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Monoamine Oxidase
Monoamine Oxidase is an enzyme that catabolizes monoamines. Monoamines are serotonin, dopamine, epinephrine, norepinephrine, GABA, melatonin, and histamine; yes, the term monoamines refers to neurotransmitters that have one amino acid group hence mono (meaning one) and amine (from the term referring to the origin of the amino acid: ammonia).
There are two types of Monoamine Oxidase: MAO-A and MAO-B.
MAO-A brakes down serotonin, norepinephrine and epinephrine while MAO-B mainly catabolizes phenethylamine. Dopamine is broken down by MAO-A and MAO-B.
Role of Monoamines
Dopamine: execution on movement, inhibition of prolactin, memory, attention, problem solving and other neuro-cognitive functions, motivation, pleasure, and reward seeking behavior.
Synthesis: phenylalanine.
Serotonin: regulation of insulin and Insulin like Growth Factor (IGF), serotonin effects appetite, sleep, and general metabolism, and blood vessel constriction. Modulates mood, anger and aggression. Stimulates cells to repair the liver and promotes osteoclasts activity.
Synthesis: tryptophan.
Epinephrine(adrenaline): It is involved in the fight-flight response: increases blood perfusion to the brain and skeletal muscles and diminishes blood supply to the GI tract. Suppresses the immune system and elevates blood sugar and breaks down lipids in cells.
Synthesis: phenylalanine.
Norepinephrine (noreadrenaline): involved in the fight-flight response. Increases blood pressure and
drops heart rate.
Synthesis: Dopamine which in turn is made from phenylalanine.
GABA: Regulates neuronal excitability and muscle tone.
Synthesis: Glutamate.
Histamine: Regulates sleep, is involved in inflammation and immune responses, has erectile and sexual functions. Protect against convulsion, stress, and ischemic lesions.
Synthesis: histidine.
Melatonin: antioxidant (mainly protects nuclear and mitochondrial DNA), regulates circadian rhythms. Enhances immune functions.
Synthesis: Tryptophan.
Phenethylamine: Acts as a releasing agent of dopamine and norepinephrine.
Synthesis: Phenylalanine.
Amino Acids Deficient in Depression
It is of common knowledge that dopamine and serotonin are the main neurotransmitters affected in people with depression. If we take a closer look to the previous list of monoamines and their functions it will be noticed that phenylalanine and tryptophan are deficient in patients with depression; these amino acids are also essential for the synthesis of other neurotransmitters: Melatonin, Phenethylamine,Norepinephrine, and Epinephrine .
It is not surprising to see a big conglomerate of signs and symptoms in people with depression: insulin resistance, high levels of homocysteine, interlukin and tumor necrosis factor besides the well known signs and symptoms of apathy, sadness, emptiness, guilt, feeling of worthlessness, polyphagia or decreased appetite, insomnia or excessive sleeping, impaired immunity, and decreased libido among others sexual problems.
Allopathic Approach to Depression
The conventional approach to depression is the use of the following medications MAOI (Monoamine Oxidaze Inhibitor) SSRI (Selective Serotonin Reuptake Inhibitor), TAC (Tricyclic Antidepressants), Tetracyclic Antidepressants (Tricyclic and Tetracyclic are known as heterotricyclic), Serotonin Modulators (5-HT2 Blockers), Norepinephrine-Dopamine Reuptake Inhibitors (NDRI), and SNRI (Serotonin-Norepinephrine Reuptake Inhibitor) and Electroconvulsion Therapy.
List of Medications
Heterocyclic Antidepressants: amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine,
maprotiline, nortryptiline, protriptyline, and trimipramine.
Selective Serotonin Reuptake Inhibitors: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline.
Monoamine Oxidase Inhibitors: isocarboxazid, phenelzine, selegiline, tranylcypromine.
Serotonin Modulators: mirtazapine, nefazodone, trazodone.
Serotonin-Norepinephrine Reuptake Inhibitors: duloxetine, venlafaxine, desvenlafaxine
Norepinephrine-Dopamine Reuptake Inhibitors: bupropion.
The Logic Behind the Medications
TAC: This medications inhibit the reuptake of serotonin and norepinephrine by blocking the serotonin and
norepinephrine transporter (SERT and NET respectively) which in turns increases the levels of serotonin and norepinephrine. The higher the level of serotonin the lower the level of melatonin and viceversa, usually melatonin increases while serotonin decreases: melatonin is metabolized from serotonin. Insulin and serotonin increase accordingly: higher levels of serotonin means higher levels of insulin. Insulin is required in order to increase bio-availability of tryptophan; the downfall is that it might cause insulin resistance which leads to diabetes. An analysis of the functions of melatonin and serotonin will make evident that this medication will cause an imbalance on the circadian rhythms, an increase on blood pressure, GI tract disorders; because norepinephrine activates fight-flight response a reduction on blood flow to the GI tract will be observed leading to slow metabolism and absorption of nutrients from the GI tract leading to poor nutrient assimilation and weight gain. Norepinephrine increases blood flow to the brain which explains why people suffer from blurred vision and dizziness when taking TAC's. Muslce stiffness and twitches are present: remember this medication activates the fight-flight response making the muscles the primary target.
Cyclics effect every receptor in the CNS which includes Histamine and Muscarinic receptors among others.
Some TAC's medications are: Anafranil, Adapin, Aventyl, Elavil, Norpramin, Pamelor, Pertofrane, Sinequan, Surmontil, Tofranil, and Vivactil.
MAOI: There are 3 types known, the one that does not discriminate and inhibits MAO-A and MAO-B and those that do discriminate and only inhibit MAO-A or MAO-B. MAOIs work by inhibiting the production of monoamine oxidase which catabolizes serotonin, epinephrine, norepinephrine and dopamine with the aim of increasing blood levels and make them bioavailable. The problem with MAOI is that they increase tyramine levels in the blood. Tyramine is synthesize from Tyrosine. Tyramine acts as a releasing agent of dopamine, epinephrine, and norepinephrine. An increase in tyramine means an increase on dopamine, epinephrine and norepinephrine therefore we will see similar side effects as with TAC's. Consumption of tyrosyne containing food will elicit the "cheese effect" where the person will have high blood pressure, headaches, and racing heart. This medication and the TAC are used as a last results due to the severe side effects.
Some MAOI medications are: Parnate, Nardil, and Marplan.
SSRI: This medication selectively inhibits the reuptake of serotonin. The side effects are logic: serotonin is
involved in the appetite, sleep, and general metabolism, and blood vessel constriction. Modulates mood, anger and aggression. Stimulates cells to repair the liver and promotes osteoclasts activity. An increase on serotonin means an effect on any of the functions it regulates.
According to the Journal of Psychopharmacology Jan 1998; vol. 12: pp. 396 - 400: SSRI's cause hyponatremia which is an imbalance
of the sodium electrolyte(calcium, chloride, magnesium and potassium are the most common electrolytes in the human body besides sodium). This sodium imbalance can cause headache, fatigue, weakness and nausea as first symptoms. More severe cases can result in confusion, seizure, coma and death. This sodium imbalance might explain why patients get headaches, fatigue, weakness or nausea when taking SSRI. Low sex drive and inability to experience orgasm or retardation of ejaculation are other symptoms which are due to their effect of different type of serotonin receptors (each receptor has effects and affects different physiological aspects of the human body).
Some SSRI medications are: Celexa, Lexapro, Luvox, Paxil, Prozac and Zoloft.
SNRI: Increases amount of serotonin and norepinephrine in the synaptic gap. At this point we should have
an idea of the possible side effects of this type of medication based upon the functions of serotonin and norepinephrine. I must add that the last 2 medications SSRI and SNRI are the most safest of all but that does not mean that side effects are absent. According to WebMD the side effects are the following: weight loss, decreased appetite, restlessness, insomnia, anxiety, constipation, dry mouth, diarrhea, dizziness, drowsiness, blurred vision, light headedness, strange dreams, constipation, fever/chills, headache, increased or decreased appetite, tremor, dry mouth, nausea. Many of these signs and symptoms can be explained to the activation of the fight-flight response while others are related to the close relationship with dopamine and its interaction with other hormones and body processes (ie activation of other serotonin receptors: S1,S2,etc)
Some SNRI medications: Effexor, Remeron, and Cymbalta.
DNRI : Dopamine-Norepinephrine Reuptake Inhibitors functions are obvious: they slow down the reabsorption of dopamine and norepinephrine allowing more concentration of the neurotransmitters. The possible side effects are obvious if we look for the functions of these 2 neurotransmitters. This medication has been linked to seizures (JAOA Vol 7. NO10. October 2007 p 441).
There are different types of DNRI: immediate release (IR), extended release (ER) and sustained release (SR).
Some DNRI medications: Bupropion ER, Bupropion IR, Bupropion SR.
ECT: Electroconvulsion Therapy is used when everything has fail; occurrence of relapse is possible.
Electroconvulsion as the name implies is the use of electrodes placed on the head to elicit seizures;
anesthesia is provided to the patient due to muscle contractions experienced during the treatment.
Possibility of memory loss.
Other effects that some antidepressant medications exert in the body is the suppression of CYP450. CYP450 is the generic name given to a group of more than 50 enzymes found in the lungs, small intestine, liver and kidneys. These enzymes are involved in the synthesis of several hormones (i.e. estrogen, testosterone), bile acids, cholesterol, thromboxane A2 and metabolism of fatty acids, degradation of vitamin D and the elimination of toxins of the body via the urine and stools. A decrease function of CYP450 can elicit a cascade of effects in our body: high cholesterol, low levels of sex hormones, poor fatty acids metabolism and many others. If we incorporate genetic determination we will notice that some patients have less active CYP450 versus others that have highly active CYP450 then it will be obvious that for some patients the side effects will be more pronounced than others. These patients with a higher CYP450 activity are referred as having "wild" CYP450.
STATISTICS
According to the newspaper Acupuncture Today December 2001 Volume 2 Issue 12 there are over 28 millions Americans taking antidepressants and anti-anxiety medications but more astonishing is what Merck Manual for Medical Conditions have to say about the efficacy of these medications : "...The chances that any given antidepressant will work for a particular person are about 65%..."
In other words there is a 35% chance that the medication will not work which makes it a big portion of patients that are still affected.
For that reason we are in our right to ask: Is there any alternative for these non-reactive patients?
The answer is yes! and in a next blog I will examine herbal medicine and acupuncture as an alternative.
In other words there is a 35% chance that the medication will not work which makes it a big portion of patients that are still affected.
For that reason we are in our right to ask: Is there any alternative for these non-reactive patients?
The answer is yes! and in a next blog I will examine herbal medicine and acupuncture as an alternative.
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