Complementary Therapies for Schizophrenia: Expanding the Clinician’s Toolbox

The information below briefly summarizes the evidence and indications for the most widely studied and most promising nonconventional treatments for schizophrenia.
Note: This is not an exhaustive listing. For further information, consult these clinician-oriented resources on complementary therapies in psychiatry. See also, a related Psychiatric Times article from 2006, Treatment Resistance in Schizophrenia: The Role of Alternative Therapies . Glycine, an amino acid that interacts with the NMDA receptor, may improve positive and negative symptoms of schizophrenia, and may improve mood and overall cognitive functioning, when used along with a conventional antipsychotic, according to clinical trials and case reports. Double-blind, placebo-controlled studies of glycine supplementation include one published in 1996 and another in 2004. Clinical trials have found that glycine did not help people taking clozapine, but it did help (in reducing negative symptoms) individuals taking risperidone and olanzapine. Several randomized, controlled trials conducted at China Medical University and Hospital in Taiwan -- including a study published in September 2007 -- have found that treatment with sarcosine (a derivative of glycine) significantly reduced positive and negative symptoms of schizophrenia when taken with antipsychotics. Caution: Glycine causes upset stomach and nausea in some patients; this can be minimized by starting at lower doses and increasing it slowly over a few weeks. There are case reports of acute psychosis in some chronically psychotic patients treated with large doses. EPA (eicosapentaenoic acid), an Omega-3 fatty acid, may improve both positive and negative symptoms when used with conventional antipsychotics. Controlled studies have yielded mixed results, however. A small open study in India (published in 2003) found that schizophrenia patients treated with EPA had a significant reduction in scores on the PANSS and BPRS scales. In a larger, placebo-controlled study of 115 treatment-refractory schizophrenics (published in 2002), clinical improvements were observed in patients taking EPA along with clozapine. According to a 2007 Cochrane Review on the subject, however, a review of 6 studies involving 353 people “suggests that supplementation with essential fatty acids may have a positive effect on the symptoms of schizophrenia,” but “the use of Omega-3 polyunsaturated fatty acids for schizophrenia remains experimental and this review highlights the need for large well-designed studies.” Similarly, a 2006 research review (conducted by an APA subcommittee) of Omega-3 fatty acids for the prevention and treatment of psychiatric disorders, concluded that “EPA and DHA appear to have some potential benefit in major depressive disorder and bipolar disorder, but results remain inconclusive in most areas of interest in psychiatry.” Folate and thiamin taken with conventional antipsychotics may reduce symptom severity in schizophrenia, especially in patients who are folate-deficient, according to the findings of some double-blind placebo-controlled trials. In a 1990 British study, folate-deficient patients with major depression or schizophrenia who took daily folic acid (methylfolate 15mg) together with their conventional antipsychotic medication had fewer positive and negative symptoms and improved more rapidly than patients taking conventional drugs alone. Supplementing antipsychotic medications with the natural steroid dehydroepiandrosterone (DHEA) may reduce the severity of negative symptoms and may improve depressed mood and anxiety in some schizophrenia patients, according to findings from clinical studies. Randomized, placebo-controlled trials conducted in Israel, published in 2003 and 2005, found that those taking up to 150 mg of DHEA along with an antipsychotic reported improved negative symptoms and improvements in some extrapyramidal side effects.

Caution: Patients with a history of benign prostatic hypertrophy or prostate cancer should consult their physician before taking DHEA, as research suggests that supplemental DHEA use may pose a cancer risk in patients with nascent or occult prostate cancer. Chinese herbal medicine may also be a beneficial adjunctive treatment. A 2006 Cochrane review evaluated 6 trials that studied the use of Chinese herbs in a Western medicine context for the treatment of schizophrenia. Though the trials were limited by their sample size and study length, the review concludes that “if used in conjunction with Western antipsychotic drugs, [Chinese herbal medicines] may be beneficial in terms of mental state, global functioning and decrease of adverse effects.” However, it adds, “further trials are needed before the effects of TCM (traditional Chinese medicine) for people with schizophrenia can be evaluated with any real confidence.” Ginkgo biloba, used at 360 mg per day, may enhance the efficacy of conventional antipsychotics by helping to reduce positive and negative symptoms, according to placebo-controlled studies conducted in the United States, China and Turkey.

Caution: Ginkgo biloba may be associated with an increase in bleeding risk, according to a 2005 systematic literature review, so caution should be taken, particularly in patients with known bleeding risks. Ginkgo biloba should not be taken with warfarin or other drugs that affect bleeding time. Possibly effective dietary approaches for psychosis include increased intake of unsaturated fats (including foods rich in Omega-3 fatty acids), reduced intake of saturated fats and gluten, and improved regulation of glucose. Findings from epidemiological studies including a 1988 study suggest that schizophrenic patients who consume a diet high in saturated fats have more severe symptoms compared with patients who follow diets with moderate fat intake. Conversely, chronically psychotic patients who consume large amounts of unsaturated fats, including Omega-3 fatty acids, generally have milder symptoms, according to a 2002 report. There is also evidence that some schizophrenic patients become more symptomatic when they eat foods containing gluten -- and therefore, eliminating gluten from the diet may be beneficial -- but most of these reports are anecdotal.

Caution: Schizophrenia patients who are considering diet changes should first consult a nutritionist or other specialist. Regular yoga practice and yoga breathing techniques may reduce agitation and anxiety in chronically psychotic patients, according to anecdotal reports. And, according to a randomized controlled trial from the National Institute of Mental Health and Neuro Sciences, in Bangalore, India (published in September 2007), yoga practice combined with antipsychotic medication improved positive and negative symptoms, social functioning and quality of life.

Caution: Certain yoga breathing practices can cause agitation and can worsen symptoms in some psychotic symptoms. Patients should therefore practice yoga only under the guidance of a skilled instructor. Spiritually oriented group therapy may benefit schizophrenia patients who are stable or have well-controlled residual symptoms, according to some observational studies and case reports. Spiritually oriented support groups have been established at various U.S. healthcare centers, including a group formed at the Nathan Kline Institute, discussed in an April 2007 report, and another formed at a New York Hospital, discussed in a 2004 report. According to the literature, these efforts have yielded significant benefits for patients with schizophrenia, including a sense of encouragement, social support, improved range of affect, improved hopefulness and self-esteem, enhanced feelings of well-being, and a deeper sense of connection with peers. The groups are typically nondenominational and may include group prayer, reading and discussion of passages from various spiritual traditions.

Caution: Mental health practitioners should use their clinical judgment when considering whether it is appropriate to invite any patient with a history of psychosis to explore spiritual issues. Involvement in religious/spiritual groups could aggravate symptoms in individuals who are experiencing religious delusions or other severe psychotic symptoms. Niacin and other B vitamins may be beneficial in some cases of chronic schizophrenia, but the results of clinical trials have been mixed. Several case reports and small double-blind placebo-controlled studies -- including a study from Ben Gurion University (Israel), published in 2006 -- suggest that niacin taken with a conventional antipsychotic results in greater improvement in psychotic symptoms compared with conventional antipsychotics alone. However, a 1991 review of 53 trials of niacin and other vitamins for the treatment of schizophrenia and other mental illnesses identified shortcomings in the research design methods and concluded that the reported findings had only marginal statistical significance.

There is ongoing debate over the effectiveness of high doses of vitamins in the management of psychosis. The American Psychiatric Association considers the approach discredited, but Lake asserts that it still “warrants serious consideration” given the “large number of positive case reports and the growing level of professional interest.” A randomized, placebo-controlled trial of the Effect of High-Dose B-Complex Vitamins on the Symptoms of Schizophrenia was recently completed at the Nathan Kline Institute for Psychiatric Research (lead investigator William M. Greenberg, MD), but results are not yet available. Related article from Psychiatric Times
Treatment Resistance in Schizophrenia: The Role of Alternative Therapies
October 2006

Have comments or questions on this article? Please e-mail the author, Sara Selis, at sselis@cmp.com.