Sunday, 27 May 2012

Citalopram, Alternative Information

Citalopram is an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depression and anxiety as well as panic disorder, premenstrual dysphonic disorder, body dysmorphic disorder, obsessive compulsive disorder, alcoholism, and hot flushes/menopausal depression (and a few other things that I won’t bother to mention).
 
What is Citalopram?

Citalopram is a synthetic chemical with the formulation 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl) 01,3-dihydro-5-isobenzofurancarbonitrile. Wiki says that it has one stereocenter. Stereo center. Interesting name. It’s not what it sounds like though. It’s not a place where devices that produce stereophonic sound are located. No, it’s an atom! So we’re dealing on the atomic level here (i.e., really small). More specifically, Wiki tells us that a stereocenter is an atom holding a set of ligands (atoms or groups of atoms) in a spatial arrangement which is not superposable on its mirror image. OK. Then, a 4-fluorophenyl group and an N,N-dimethyl-3-aminopropyl group bind to it. Right, I can’t imagine what this means. But never mind, maybe the important bit is that due to this chirality, the molecule exists in (two) enantiomeric forms (mirror images). They are termed S-(+)-citalopram and R-(–)-citalopram. Perhaps the diagrams will clarify this, but perhaps not. Either way, please stay with me.


  

Citalopram is sold as a racemic mixture, consisting of 50% (R)-(−)-citalopram and 50% (S)-(+)-citalopram.  Purportedly, only the (S)-(+) enantiomer has the desired antidepressant effect, but there is no reference on Wiki for this claim. However, if it’s true that only half is dealing with a patient’s depression, I wonder what the other half is up to. I’m open to suggestions.

Never mind that half of the drug is ignored as to what effect it is having, “some research suggests that citalopram interacts with cannabinoid protein-couplings in the rat brain, and this is put forward as a potential cause of some of the drug's antidepressant effect.”  Which brings me to the question, what does Selective Serotonin Reuptake Inhibitor (SSRI) mean?

What does Selective Serotonin Reuptake Inhibitor (SSRI) mean?

It is estimated that 90% of the body’s serotonin is located in the gut, specifically in the enterochromaffin cells.  These cells regulate intestinal movements.  Blood platelets absorb serotonin that is secreted from the enterochromaffin cells.  But what is of most importance here is the serotonin made in cells in the central nervous system with a chemical reactor called tryptophan hydroxylase and tryptophan, a building block to proteins.

“Of the approximately 40 million brain cells, most are influenced either directly or indirectly by serotonin.”  It is a monoamine neurotransmitter meaning that it assists in the transmission at synapses of nerve impulses.

“Although it is widely believed that a serotonin deficiency plays a role in depression, there is no way to measure its levels in the living brain. Therefore, there have not been any studies proving that brain levels of this or any neurotransmitter are in short supply when depression or any mental illness develops. Blood levels of serotonin are measurable -- and have been shown to be lower in people who suffer from depression – but researchers don't know if blood levels reflect the brain's level of serotonin.”

“Also, researchers don't know whether the dip in serotonin causes the depression, or the depression causes serotonin levels to drop.”

“The SSRIs work by stopping (inhibiting) this re-uptake of serotonin. As the serotonin is not soaked up again, more will be present to pass on messages to nerve cells nearby.”  So they say.

“Antidepressant medications that work on serotonin levels -- SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin and norepinephrine reuptake inhibitors) -- are believed to reduce symptoms of depression, but exactly how they work is not yet fully understood.”

Lots of believing in the quotes above, a reminder that we should choose our beliefs carefully.  On this note, I’d like to share some of the side effects of citalopram.

Side Effects

Sexual Dysfuntion

Sexual Dysfuntion includes impotence and problems with ejaculation, reduced libido, and for women, problems in reaching an orgasm. If the problem persists, one may develop an inability to respond to sexual stimuli and even genital anesthesia (in other words, no feeling down there at all). I don’t know about others, but that alone would depress me! The good news is that this side-effect should be reversible when the drug is discontinued, but one shouldn't get too excited yet as it may take years!!! There’s a cute little name for it: Post SSRI Sexual Dysfunction. However, I would suggest that this, as with all the side-effects listed in this article, would be greatly helped by changing one's diet and lifestyle.  Here's an interesting article called “How to increase serotonin in the human brain without drugs.”

Emotional Flattening

Perhaps it’s because the sex drive is lessened or perhaps it’s because of the decrease in dopamine release that is associated with increased serotonin.  Whatever the reason, citalopram users are likely to develop trouble expressing feelings in ways other than sexually. Personality changes may include an apathetic attitude and/or malaise may pervade.  In other words, there may be no depression, but no joy either.

Digestive Complaints

Nausea, vomiting, diarrhea, and weight changes are all common.

Mind Matters

Confusion and impaired concentration are frequent side-effects, as well as dominant behaviour, aggression, social withdrawal, anger, irritability, hostility, amnesia, and taste disturbance.  The depressive state may even be aggravated.

Other Common Side Effects

Other familiar side-effects are drowsiness (may cause a need for caffeine or other perk me ups), insomnia (especially if relying on perk me ups), abnormal dreams, frequent urination (again especially if taking perk me ups), dry mouth, sweating, trembling, coughing, excessive yawning and fatigue.

Caution is required for patients with an undiagnosed bipolar disorder.  This could be anyone who suffers from depression.  If bipolar symptoms are present before taking citalopram, then after taking it, the drug may cause depressed and manic behaviour simultaneously. Wiki explains this under mixed state.

There are other side-effects, but I believe the ones I’ve mentioned are the most popular.

Alcohol and Citalopram

As alcohol and citalopram both affect similar chemicals in the brain, most professionals recommend that it is best to avoid alcohol while taking this medication.

It is well known that alcohol makes depression even worse. Drinking alcohol and taking citalopram is like drinking coffee and taking a sleeping pill at the same time. Which substance will win out at any given time is anyone’s guess, but I don’t doubt that both scenarios will impair health. Mixing these substances may even cause a mixed state without having had bipolar tendencies beforehand!

So much for what citalopram is and the side effects, I would now like to point out that the tablets contain things other than the active chemical, which mostly comprise of a bunch of highly processed chemicals.  They are in small amounts in the tablets, but there may be a negative cumulative effect or even an allergic reaction.  Remember also that such highly processed products have lots of scope for mistakes.

Inactive Ingredients in Citalopram tablets, generic version from Amneal Pharmaceuticals in the US.

Povidone K12: a pharmaceutical chemical that is made by modifying castor oil and comes in white to off-white powder form.  It is a synthetic polymer (large molecule) used as a binder for the tablets.

Corn Starch: most likely made from genetically modified corn.

Glycerin: a by-product of soap making that is used as a tablet holding agent.  It is a humectant (draws water from its surroundings) and I’ve been avoiding it for decades.

Lactose Monohydrate: a natural sugar obtained from milk although it may be physically modified.  It consists of one glucose and one galactose moiety.  Like everything else that’s processed, the makers seem to want to ensure that the tablets taste good!

Magnesium Stearate: created by the reaction of sodium stearate with magnesium sulfate and used in the tablets for its lubricating effect.  It is manufactured from both animal and vegetable oils.

Microcrystalline Cellulose: refined wood pulp used as a filler.

Polyvinyl Alcohol, mmm, some plastic alcohol.  Well to be more exact, it’s a water-soluble synthetic polymer.  Polyvinyl alcohol is not known to occur as a natural product.”

Polyethylene Glycol: prepared by polymerization of ethylene oxide, it’s used as a binder.

Sodium Starch Glycolate Type A Potato: the sodium salt of carboxymethyl ether of starch from potato origin. Sodium starch glycolate absorbs water rapidly which results in swelling that leads to rapid disintegration of the tablets.  (I hope it doesn’t cause anything else in the body to rapidly disintegrate!)

Talc: a mineral added just prior to compression to increase flowability. Talc is not soluble in water.

Titanium Dioxide: another mineral.

Ferric Oxide Red and Ferric Oxide Yellow: made from iron and used as a colouring (the tablets need to look good after all!).

As much as I dislike dwelling on ingredients lists, I have to confess that I found another one that is quite different from the one above.  This is the UK generic version from Activis.

mannitol (E421), a sugar alcohol commonly formed via the hydrogenation of fructose.

microcrystalline cellulose (E460), as above.

colloidal silica anhydrous:  a nano metric particle size solution of silica particles in water or other mediums (may cause Sarcoidosis).

magnesium stearate: as above.

The film-coat contains hypromellose (E464): a semi-synthetic, inert, viscoelastic polymer used as an excipient (carrier) and controlled-delivery component.

macrogol: polyethylene glycol, as above.

titanium dioxide (E171): mineral.

It’s a Depressed World

The UK is pretty depressed as a nation as I discussed in my article called Antidepressants in the UK but it’s not just the English or the Americans who suffer from this mental illness.  Citalopram is sold all over the world with various brand names as shown below (from Wiki).

Celexa (U.S. and Canada, Forest Laboratories, Inc.), Citalopram (USA, United Kingdom, Denmark), Citta (Brazil), Cipramil (Australia, Brazil, Belgium, Finland, Germany, Netherlands, Ireland, Israel, Norway, Sweden, United Kingdom, New Zealand, South Africa, Russia), Elopram (Italy),Citol (Russia), Vodelax (Turkey), Citrol, Seropram,Talam (Europe and Australia), Citabax, Citaxin (Poland), Citalec (Slovakia, Czech Republic), Recital (Israel, Thrima Inc. for Unipharm Ltd.), Zetalo (India), Celapram, Ciazil (Australia, New Zealand), Zentius, Cimal (South America, by Roemmers and Recalcine), Ciprapine (Ireland), Cilift, Cilate (South Africa), Citox (Mexico), Temperax (Chile, Peru, Argentina), Talohexal(Australia), Citopam (Australia), Akarin (Denmark, Nycomed), Cipram (Turkey, Denmark, H. Lundbeck A/S), Dalsan (Eastern Europe), Pram (Russia), Pramcit (Pakistan), Celius (Greece), Humorup (Argentina), Humorap (Peru), Oropram (Iceland, Actavis), Opra (Russia), and Zylotex (Portugal).  Whew!

Final Comments

“It is estimated that over 30 million patients have been treated with citalopram since market introduction.”  It was created in 1989 by the pharmaceutical company Lundbeck.

The process of producing medications is environmentally unfriendly.  It also involves testing on genetically modified animals and then humans.  As a by the way, a long-term test on rats is 14-days.  I find this rather alarming when most people prescribed this drug will likely be taking it for years.  In addition, nanotechnology is being used in the production of this medicine which is highly controversial.