Functional Treatment of Obsessive-Compulsive Disorder (Townsend Letter)

By James Greenblatt, MD. Article originally posted in the Townsend Letter, November 2021.

While it is human nature to occasionally ruminate or overanalyze important decisions, these thought patterns normally dissipate quickly, freeing us of those fleeting moments of inner turmoil. However, for those suffering from obsessive compulsive disorder (OCD), letting go of repetitive thoughts is not so effortless, often leading to tremendous amounts of anxiety.

Unfortunately, anxiety disorders have become a problem of epidemic proportions. Surveys suggest that more than one-third of individuals experience an anxiety disorder during their lifetime.¹ And while the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) no longer classifies OCD as an anxiety disorder, strong overlaps between anxiety and OCD are obviously prevalent. In fact, research suggests that three-quarters of patients with OCD also have a comorbid anxiety disorder.²

For individuals with OCD, relentless ideas, impulses, or images inundate the brain leaving the individual mentally imprisoned to an existence of recurrent, irrational thought patterns. These senseless obsessions often drive the individual to perform ritualistic behaviors or compulsions in an effort to temporarily relieve their anxiety. Sufferers stagger through life with a sense of pure powerlessness against their disorder, fully aware that the behavior is abnormal, yet unable to stop.

Psychotropic medications such as selective serotonin reuptake inhibitors (SSRIs), clomipramine (Anafranil), and cognitive behavioral therapy are the conventional treatment options for obsessive compulsive disorder. Sadly, first-line treatment of OCD does not benefit 40-60% of individuals, leading to significant morbidity.³ Inadequate treatment and limited biomedical options contribute to the high relapse rate as conventional medicine does not address underlying nutritional deficiencies or the root cause of the condition.

Although unlikely to be caused by deficiencies alone, addressing nutrient deficits is a critical aspect of treating OCD since certain vitamins, minerals, and amino acids significantly impact serotonin neurotransmission. Specifically, natural therapies, including 5-HTP, niacin (B3), pyridoxal-5-phosphate (B6), folate (5-MTHF), vitamin C, zinc, magnesium, inositol, and taurine, are important for serotonin synthesis and overall function. Therefore, the combination of the aforementioned nutrients taken in therapeutic dosages should be part of an integrative treatment approach for OCD. The supplement SeroPlus by Pure Encapsulations was formulated for just such a purpose.

As the fourth most common psychiatric illness in the United States, OCD onset typically occurs by adolescence or youth, usually between the ages of 10-24, with one-quarter of all cases appearing before age 14 and two-thirds occurring before age 25.^4,5 Despite its prevalence, it is often underdiagnosed and undertreated with patients having full symptoms for 11 years on average before diagnosis.⁶ Gender has minimal influences on susceptibility, with males being more frequently diagnosed in childhood, but females diagnosed more often in adolescence and adulthood.⁷

From the research on medications for OCD, it is clear that enhancing serotonin neurotransmission through psychotropic medications helps the brain to “shift into gear,” reducing repetitive thoughts.⁸ But what exactly causes this glitch in the serotonin system to begin with?

A number of likely actors, including genes, diet, stress, neurotoxins, and inflammation, are responsible for inadequate serotonin synthesis or disruption in serotonin signaling. Amino acid availability for neurotransmitter synthesis is dependent upon certain digestive enzymes, and their activation is dependent on adequate stomach acid. Without sufficient amino acid availability, neurotransmitter synthesis will suffer similar to what’s seen in diets deficient in L-tryptophan.⁹

Availability of the essential amino acid L-tryptophan is required for serotonin production. Because serotonin synthesis depends on the availability of L-tryptophan and essential cofactors, including vitamin B3, folate (5-MTHF), vitamin B6, and zinc, serotonin levels will be less than optimal if any of the required building blocks are deficient. The process of serotonin synthesis starts when L-tryptophan is converted into 5-hydroxytryptophan with the help of tryptophan hydroxylase (a vitamin B3 dependent enzyme), which requires 5-MTHF. 5-Hydroxytryptophan (5-HTP) then converts to serotonin with the aid of decarboxylase, vitamin B6-dependent enzymes, and zinc.

Supplemental 5-hydroxytryptophan (5-HTP) can be beneficial for individuals as it essentially bypasses the problems around L-tryptophan availability. Easily crossing the blood brain barrier, 5-HTP works like a targeted missile directly increasing brain serotonin levels.¹⁰ It does not require a transport molecule for crossing the blood brain barrier, and unlike L-tryptophan, it is not incorporated into proteins or converted to niacin.¹¹ What’s more, promising research indicates that the therapeutic effect of 5-HTP is potentially equivalent to fluoxetine (Prozac). In a head-to-head comparison, the antidepressant effects of 5-HTP were prevalent in as little as two weeks.¹²

The strongest clinical research on 5-HTP for OCD was a recent trial on its use combined with fluoxetine. The combination was more effective than fluoxetine alone at reducing OCD symptoms.¹³ I recommend starting all patients with 50 mg of 5-HTP and titrating slowly every two weeks up to a maximum of 200 mg per day. Side effects of 5-HTP include nausea, irritability, and occasionally, anxiety. Keep in mind, if combined with an SSRI there is always a possibility for life-threatening serotonin syndrome.

In my experience, inositol has proven particularly effective for SSRI-resistant OCD patients. Specifically, OCD patients experiencing lack of response or problematic side effects with SSRIs or clomipramine have been examined. One small study found that dosages of 18 grams of inositol per day were effective for OCD treatment. Improvement in symptoms were reported at six weeks of treatment with no reported side effects.¹⁴ However, a trial investigating adjunctive inositol with SSRI medication found no benefits with its addition.¹⁵ Of note, the trial was quite small, including only 10 patients, and may not be the final word on the matter.

Inositol’s effect on treatment-resistant patients is likely due to its role in the neurotransmission process.¹⁶ Operating as a secondary messenger, it enhances the sensitivity of serotonin receptors on the postsynaptic neuron using signal transduction. Upon binding to its receptor, messages from serotonin are then translated into signals that are expressed through behaviors such as positive mood, relaxation, and reduced obsessions. Due to its role in serotonin signaling, patients resistant to SSRI treatment may not necessarily have an issue with serotonin synthesis but rather decreased receptor sensitivity.

Controlled trials of inositol have shown therapeutic effects in a wide spectrum of psychiatric illnesses generally treated with SSRI’s, including OCD, depression, panic disorder, and bulimia.^17-21 In particular, in my own practice, children exhibiting OCD symptoms have shown considerable life-altering improvements with inositol treatment. For instance, “S.M.,” a socially withdrawn, 11-year-old child who obsessively feared fire and contamination, transformed into a “completely different child” with inositol treatment. Similarly, “P.J.,” treated with inositol and 5-HTP, showed significant improvement in OCD symptoms. A third clinical case, “C.K.,” had suffered immensely with severe adverse side effects to Celexa and Prozac, including aggressive thoughts of self-harm. Upon treatment with inositol, no side effects were reported, and the child began to improve.

Even though research studies have used 18 grams of inositol per day, I start all patients with OCD on approximately 3 grams (½ teaspoon, 3 times per day). This minimizes GI side effects including bloating and nausea. If needed, inositol dosages can be titrated up slowly with most patients responding below 12 grams per day.

Improving serotonin production and neurotransmission is integral to boosting serotonin levels and combating symptoms of OCD. However, preventing over-activity of neurotransmitters should also be considered for OCD patients. Taurine is an essential amino acid and an agonist to gamma aminobutyric acid (GABA) receptors, an inhibitory neurotransmitter. Widely known for its calming effect, taurine’s therapeutic use for anxiety and depression treatment has been explored. In an animal model of depression in diabetic rats, treatment with taurine improved depressive behaviors.²² Furthermore, numerous animal studies have found anxiolytic activity with taurine.^23-26 Although taurine does not directly target serotonin production, it is still worth considering as its inhibitory effect may reduce racing thoughts associated with anxiety disorders such as OCD.

Based on scientific evidence supporting the relationship of these nutrients with serotonin production, combined with decades of clinical experience, I developed SeroPlus. SeroPlus is a nutritional supplement to help patients with OCD and depression. The formula provides serotonin building blocks, including therapeutic doses of 5-HTP (the direct precursor to serotonin), inositol, and taurine in addition to the vital cofactors magnesium, vitamin C, pyridoxal-5-phosphate (activated B6), and Metafolin® (activated folate). Inositol elevates sensitization of serotonin receptors while taurine maintains healthy sympathetic nervous system tone. The formula also includes niacin to reduce conversion of tryptophan to B3 and zinc with its established benefits for mental health.²⁷ Synergistically, these ingredients optimize serotonin production and restore healthy serum levels of common nutrient deficiencies contributing to abnormalities in serotonin neurotransmission.

As with any psychiatric illness, treating OCD is complex and requires a comprehensive multi-prong approach beyond basic SSRI prescriptions and behavioral therapy. Although directly enhancing serotonin production through natural therapies such as 5-HTP as well as correcting underlying B3, B6, zinc, magnesium, folate, and inositol deficiencies is at the heart of integrative treatment, there are a number of alternative factors that may also contribute. Low levels of vitamin B12, essential fats, magnesium, and vitamin D must be addressed if present.

A prisoner to their own thoughts, OCD sufferers are frustrated and searching for alternative treatment options. The complex etiology of OCD includes genetics, inflammation, and the dysfunction of serotonin synthesis. While SSRIs may help, a number of OCD patients do not experience long-term results. Thus, identifying key nutrient depletions and replenishing them through dietary modification and supplementation is essential to increasing chances of long-term recovery.