Major depressive disorder future or investigational therapies

Jump to navigation Jump to search

Major depressive disorder Microchapters


Major Depressive Disorder (Patient Information)


Historical Perspective




Differentiating Major depressive disorder from other Diseases

Epidemiology and Demographics

Risk Factors


Natural History, Complications and Prognosis

Substance/Medication-induced Depressive Disorder

Depressive Disorder due to a Medical Condition


Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

Other Imaging Findings

Other Diagnostic Studies


Medical Therapy




Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies



Case Studies

Case #1

Major depressive disorder future or investigational therapies On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides


American Roentgen Ray Society Images of Major depressive disorder future or investigational therapies

All Images
Echo & Ultrasound
CT Images

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mitra Chitsazan, M.D.[2]

Future or Investigational Therapies

Repetitive transcranial magnetic stimulation (rTMS)

There are as-yet unproven claims that using magnets or electrical currents can, in some yet to be explained way, reduce depression. In Repetitive transcranial magnetic stimulation (rTMS) a magnetic field is applied to the left prefrontal cortex.

Light Therapy

Light therapy involves exposing a person to bright light, usually from a fluorescent bulb, for a regular interval daily, usually in the morning. The evaluation of light therapy has provided unique challenges in the area of experimental design to researchers attempting to evaluate its effectiveness, especially in comparison to antidepressant medications. Like other forms of treatment for depression, the mechanisms of action of light therapy are poorly understood. There is evidence that light therapy, similarly to both some antidepressant medications and total sleep deprivation, has an antidepressant effect through affecting serotonin transport.[1]

Bright light (both sunlight and artificial light) has been shown to be effective in seasonal affective disorder.[2] It has also been shown to be effective in non-seasonal depression as well.[3] A randomized controlled trial published in 2005 found light therapy to be about as effective as most antidepressants.[4] Light therapy has the advantage of producing faster results (typically within one week) than treatment by most antidepressants (many of which take several weeks for any noticeable effects).[5] A preliminary study found that light therapy is comparable to antidepressants for postpartum depression, and called for further studies.[6] It also avoids some of the side effects of such medication. However, like SSRIs, it also leaves patients vulnerable to mood sensitivity to rapid tryptophan depletion.[7]


While some small studies have reported promising results, a recent Cochrane Review concluded that there is at present insufficient scientific evidence to judge the efficacy of acupuncture in the management of depression.[8]


Studies have indicated that changes in lifestyle, such as regular exercise, when used in conjunction with medication with non-suicidal patients can have beneficial effects in preventing the return of depression. Patients that completed 30 minutes of brisk exercise at least three times a week were found to have a significantly lower incidence of relapse.[9]


In recent years, cognitive hypnotherapy, in conjunction with behavior therapy has been cited as an alternative method of treating clinical depression.[10] Some studies have shown that hypnotherapy can help to reduce symptoms and to aid in teaching coping skills and strategies to help reduce the chance for recurrence.[11]


Meditation is increasingly seen as a useful treatment for some cases of depression.[12] The current professional opinion on meditation is that it represents at least a complementary method of treating depression, a view that has been endorsed by the Mayo Clinic.[13] Since the late 1990s, much research has been carried out to determine how meditation affects the brain (see the main article on meditation).

Deep Brain Stimulation

Though still experimental, a new form of treatment called deep brain stimulation is available for treatment resistant clinical depression. In a 2005 article in the journal Neuron, Helen Mayberg described the implanting of electrodes in a region of the brain known as Area 25.[14] The electrodes act in an inhibitory fashion, on an otherwise overactive region of the brain. Further research is required before it becomes available as a method of treatment, but it offers hope for those suffering from treatment resistant depression.


Self-medication is the use of drugs or alcohol to treat a perceived or real malady, usually of a psychological nature. Typically the use of non-prescription chemicals are taken with the intent of the user to alter a mood state for a temporary amount of time. In one study, cannabis users who use once a week or less were shown to have fewer symptoms of depression than non-users.[15]

Cigarette smoking is a popular form of self-medication. In clinical studies, nicotine is shown to be an effective anti-depressant among rats.[16]

Herbal and Dietary Supplements

5-HTP supplements are claimed to provide more raw material to the body's natural serotonin production process. There is a reasonable indication that 5-HTP may not be effective for those who have not already responded well to an SSRI because of their similar function: SSRIs prolong serotonin concentrations in the synapse, while 5-HTP induces production of more serotonin.[17]

S-adenosyl methionine (SAM-e) is a derivative of the amino acid methionine that is found throughout the human body, where it acts as a methyl donor and participates in other biochemical reactions. It is available as a prescription antidepressant in Europe and an over-the-counter dietary supplement in the United States. Clinical trials have shown SAM-e to be as effective as standard antidepressant medication; however, some studies have reported an increased incidence of mania resulting from SAM-e use compared to other antidepressants.[18][19] Its mode of action is unknown.

Omega-3 fatty acids (found naturally in oily fish, flax seeds, hemp seeds, walnuts, and canola oil) have also been found to be effective when used as a dietary supplement (although only fish-based omega-3 fatty acids have shown antidepressant efficacy.[20]) In addition to the total amount of omega 3 oils in the body, the level of omega 6 fatty acids have also been found to be implicated. An excess of omega 6 appears to be associated with depression.[21]

Dehydroepiandrosterone (DHEA), available as a supplement in the U.S., has been shown to be effective in small trials.[22]

Magnesium supplementation has gathered some attention as a possible treatment for depression.[23] Some case reports demonstrate rapid recovery from major depression using magnesium treatment.[24]

The herb St John's Wort has antidepressant properties. It should not be used with SSRIs or MAOIs without medical supervision because of the risk of serotonin syndrome.[25]

Ginkgo Biloba is a natural antidepressant[26] said to stabilise cell membranes, inhibiting lipid breakdown and aiding cell use of oxygen and glucose. Subsequently, it improves neurotransmitter production. It is also popular for treating mental concentration (such as for Alzheimer's and stroke patients).

Zinc has had an antidepressant effect in an experiment.[27]

Biotin: a deficiency has caused severe depression. The patient's symptoms improved after the deficiency was corrected.Empty citation (help)

B vitamins: Symptoms of a deficiency in vitamins such as vitamin B6, B12, and others can include depression and other psychiatric disorders.[28]

Chromium: Evidence has emerged that supplementing with high doses of chromium (ie: in doses of several hundred to 1000 mg) exerts antidepressant effects[29]. It has been found to enhance the availability of serotonin and norepinephrine. Chromium in the form of chromium picolinate has generated some controversy as it has been shown to increase damage to DNA in the ovary cells of hamsters, possible increasing the risk of cancer.[30]

Rhodiola rosea: Rhodiola is a herb growing in cold climates that has just recently been introduced to the west. It has been shown to help alleviate depression and fatigue. It is believed to elevate extracellular levels of monoamines and beta-endorphins.[31]


  1. Antidepressant effects of light therapy combined w...[Biol Psychiatry. 2003] - PubMed Result
  2. Light therapy for seasonal affective disorder. A r...[Neuropsychopharmacology. 1989] - PubMed Result
  4. The Efficacy of Light Therapy in the Treatment of Mood Disorders: A Review and Meta-Analysis of the Evidence - Golden et al. 162 (4): 656 - Am J Psychiatry
  5. Light treatment for nonseasonal depression: speed,...[J Affect Disord. 1998] - PubMed Result
  6. Randomized Clinical Trial of Bright Light Therapy for Antepartum Depression: Preliminary Findings
  7. Response to tryptophan depletion in major depressi...[Biol Psychiatry. 2004] - PubMed Result
  8. Smith, CA (2005). "Acupuncture for Depression". Cochrane Database of Systematic Reviews. 2005 (2): CD004046. doi:10.1002/14651858. Unknown parameter |coauthors= ignored (help); |access-date= requires |url= (help)
  9. Merritt, Richard (2000-09-22). "Study: Exercise Has Long-Lasting Effect on Depression". Duke University News. Retrieved 2007-10-20.
  10. Aladdin, Assen (2007-05-01). Handbook of Cognitive Hypnotherapy for Depression: An Evidence-Based Approach. Lippincott Williams & Wilkins. ISBN 0781766044. Retrieved 2007-11-16. line feed character in |publisher= at position 20 (help)
  11. Yapko, Michael (2001-05-04). Treating Depression with Hypnosis. Psychology Press. ISBN 1583913041. Retrieved 2007-11-16.
  12. MBSR and depression | Wildmind Buddhist Meditation
  13. Meditation: Take a stress-reduction break wherever you are -
  14. Clincal Study: Deep Brain Stimulation for Treatment-Resistant Depression published in Neuron
  15. Decreased depression in marijuana users. [Addict Behav. 2006] - PubMed Result
  16. Antidepressant effect of ingested nicotine in female rats of Flinders resistant and sensitive lines.
  17. 5-HTP (5-Hydroxytryptophan) vs. Prozac (SSRIs), by Ward Dean, MD, James South, MA, and Jim English
  18. Delle Chiaie, Roberto (2002). "Efficacy and tolerability of oral and intramuscular S-adenosyl- L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies". Am J Clin Nutr. 76 (5): 1172S?1176S. Unknown parameter |coauthors= ignored (help)
  19. Mischoulon, D (2002). "Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence". Am J Clin Nutr. 76 (5): 1158S?61S. Unknown parameter |coauthors= ignored (help)
  20. Omega-3 fatty acids
  21. ScienceDaily: Study Links Brain Fatty Acid Levels To Depression
  22. Double-Blind Treatment of Major Depression With Dehydroepiandrosterone - Wolkowitz et al. 156 (4): 646 - Am J Psychiatry
  23. Magnesium-deficient diet alters depression- and an...[Neuropharmacology. 2004] - PubMed Result
  24. Rapid Recovery From Depression Using Magnesium Treatment
  25. The scientific, quasi-scientific and popular liter...[J Affect Disord. 1998] - PubMed Result
  26. Ginkgo biloba
  27. Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study. Pol J Pharmacol 2003 Nov-Dec;55(6):1143-7
  28. Vitamin B12 Deficiency and Depression in Physically Disabled Older Women: Epidemiologic Evidence From the Women's Health and Aging Study - Penninx et al. 157 (5): 715 - Am J Psychiatry
  29. Psychology Today: A Mineral for Mental Energy
  30. Could Chromium Picolinate Cause Cancer?
  31. Rhodiola rosea: A Possible Plant Adaptogen Smart Drugs

Template:WikiDoc Sources