Complementary Therapies for Schizophrenia: Expanding the Clinician’s Toolbox

Given the burdens of living with schizophrenia and other psychotic disorders, and the increasing emphasis on improving patients' quality of life, it's no wonder that clinicians and patients are seeking additional treatment options for psychotic disorders. Clinicians who use, study and advocate for nonconventional or “complementary” therapies in psychiatry -- treatments ranging from dietary supplements to Chinese herbs to yoga -- see an opportunity to expand the acceptance and use of these therapies as adjuncts to conventional treatments for schizophrenia.

These practitioners acknowledge that the evidence supporting most nonconventional therapies for schizophrenia is still decidedly modest: The number of rigorous, well-designed studies is limited, and research findings on several of the therapies are inconsistent.

Still, dozens of studies in recent years have found evidence that when combined with antipsychotics, several nontraditional therapies -- most notably Omega-3 fatty acids, glycine, folate, Chinese herbal medicines, yoga practices and spiritually focused group therapy -- yield measurable and sometimes clinically significant benefits in some schizophrenic patients. Based on limited and mainly small or uncontrolled studies, nonconventional therapies may be effective particularly in easing negative symptoms, cognitive symptoms and/or antipsychotic side effects.

Expanding the clinician's toolbox

As Richard P. Brown, MD, sees it, psychiatrists owe it to their patients to be open to evidence-based nonconventional approaches. "Patients and families are desperate -- they're saying, 'There's got to be more you can do for us,' " says Brown, an associate professor in clinical psychiatry at Columbia University, who has devoted much of his work in the past 15 years to the study and practice of complementary therapies, with an emphasis on yoga practices. Brown says he’s seen increasing demand for this approach among patients and families. In fact, he spends 3 or more hours each week responding to calls and e-mails from individuals who seek his help -- typically refractory cases of patients who’ve tried several conventional therapies with little relief. He gives workshops and talks internationally, including a presentation on complementary therapies for schizophrenia, given in May at the American Psychiatric Association's 2007 annual meeting. Brown views complementary therapies as a broader set of tools that clinicians can employ to help patients live less disrupted, more fulfilling lives. "It's like going to a car mechanic," he explains. "Some mechanics know how to fix only Toyotas or GM cars. Some mechanics can fix any kind of car. So I say, What kind of mechanic do you want to be?" With complementary therapies, "we can give you tools so you can help any patient who walks in the door."

Increasing interest among clinicians

Among most U.S. psychiatrists, Brown admits, there has traditionally been little interest in complementary therapies, particularly for serious disorders like schizophrenia where conventional medications produce the most dramatic improvements. "Most psychiatrists are quite frightened by the idea of alternative medicine," he says. Still, Brown has seen an upswing in interest among some psychiatrists, particularly younger physicians and those from Asian countries. "When I give talks on this, the room is stuffed and people are overflowing out into the hall." It's a sign, he says, that "clinicians aren't satisfied with the treatments we have to offer." According to a nationwide survey of psychiatrists, conducted in fall 2006 regarding schizophrenia treatment, 95% of respondents said new, more effective treatment options were needed for schizophrenia. And 80% said they had changed medications for their schizophrenia patients more than once in the previous 12 months, with the drugs’ lack of efficacy as the primary reason.

James H. Lake, MD, is a frequent presenter at major conferences on nonconventional approaches in mental health care, chairs the American Psychiatric Association’s Caucus on Complementary, Alternative and Integrative Care -- which counts 100-plus members -- and was recently appointed to an APA Task Force on Complementary and Alternative Medicine. He is on the clinical faculty at Stanford University’s Department of Psychiatry and has a full-time private practice in integrative psychiatry -- an approach that uses both conventional biomedical therapies and evidence-based complementary therapies alone or in combination, depending on the unique symptoms and preferences of each patient. Lake attributes the growing interest in complementary therapies to concerns about the safety, effectiveness and cost-effectiveness of antipsychotic medications, in light of research findings including findings from the recent CATIE trials.

Textbooks synthesize evidence for complementary therapies

Based on his clinical experience, training in complementary medicine, interviews with clinician-researchers, and an extensive review of the scientific literature on nonconventional therapies used to treat psychiatric disorders, Lake has produced two books for clinicians: the Textbook of Integrative Mental Health Care (Thieme Medical Publishers, October 2006, by James H. Lake) and Complementary and Alternative Treatments in Mental Health Care (American Psychiatric Publishing, December 2006, co-edited with David Spiegel, MD).

The Textbook of Integrative Mental Health Care provides critical reviews of the evidence for nonconventional and integrative approaches to core symptoms including depression, anxiety and psychosis. The key goal of the book is to evaluate nonconventional approaches used to assess and treat common mental health problems, and to present evidence-based guidelines for their appropriate use. Lake hopes to transform the APA’s Caucus on Complementary, Alternative and Integrative Care into a full-fledged committee that will eventually recommend specific clinical practice guidelines to governing bodies within the association. (Most APA guidelines currently do not discuss complementary approaches.)

Not a substitute for Rx meds

Lake emphasizes that as properly practiced, "integrative psychiatry" is based on compelling evidence from randomized controlled trials, and is meant to supplement, not supplant, conventional medications. "By no means am I trying to replace antipsychotic medications with herbs," he says. "I prescribe conventional antipsychotics all the time -- they are very important." Lake notes that several schizophrenic patients have come to him seeking to discontinue conventional medications. In most cases, he advises against it but often recommends augmentation strategies. In limited cases, he will agree to work with a patient toward the goal of reducing doses or even discontinuing antipsychotics, but the patient must be stable, have a history of good compliance, follow an appropriate regimen of complementary therapies, and must be committed to a holistic program including healthy diet, exercise, and preferably a mind-body practice such as yoga or tai-chi.

Three levels of evidence

For each of the core symptoms for which Lake has reviewed the evidence for nonconventional treatment approaches, he has classified potentially beneficial therapies into 1 of 3 categories:

•Substantiated therapies are those for which there is "compelling research evidence" -- by Lake's criteria, based on positive findings of a meta-analysis or systematic review of at least 3 well-designed, randomized, placebo-controlled trials with significant statistical power.

•Provisional therapies are those for which there is "significant positive evidence" -- meaning 1 or 2 well-designed, randomized controlled trials, and if a meta-analysis of studies has been performed, the findings are promising but not compelling.

•Possibly effective therapies are those often supported by anecdotal evidence or for which the evidence from research studies is limited or inconsistent.

For schizophrenia, Lake's Textbook of Integrative Mental Health Care concludes that "there are no substantiated nonconventional treatment approaches at the time of writing" (October 2006). In interviews, however, Lake explains that this reflects the paucity of large, well-designed studies on the subject, rather than the limited effectiveness of nonconventional treatments for schizophrenia per se.

Indeed, Lake writes, "It is important to remark that many conventional approaches in current use are also provisional or possibly effective when the same rigorous criteria are applied." In this context, "the effectiveness of many provisional nonconventional approaches is probably comparable to that of many treatments used in conventional mental health care."

Lake expects that future studies will produce compelling evidence for some complementary therapies for schizophrenia and other psychotic disorders. Meanwhile, he is encouraged by the steady pace of research on nonconventional treatments. The amount of funding that the National Institute of Mental Health has devoted to studying complementary therapies has ranged from $6.7 million in 2001 to $3.9 million in 2002, with an estimated $4.3 million in funding for 2007, according to data from the NIH’s National Center for Complementary and Alternative Medicine.

"Provisional" and "possibly effective" therapies for schizophrenia

Lake's synthesis of published research evidence has identified these nonconventional therapies as "provisional treatments for psychosis" (see page 3 for more detailed information):

•glycine

•EPA (eicosapentaenoic acid), an Omega-3 fatty acid

•DHEA (dehydroepiandrosterone)

•folate, niacin and thiamine

•spiritually oriented group therapy

In addition, Lake’s work has identified the following therapies as "possibly effective for psychosis”:

•dietary changes (decreased intake of saturated fats and gluten; increased intake of Omega-3 fatty acids; improved glucose control)

•ginkgo biloba

•yoga practices

•mineral supplements (manganese, selenium, zinc)

Based on some clinical studies, Chinese herbal medicine has also been identified as a promising complementary therapy for schizophrenia (though it is not mentioned in Lake’s work).

Guidance for using complementary therapies

Leaders in complementary psychiatry have the following guidance for clinicians who are considering or starting to use the approach:

• Take a comprehensive patient history that includes
  -the patient's overall health history
  -previous mental-health problems
  -family history of psychiatric disorders
  -when symptoms of psychosis started
  -frequency and severity of psychotic episodes
  -which therapies the patient has tried (conventional and  complementary); how well they worked (or didn't); side effects they  produced
  -patient's daily activities, sleep/wake patterns, and sources of stress
  -patient's family situation, living situation and significant relationships
  -diet and exercise habits
  -spiritual/religious beliefs and activities

• Determine whether the patient poses a danger to himself or others. If so, make sure he gets immediate treatment in an emergency or inpatient setting, and emphasize to the patient the importance of staying on his prescribed medications.

• Ask about patients’ use of complementary therapies -- and don’t be judgmental of their response. A 2006 research review of complementary therapies in psychiatry found that, depending on the criteria used, between 8 and 57% of psychiatric patients use nonconventional therapies. A 2005 study from the Scott & White Memorial Hospital and Clinic found that among 82 psychiatric inpatients, 63% had used a complementary modality in the previous year, but most respondents had not discussed it with their psychiatrist. This may have dangerous repercussions, since some herbs and supplements can cause adverse reactions when taken with conventional medications.

Many patients avoid mentioning complementary therapies because they fear their doctor’s disapproval, notes William M. Greenberg, MD, clinical associate professor of psychiatry at New York University, whose private practice incorporates complementary therapies including dietary supplements, meditation and spirituality.

• "I approach patients individually and broadly," Greenberg says. If a patient seeks to use natural remedies in place of medications, he usually advises against it. Still, he says, "I don't reject that attitude outright. I find that the clinician being open to it really strengthens the therapeutic alliance."

Until recently, Greenberg was director of outpatient research at the Nathan Kline Institute for Psychiatric Research, where he led a randomized, placebo-controlled trial on the Effect of High-Dose B-Complex Vitamins on the Symptoms of Schizophrenia (results are not yet available).

• Determine whether psychosis is the patient's only primary symptom , or whether there are comorbid symptoms, such as anxiety or depression. Lake's Textbook of Integrative Mental Health Care includes tables and an algorithm that provide guidance on assessing and treating patients with comorbid symptoms in addition to psychosis, vs. psychosis alone.

• Try all substantiated conventional therapies before starting complementary therapies. "If the patient has tried all the antipsychotics except one, I'd try that one before going to [nonconventional] treatments," Lake says.

• Start slow. When introducing or changing therapies (conventional or nonconventional) for a patient, avoid making quick or drastic changes. Start with the lowest recommended dose, then increase it incrementally if it's not having the desired effect. Always aim for the lowest possible effective dose of any treatment, to minimize the risk of adverse effects while increasing compliance.

• Consider cost. Nonconventional treatments are rarely covered by insurance, and many schizophrenia patients have limited financial resources, making it difficult for them to pay for treatments out-of-pocket. While common dietary supplements typically cost $20 to $50 per month, other treatments -- such as Chinese herbal medicines or less-common supplements -- can cost several hundred dollars a month.

• Carefully explain to patients the rationale for the complementary therapies you’re recommending; the risks involved -- including potential herb-drug interactions -- and the importance of staying on the patient’s prescribed medication regimen. Document these discussions, and get the patient's written consent before beginning treatment.

• Refer patients to high-quality brands and suppliers of complementary remedies. Since the FDA does not regulate herbs or dietary supplements, there are no guarantees about the products’ contents or quality. One helpful guideline is to look for a certified “GMP” (Good Manufacturing Practices) certification (the GMP stamp will appear on the label), as well as products that have a “USP” (United States Pharmacopeia) stamp. Independent evaluations of the safety and efficacy of dozens of dietary supplements are available (for a modest fee) at ConsumerLab.com. Greenberg often suggests the Life Extension Foundation brand and Web site for herbs and supplements (he has no ties to the foundation).

• Listen. "Doctors can seem more interested in technology than in the patient's feelings. Patients miss having that emotional connection," Brown explains. "Just listening is very important." Effective listening, he notes, requires quieting the mind, eliminating distractions and focusing on the patient.

Resources to learn more about complementary therapies in psychiatry

 The following resources can help educate mental-health clinicians about the use of complementary therapies in psychiatry:

• Two books published last year -- the Textbook of Integrative Mental Health Care (Thieme Medical Publishers, October 2006, by James H. Lake) and Complementary and Alternative Treatments in Mental Health Care (American Psychiatric Publishing, December 2006, co-edited by Drs. James H. Lake and David Spiegel) -- identify what Lake and Spiegel regard as safe, effective complementary treatments for psychiatric disorders, and present evidence-based guidelines for their use.

• The American Psychiatric Association’s Caucus on Complementary, Alternative and Integrative Care offers an e-mail newsletter, information on meetings and events in complementary psychiatry, and an e-mail discussion group for clinicians. The group is building an online database of research evidence on complementary therapies in psychiatry.

• The American Psychiatric Association’s annual research meeting includes presentations and workshops on nonconventional treatments in psychiatry.

• The NIH’s National Center for Complementary and Alternative Medicine, known as NCCAM, lists on its Web site training resources for clinicians, including online CME courses, although these resources are not focused specifically on psychiatry.

COMPLEMENTARY TREATMENTS FOR SCHIZOPHRENIA: A summary of the evidence and indications

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