Anxiety, Depression, Insomnia, Migraine, Fibromyalgia

These conditions, as a group, are known as neurotransmitter diseases (NTD). Neurotransmitters (NT) are chemicals that are used to relay, amplify and modulate signals between a nerve cell (neuron) and another cell. The NT normally associated with depression symptoms are serotonin, norepinephrine and (occasionally) dopamine. These three NT are in a chemical class known as monoamine NT.

The cause of anxiety and depression is mutifactorial, and so normally requires more than simply the replacement of the monoamine NT. The other factors include (but are not limited to) diet, nutrient deficiencies, lifestyle, concomitant disease states, pharmaceutical drugs, illicit drugs and relationships.

Alpine Physicians uses scientifically proven and effective methods developed by Marty Hinz, MD at NeuroResearch Clinics, Inc. to raise levels of monoamine NT in the brain. Caveat : The restoration of effective levels of NT via amino acid therapy or the re-uptake inhibition of NT by antidepressant drugs are both examples of the monoamine hypothesis.

The NeuroResearch protocols work very effectively; caveat, they are very supplement intensive and quite expensive. Neurotransmitter testing needs to be repeated until correct dosing is acheived, and this in itself can be very challenging for the patient. By supplement intensive the following example can be used: at level 3 dosing, the most intensive stage, doses of supplement are taken four (4) times daily with a total of 22 capsules. To reiterate - these protocols are very effective and take a lot of determination on the part of the patient to work as they should.

According to the monoamine hypothesis, NTD are caused by insufficient NT to effectively stimulate neuron signaling. NT deficiencies can be caused by:
· Deficient B-vitamins that are required to synthesize the neurotransmitters
· Lack of the amino acids required to build the neurotransmitters
· Hormone deficits leading to abnormal body metabolism in general and poor function of the brain and nerves specifically. For example, hypothyroidism is a leading treatable cause of depression
· Neurotoxins that interfere with normal neuron and neurotransmitter function. For example, the carbamate and organophosphate pesticides work by inhibiting cholinesterase. Cholinesterase is an important enzyme of the nervous system, and if it is not present, as in the case of pesticide poisoning, the nerves do not function and muscles do not work. Respiratory failure can be a consequence leading to death

Depression, anxiety and sleep drugs. Drugs such as Zoloft, a selective serotonin reuptake inhibitor (SSRI), and Cymbalta, a serotonin and norepinephrine reuptake inhibitor (SNRI), work by keeping neurotransmitters from being removed from the synapse or space between nerve cells. Although the precise mechanism of action isn't clear, it's thought that keeping the neurotransmitters in the synapse enhances neurotransmission — the sending of nerve impulses — and so improve and elevate mood. (http://www.mayoclinic.com/health/antidepressants/MH00067).

Why not take prescription antidepressants?
The problem is, the SSRI and SNRI drugs do nothing to increase the body’s supply of neurotransmitters. Over time, people treated with the antidepressant drugs experience even lower levels of neurotransmitters due to breakdown within nervous system by normal enzymes such as monoamine oxidase (breaks down serotonin, norepinephrine and epinephrine and dopamine). Over time the drugs loose effectiveness. Medications that work with neurotransmitters do not work if there are not enough neurotransmitters with which to work. When the drugs quit working the symptoms of the disease return; this includes depression, anxiety, insomnia, fibromyalgia, and migraine (Sumatriptan or Imitrex).
All of the drugs that work with neurotransmitters deplete the neurotransmitters, making the cause of the problem worse. Conventional practice is to increase the dose of antidepressant, change drugs or add other drugs; this burns out and depletes the neurotransmitters even more and none of the drugs have a beneficial effect. The only way to increase central nervous system neurotransmitters levels in the brain is to provide the amino acids that are used to synthesize them in the body.

SSRI and SNRI Discontinuation Syndrome
Drugs that deplete the neurotransmitters create conditions where the person feels much worse when they try and stop the reuptake inhibitor drug. A growing number of discontinuation reactions have been described relating to SSRIs. Discontinuation reactions have been reported for all the SSRIs in clinical use today. They are: Fluoxetine (Prozac); Fluvoxamine (Luvox); Paroxetine (Paxil); and Sertraline (Zoloft). Although no double-blind studies comparing discontinuation from different SSRIs have been published, data on relative incidence of discontinuation symptoms have been gleaned from several venues.
The symptoms have been misdiagnosed or diagnosed as a side effect of another disease, syndrome or medication. There are several terms used to categorize these symptoms such as, SSRI Discontinuation Syndrome, or Serotonergic Withdrawal Syndrome. Remember, that a syndrome is a group of symptoms. The four most common symptoms in one study included dizziness, nausea, lethargy, and headache. Other symptoms include anxiety, parasthesia, confusion, tremor, sweating, insomnia, irritability, memory problems, and anorexia.
Haddad, P. (1997). Newer antidepressants and the discontinuation syndrome. Journal of Clinical Psychiatry, 57, (7), 17-21.
Dominguez, R.A. & Goodnick, P.J. (1995). Adverse events after the abrupt discontinuation of paroxetine. Pharmacotherapy, 15, (6), 778-780.


History and evolution of the monoamine hypothesis of depression
The symptoms of depression can be improved by agents that act by various mechanisms to increase synaptic concentrations of monoamines. This finding led to the adoption of the monoamine hypothesis of depression, first put forward over 30 years ago, which proposes that the underlying biological or neuroanatomical basis for depression is a deficiency of central noradrenergic and/or serotonergic systems and that targeting this neuronal lesion with an antidepressant would tend to restore normal function in depressed patients. The hypothesis has enjoyed considerable support, since it attempts to provide a pathophysiologic explanation of the actions of antidepressants. However, in its original form it is clearly inadequate, as it does not provide a complete explanation for the actions of antidepressants, and the pathophysiology of depression itself remains unknown. The hypothesis has evolved over the years to include, for example, adaptive changes in receptors to explain why there should be only a gradual clinical response to antidepressant treatment when the increase in availability of monoamines is rapid. Still, the monoamine hypothesis does not address key issues such as why antidepressants are also effective in other disorders such as panic disorder, obsessive-compulsive disorder, and bulimia, or why all drugs that enhance serotonergic or noradrenergic transmission are not necessarily effective in depression. Despite these limitations, however, it is clear that the development of the monoamine hypothesis has been of great importance in understanding depression and in the development of safe and effective pharmacologic agents for its treatment.
Hirschfeld, RM. History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry. 2000;61 Suppl 6:4-6.

And another view . . .

Depression: the case for a monoamine deficiency
The monoamine hypothesis of depression predicts that the underlying pathophysiologic basis of depression is a depletion in the levels of serotonin, norepinephrine, and/or dopamine in the central nervous system. This hypothesized pathophysiology appears to be supported by the mechanism of action of antidepressants: agents that elevate the levels of these neurotransmitters in the brain have all been shown to be effective in the alleviation of depressive symptoms. However, intensive investigation has failed to find convincing evidence of a primary dysfunction of a specific monoamine system in patients with major depressive disorders. Understanding of the etiology of depression has been hampered by the absence of direct measurements of monoamines in humans. However, the monoamine depletion paradigm, which reproduces the clinical syndrome, allows a more direct method for investigating the role of monoamines. Results from such studies show that antidepressant responses are transiently reversed, with the response being dependent on the class of antidepressant. In contrast, monoamine depletion does not worsen symptoms in depressed patients not taking medication, nor does it cause depression in healthy volunteers with no depressive illness. In conclusion, it is clear that antidepressant agents in current use do indeed require intact monoamine systems for their therapeutic effect. However, some debate remains as to the precise role that a deficiency in monoamine system(s) may play in depression itself.
Delgado, PL. Depression: The case for a monoamine deficiency. J Clin Psychiatry 2000; 61 Suppl 6:7-11·