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DEPRESSION
A very common consequence of TBI resulting either from damage to the part of the brain which regulates mood, the psychological reaction to being disabled, or both. Depression is associated with insomnia, decreased concentration, reduced memory encoding and increased irritability. Depression is both a result of and a contributor to stress. As depression and stress re-enforce each other, the sufferer becomes short, snappish and biting towards others, including the people trying to help her. Recent research demonstrates that brain output of serotonin (a key neurotransmitter for leveling out mood) is suppressed by increased output of stress hormones from the pituitary-hypothalamic-adrenal system. Major depression is associated with hopelessness, suicidal thoughts and impulses. The National Institute of Mental Health recently did a survey of 8,000 people about their mood and sleeping habits. The survey indicated the following. Of the 10% of responders who had insomnia, 50% had a psychiatric disorder. Of the 90% who slept normally only 7% had a psychiatric disorder. 60% of those who complained of serious insomnia were seriously depressed.

Anti-depressants are a mainstay of drug treatment for people with a TBI, because good anti-depressants not only improve mood, but may help with insomnia, headaches or both, as well. This is because a deficiency in serotonin is a primary factor in causing depression and migraine, and some cases of insomnia. Older agents called tricyclic anti-depressants (Elavil, Pamelor and Sinequan) help depression and are effective in migraine prevention (reducing the frequency of migraine by 50% or more). Elavil in particular helps many patients sleep better. However, these drugs have side effects, such as weight gain, dry mouth, constipation and sedation. Wellbutrin should not be used by persons with a history of TBI or epilepsy. Newer agents called SSRIs (selective serotonin re-uptake inhibitors) are as effective as the tricyclics in alleviating depression with less side effects, but they do not prevent migraine. Examples of SSRIs are Prozac, Zoloft, Paxil, Celexa and Luvox. SSRIs make some patients drowsy, especially Luvox, and for these patients it is best to take the medicine at night just before bed. Some people lose sex drive on SSRIs, and continue to take them in combination with Viagra or testosterone. Celexa apparently has less of a dampening effect on sexuality than Zoloft. Some people who do not respond to swallowing a Prozac pill, do better with sublingual administration. In Feb. 2001 the FDA approved a once-a-week formulation of Prozac called Prozac Weekly. This takes advantage of the 4-6 day half-life of the drug in the human body, and will be a boon to people who either dislike daily doses of the medication or cannot remember to take their pill. Approximately 1 out of 10 consumers suffered headache, nervousness, runny nose or fatigue as a side effect of the weekly pill. J. Clinical Psychiatry 2000; 61:851-857.

Some of the SSRIs are helpful with obsessive-compulsive disorder (OCD), especially Prozac and Paxil. However, patients already taking BuSpar for anxiety or OCD should not take Prozac, as taking both worsens their condition. A new combination drug called Effexor (containing an SSRI and an adrenaline booster) has proven of great benefit to some depressed patients who did not respond to an SSRI. Effexor stimulates alertness as well as improving mood. For some patients an anti-depressant that worked well initially may gradually lose its effect as the body grows less responsive. When this occurs it is generally better to try a new anti-depressant rather than keep increasing dosage. People who decide to stop taking an SSRI need to taper their dosage instead of going cold turkey. Suddenly stopping Zoloft or Paxil is associated with "rebound depression," in which the depression comes back more severely than the depression the patient had when he started the pill. Some TBI patients are trying St. John's Wort for depression. FDA studies are now underway. Although it may help, it appears to have toxic interactions with some medications, such as cyclosporin (Neoral), warfarin (coumadin) and the protease inhibitor indinavir (crixivan). A word of caution. People taking any anti-depressants should avoid alcohol, as co-consumption increases the bad effects of alcohol. Anyone taking a tricyclic or SSRI anti-depressant must stop for at least two weeks before starting an MAO inhibitor (Parnate, Nardil) or death can result from hypertension or convulsions.

SSRIs are only effective in 2/3rds of depressed patients. Researchers are actively seeking alternatives for the 1/3rd who do not respond. The May-June issue of the Journal of Psychiatric Research discussed a new drug now in Phase II FDA trials which offers some hope to these people. The drug works by dampening the stress response. It blocks the action of CRF (corticotropin releasing factor) in the brain. CRF is what tells the pituitary gland to secrete ACTH (adrenocorticotropic hormone) which stimulates the release of stress hormones like cortisol. People who suffer from anxiety, and some depressed patients, become highly stressed in response to small irritations and disappointments of life, because their brains produce an excessive amount of cortisol. Wylie Vale, Phd is the neuroendocrinologist at the Salk Institute for Biological Studies who has done the pioneering work on these compounds during the past 20 years.
Anti-depressants are a very important part of the treatment for depression following TBI. However, they do not supplant or extinguish the need for neuropsychological counseling. Following a TBI there are many cognitive and psycho-social issues which must be addressed to restore normal functioning and to achieve successful reintegration into family, work and community. The context in which the TBI occurs must always be considered. A TBI will have different impacts on people depending on gender; stage of life; and whether they are single, married, childless or parents. Some psychologists counsel TBI patients within the framework of Eric Erikson's personal development scheme or Maslow's hierarchy of needs.
Aging is another factors associated with depression. In women aging brings menopause. Recent studies show that peri-menopausal as well as menopausal women may be depressed as a result of low estrogen, and will feel better after going on a hormone replacement such as Premarin. If a woman who is taking Premarin sustains a TBI and becomes depressed, we can then be pretty sure that estrogen levels play no factor in her post-TBI depression. This is an issue that comes up in TBI litigation, because insurance company doctors are quick to blame menopause for a host of difficulties caused by a TBI. Another recent study showed that depressed pre-menopausal women showed better outcomes on Zoloft (sertraline) than Imiprimine; whereas age-matched men with depression did better on Imiprimine than Zoloft. The authors concluded that high estrogen levels may make for increased responsiveness to SSRIs like Zoloft, and caution physicians to always consider gender and menopausal status when prescribing anti-depressants. See American Journal of Psych. 2000; 157:1445-1452.

Aging also brings a sharp drop in blood levels of DHEA, the adrenal steroid known as dehydroepiandrosterone. The brain tissue of young adults has 6.5 times the level of DHEA as other bodily tissues. The depletion of DHEA in older adults has been associated with cognitive decline and Alzheimer's.

Addition of small amounts of DHEA to neurons in vitro has stimulated explosive growth of synapses. Putting DHEA into the diets of rats has improved their memories. New research on depression suggests that a missing part of the equation is excessive levels of cortisol (the stress hormone). High levels of cortisol in the blood appear to trigger mood disorders, including depression. Biological psychiatrists are looking for ways to reduce blood levels of cortisol including inhibition of steroid synthesis by use of ketoconazole. According to R. McQuade and AH Young, DHEA holds much promise because it is a natural, non-toxic substance that can block the glucocrticoid receptors which bind with cortisol. See British Journal of Psychiatry 2000; 177:390-395.

Any medication powerful enough to relieve or mitigate depression is going to have side effects. Each anti-depressant has its own side effect profile, which should be checked out with the prescribing physician and the PDR. Commonly known side effects include fluid retention with weight gain, feeling jittery or fatigued and loss of sex drive. Some side effects are not well known. Persons with a previous history or family history of bi-polar disorder may become acutely manic on anti-depressants, while persons with a previous history or family history of schizophrenia may become acutely psychotic from taking them. See Journal of Clinical Psychiatry 2001;62(1):30-3. Use of lithium therapy can relieve or reduce problems with anti-depressant associated mania. Journal of Clinical Psychiatry 2001;62(4):249-255.

Given medication side effects, there has been interest in natural remedies for depression. Scientific studies on the efficacy of St. John's Wort have been mixed, some finding an effect greater than placebo and others not.

A recent study found that 1 gram per day of EPA (the Omega 3 fatty acid called eicosapentaenoic acid) did improve depression better than placebo in chronically depressed patients, see Archives of General Psychiatry 2002;59:913-919. This is not surprising since deficiency of Omega 3 fatty acids has long been associated with brain dysfunction, including memory loss and depression. This subject is discussed at greater length in the Nutrition Section of this website.