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Topamax: The Drug with 9 Lives

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Topamax Side Effects

Is Topamax a Wonder Drug?

Over the past week alone, I have talked to several people about their doctor visits. Each one of them had a different illness and each one of them was prescribed the drug Topamax.  I cannot help but wondering, how it is possible that one medication can treat so many disparate illnesses. I suspect it cannot and the overreach is driven more by marketing than medicine. This led me to do some digging into Topamax.

What I found is not good. Topamax is prescribed for a broad scope of illnesses for which there is likely little evidence of its efficacy. Take a look at the list below.

Illnesses or Conditions for which Topamax is Prescribed

  1. Obesity1. Medicine: Topamax
  2. Seizures1. Medicine: Topamax
  3. Migraine1,2. Medicine: Topamax
  4. Impulsivity3. Medicine: Topamax
  5. Diabetes with nerve damage4. Medicine: Topamax
  6. Bipolar disorder5. Medicine: Topamax
  7. Depression6. Medicine: Topamax
  8. Alcohol addiction7: Topamax
  9. Fibromyalgia8. Medicine: Topamax

I would like to add a 10th to that: I have broken a nail…can I get Topamax?

Honestly, off-label prescribing has gone too far! Does Topamax really treat so many disparate conditions that doctors prescribe it for everything, even when it is not FDA approved for these conditions? I must add that Topamax is one of the most dangerous drugs in the prescription market today. Not only is it a diet pill made from sugar derivatives  (actually a sugar substitute) but it uses two dangerous methods (blocking both voltage dependent calcium and voltage gated sodium channels at once) to achieve what several classes of drugs normally do separately; and thus, with one medicine it affects and potentially damages the two circuits that are critical for brain function. Topamax (an anticonvulsant under additional name Topiramate (generic) and in time release Trokendi XR) is important to discuss because it was initially formulated as a diet pill. Yet over 50% of the new members who join my migraine group arrive with Topamax on their prescription list.

I have yet to find a single person on this drug who is not seriously considering dropping it due to its adverse effects, not to mention that it does not appear to work as a pain killer. Unfortunately, Topamax is difficult to quit. The most difficult problem is that doctors are under the false impression that a drug that blocks the voltage dependent calcium and potassium channels can just be easily stopped by a few days of reduction. However, since the voltage dependent calcium channel is a high voltage channel, for some people the discontinuation may end in seizures.

Evidence is also accumulating that Topamax can cause brain damage 4. Personally, I have heard of many cases where it in fact has done just that.

Topamax is a sugar substitute that failed as a diet pill but is somehow permitted by the FDA to be used for epileptic seizures. It also received approval for use against migraines. The reasons for such a turn of events is unclear; how can a drug that fails approval for a diet pill suddenly be a perfect match for seizures and migraines? Don’t we all wish for sugar pill to be a pain killer? Unfortunately, sugar or sugar substitutes do not have such serious adverse effects  as Topamax (they happen to have different ones).

Adverse effects of Topamax

If we look at the list of adverse effects associated with this drug (as provided by Wikipedia – Topamax), it is clear that Topamax is not very safe. Indeed, the list is very long.

Dizziness, Weight loss, Paraesthesia (pins and needles), Somnolence, Nausea, Diarrhea, Fatigue, Nasopharyngitis – common cold, Depression, Weight gain, Anaemia, Disturbance in attention, Memory impairment, Amnesia, Cognitive disorder, Mental impairment, Psychomotor skills impaired, Convulsion, Coordination abnormal, Tremor, Lethargy, Hypoaesthesia, Nystagmus, Dysgeusia, Balance disorder, Dysarthria, Intention tremor, Sedation, Vision blurred, Diplopia, Visual disturbance, Vertigo, Tinnitus, Ear pain, Dyspnoea, Epistaxis, Nasal congestion, Rhinorrhoea, Vomiting, Constipation, Abdominal pain, Dyspepsia, Dry mouth, Stomach discomfort, Paraesthesia oral, Gastritis, Abdominal discomfort, Nephrolithiasis, Pollakisuria, Dysuria, Alopecia (hair loss), Rash, Pruritus, Arthralgia, Muscle spasms, Myalgia, Muscle twitching, Muscular weakness, Musculoskeletal chest pain, Anorexia, Decreased appetite, Pyrexia, Asthenia, Irritability, Gait disturbance, Feeling abnormal, Malaise, Hypersensitivity, Bradyphrenia, Insomnia, Expressive language disorder, Anxiety, Confusional state, Disorientation, Aggression, Mood altered, Agitation, Mood swings, Anger, Abnormal behavior, Crystal urine present, Tandem gait test abnormal, White blood cell count decreased, Bradycardia, Sinus bradycardia, Palpitations, Leucopenia, Thrombocytopenia, Lymphadenopathy, Eosinophilia, Depressed level of consciousness, Grand mal convulsion, Visual field defect, Complex partial seizures, Speech disorder, Psychomotor hyperactivity, Syncope, sensory disturbance, Drooling, Hypersomnia, Aphasia, Repetitive speech (stuttering), Hypokinesia, Dyskinesia, Dizziness postural, Poor quality sleep, Burning sensation, Sensory loss, Parosmia, Cerebellar syndrome, Dysaesthesia, Hypogeusia, Stupor, Clumsiness, Aura, Ageusia, Dysgraphia, Dysphasia, Neuropathy peripheral, Presyncope, Dystonia, Formication (the sensation of insects crawling under the skin), Visual acuity reduced, Scotoma, Myopia, Abnormal sensation in eye, Dry eye, Photophobia, Blepharospasm, Lacrimation increased, Photopsia, Mydriasis, Presbyopia, Deafness, Deafness unilateral, Deafness neurosensory, Ear discomfort, Hearing impaired, Dyspnoea exertional, Paranasal sinus hypersecretion, Dysphonia, Pancreatitis, Flatulence, Gastrooesophageal reflux disease, Hypoaesthesia oral gingival bleeding, Abdominal distension, Epigastric discomfort, Abdominal tenderness, Salivary hypersecretion, Oral pain, Breath odour, Glossodynia, Calculus urinary, Urinary incontinence, Haematuria (blood in urine), Incontinence, Micturition urgency, Renal colic, Renal pain, Anhidrosis, Hypoaesthesia facial, Urticaria, Erythema, Pruritus generalized, Rash macular, Skin discolouration, Allergic dermatitis, Swelling face, Joint swelling, Musculoskeletal stiffness, Flank pain, Muscle fatigue, Metabolic acidosis, Hypokalaemia, Increased appetite, Polydipsia, Hypotension, Orthostatic hypotension flushing, Hot flush, Hyperthermia, Thirst, Influenza like illness, Sluggishness, Peripheral coldness, Feeling drunk, Feeling jittery, Learning disability, Erectile dysfunction, Sexual dysfunction, Suicidal ideation, Suicide attempt, Hallucination, Psychotic disorder, Apathy, Lack of spontaneous speech, Sleep disorder, Affect lability, Libido decreased, Restlessness, Crying, Dysphemia, Euphoric mood, Paranoia, Perseveration, Panic attack, Tearfulness, Reading disorder, Initial insomnia, Flat affect, Thinking abnormal, Loss of libido, Listless, Middle insomnia, Distractibility, Early morning awakening, Panic reaction, Elevated mood, Blood bicarbonate decreased, Neutropaenia, Apraxia, Circadian rhythm sleep disorder, Hyperaesthesia, Hyposmia, Anosmia, Essential tremor, Akinesia, Unresponsive to stimuli, Blindness unilateral, Blindness transient, Glaucoma, Accommodation disorder, Altered visual depth perception, Scintillating scotoma, Eyelid edema, Night blindness, Amblyopia, Calculus ureteric, Renal tubular acidosis, Stevens-Johnson syndrome, Erythema multiforme, Skin odour abnormal, Periorbital oedema, Urticaria localized, Limb discomfort, Acidosis hyperchloraemic, Raynaud’s phenomenon, Face edema, Calcinosis, Mania, Anorgasmia, Panic disorder, Disturbance in sexual arousal, Feeling of despair, Orgasm abnormal, Hypomania, Orgasmic sensation decreased.

The FDA Black Box on Topamax

According to the FDA and their listed label update in 2014, Topomax includes a black-box warning that has the following known adverse effects:

  • Acute myopia and secondary angle closure glaucoma: Untreated elevated intraocular pressure can lead to permanent visual loss. The primary treatment to reverse symptoms is discontinuation of TOPAMAX as rapidly as possible (5.1)
  • Visual field defects: These have been reported independent of elevated intraocular pressure. Consider discontinuation of TOPAMAX (5.2)
  • Oligohidrosis and hyperthermia: Monitor decreased sweating and increased body temperature, especially in pediatric patients (5.3)
  • Metabolic acidosis: Baseline and periodic measurement of serum bicarbonate is recommended. Consider dose reduction or discontinuation of TOPAMAX if clinically appropriate (5.4)
  • Suicidal behavior and ideation: Antiepileptic drugs increase the risk of suicidal behavior or ideation (5.5)
  • Cognitive/neuropsychiatric: TOPAMAX may cause cognitive dysfunction. Patients should use caution when operating machinery including automobiles. Depression and mood problems may occur in epilepsy and migraine populations (5.6)
  • Fetal Toxicity: TOPAMAX use during pregnancy can cause cleft lip and/or palate (5.7)
  • Withdrawal of AEDs: Withdrawal of TOPAMAX should be done gradually (5.8)
  • Hyperammonemia and encephalopathy associated with or without concomitant valproic acid use: Patients with inborn errors of metabolism or reduced mitochondrial activity may have an increased risk of hyperammonemia. Measure ammonia if encephalopathic symptoms occur (5.10)
  • Kidney stones: Use with other carbonic anhydrase inhibitors, other drugs causing metabolic acidosis, or in patients on a ketogenic diet should be avoided (5.11)
  • Hypothermia has been reported with and without hyperammonemia during topiramate treatment with concomitant valproic acid use (5.12) (FDA Topamax Label)

According to the label, Topamax is only indicated for seizures as a secondary medication in support of a primary kind and for migraines and nothing else (not even for diet anymore). Yet, I see people being prescribed this drug for all types of off-label use that are unrelated to either seizures or migraines. The large migraine group I run on Facebook grown to over 4000 migraineurs in the past two years.

Because I have found that Topamax is the #1 prescribed medicine to migraineurs when they join the group in despair and hopelessness, I have decided to designate Topamax also as the #1 medicine discussed on the series titled drugs of shame. This is apt because it affects (and often damages) the neurotransmitters (hormones of the brain) and thereby puts the whole hormonal structure of the body in chaos.

The Problem: Brain Slowing

Topamax may cause brain function slowing. Why? Topamax is a voltage dependent calcium channel blocker (also called voltage-gated calcium channel blocker), which is a key channel for neuron communication via neurotransmitter release. Topamax is systemic, meaning it doesn’t just act on a particular type of neurons but all neurons. This means that neurons that are responsible to organize how the heart beats, how the lungs function, how you blink, and how you digest are all affected by Topamax in a negative way: the neurons cannot release neurotransmitters and so the communication between hormones of the brain and the hormones of the body are broken. Many of the side effects of Topamax are so strong that migraineurs who start Topamax stop within weeks (some on day 3) of initiating this medication. The drawing below shows how voltage dependent calcium channels work and what happens when they cannot work because they are blocked.

Voltage Dependent Calcium Channel Blockers

Voltage gated calcium channels plugged and unplugged
Voltage gated calcium channels plugged and unplugged.

Figure 1. How Voltage Dependent Calcium Channels Work

 

In figure 1 you see a simplified neuron on the left and the axons of another neuron on the right. In the synaptic cleft normally neurotransmitters work like a domino effect. One neuron receives a signal from a sensory organ that stimulates the release of neurotransmitters that are specific to the type of stimulus. The neurotransmitters then get to be picked up by the neuron connected to the releasing neuron and pass the signal along. When the signal volume, intensity, frequency reaches a particular threshold, the brain sends a command to the body: wipe nose, for example.

Blocking the voltage dependent calcium channels from firing means that no neurotransmitters can be released and thus no message is passed on to the necessary number of neurons to reach the threshold. Since Topamax is systemic, every function of the body is hampered to some degree.

Neurons have five types of voltage dependent calcium channels based on voltage requirements:

  1. L-type that directs skeletal muscles, cardiac related muscle cells, endocrine cells, adrenal, etc., associated with contraction, hormone release and synaptic integration (neurons working together)
  2. P/Q-type that activate neurons and neurotransmitter and hormone release
  3. N-type works at the nerve terminals similarly to P/Q for neurotransmitter and hormone release
  4. T-type think of it as the pacemaker of the brain for firing with a particular frequency
  5. R-type that works with cerebral cells and some neurons

For each of these, the current required is different so fine-tuning is necessary. The calcium channel must go through all stages of voltage levels to be able to perform all five types of actions, as the body requires all of them. Note that when the voltage gated calcium channels are blocked, none of these 5 types of actions can properly function. The body will utilize its reserves to maintain vital functions. People who take Topamax can still breathe and their hearts beat – but they have serious issues, for example, with body cooling, which is a pretty basic, built-in automatic motor function. People who take Topamax overheat and cannot cool themselves. Most interestingly Topamax prevents the very functions a migraine brain needs for relief the most because it blocks those channels that would instruct the brain to cool the body.

In addition, Topamax blocks both voltage dependent sodium-potassium channels. I have written extensively on voltage dependent sodium-potassium channels in previous articles so here I just present a short summary. Voltage dependent (or gated) sodium-potassium channels have the critical function of sodium and potassium exchange in the cell to ensure that proper voltage is created in the cell membrane. Proper voltage is required so that the channels can open and close their gates, nutrients can enter and waste products can leave. Neurons cannot manufacture neurotransmitters without the availability of various minerals, many of which must be able to enter the neuron via voltage gated sodium-potassium channels. When these channels are not able to generate the proper action potential, nothing moves in or out of the neuron. By blocking voltage dependent channels, the high voltage needed to release the neurotransmitters is dulled as well.

Topamax robs the brain from its most important vital roles: making neurotransmitters that transmit messages and regulate brain and important autonomic body functions such as, cooling the body when it is too hot,  maintaining and appropriate heart beat, or simply making a decision1.  I think, Topamax is one of the more dangerous drugs on the market. From what I can gather from the research and my work with migraineurs, Topamax does not appear to work for pain. It only slows brain function. I would not be surprised to see researchers soon showing a connection between Topamax use and dementia. Until then, proceed with caution.

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Sources

1          Sommer, B. R., Mitchell, E. L. & Wroolie, T. E. Topiramate: Effects on cognition in patients with epilepsy, migraine headache and obesity. Therapeutic Advances in Neurological Disorders 6, 211-227, doi:10.1177/1756285613481257 (2013).

2          Nelles, G. et al. Prevention of episodic migraines with topiramate: results from a non-interventional study in a general practice setting. The Journal of Headache and Pain 11, 33-44, doi:10.1007/s10194-009-0163-x (2010).

3          Navarrete, F., Pérez-Ortiz, J. M. & Manzanares, J. Pregabalin- and topiramate-mediated regulation of cognitive and motor impulsivity in DBA/2 mice. British Journal of Pharmacology 167, 183-195, doi:10.1111/j.1476-5381.2012.01981.x (2012).

4          Garvey, W. T. Phentermine and topiramate extended-release: a new treatment for obesity and its role in a complications-centric approach to obesity medical management. Expert Opinion on Drug Safety 12, 741-756, doi:10.1517/14740338.2013.806481 (2013).

5          Geddes, J. R. & Miklowitz, D. J. Treatment of bipolar disorder. Lancet 381, 10.1016/S0140-6736(1013)60857-60850, doi:10.1016/S0140-6736(13)60857-0 (2013).

6          Campayo, J. G. et al. Effectiveness of topiramate for tobacco dependence in patients with depression; a randomised, controlled trial. BMC Family Practice 9, 28-28, doi:10.1186/1471-2296-9-28 (2008).

7          Johnson, B. A. & Ait-Daoud, N. Topiramate in the New Generations of Drugs: Efficacy in the Treatment of Alcoholic Patients. Current pharmaceutical design 16, 2103-2112 (2010).

8          Pereira, A. G., Michael J.; Gross, Robert A.; Posner, Kelly; Dworkin, Robert H. Suicidality associated with anti-epileptic drugs: implications for the treatment of neuropathic pain and fibromyalgia. Pain 154, 345-349 (2013).

This article was first published on September 10, 2015.

Related posts:

adverse drug reactionsAdverse Drug Reactions (ADRs): We’re ALL at Risk adverse drug reactions are like earthquakesAdverse Drug Reactions Are Like Earthquakes Migraine brainMigraine: Do We Have It All Wrong?

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Triptans ± SSRIs ± Migraines ± Depression: Flip a Coin!

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Angela Stanton, PhD

Migraines and depression are understood to be neurological diseases though many consider them to be mental illnesses [1, 2]. Recent research sheds light on both conditions and shows us how much they have in common. Both migraines and depression can be stopped by voltage applied to the brain. In the case of depression, voltage has only been applied via open-brain surgical procedures as deep brain stimulation of the specific brain region, shown in the scanner as dark region [3-6]. For migraines the stimulation has been tried both outside of the brain [7, 8] and internally via deep brain electrical stimulation [9]. The cause inn both migraine and depression is seen in scanners [1, 10] as cortically depressed areas. These are dormant regions that have no observable electrical activity. When electrical stimulation is applied to a dormant brain region, it regains its function. Crucially for migraines, it has been demonstrated that a dormant area be shocked by a wave of electricity generated by the brain itself, called cortical spreading depression, energizing the dormant area to be able to create action potential again [11-14]. This is quite similar to a cardiac arrest patient receiving an electrical shock to the heart which restarts electrical activity. The difference is that in the case of the heart the electricity is applied externally by others, whereas in the case of the brain the electric shock is applied by the brain itself by using its functioning brain regions to energize nonperforming regions. Because neurons communicate to each other via neurotransmitters and are connected to each other, neurons that do not manufacture neurotransmitters and do not participate in communication exchange cannot hide. The healthy, energized regions send a wave of energy within the brain. However, this wave reaches the meninges where all pain sensory neurons are located [14] and hence migraine pain.

Similarly to how a cardiac arrest does not always get the heart to continue beating again, the electric shock of the spreading cortical depression may not awaken the dormant regions either. Energy for proper functioning of either the heart or the brain – or indeed for any living tissue – cannot be created from nothing. To continue to generate voltage after the initial shock, the proper minerals have to be available. One can only drive a car on fumes for so long. Interestingly we understand this very well when it comes to our cars but we tend to forget it when it comes to our body. Our body uses energy it receives from what we eat and drink. The energy is carried to the cells by electrolytes. Electrolytes are water mixed with vital nutrients. Electrolytes take up 55%-70% of our body per gender and age with salt about 9 grams per liter. Those brain regions that lack important nutrients will not function.

We now understand that brain regions that are starved of energy and that are not able to generate action potential cause abnormal synaptic transmissions [15, 16]. Yet rather than replenishing the brain by restocking it with nutrients, the current favorite treatment method is some form of serotonin medicine, such as triptans for aborting an ongoing migraine, or serotonin reuptake inhibitors (SSRIs or SNRIs) for prevention for both migraines and depression. Many unlucky migraineurs and depression patients also receive a voltage dependent calcium channel blocker, one of which I discussed in my last article. Given that these medications are so often prescribed, one would think that they actually work. But do they?

They actually don’t work for depression over 70% of the time. And for migraines? Well, that is another story as I am about to discuss.  It is also important to note that where energy is needed, medicines that block energization via electrolytes actually work against recovery and dull the brain, using symptom management instead.

Why Triptans and SSRIs/SNRIs are Hit or Miss for Migraines

Serotonin for migraines only works sometimes and even then with tremendous side effects, often causing depression (see adverse reaction tables below), violence, and fatalities. Based on my migraine group where thousands of migraineurs have passed through over the years, the statistics show that 80% of those who join the group take some serotonin preventive, usually an SSRI or SNRI but they still need to take abortives, such as triptans, and yet they still have migraines! Not only does this show that serotonin does not work but also that there is a very dangerous practice of “more is better,” which may be followed by fatal consequences, such as serotonin syndrome. The dangerous practice is common because of five critical reasons:

  1. Doctors should know better than to prescribe multiple serotonin medications to the same patient and if they don’t know what their patients take, they owe the courtesy to ask before they prescribe!
  2. Pharmacies have records of all medicines a patient takes. If a doctor makes a mistake, it is the responsibility of the pharmacist to catch the mistake and warn the doctor and the patient. This has never happened in the entire history of my migraine group! I usually analyze their medicines and point out the pharmacological interactions and duplication that they print out and hand to their doctors. Only after the patient’s intervention will doctors initiate removal of dangerous medicines. Last time I checked: The patients are not responsible for the medicines they are being prescribed.
  3. 85% of the doctors do not recognize serotonin syndrome. The sad truth is that while 100% of the doctors can prescribe SSRIs and similar medications with a few scribbles, 85% of them do not recognize if it reaches toxic levels in their patients. I estimate that the majority of doctors are not familiar with the mechanisms of the medicines they prescribe; they cannot tell if one is a voltage dependent calcium channel blocker or a voltage dependent sodium channel blocker or both or neither.
  4. This is the saddest of them all: financial incentives actually cause many doctors to be angry with patients who wish to reduce their medicines. Many members in my migraine group faced rude and angry doctors who placed them on such quick reduction from these highly “discontinuations syndrome” (politically correct for addictive) medicines that they were forced back on the medicines and of course that increased again the lunches and dinners or straight cash flow of the prescribing doctors—search out your doctor’s name and see what she/he has been earning on your medicines in 2014!
  5. The side effects of many of these serotonin medicines are worse than the initial problem they are prescribed for; reduction is slow and painful. While the adverse effects hit all at once when starting a medicine, the very same adverse effects return in slow motion as the patients reduce. For example, they may not even realize that they had increased blood pressure, nausea, dizziness, and diarrhea all at once for a few days or weeks while starting the medication since these adverse effects showed up at once. But in reversing and stopping the medicine, each of these effects can last for weeks and is highly pronounced, frightening the patient. Furthermore, adverse effects are updated on the go by the FDA. Most users are not informed about these by their prescribing physicians.

I randomly picked two very common medications I see prescribed all the time. Zoloft, used for depression, is a selective serotonin reuptake inhibitor (SSRI), and Elavil, a tricyclic antidepressant (TCA), prescribed for migraines frequently. The list of side effects for Zoloft (Sertraline) is huge (Wikipedia). I must say that if I were not depressed before taking this medicine, I most certainly would be after reading this list:

Adverse effects: Fatigue, Insomnia, Somnolence (sleepiness), Nausea, Dry mouth, Diarrhea, Headache, Ejaculation disorder, Dizziness, Agitation, Anorexia, Constipation, Dyspepsia (indigestion), Decreased libido, Sweating, Tremor, Vomiting, Impaired concentration, Nervousness, Paroniria (i.e., depraved or morbid dreaming/nightmares), Yawning, Palpitations, Increased sweating, Hot flushes, Weight decrease, Weight increase, Myoclonus, Hypertonia, Bruxism (teeth grinding), Hypoesthesia, Menstrual irregularities, Sexual dysfunction, Rash, Vision abnormal, Asthenia, Chest pain, Paranesthesia, Tinnitus (hearing ringing in the ears), Hypertension (high blood pressure), Hyperkinesia, Bronchospasm, Esophagitis (swollen esophagus), Dysphagia, Hemorrhoids, Periorbital Edema, Purpura, Cold Sweat, Dry skin, Nocturia, Urinary Retention, Polyuria (excessive urination), Vaginal Hemorrhage, Malaise, Chills, Pyrexia (fever), Thirst, Pollakiuria, Micturition disorder, Salivary Hypersecretion, Tongue Disorder, Osteoarthritis, Muscular Weakness, Back Pain, Muscle Twitching, Eructation (belching), Dyspnea (air hunger), Epistaxis (nose bleed), Edema peripheral, Periorbital edema, Syncope, Postural dizziness, Tachycardia (high heart rate), Urticaria (hives), Migraine, Abnormal bleeding (esp. in the GI tract), Muscle cramps, Arthralgia, Depressive symptoms, Euphoria, Hallucination, Alopecia (hair loss), Urinary Retention (being unable to pass urine), Pruritus, Amnesia memory loss., Urinary incontinence, Eye pain, Asymptomatic elevations in serum transaminases, Abnormal semen, Melena (black feces due to a bleed in the stomach), Coffee ground vomiting, Hematochezia, Stomatitis (swollen mouth), Tongue ulceration, Tooth Disorder, Glossitis (soreness/swelling of the tongue), Mouth Ulceration, Laryngospasm, Hyperventilation (breathing more often than required to keep one’s blood sufficiently oxygenated), Hypoventilation (breathing less often than required to keep one’s blood sufficiently oxygenated), Stridor, Dysphonia (voice disorder), Upper Respiratory Tract Infection, Rhinitis (irritation/inflammation inside the nose), Hiccups, Apathy, Thinking Abnormal, Allergic reaction, Allergy, Anaphylactoid reaction, Face edema, Priapism, Atrial arrhythmia, AV block, Coma, Peripheral Ischemia, Injury, Vasodilation Procedure, Lymphadenopathy, Involuntary muscle contractions, Galactorrhea (lactation that is unrelated to pregnancy or breastfeeding), Gynecomastia (swelling of breast tissue in men), Hyperprolactinemia (high blood prolactin levels), Hypothyroidism (underactive thyroid gland), Syndrome of inappropriate secretion of antidiuretic hormone (SIADH), Pancreatitis (swollen pancreas), Altered platelet function, Hematuria (blood in the urine), Leukopenia (low white blood cell count), Thrombocytopenia (low blood platelet count), Increased coagulation times, Abnormal clinical laboratory results, Hyponatremia (low blood sodium), Conversion Disorder, Drug Dependence, Paranoia, Myocardial Infarction (heart attack), Bradycardia, Cardiac Disorder, Suicidal Ideation/behavior, Sleep Walking, Premature Ejaculation, Hyperglycemia (high blood sugar), Hypoglycemia (low blood sugar), Hypercholesterolemia (high blood cholesterol), Vasculitis, Aggressive reaction, Psychosis (hallucinations and delusions), Mania (a dangerously elated mood), Menorrhagia (an abnormally excessive amount of menstrual bleeding), Atrophic Vulvovaginitis, Balanoposthitis, Genital Discharge, Angioedema, Photosensitivity skin reaction, Enuresis, Visual field defect, Abnormal liver function, Dermatitis, Dermatitis Bullous, Rash Follicular, Glaucoma, Lacrimal Disorder, Scotoma, Diplopia, Photophobia, Hyphemia, Mydriasis, Hair Texture Abnormal, Neoplasm, Diverticulitis, Choreoathetosis, Dyskinesia, Hyperesthesia, Sensory Disturbance, Gastroenteritis, Otitis Media, Skin Odour Abnormal, QTc prolongation, Anaphylactoid Reaction, Allergic Reaction, Allergy, Neuroleptic malignant syndrome. A potentially fatal reaction that most often occurs as a result of the use of antipsychotic drugs. It is characterized by fever, muscle rigidity, rhabdomyolysis (muscle breakdown), profuse sweating, tachycardia, tachypnoea (rapid breathing), agitation, Stevens-Johnson syndrome a potentially fatal skin reaction, Toxic epidermal necrolysis another potentially fatal skin reaction, Torsades de pointes a potentially fatal change in the heart’s rhythm., Cerebrovascular spasm, Serotonin syndrome similar to neuroleptic malignant syndrome but develops more rapidly (over a period of hours instead of days/weeks for neuroleptic malignant syndrome), Bone fracture, Movement disorders, Diabetes mellitus, Dyspnea, Jaundice yellowing of the skin, mucous membranes and eyes due to an impaired ability of the liver to clear the haem breakdown by product, bilirubin, Hepatitis, Liver failure. This medicine can cause serotonin syndrome on its own.

For migraine I picked Elavil (Amitriptyline) which is a TCA. While it has fewer side effects (Wikipedia) than Sertraline (SSRI), one of its major side effects is headache. Why would a competent doctor prescribe a known headache causer to a migraineur?

Here are some of the other adverse effects: dizziness, headache, weight gain, delirium, confusion, anxiety, agitation, orthostatic hypotension (low blood pressure), sinus tachycardia, loss of libido, impotence, sleep disturbances such as drowsiness and insomnia. Most importantly, Amitriptyline inhibits sodium channels, L-type calcium channels, and voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well.

Recall my argument of a car only able to go on fumes for so long? This drug, by blocking all possible energizing channels, blocks the inflow of nutrients and the outflow of toxins. This car is not going anywhere!

Yet many migraineurs who join my group have been taking Elavil, which of course doesn’t work, so then they end up having to take several other medicines to replace activities the brain cannot do: they often receive prescriptions for other types of SSRIs, sometimes voltage dependent calcium blockers, barbiturates, NSADs, muscle relaxers, steroids and even triptans to come full circle, and add the very ingredient they blocked from being released the first place!

Does Serotonin Use Make Any Sense At All?

When a brain region is not able to generate action potential, as shown, lack of serotonin is not the cause. It is entirely possible that the particular neurons that cannot generate enough energy happen to be responsible for serotonin production, in which case adding serotonin will indeed take the pain away. However, it will not treat the underlying cause of not having enough energy for generating action potential. The fact that it is energy shortage rather than serotonin shortage that causes depression is clearly demonstrated by the deep brain stimulation experiments on live humans, where the voltage stimulation lifted their depression right there during the experiment without any serotonin. The patients were able to explain what they felt and how their depression lifted during the procedure [4-6, 17]. It all sounds very simple actually since we know what generates action potential in the brain: salt.

So why do migraine and depression sufferers keep on getting serotonin medications knowing that serotonin has absolutely nothing to do with migraines? This is a great question that I would like to ask many physicians! Habits are hard to break but eventually they must!

Concluding Thoughts

There is only a small chance that triptans or SSRIs will work for your migraines or depression but it is 100%  certain that adverse effects will prevent your brain from working properly. In the long run, these drugs cause permanent damage. Do yourself a favor and learn what migraines are and how to prevent them. Since migraines and depression have the same cause as seen in the scanners, why not try the same solution? Many who joined my migraine group with depression and migraine are now free of both, as well as all their medicines! Join the movement for healthy life without medicines.

Sources

  1. Gasparini, C.F., H.G. Sutherland, and L.R. Griffiths, Studies on the Pathophysiology and Genetic Basis of Migraine. Current Genomics, 2013. 14(5): p. 300-315.
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