sadnessThe treatment of severe depression remains a forbidding scientific frontier (Nemeroff, 2007). No current pharmacological therapy seems more than occasionally effective on those who suffer from it. Of the traditional device-based treatments, only Electro-Convulsive Therapy (ECT) has shown itself effective, and ECT is only effective to some extent and in some cases. ECT also comes with a significant price tag and consistent mid-level side effects. Many patients do not respond to any therapy, while the suicide rate among victims of severe depression remains tragically high.

Treatment-resistant depression, whether moderate or severe, is an unusually expensive disorder because it tends to affect people at relatively young ages, making them less able to perform at work, frequently absent from work, or simply unable to work at all for decades on end (Crown, 2002). Researchers are currently investigating various novel approaches to the treatment of severe depression. But expanding the range of possible approaches to such a refractory syndrome can in the long run lead to a more optimal outcome. Here are three new approaches not currently under consideration.

Sonoluminescence Therapy

Sonoluminescence Therapy is a variant of Biophotonic Therapy (BT) (Photoluminescence, Ultraviolet Blood Irradiation Therapy) that substitutes ultrasound stimulation of blood for the activation of the chemiluminescence of the blood via ultraviolet, visible, or infrared light (Dillon, 1998, 2003). BT has been used as a treatment of more than one million patients over the past 80 years. It is the subject of hundreds of journal articles and a dozen books in various languages. BT possesses a rather well-characterized profile in neuromedicine. It seems to be at least as effective as pharmacological therapies in the treatment of neurological and psychiatric disorders, including depression. However, several factors militate against the use of BT in this indication.

First, BT is little known outside of the former Soviet Bloc and Germany, even though it was invented in the United States and is currently used for various indications by several hundred American practitioners. Second, its applications in neuromedicine are not as thoroughly documented as its use in other indications such as to treat bronchial asthma. Third, the whole idea of treating the blood with ultraviolet irradiation goes counter to deeply held taboos in the medical profession. So it seems advisable to find ways to apply BT in forms that do not raise objections among those mistrustful of new approaches, as BT often does.

One such approach is to use ultrasound as a kind of Sonoluminescence Therapy. While Russian researchers have used ultrasound to generate chemiluminescence in the blood for diagnostic purposes, there is no evidence that anyone has done so for therapeutic purposes. Yet the procedures would be simple enough. Instead of using ultraviolet light, one would simply administer ultrasound treatment to a sample of blood withdrawn from a vein, then retransfuse the blood into the vein. The amounts of blood are prescribed in BT protocols, and one could readily calibrate the dose of ultraviolet to provide a sonoluminescent/chemiluminescent effect equal to the chemiluminescence kindled by BT. An alternative approach would transmit the ultrasound via a waveguide intravenously, as is done in low-intensity laser BT. Both extracorporeal and intravenous Sonoluminescence Therapy could be predicted to convey roughly the same effect as each other, and roughly the same effect as equivalent amounts of BT.

In contrast to BT, Sonoluminescence Therapy would, by avoiding the suggestive term “irradiation”, presumably encounter far fewer obstacles to gaining acceptance. Sonoluminescence actually has a benign and even attractive image as a wondrous phenomenon of Nature. So it could convey a significant placebo effect in some cases, especially when contrasted with the malignant image of BT.

Electro-Aerosol Therapy (EAT)

Starting in Germany in the 1930s, medical doctors used cathode discharges to impart to water, saline, and other aerosols a tiny, uniform charge–usually negative (Wehner, 1962, 1968). This charge helped stabilize the aerosol, enhancing penetration and effectiveness. The treatment was used for various respiratory disorders with excellent efficacy and low side effects. The extremely low current cancels out any danger from the high voltage used in EAT, and devices are equipped with additional safeguards. There is no report of any electrical accident in treatment with EAT.

The study and use of EAT spread to the former Soviet Union, where researchers identified its effects as being the same as those of BT except that the stimulation of nerves in the lungs provided a superior effect (Vasiliev, 1953). EAT was studied in many countries over the succeeding several decades. Ultrasonic nebulizers were devised in an attempt to achieve an even more uniform and stable aerosol. However, Scientific Rejectionism and the conservatism of the medical profession caused EAT to be restricted to a small group of knowledgeable practitioners.

At present, EAT is used only in a few Central and East European spas, where it continues to achieve excellent results against an ever-increasing range of indications that, in all likelihood, is virtually identical to the range of BT. Since BT has such a promising profile in neuromedicine and seems especially interesting as a treatment of severe depression, it makes sense to investigate the use of EAT in treating severe depression as well. In fact, EAT may have an additional mechanism of action via its stimulation of the olfactory nerve leading directly to the brain, so it may be even more effective and open to scientific investigation than had otherwise been thought.

A particular attraction of EAT is its unusually benign administration. The patient sits about 1.5 meters away from the outlet of the device and breathes normally, generally for a 30-minute session. Depending on the condition being treated, from 3-4 up to 15-20 sessions are used. Or a group of patients can sit in a circle around a larger device with vents on its sides. In theory, EAT would be able to achieve similar or better results than ECT, and with far fewer side effects.

Saffron Nanospheres

In a series of clinical studies, Iranian researchers have reported very good results from the use of oral saffron capsules in the treatment of depression and other mental disorders (Akhondzadeh S, 2005). Practitioners of traditional medicine in Iran had long used saffron to treat depressive symptoms, but these studies were the first scientific ones to investigate this approach. The effectiveness proved roughly parallel to that of fluoxetine (Prozac), but with lower side effects. In a significant step forward, the Iranian researchers demonstrated that saffron petal (cheap to gather) conveys an effect equivalent to that of saffron stigma (extremely expensive because of the cost of collection and handling), making saffron-based drugs much more affordable.

Meanwhile, decades of research in microspheres and nanospheres for drug delivery have refined their composition and deployment to achieve superior outcomes in the treatment of a range of disorders. Typically, the intravenous route is used, but various modes of drug delivery exist with such microspheres and nanospheres. Of special interest are lipid nanospheres. They are natural and so create fewer side effects than artificial drug delivery vehicles. Lipid nanospheres are also inexpensive and well-characterized, with the most common being based on soy.

Now the opportunity exists to use the lipid nanospheres to deliver saffron extract. The most obvious routes would be intravenous (to avoid digestive decomposition of oral compounds) and via inhaled aerosols. The hypothesis would be that the improved delivery characteristics permitted by the nanospheres, including better penetration of the blood-brain barrier (Torchilin, 2006), would enhance the effectiveness and reduce the already low side effects of saffron in the treatment of normal depression and thereby qualify this new approach as a promising treatment of severe depression. In particular, the presumably very low side effects of this treatment would permit it to be used in higher doses to achieve better outcomes in refractory severe depression. Ultimately, it might be possible to replace the soy nanospheres with lipid nanospheres composed of saffron oil, thereby conveying an improved anti-depressive effect. As a fully natural yet high-tech solution, saffron nanospheres would potentially benefit from a powerful placebo effect in at least some cases.

A Concluding Thought

While we can hope that with these and other new modalities more and more sufferers of severe depression can gain some relief from their condition, this problem will likely be with humankind for a long time. Therefore, it makes sense to find handy palliatives and other remedies. For three such approaches, see Fruitful Matching: A Technique to Counteract Negative Thinking, Special Properties of the Organ for Music Therapy, and Afghan Herbal Medicines for Addiction and Depression.


Akhondzadeh S et al. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytotherapy Research. 2005;19:148-51

Crown WH et al. The impact of treatment -resistant depression on health care utilization and costs. Journal of Clinical Psychiatry. 2002;63(11):963-71

Dillon, Kenneth J. Close-to-Nature Medicine. Washington, D.C.: Scientia Press, 2003

Dillon, Kenneth J. Healing Photons. Washington, D.C.: Scientia Press, 1998

Dillon, Kenneth J. Intriguing Anomalies. Washington, D.C.: Scientia Press, 2008

Nemeroff CB. The burden of severe depression: A review of diagnostic challenges and treatment alternatives. Journal of Psychiatric Research. 2007;41:189-206

Torchilin, Vladimir P., ed. Nanoparticulates as Drug Carriers. London: Imperial College Press, 2006, 539-42

Vasiliev LL. Theory and Practice of Treatment with Ionized Air. [Russian] 2nd edition. Leningrad, 1953; English translation of 1st edition (Leningrad, 1951): Theory and Practice of Ionized-Air Therapy. Wright-Patterson Air Force Base, Ohio, 1966

Wehner AP. Electro-aerosol therapy. American Journal of Physical Medicine. 1962;41(1):24-40;(2):68-86

Wehner AP. Electro-aerosols, air ions and physical medicine. American Journal of Physical Medicine. 1968;48:119-49


Kenneth J. Dillon is an historian who writes on science, medicine, and history.  See the biosketch at About Us.


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