the past two years, she had been unable to taper off Zoloft and was feeling quite discouraged at the time of her initial evaluation. Anytime she attempted to reduce her 200 mg dose of sertraline, even by small amounts, she would experience intolerable withdrawal, including “brain zaps,” irritability, agitation, insomnia, and severe nausea.

She was otherwise healthy with no significant medical history and did not take any other medications. She reported eating a nutrient dense diet and was intentional about including protein and healthy fats at each meal. She exercised regularly, including a mix of brisk walking, yoga, and strength training with a personal trainer. She also engaged in a daily meditation practice. Even with all of these supportive lifestyle practices in place, she would reliably “spiral” every time she attempted to lower her medication dose.

Initial Relevant Labs

The initial battery of laboratory testing revealed the following:

• Most of her mineral levels were low or trending low on hair tissue mineral analysis (HTMA)
• Numerous low or borderline low amino acids on plasma amino acid testing

Working Diagnosis:

• Antidepressant withdrawal
• Impaired digestion and absorption

Initial Treatment

• Digestive enzymes with betaine hydrochloric acid (HCl), 2 capsules with each meal
• Free-form amino acid powder, 1 tsp daily between meals
• B-Complex, 1 capsule daily
• Trace mineral supplement, 1 capsule daily
• Magnesium Glycinate 120 mg two times daily

Explanation

The patient was started on digestive enzymes with HCl, a free-form amino acid supplement, B-complex, a multi-mineral supplement, and magnesium to address underlying dynamics likely contributing to her difficulty tapering off Zoloft. Plasma amino acid testing revealed low amino acid levels, and hair testing showed mineral deficiencies, despite her nutrient-dense, protein-adequate diet.

This indicated impaired digestion and absorption, which can hinder the body’s ability to produce neurotransmitters essential for mood regulation. The association between acid-lowering medications like proton pump inhibitors (PPIs) and depression has underscored the importance of adequate hydrochloric acid levels in staving off depression via its role in absorbing amino acids for neurotransmitter synthesis (Murthy et al., 2023).

With age, natural declines in stomach acid (HCl) and pancreatic enzyme production can reduce the efficiency of protein and nutrient breakdown, impacting absorption (Remond et al., 2015). By supporting her digestion with enzymes and HCl, nutrient availability can be enhanced. Free-form amino acids directly supply building blocks for neurotransmitter synthesis, while the B complex, multi-mineral supplement, and magnesium replenish deficiencies, further supporting nervous system function. The goal with these interventions was to create a foundation for better resilience and a smoother transition off her antidepressant.

Follow-up Presentation

After 4 weeks on the above regimen, Pam reported increased energy, less bloating after meals, and improved sleep. With the digestive and micronutrient support on board, her dose of Zoloft was decreased by 12.5 mg with a plan to follow up in two weeks to review her progress.

During the two-week follow-up, Pam was excited to share that she had largely tolerated the dose reduction without significant adverse effects. While she did feel a little more irritable, she noted that “it’s been so much better than any of the other times. I can function.” She denied any brain zaps, nausea, or sleep disruption as she had with previous attempts to lower her dose. Overall, she was delighted with the progress and hopeful that she would indeed be able to come off Zoloft, albeit slowly.

Follow-up Testing

After 6 months of the above treatment, testing was repeated, revealing the following:

• Repeat hair tissue mineral analysis revealed improvement in most minerals but persistently low lithium level
• Plasma amino acid testing revealed normalization of all amino acids

Follow-up Treatment

• Continue previous treatments
• Start lithium orotate 1 mg nightly
• Start Seroplus (Pure Encapsulations), titrated up to 2 capsules twice daily between meals

Explanation

Pam was able to taper her Zoloft down to 50 mg daily, however at that point she began to experience higher levels of irritability and anxiety. Follow-up testing revealed low lithium stores. Given its mood-stabilizing properties and excellent safety profile, lithium orotate was initiated (Pacholko & Bekar, 2021). Direct and indirect serotonin support was provided in the form of Seroplus, a combination of 5-HTP, a direct precursor to serotonin, and the micronutrient cofactors required for serotonin synthesis.

The additional supplements allowed her to continue her taper.

Case Summary

While antidepressant withdrawal has often been regarded as psychosomatic or confused with a relapse of depression symptoms, literature supporting the potentially debilitating phenomenon has been accumulating for decades (Horowitz et al., 2023). This case highlights the importance of a holistic, multi-pronged approach to successfully tapering off antidepressants. In this case, a comprehensive evaluation revealed impaired digestion and absorption, as evidenced by low plasma amino acids and mineral deficiencies despite a nutrient-dense diet. These findings underscored the need to optimize her foundational health before attempting to reduce the dose of her medication.

Treatment focused on improving digestion and absorption through digestive enzymes with HCl and replenishing deficiencies with a free-form amino acid supplement, a B complex, a multi-mineral supplement, and magnesium. This laid the groundwork for supporting neurotransmitter synthesis, which is crucial for stabilizing Pam’s mood during the taper.

In addition to this foundational support, the taper process was carried out very slowly to minimize withdrawal symptoms. Direct neurotransmitter precursors, in this case 5-HTP, were added near the end of the taper to provide additional support. Starting 5-HTP near the end of an antidepressant taper rather than earlier is crucial to minimize the risk of serotonin syndrome, a rare but dangerous condition caused by excessive serotonergic activity. Combining 5-HTP with antidepressants, particularly SSRIs or SNRIs, can lead to an additive effect on serotonin levels, increasing this risk.

Waiting until the antidepressant dose is significantly reduced allows the brain’s serotonin system to recalibrate, reducing the likelihood of adverse effects. Clinicians should watch for symptoms of serotonin syndrome, such as agitation, confusion, rapid heart rate, sweating, muscle rigidity, and in more severe cases, fever, which can be life-threatening. These symptoms are possible but unlikely if 5-HTP is combined with lower doses of serotonergic medications.

With more and more individuals struggling with antidepressant withdrawal, it is essential for providers to adopt a systematic, holistic approach, as these challenges often indicate underlying biochemical imbalances that must be addressed to facilitate a comfortable and sustainable taper.