GH3 - GEROVITAL Articles (VII)The Anti-depressant Effects of Gerovital-H3® Treatment
By Mircea Dumitru M.D. PhD.As people grow old, the brain undergoes macroscopic, microscopic, biochemical and electrophisiological changes. The number of neurons (nervous cells) decrease, dendridic changes occur (the link among cells), as well as neurofibrillas and plates (described by Marinescu and Block) appear in the nervous cells.
Recent data shows that neuron losses do not occur in all the brain's area (for instance, the parietal area). There are markers which confirm the aging process: ischemia, plates of lipofuscin, neurofibrillas (a net of intraneuronal fibres very frequent in Alzheimer's disease). The prefrontalis and frontalis are the areas most altered by aging. Changes also occur within the cerebral vascular system: haemorrhages, atheromatous plates and obstruction of some small vessels.
The cognitive changes are quite normal in the elderly (the topic is still under discussion). Nevertheless, old age brings about changes of the intellectual ability). The impairment of the cognitive functions begins about age of 35-40, although being insignificant till the age of 60-65. The primary memory (sense memory) and the long-term memory do not change. On the contrary, the short-term memory (from 1 hour to 1 week) is altered. The elderly can hardly remember the names and the events that happened and the things they read over this period. The use of calendar and written notes help them most. It is very easy for the elderly to remember knowledge stored in the past to which their lifetime experience is added.
Effects of Old Age
The decrease of the psychomotory activity is another important feature of old age, which is obvious in everyday life (the subtle movements lose their accuracy, the reaction speed lowers). With normal aging these changes do not infringe upon the elderly's independence and ability to meet their own needs.
The above mentioned changes are normal in the elderly. Biochemical changes of the neurotransmitting systems (GABA, dopaminic, cholinergic and serotoninic) and the influence of some exogenous factors bring forth the metabolic changes which cause depression's onset. In the presence of an old patient with cognitive impairments and changes of behaviour, the geriatrician and the psychologist should distinguish the trilogy:
Is it a normal change?
Are they the indices of a depression?
Is it an incipient Alzheimer's disease?
In general, the patients suffering from depression exaggerate their sufferings, while those with Alzheimer's disease or with other incipient dementias deny or minimise them.Depression
Depression is one of the elderly's major diseases. It is also frequent in adults. Depression is a syndrome (a series of symptoms) including physiological, emotional and cognitive symptoms. The criteria worked out by The American Psychiatric Association in The Diagnostic and Statistical Manual of Mental Disorders (3rd revised edition) include:
Change of appetite and weight.
Sleep disorders.
Inner strain or belated motory reactions.
Lack of energy, fatigue.
Nervousness.
Concentration and memory disorders.
Lack of pleasure and interest in almost any kind of activity.
Tendencies of guilt.
Thought or attempt of suicide.
The presence of 5 of these symptoms shows a major depression fit. These symptoms are often assigned to normal age, both the physician and the patient being mostly concerned with physical diseases and ignoring depression.In the elderly, depression occurs within a complex clinical and social context. The older patient may suffer from 2-3 or even more diseases, some of them leading to infirmities, and the social relationships may be non-existent. The diagnosis of depression should be preceded by a thorough analysis of the patient's present state and case history. The clinical history, physical examination and bilogical check-up, as well as a study of the social background are current possibilities of assessing the diagnosis of depression.
Some author consider that many elderly have a depressive state. According to the National Health Institute of Bethesda, 30% of the elderly (over 65) suffer from depression. Other researchers mention a higher rate - 50% and even more in the elderly of the 8th, 9th and 10th age decades. This suffering often remains hidden, unknown, being masked by physical diseases, and neither the patient nor the care staff, homes for the aged, nursing homes for the elderly people recognise it.
Despite the great progress of diagnosis, treatment and care of these patients, many aspects of depression are still unsettled. For the readers of this article interested in the promotion of an active life, it is important to know:
The conditions and factors responsible for the depressive states;
The peculiarities of depression in the elderly, and
The treatment.
For women who lead a life of deprivation i.e., widows stressed and lacking a moral and economic support - often suffer from depression. After the age of 65, chronic diseases such as cancer, stroke, diabetes, mellitus, deforming and painful arthritis, by their nature multiply the implications and induce a depressive state. Half of the patients suffering from depression have several episodes during their life span. Suicide and suicidal tendencies are frequent after the age of 80.Polymorbidity
Depression in the elderly is not quite different from the adult's depression. After the age of 65, polymorbidity (association of several diseases in the same patient) is very frequent. The somatic disorders - cardiovascular, digestive, respiratory, loss of weight - raise several questions as concerns the positive and differential diagnosis. 20-30% of the patients have a depression which is mostly masked by an organic symptomatology. The visceral symptomatology is expressed subjectively only under the form of cenestopathic symptoms of a hypochondriac type. These symptoms mostly occur in adult women. Certain disorders which point out "de facto" a visceral suffering may be wrongly assigned to a depressive state. The phenomenologic analysis of depression's symptomatology will reveal the circadian variation, much more obviously in the morning when the incidence of suicide is at its greatest.
Therapy
Any depressive symptom may impair life's quality, so a therapy is absolutely necessary. The treatment may be medical and psycho-social. To be effective, the treatment should be administered over a period of time and in optimum doses.
Since 1945, Prof. Aslan had been injecting procaine into patients with painful arthritis in order to relieve their joint pains. Many of her patients noted an improving memory, less depression, more energy and a generalised feeling of well-being. These results encouraged her to carry out additional studies to test the effects of procaine on thousands of patients. She found that by adding an antioxidant, the procaine molecule was stabilized and the effects were more than with procaine alone. She called her improved form, Gerovital-H3®.
Aslan said that "due to the effects of its main active elements, the procaine and procaine's metabolites - paraaminobenzoic acid (PABA) and diethylaminoethanol (DEAE) -, Gerovital-H3® belongs to Pregeriatric and Geriatric drugs having an eutrophic effect on the organism". Starting from 1949, she noticed an obvious improvement of the physical state in old people. Gerovital-H3® acts upon the human body participating in the regulation of the intermediary metabolism, acetylcholine synthesis and inhibits the monoamineoxidase (MAO). MAO is an enzyme that catalyses the breakdown of monoamines (dopamine, epinephrine and norepinephrine) which play a transmitter role between nervous cells. A MAO inhibitor blocks a breakdown of certain monoamine neurotransmitters and that can used to treat depression. Robinson and his colleague, in the 'Lancet' magazine, Feb.,1972 (1), showed that starting around the age of 40, the level of MAO increase is directly related to the aging process and depression phenomena.
Gerovital-H3® has a certified antidepressive effect, especially in light and moderate depressive syndrome, thanks to its MAO-inhibitory effect. The antidepressive effect of Gerovital-H3® as well as the lack of any side effects can be accounted on the fact that it is a reversible and competitive-MAO inhibitor.
Paul Luth (2) mentioned that "procaine influence on the patient's psychic condition was signalled for the first time in the medical literature by Aslan". Subsequent to Aslan's investigations on the psychic effect of procaine (3), Pfeiffer (4) carried out pharmacological studies on demethylaminoethanol (DMAE) action and noticed a mental stimulation. This study placed emphasis on the relations existing between DMAE and acetylcholine. DMAE breaks through the blood-brain barrier taking part in the metabolic process of the nervous cells fixing their proteic and lipid fractions and changes into choline and acetylcholine.
Hrachovec, from Los Angeles University, published in 1972 the results of a comparative study showing that Gerovital-H3® has an inhibitory effect upon the MAO-brain, liver and the heart of the rabbit (5).
Gerovital-H3® Mechanisms
Yau made a pharmacological study upon Gerovital-H3® and summarised as such its basic mechanisms (6):
It competitively and reversibly inhibits the MAO;
It acts as an antidepressive through the modification of the monoamine level in the brain and it is very selective in the oxidative desamination inhibition;
The oxidative desamination of monoamines is done in such a way as to eliminate the hyper-blood-pressure peaks so typical after administering other MAO inhibitors.
McFarlane proved the increasingly inhibitory action of Gerovital-H3® upon MAO from 17.8% to 87.7% depending on the dose administered (7). McFarlane appreciated Robinson's important contribution to the understanding of a biochemical modification connected with the ageing process. He noticed that Gerovital-H3® induces a stronger MAO inhibition than the normal procaine hydroclorate and its action is reversible and competitive (8).Depression Treatment
William Zung from Duke University, North Carolina, applied Gerovital-H3® treatment for 28 days, using the double-blind method, on three groups of patients who suffered from depression (9). One group of patients aged 60 were submitted - before, during and after the treatment - to a battery of psychological tests (Zung is the author of a well-known scale of psychological tests) which proved the Gerovital-H3® efficiency in the treatment of depression.
In a double-blind study (10) conducted on depressive patients, the antidepressive effect of Gerovital-H3® was evaluated by means of psychiatric and psychological investigations. The tests on depression showed a higher percentage of improvement for Gerovital-H3® treated patients. The following items were alleviated: depressed mood, sociability and fatigue-70%, agitation-60%, anxiousness and hypochondriasis-45%.
Durk Pearson and Sandy Shaw noted in their book, "Life Extension" (a national best-seller): "here is how you might be able to better handle depression... MAO increases in activity with age, thus resulting in lowered levels of these signal-transmitting brain chemicals. Procaine - or the procaine compound Gerovital-H3® (GH3) developed by Dr. Ana Aslan of Romania, is a mild reversible MAO inhibitor. When using most MAO inhibitors, it is necessary to avoid excessive dietary intake of monoamine precursors such as the amino acids tyrosine and phenylalanine to avoid too high levels of the monoamines, which can lead to higher blood pressure. Procaine - or GH3 - does not interfere".
Recently, I did a double-blind study (unpublished) on 50 patients with low, moderate and severe depression. After two series of treatments, the difference was statistically significant between the patients with Gerovital-H3® and placebo. The Hamilton score was constantly positive and the medium reduction was significant (p=0.0001) much more so for Gerovital-H3® than for the placebo. All the statistics were proved with the technique of Covariance analysis.
REFERENCES
Robinson D.S.et al.: Aging. Monoamine and Monoamineoxidase Levels. Lancet, 1972, p.290.
Luth P.: Uber die Allgemeinwirkung des Procains in ihren Zusammenhang mit Gehirnstoffwechsel. Arztl. Forsch. 1959, 4, p.177-186.
Aslan Ana: Novokain als Eutrophischer Faktor und die Moglichkeit einer Verlangerung der Lebensdauer. Therapeutische Umschau, 1956, 9, p.165-172.
Pfeiffer C.C. and al.: Stimulant Effect of 2-Diethylaminoethanol a Possible Precursor of Brain Acethylcholin. Science, 1957, 3274, p.610.
Hrachovec D.J.: Inhibitory Effect of Gerovital-H3® on MAO of Rat Brain, Liver and Heart. The Physiologist, 1972, 15, p.3-20.
Yau T.M.: Gerovital-H3®, MAO and Brain Monoamines. Symp. on Theoretic Aspects of Ageing. Florida, Miami, Febr. 1974.
McFarlane M.D.: Procaine (Gerovital-H3®) Therapy: Mechanism of Inhibition of MAO. J. of Amer. Geriatrics Soc. 1974, XXII/8, p.365-371.
McFarlane M.D.: Aging, Monoamine and MAO Blood-levels. Lancet, 1972,II, 7772, p.337.
Zung W.W. et al.: Pharmacology of Depression in the Aged: Evaluation of Gerovital-H3® as an Antidepressant Drug. Psychosomatics, 1974, 15, p.127-131.
Balaceanu C.S. et al.: Double blind Study Concerning the Antidepressive Effects and the Clinical Tolerance of Gerovital-H3®. Romanian J. of G. & Geriatrics, 1996, Tome 1-2, Vol. 17, p.46-61.
Durk Pearson and Sandy Shaw: "Life Extension", 1983, Printed in the USA, A Time Warner Company.
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