The psychotherapeutic drug market, comprised of drugs like Prozac, Zoloft and Ritalin, which are prescribed to treat conditions of depression, anxiety, psychosis, ADHD (attention deficit hyper­activity disorder) and other related disorders, is worth an estimated $37 billion, according to "World Market for Psychotherapeutic Drugs" (Kalorama Information, NY, January 2007), and segment revenues are forecasted to grow more than 50% by 2010.

But the known side effects of prescription psychotherapeutic drugs have sent a steady stream of consumers out of the pharmacy and into the natural remedy aisle in search of nutraceutical alternatives. Up until a few years ago, St. John's Wort and kava kava were the natural product industry's most well-known answers to depression and anxiety, respectively. But when St. John's Wort's effectiveness on depression was discredited and kava was linked to liver toxicity, consumer confidence waned, leaving natural ingredient suppliers to wonder which ingredient(s) would step in to fill the void. Although there are many natural anxiety and depression remedies currently on the market, the void remains largely unfilled. As pharmaceutical coffers continue to fill, the nutraceuticals market is struggling to find ways to even the psychotherapeutic playing field.

Julie Thibeau, director of sales and marketing, NutriScience Innovations, LLC, Trumbull, CT, said the manner in which prescription drugs are currently marketed to consumers leads to a two-fold problem of higher costs and possible drug dependence. "Drug companies are spending millions of dollars in advertising to promote their products, encouraging people to go to their doctor's office and specifically request a 'treatment' for their ailments," she said, noting that the increased marketing ultimately translates into a higher drug costs for consumers. "In some cases, doctors are becoming nothing more than glorified drug dealers…especially when the drug companies reward doctors for the amount of prescriptions they write. Instead of 'fixing' the problem, they contribute to unnecessary life-long use of prescription drugs.

"The nutraceuticals market can stand to benefit from this negative trend by finding and researching alternatives to prescription drugs," she continued. "However, the same care in approving prescription drugs should also be enforced for dietary supplements. It's important that consumers are confident about their safety and efficacy."

Don Stanek, director of sales, Linnea Inc., Easton, PA, believes the natural products industry's lack of collective clout is partly to blame for the industry's distant second place finish behind the pharmaceutical industry. "Because of the disparate nature of this industry, even with a plethora of trade groups, there is no one forum that has the strength of, for instance, the Pharmaceutical Manufacturers Association to counter the pharmaceutical industry," he said. "The pharmaceutical industry attacks the natural products industry very well because they know the American consumer, who, relative to other consumers, likes the quick fix."

But Ms. Thibeau feels the tide is turning. "We believe that consumers are now changing their outlook on natural remedies because they have lost confidence in prescription drugs, mainly due to the potential negative side effects, adverse reactions and unmanageable costs," she said. "However, consumers are still hesitant to pursue natural stress remedies, simply because there are many products available in the market that are ineffective. It is our responsibility to inform and educate consumers that there is an effective, safe and affordable alternative."

Supplement regulations also pose some challenges, and opportunities. "While the cost per dose of one prescription medicine is far more than the cost of a natural-based medicine, the latter is not heavily regulated by the government. This is a good and bad thing," explained Steve Siegel, vice president, Ecuadorian Rainforest LLC, Belleville, NJ. "The good: more consumers have access to herbs and botanicals that may help them. The bad: more consumers have access to herbs and botanicals that may hurt them. It's a double-edged sword that has been highly debated for years."

Defining and Addressing Needs

For every person clinically diagnosed with stress- and anxiety-related ailments, there are countless more in search of remedies to assuage stress-related sleep loss, lack of focus and other problems that can arise from busy lifestyles and general over-stimulation.

Ron Sosenko, founder, Koppla Nutrients, a division of Natural Chemistry Inc., Stamford, CT, asserts that it's not so much the physical aspect of stress, as it is not being able to let go of the intensity of the thoughts in the brain that plagues most people. "Our culture has evolved into being bombarded by messages and stimuli," he said. "There aren't too many places in our lives where we can be in a truly quiet, peaceful setting to calm the breathing and clear the head."

Ecuadorian Rainforest's Mr. Siegel claims that our culture is growing ever more attuned to helping consumers alleviate their stress, as evidenced by the popularity of mainstream salons, spas and natural remedy stores. "Stress and anxiety, unlike let's say cancer, are not always diagnosed as a disease. Consumers who are 'stressed out' sometimes prefer to go to a spa or take a vacation," he said. "In addition to these actions, consumers may, for example, take an herbal relaxant, drink a tea, or indulge in a massage with natural oils. All of these may decrease stress. Since there are easier, more accessible ways to de-stress, consumers are less likely to seek a prescription for their stress and anxiety issues."

Likewise, consumers are looking at nutraceuticals as being healthy choices. As a result, they continue to consult various sources for more background on them. "We are living in the information age," said Mr. Sosenko. "If people have a health problem, they turn to the Internet to take in a wealth of information. Because of that, certain natural ingredients have gained a mainstream awareness, prompting people to experiment with these ingredients. Good experiences with supplements are spread by word of mouth, and consumers tend to rely more often on the word of a friend or family member."

When it comes to alleviating stress, Mr. Sosenko suggested consumers examine the definition of stress before they at­tempt to manage it. "The adult definition of energy isn't a spike of energy and consequential drop afterward, it's a balanced state: the feeling when you're physically calm, when your head is clear, a centered state where you feel most functional. Chamomile tea effectively sedates the body for a restful sleep, but during the day the body needs to be calmed, not shut down."

Mr. Sosenko's company has tapped into this desire for calm with Koppla, a citrus flavored "adaptogenic" powdered beverage mix formulated to restore the body's natural resources to handle stress and manage energy. The product takes its name from the Swedish expression "koppla-av," or "to relax."

Formulated by Eigil Jensen, a Swedish master herbalist with a background in stress relief remedies, Koppla combines lemon balm, a brain tonic, with oat flowers for the nervous system, linden to detoxify the liver (where, Mr. Sosenko said, many toxins tend to pool during stress), and hawthorn and red ginseng to support the heart and create a "warming element" that aids in the absorption of the formula.

"Koppla's adaptogenic formula brings the body's circulation and oxygen and blood balance back to normal," Mr. Sosenko noted. "Instead of sedating your stress or jolting your energy with this beverage, we wanted to find the common link to stress and energy and that brings you back into balance. Adaptogenic products are the bull's eye the nutraceutical industry is looking for. They facilitate energy coming into a balanced, more centered state and under those conditions, when your blood flow and oxygen are normal, all health problems are benefited simply by having the even keel of your fuel."

When selecting supplements, consumers often relate to those that have a "story" behind them, be it about plant origins or even native folklore, as was part of the case with kava and its Polynesian roots. In a consumer's eyes, an ingredient's history can serve to underscore the ingredient's legitimacy and historical staying power.

Ecuadorian Rainforest has long associated ingredients with their native use. "A new ingredient that has yet to catch on, but that we believe will grow is Sceletium tortusum, a plant used for centuries in South Africa as a mood enhancer, relaxant and empathogen (induce feelings of empathy)," said the company's Mr. Siegel. "Its use is similar to kava. It is consumed in a tea infusion or taken in capsule form. Just like kava, it has a mild anesthetic effect in the mouth. Once the plant takes effect on the person it produces a euphoric feeling that slowly fades into a lull or relaxation." Ecuadorian Rainforest is currently one of the only suppliers of sceletium in the U.S.

Another ingredient of interest to the stress and anxiety consumer is valerian, a perennial plant. "Standardized extracts of valerian are often found in sleep formulas," Mr. Siegel noted. "The root of the valerian herb has been shown to effectively calm the user. Ecuadorian Rainforest recommends a standardized extract of at least 0.8 valerenic acid. The herb takes approximately 30 minutes to one hour to relax the user."

Beyond some of the traditional ingredients, there are far more that may lend a helping hand, and some haven't even been discovered yet. "For the herbal supplement segment, there are still thousands of undiscovered plants with unknown applications, dozens of which may be suitable as anti-anxiety ingredients," commented international botanical specialist Dr. Joerg Gruenwald, president of analyze & realize ag, Berlin, Germany, and author of the PDR for Herbal Medicines. "Also, and more importantly, various traditional remedies that have been used for hundreds of years in remote parts of the world are only now being discovered and formulated for mainstream use. An example here is Kamishoyosan, a traditional Japanese Kampo medicine that, according to preliminary research, has an anxiolytic effect. Clinical proof of safety and efficacy will go on increasing consumer confidence in these safe alternatives to synthetic drugs."

Dr. Gruenwald also continues to advocate St. John's Wort, because, as he put it, "it has been prescribed against states of anxiety up to and including mild to medium depression for many years, and has proven efficacy according to a number of clinical trials. Its efficacy, mode of action, and reaction time is equal or even superior to synthetic alternatives, and there are much fewer side effects."

Dr. Gruenwald also pointed to the proven efficacy of other traditional herbal anti-anxiety remedies, including valerian and hops, as well as lemon balm, for their relaxing properties. In addition, he said recent research by Dr. Veronika Butterweck of the University of Florida indicates that there is much potential in the extract of Apocynum venetum leaves in the treatment of anxiety and stress.

Whatever Happened to Kava?

Not so long ago, kava was the natural products industry's most credibly renowned anti-anxiety remedy, but it didn't take long for kava to all but drop off the supplement radar after the FDA issued a warning in 2002 citing the "occurrence of severe hepatic toxicity possibly associated with the consumption of products containing kava (i.e., kava kava or Piper methysticum)."

Despite the fact that kava had been used for 2000 years by Polynesian natives, and had been developed into a registered herbal drug for the treatment of anxiety in Europe, some six years ago Swiss and German health authorities began reporting cases of potential liver toxicity in people using kava drugs, and shortly thereafter, all kava products had to be taken off the market. "This decision has since been under strong scientific criticism, as only a very small number of cases could be clearly linked to kava while the existing other drugs used in this indication not only have much higher incidences of liver toxicity but other side effects as well, and they also clearly lead to physical addiction," explained Dr. Gruenwald. "Nevertheless, kava products cannot be sold in the market in Europe at present, but strong efforts are being undertaken to change this. New toxicological results have not confirmed toxicity, but the authorities are asking for more data.

"Still, Europe is a unique situation," he added. "In the rest of the world, kava can be and is legally marketed in different forms like as dietary supplements in the U.S., or as drugs in South America. And I would still recommend kava as the best anti-anxiety herb currently available."

More Products to Watch

When stressed, some people instinctively reach for food, which can be both good and bad, as evidenced by the following two anti-anxiety remedies.

To some, chocolate is a suitable antidote to stress thanks to its combination of sugar, caffeine and innate chemical compounds. And with the creation of The Doctor's Chocolate, Dr. Keith Scott-Mumby, a British MD/nutritionist, comes the contention that chocolate no longer need be a guilty pleasure.

According to company literature, eating two pieces of The Doctor's Chocolate each day "relieves stress and puts the joy back in living." The all-natural dark chocolate truffles combine unprocessed chocolate, raspberries and L-theanine to help reduce "daily stress and tension while improving mental clarity and focus."

Each piece of The Doctor's Chocolate contains 20 calories, one gram of fat, and is sweetened with a small amount of fruit paste and xylitol.

The active L-Theanine ingredient in The Doctor's Chocolate is Suntheanine, a product of NutriScience Innovations, manufactured by Japan-based Taiyo Kagaku Co., Ltd. Suntheanine is enzymatically fermented from green tea through a natural process and NutriScience Innovations' Ms. Thibeau claims that it's supported by numerous scientific studies and clinical trials, as well as international patents for several applications, including stress. "Suntheanine has been shown in human clinical trials to promote the generation of alpha-brain waves, an indication of an alert, yet relaxed state of being," she said, adding that to date no negative side-effects, contraindications or negative interactions have been reported with the use of Suntheanine, and it is neither habit forming nor addictive.

The second anti-anxiety remedy to watch is Relora, from Next Pharmaceuticals, Carlsbad, CA. A natural proprietary blend of a patented extract of Magnolia officinalis and a patent-pending extract from Phellodendron amurense, Relora was developed as an ingredient to be used in dietary supplements and functional foods formulated for stress management and stress-related appetite control.

The company's own Deanne Dolnick, director of sales, said she started taking Relora in place of Xanax to quell the anxiety that came during her second bout with breast cancer. "I grudgingly gave Relora a try, not really believing that it would work. I was stunned that it worked so fast and so well. It's been over a year and I have never taken another prescription anti-anxiety product," she said. "It works when I have to have an MRI and it works when I fly. As an added benefit, it has improved my sleep tremendously, which is not something I can say about Xanax."

If the "World Market for Psychotherapeutic Drugs" study is correct in its long range predictions for the pharmaceutical segment, there's little doubt that the natural products industry is poised to become a bastion for those seeking non-prescription relief of stress and anxiety. Dr. Gruenwald aptly surmised: "Since there is a narrow margin between efficacy and severe side effects in most anti-anxiety drugs on the market today, there exists a strong incentive for conducting more research on herbal alternatives."NW