Food and Nutrients in Disease Management
escitralopram and citalopram (P = 0.03).35 Treatment of the elderly in the primary care setting under the monoamine theory reveals no relief
of symptoms versus placebo. In the elderly (79.6 years, SD = 4.4, N = 174), it was concluded that citalopram, “was not more effective than placebo for the treatment of depression.”27 In treatment of
depression in patients over 60 years of age with a mean age of 68 years, “Escitalopram treatment was not signifi cantly different from placebo treatment” (N = 264).29
Depression treatment of children and adolescents ages 7 to 17 (N = 174) with citalopram, under a double-blind 20 mg/day, 40 mg/day option, found 24% of patients treated with placebo showed
improvement versus 36% of patients taking citalopram.28 Other studies of other reuptake inhibitors revealed similar results.50–55 Reuptake inhibitors are effective in treating other disorders than those for which they were initially
developed, such as obesity, panic disorder, anxiety, migraine headaches, ADHD/ADD, premenstrual syndrome, dementia, fi bromyalgia, psychotic illness, insomnia, obsessive-compulsive
disorder, and bulimia/anorexia; yet not all drugs that increase serotonin or catecholamine transmission are effective when treating depression.1
Treatment with reuptake inhibitors is based on the monoamine theory, which does not explain why most subjects studied achieve results no better than placebo and why treatment is much less
effi cacious in the elderly. Neither does it explain the effi cacy of treating other conditions. In sum,the mechanism and corresponding medication for the treatment of depression suggest there may be
more to the underlying pathophysiology.
<b>Parkinsonism Model</b>
Insights into the pathophysiology of depression can be gained from understanding another monoamine neurotransmitter disease, Parkinson’s disease. Parkinsonism is caused by damage to the
dopamine postsynaptic neurons of the substantia nigra at levels that result in clinical compromise of fi ne motor movement.Parkinson’s disease has a study model of neurotoxin damage.49 A great deal of understanding about
Parkinson’s disease has resulted from research and case studies involving the neurotoxin MPTP (1-methyl4-phenyl 1,2,3,6-tetrahydropyridine). In 1982, the fi rst writings on MPTP appeared in the medical literature after several heroin addicts administered synthetic heroin (MPPP) that contained the byproduct
of synthesis, MPTP.9 Since that time, the MPTP mechanism of action has become the prototype in the study of Parkinson’s disease. At present, most medical school students study the ability of MPTP to
quickly induce advanced Parkinson’s symptoms in patients without prior history of the disease.MPTP is a free radical neurotoxin, which interferes with mitochondrial metabolism and leads
to cell death (apoptosis). It freely crosses the blood-brain barrier and has an affi nity for the postsynaptic dopamine neurons of the substantia nigra, which it destroys. MPTP is chemically similar
to MPPP (synthetic heroin) and may be produced as a byproduct during the illegal manufacturing of MPPP and other narcotics.9 The MPTP model of Parkinson’s disease has taught us a lot about
the dopamine neurons of the substantia nigra. The main point is that if enough dopamine neurons are damaged, the fl ow of electrical impulses is compromised and Parkinson’s symptoms will occur.
The way to compensate for neurotoxin-induced damage is to increase neurotransmitter levels higher than is normally found in the system.9 Consistent with the fi ndings of the MPTP model, the pharmacologic treatment is dopamine
agonists, which raise the existing levels of this neurotransmitter above population norms in order to boost damaged neurons. Dopamine agonists, such as bromocriptine, pergolide, ropinirole, pramipexole,
and cabergoline can be used as a monotherapy or in combination with L-dopa. L-dopa crosses the blood-brain barrier and is freely synthesized into dopamine without biochemical regulation.3
The elevation of dopamine in the central nervous system stimulates the remaining viable dopamine neurons of the substantia nigra by increasing the electrical fl ow, which results in restoration of the
regulator function of the dopamine bundles and improvement of disease symptoms.7 The shortcoming is tachyphylaxis, where the dopamine agonist and/or L-dopa become ineffective.
With Parkinson’s patients, establishing dopamine levels in the reference range reported by the laboratory does not provide relief of symptoms. For example, the reference range of urinary dopamine
reported by the laboratory is 40 to 390 micrograms of dopamine per gram of creatinine (the neurotransmitter-creatinine ratio compensates for dilution of the urine). In our years of research,
we have not observed a patient with Parkinson’s who