Integrative Medicine in Psychiatry

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Since the introduction of chlorpromazine in 1954, pharmaceutical approaches have been the mainstay treatment for mental health conditions. And although these agents are helpful, treatment resistance remains common. For instance, a 2021 analysis found that approximately 31% of patients with major depressive disorder (MDD) experienced treatment resistance.¹ Related costs for treatment-resistant cases is estimated to be approximately $92.7 billion in the United States, and represent higher levels of unemployment, reduced productivity, and increased health care expenditures.¹

As research continues to look for strategies that result in better treatment outcomes, consensus has slowly been building that additional interventions should play a role in treating mental health conditions. Patients with mental illness have been consistently found to have lower levels of certain nutrients, including vitamin D, omega-3 fatty acids, and zinc, among others.^2-4 Adjunctive treatments focusing on these deficiencies have yielded promising, positive results. Diet also appears to play an important role in mental health, including the reduction of ultra-processed foods to the potential benefits of implementing a ketogenic diet (Table).

Table. Several Important Recent Meta-Analyses on Integrative Psychiatry

Recent studies highlight the potential of integrative approaches for mental illness:

-A pilot study from Stanford found that a ketogenic diet was capable of reversing metabolic syndrome, improving schizophrenia symptoms by 32%, and reducing symptom severity in bipolar disorder in 69% of individuals.⁵

-For veterans, vitamin D supplementation was associated with an almost 50% reduction in suicide risk. For Black veterans and those who were more deficient in the vitamin, risk was reduced by 64%.⁶

-In a trial at a residential addiction clinic, substituting low-dose lithium for antidepressants and benzodiazepines resulted in halved opiate doses, benzodiazepine use was almost eliminated, polypharmacy was reduced by 79%, smoking cessation participation increased 300%, and program completion rates almost doubled.⁷

-A study found that for every 10% increase in ultra-processed food in the diet, risks for cognitive impairment and stroke increased by 16% and 8%, respectively.⁸

-A case study shared the story of a woman with poor dietary habits, MDD, and suicidal ideation who had rapid and complete relief of her mental-emotional symptoms following intravenous thiamine.⁹

These studies and other reports continue to show the practical utility of an integrative approach to psychiatric care. By evaluating patients for nutritional deficiencies that can contribute to physical and mental health symptoms, a personalized treatment plan can be developed to improve outcomes, especially when combined with medications and psychotherapy.

Integrative Medicine and Integrative Psychiatry

The National Center for Complementary and Integrative Health (NCCIH) shares the following clarifications¹⁰:

If a nonmainstream approach is used together with conventional medicine, it’s considered complementary. Integrative health brings conventional and complementary approaches together in a coordinated way. Integrative health also emphasizes multimodal interventions, which are 2 or more interventions such as conventional health care approaches (like medication, physical rehabilitation, psychotherapy), and complementary health approaches (like acupuncture, yoga, and probiotics) in various combinations, with an emphasis on treating the whole person rather than, for example, 1 organ system.

Thus, integrative medicine or “integrative health” is defined in relation to mainstream or conventional medicine. According to this description, it includes anything that is nonmainstream.

For our purposes, we can introduce the term integrative psychiatry. For simplicity, integrative psychiatry is the use of research-supported, nonpharmaceutical treatments for mental health conditions that may be integrated or combined with conventional pharmaceuticals and psychotherapy. Common examples of integrative psychiatry include the use of vitamins and minerals to treat nutritional deficiencies, probiotics, herbal medicines, and hormonal therapies like testosterone or triiodothyronine.

Nutrition and Metabolic Psychiatry

Some of the evidence for integrative psychiatry revolves around nutrition and what is often referred to as metabolic psychiatry. Metabolic psychiatry recognizes the fact that obesity and metabolic syndrome are correlated with negative mental health outcomes.^11,12 By addressing these conditions in patients with mental health concerns, mental health is often improved. Although not a prerequisite, metabolic psychiatry frequently makes use of low carbohydrate and ketogenic diets to address obesity and insulin resistance.

Ketogenic Diets and Mental Health

Although preliminary, the data on a ketogenic diet for treating mental health conditions is intriguing. In another study, of 31 patients with chronic, severe mental illness had promising results following a hospital-administered ketogenic diet: Depression scores decreased by approximately two-thirds.¹³ In patients with schizoaffective illness, symptom scores were reduced by just under 50%. Case studies documenting the reversal of psychosis with a ketogenic diet have also been reported.¹⁴ The first case was of a woman diagnosed with schizophrenia at age 17. Over the course of her life, she had been hospitalized for suicide attempts and psychosis. At age 70, she started a ketogenic diet to lose weight and had complete remission of psychotic symptoms and suicidality. Within months, she was also able to stop all her medications. She continued the diet and remained stable over the ensuing 12 years.

Proposed mechanisms for the effect of a ketogenic diet include improvements in insulin resistance and energy production, modulation of neurotransmitter systems, decreased free radical burden, changes in the gastrointestinal microbiome, and decreased inflammation.^15,16

Other Dietary Interventions

Other dietary measures may also be relevant for improving mental health within an integrative medicine framework. Dietary studies that evaluated depressive symptoms in individuals with clinical depression and nonclinical depression found a reduction in depressive symptoms with a number of dietary changes, including reduced fat intake, weight loss diets, and working with a nutritional professional.¹⁷

Diets high in ultra-processed foods have been associated with a negative effect on both physical and mental health.¹⁸ Higher consumption of ultra-processed foods has been linked with a higher risk for developing depression.¹⁹ Thus, removing or reducing ultra-processed foods is another potential dietary strategy to improve mental health outcomes.

Nutrients and Mental Health

Research on a number of specific nutrients is also finding relevance for integrative psychiatry. Some of the strongest evidence revolves around omega-3 fatty acids, vitamin D, zinc, and folate.

Omega-3 Fatty Acids

While controversy around the benefits of omega-3 fatty acids has been prevalent since the suggestion that eating more fish can improve mental health, the latest data strongly suggests a place for omega-3 fatty acids in the treatment of mental health conditions. A meta-analysis from 2023 concluded that supplements containing more than 60% eicosapentaenoic (EPA) and doses between 1 and 2 grams per day showed therapeutic potential for depression treatment.²⁰ An umbrella review of meta-analyses also concluded that omega-3 fatty acids, based on current evidence, could be considered an effective add-on treatment for improving depression symptoms.²¹

The development of psychosis and its progression to schizophrenia can be devastating for patients and families, causing life-long disability. Over the last decade, efforts at preventing psychosis in high-risk individuals have been gaining steam. A recent meta-analysis from 2024 evaluated the use of omega-3 fatty acids in the prevention of the transition to psychosis in high-risk patients.²² The analysis found that after 2 years or more, the transition risk was decreased by 84% with omega-3 fatty acid supplementation as compared with placebo or control patients, although more research is needed to fully confirm the findings. These benefits are so large that the potential ramifications of omega-3 fatty acids for prevention are difficult to overstate.

Vitamin D

Low vitamin D levels have been found to be associated with numerous health conditions, including depression. A meta-analysis from 2022 found that low vitamin D levels increased the risk of developing depression by 51%.²³ A separate meta-analysis found that vitamin D supplementation in depressed adults provided significant benefits for treating depression.²⁴

Other conditions like schizophrenia also appear to be linked with lower vitamin D levels.²⁵ although more research is needed on its use for treatment.

Zinc

As a mineral, zinc is important for brain health and brain function. Lower levels of zinc have been reported in numerous mental health conditions, including depression, anxiety, and schizophrenia.^26-28

Using zinc as a treatment for mental health conditions has also shown significant success. A meta-analysis from 2022 found that preliminary evidence suggests that zinc is effective as an adjunctive treatment combined with medication for decreasing depressive symptoms.²⁹ A systematic review on zinc for anxiety concluded that there is “plausible evidence” that zinc supplementation is helpful for anxiety symptoms.²⁷ A meta-analysis on zinc for attention-deficit/hyperactivity disorder (ADHD) also found that zinc may be helpful, providing a significant reduction in overall ADHD symptoms.³⁰

Folate

Folate is involved in one-carbon metabolism which is important for the production of purines and for recycling homocysteine. Folate also plays a part in neurotransmitter synthesis.³¹ Of interest, a number of common single nucleotide polymorphisms (SNPs) can reduce the efficiency of the enzymatic conversion of folic acid to the active forms of folate.³² To avoid the conversion problems, supplementation with folinic acid or 5-methylfolate may be necessary.

A systematic review of the clinical studies on folate for mental health conditions found consistent evidence suggesting benefits for a number of different conditions, including MDD, schizophrenia, autism, ADHD, and bipolar disorder.³³ A meta-analysis of 5-methylfolate for depression found modest benefits with its use as an adjunctive treatment with standard medication.³⁴

The Benefits and Challenges of Integrative Medicine

The Benefits

The action of combining standard and integrative medical approaches to mental health conditions can yield significant benefits for patients. Symptoms can be addressed more effectively, and arguably, integrative medicine can help to treat several overlooked factors that contribute to health and well-being.

Demand for integrative medicine has been increasing and research suggests that patients appreciate the additional treatment options and are satisfied when presented with integrative care.³⁵

The Challenges

While the benefits of integrative medicine may be significant, they also come with challenges. Integrative medicine is not always well standardized, from over-the-counter herbal therapies to education in training and treatment. While standardization can be an issue, potential solutions are also being explored. Research on techniques for characterizing and standardizing herbal extracts through analytical fingerprinting techniques already exist.³⁶ A number of institutions offer accredited training courses and programs in integrative health.³⁷

Even with the current level of evidence suggesting benefits, many clinical trials of integrative medicine suffer from poor methodology or conflicts of interest. In some cases, larger, well-done studies are needed to confirm the benefits. Patients may not be familiar with or understand integrative medicine, or they may have unrealistic expectations about what is possible, avoiding standard treatments that may be needed or helpful. Out-of-pocket expenses are often high since insurance frequently refuses to cover integrative care.

Other challenges include negative perceptions of integrative medicine from practitioners unfamiliar with integrative models of treatment. Considering that 57.6% of adults in the United States are taking dietary supplements,³⁸ their use is common and frequently encountered in general practice. When doctors are unwilling to support patients utilizing integrative therapeutics, it is more likely to break trust with patients who may decide to use the treatment anyway without the doctor’s knowledge, a situation that complicates care.

Concluding Thoughts

The trajectory of mental health care is evolving, providing new and valuable options for improving treatment outcomes. Research-based integrative medical strategies provide valuable insights and opportunities to help patients improve or even restore their well-being. The application of integrative psychiatry, including nutrition and metabolic assessments, provides a more comprehensive, personalized approach to care.

For years, the medical profession has been expanding to include a personalized medical approach to treatment. In oncology, where personalized medicine is more widely practiced, survival rates from lung cancer have improved 22% in just the last 5 years, while breast cancer survival has more than doubled since the 1970s.^39,40 Simply stated, integrative psychiatry is a part of the evolution of personalized mental health care. Once fully integrated, the benefits could be profound.

Dr Greenblatt has served as the chief medical officer at Walden Behavioral Care in Waltham, MA for nearly 20 years, and is an assistant clinical professor of psychiatry at Tufts University School of Medicine and Dartmouth College Geisel School of Medicine.

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