Depression Treatments

What’s Current, What’s New and What’s on the Horizon

Laurie Long 4/06
(Includes parts of “Depression Treatments for MSers” by Ann Crickmer, 1999)

Because depression affects more than half of individuals with MS, and because there is a growing body of evidence that untreated depression worsens the course of other medical illness, all MS patients should be screened for depression by their health care providers.  Depression is still under-recognized and under treated - which is unfortunate, since antidepressants are able to help a large percentage of those suffering from this condition. In addition to the almost two-dozen antidepressants on the market, new treatments and techniques will soon allow treatment-resistant patients additional choices to combat depression.

Antidepressants

Antidepressants separate into several classes of drugs. These classes differ in chemical structure and in the way they affect brain chemistry. Because we are all different, a drug that may be effective in helping one person’s depression may not work at all for another person. Another drug may cause severe side effects in one patient and not cause any in another. These differences often mean a trial and error search to find the right antidepressant, or combination of antidepressants, for each individual. But the general effectiveness of antidepressants and the wide range available greatly increases the probability of finding the right one for you.

Some of the oldest drugs used to combat depression are the tricyclics and the MAOIs (monamine oxidase inhibitor). The tricyclic antidepressants include Elavil, NorpraminTofranil and Pamelor. They have largely been supplanted by the SSRIs (Selective Serotonin Reuptake Inhibitors) because the SSRIs have fewer side effects and have a high degree of safety.

MAOIs (Nardil and Parnate) are also not generally a first choice for prescription because they can reduce the effectiveness of other drugs and because patients must avoid certain foods while on the MAOI. SSRIs must never be combined with an MAOI antidepressant.

SSRIs like Prozac, Zoloft, Paxil, and Celexa are currently the most prescribed antidepressants because they have fewer side effects and are well tolerated. The latest SSRIs, such as Lexapro, improve on earlier SSRIs with lower dosages (10mg/day for Lexapro vs. 40mg/day for Celexa) and very low levels of intolerance.

The newest classes of antidepressants include Atypical Cyclics such as Desyrel and Wellbutrin, and SSNRIs (selective serotonin noradrenergic reuptake inhibitors) such as Effexor. The antidepressant Serzone is classified both as an SSRI and a receptor antagonist.

Other changes in antidepressant prescribing are the use of more than one antidepressant at a time to help boost the primary drug. Cytomel, Lithium and Ritalin are used as booster medications to increase the effectiveness of the primary antidepressant.

(See the chart at the end of this article for antidepressant classifications.)

Mood Swings

As many as fifteen percent of people with MS may be bipolar (i.e. cycles of extreme high and low moods). If a person who is bipolar takes only an antidepressant, it can make their mood disorder more difficult to treat. They also need an anti-manic drug such as Lithium, Depakote or Zyprexa as well as the antidepressant to stabilize their emotions. Consult with your doctor to see which combinations of medications will help any individual person.

New Treatments for Depression – What’s on the Horizon

Emerging treatments for depression may target different neurotransmitters or use completely new therapies to achieve their aims. This is good news for the people for whom standard antidepressants will not work. Many of the new classes of antidepressants were originally designed for other purposes, but were also found to produce an anti-depressant effect. The eugeroic drugs, adrafinil and modafinil (Provigil), were designed as stimulants. They selectively enhance the activity of noradrenaline. The "highs and lows" associated with other stimulants are absent with eugeroics. Their unique action not only stimulates, but apparently improves the feeling of well-being in many patients.

Reboxetine also targets noradrenaline, but does so as a selective noradrenaline reuptake inhibitor(NARD). In a large trial with the elderly, nearly 88% improved their depression. Another study with over 500 participants showed Reboxetine to be equally if not more effective than Prozac, with few and minor side effects.

Yet another drug, Tianeptine, seems to function by working exactly opposite to the SSRIs. Tianeptine is a serotonin reuptake accelerator. While SSRIs increase serotonin, Tianeptine takes it out of circulation and, at the same time, it reduces the body’s response to stress. This drug is well tolerated and is particularly effective in depressed patients who also suffer from anxiety and disturbed sleep.

Another promising drug, Picamilon, shows both stimulatory and anti-depressive qualities. This anti-anxiety drug is an effective vasodilator, improving blood flow to the brain. While this drug counteracts both stress and anxiety, it doesn’t have a sedative action, and can have a mild stimulatory action. Although Picamilon produces a mild tranquilizing effect that counteracts stress, it does not induce muscle relaxation, lethargy or drowsiness.

In addition to the new types and formulas of antidepressants pouring into the market, other new therapies for depression are beginning to gain acceptance. Hormone therapy is one new method for treating depression, especially for people who don’t respond to many of the other antidepressants. Dr Andrew Herzog of the Beth Israel Deaconess Medical Center in Boston believes that some women can become depressed due to imbalances of estrogen and progesterone in their brains. He has had remarkable success treating women who were deemed “untreatable” with these hormones. “Hormones are psychoactive,” Herzog explains, “and there’s no doubt that they can have huge effects on our feelings.”

Before you can try hormone treatment for depression you must see a knowledgeable neuroendocrinologist to undergo a hormone profile, having your levels of progesterone and estrogen measured at the beginning and end of the month.

Another new method to relieve depression is vagus nerve stimulation (VNS), sometimes referred to as a pacemaker for your brain. The vagal nerve connects your brain stem to your upper body, relaying information to and from your central nervous system. VNS instigates changes in norepinephrine and serotonin, two neurotransmitters closely associated with mood. In 2003 Cybertronics, makers of the VNS, announced the results of a 235-patient clinical study on the safety and efficacy of VNS in patients with chronic or recurrent depression. Those results, and the results of the 60-patient pilot study, indicated that, “positive open trial results in a severe, treatment-resistant depression patient group suggest that VNS is a safe and effective treatment for a significant proportion of these patients.” In July 2005, the FDA approved VNS for depression patients who have run out of treatment options. More tests, however, will need to be done before the safety and efficacy of VNS can be firmly established. Also, the VNS device itself costs $12,000 and the cost of the surgery to implant it can run as much as $15,000. At present, insurance companies will not cover this still-experimental treatment.

An additional experimental treatment for depression is transcranial magnetic stimulation (TMS). In TMS the doctor moves a hand-held wire coil over the patient’s scalp. An electrical current passes through this wire to create a powerful magnetic pulse, which travels through the scalp to stimulate nerve cells in the brain. Researchers believe that they can target brain structures that are involved with the creation and maintenance of depression and anxiety. Studies indicate that TMS performed once a day for two or more weeks can relieve a typical patient’s symptoms by almost 30%.

Although this is still an experimental treatment, some hospitals and clinics offer it.

Herbal Warnings

Many people with MS explore the “natural” herbal treatments in preference to FDA approved medication but, according to a recent article in The Lancet, the use of St. John’s Wort can reduce the effectiveness of oral contraceptives, cholesterol-lowering drugs, asthma, migraine and seizures medications, as well as HIV treatments and immune drugs that prevent transplant rejection. About 50 drugs could be affected by this interaction. Since St. John’s Wort is an MAOI type antidepressant, there may also be adverse interactions with certain types of foods. It is important for patients to tell their MD about their use of any herbal products. Please report any serious adverse event associated with the interaction of prescription drugs and herbal products to the FDA.

Summary

Depression is a treatable symptom of MS. More than 50% of those with MS may suffer from depression during the course of their disease, but screening by health care providers can catch this condition, and a new range of antidepressants and treatments provide the means to combat this hidden MS symptom.

Antidepressant Chart

Upcoming Therapies

If you would like to learn more about upcoming drug therapies, please refer to “Depression – New Drug Treatments” by Robert Mason, Ph.D. (www.smart-drugs.com/depression-new-drugs.htm).

If you would like to read more about other new therapies, please refer to “Beyond Prozac: New Treatments, New Hope” by Lauren Slater (www.healthyplace.com/Communities/Depression/Site/story_depression_tx.htm).

If you would like to read Ann Crickmer’s original article “Depression Treatments for MSers”, please email your request to msakc@msakc.org or call 206-633-2606.

Was this information helpful? Then please consider making a donation. We are a small, independent nonprofit agency and are dependent on donations from our supporters. Thank you from all the staff at the MSA.

References and Bibliography

Crickmer, A., MSW. Depression Treatments for MSers . Multiple Sclerosis Association of King County, 1999.

Mason, Robert, Ph.D., Depression – New Drug Treatments. Smart-Drugs.com.

Slater, Lauren. Beyond Prozac: New Treatments, New Hope. August 2002.

VNS, Vagus Nerve Stimulation For Treating Depression . www.healthyplace.com

Rush, AJ, George, MS, et. al. Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study. Biol Psychiatry, Feb 2000, 15;47(4):273-5.

Schimelpfening, Nancy. The Future of Depression Treatments. About.com. Dec 11, 2003.

Rasgon, NL, Altshuler, LL, et. al. Estrogen replacement therapy in the treatment of major depressive disorder in perimenopausal women. Journal of Clinical Psychiatry, 2002;63 Suppl 7:45-8.

Soares, CN, Almeida, OP, et. al. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry, June 2001, 58(6):529-34.

Rush, John, M.D., Trivedi, Madhukar H. Primary Results for Sequential Treatment Alternatives to Relieve Depression (STAR*D) Study – Level 2 Results. National Institutes of Health (NIMH). New England Journal of Medicine, Mar 23, 2006.

Mixed News on Depression Drugs . CBS News.com. Mar 23, 2006.

Kanner, AM, Barry, JJ. The impact of mood disorders in neurological diseases: should neurologists be concerned? Dept. of Neurological Sciences, Rush Medical College. Epilepsy Behav. 2003 Oct;4 Suppl 3:S3-13.

Kanner, AM. Should neurologists be trained to recognize and treat comorbid depression of neurologic disorders? Yes. Epilepsy Behav. 2005 May;6(3):303-11.

Macritchie, KA, Young, AH. Emerging targets for the treatment of depressive disorder. Expert Opin Ther Targets Oct 2001. 5(5):601-612.

Crickmer, A., MSW. Maintaining a Sense of Well Being – MS and the Emotional Intensity Control Knob. Multiple Sclerosis Association of King County, 1999.

Joffe, R.T., Lippert, G.P., et. al. Multiple Sclerosis and Mood Disorders. Multiple sclerosis patients have a high incidence of depression and manic-depressive illness. Archives of Neurology, Apr 1987, Vol. 44, pp.376-8.

Koutsouraki, E., Tsavdaridou, Th., et. al. Depression and cytokines in multiple sclerosis. Presentation in ENS Congress, Milan, 1999. J. of Neurology, June 1999, Vol. 246, Suppl 1, 156.

Yirmiya, R. Depression in Medical Illness: The Role of the Immune System. West. J. of Medicine, 2000, 173(5):333-336.

Brown, D., N.D., Gaby, A.R., M.D., Reichert, N.D. Altering the Brain’s Chemistry to Elevate Mood:Phytomedicine Considerations. Extract from Depression (Natural Product Research Consultants), 1997.

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