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Tuesday, May 27, 2014

Is Zopiclone Bad for Seniors?

Zopiclone + Seniors = Bad Mix

by Rudy Sanchez, B.Sc.Pharm, RPH


The most popular prescription drug for insomnia may not be the best choice for seniors. 

If you or someone you know is a senior and is one of the millions of patients taking these oval blue pills to help you sleep, you should read on. (Note: we are not talking about the “other” popular blue pill).

Zoomers are active, vital and healthy...not groggy, tired and sedentary.

What is our definition of a senior? Someone who actually watched the Beatles on the Ed Sullivan TV show, not on YouTube. Or maybe it is someone who has no idea what YouTube is.

zopiclone, a sleeping pill

Read on to find out…

               -why zopiclone is a poor choice for seniors

               -why you should not drive the morning after taking zopiclone

               -why you may not be as smart as you were if you take zopiclone

               -why zopiclone may land you in the hospital with a broken hip

               -why it is so hard to get off the drug

               -what are some alternatives if you are on zopiclone and want off

What is zopiclone?

Pharmacists and biochemists love molecular structures.. everyone say MEH

Zopiclone belongs to a class of drugs called cyclopyrrilones which also include eszopiclone (Lunesta), zolpiderm (Ambien) and zaleplon (Sonata). They are also called Z Drugs, because they all start with Z and it’s a convenient, neat marketing tool for drugs that helps you get the ZZZ’s. So clever, these pharmaceutical people. 

increase in GABA activity produces relaxation

The inventors of the drugs were been able to classify them as non-benzodiazepine, removing them from the tainted reputation of Xanax.  The developers of the drug found  a different  mechanism of action. Whereas benzodiazepine drugs mimic GABA (gamma-amino butyric acid) at the receptors, the cyclopyrrilones increase the transmission of GABA. The net effect is the same: they both increase the effect of GABA. Side effects and drug cessation symptoms are similar between zopiclone and benzodiazepine.  It is not necessarily a better drug, but the marketing of a non-benzo is definitely better.

remember the Xanax controversy?

Why is GABA so important? It is the most plentiful neurotransmitter in the brain and reduces excitability of neurons. It manages this by increasing the passage of chloride ions into the neuron cells, leading to decreased neuronal activity, increased relaxation and decreased anxiety.

GABA ia a major inhibitory neurotransmitter in the brain

Think of GABA as the anti-caffeine. You know how caffeine makes you awake, energetic and jittery? Caffeine does this by neutralizing GABA in the brain. So consider GABA as caffeine in reverse.

think of GABA as the anti-caffeine (and caffeine as anti-GABA)
Shortly after the introduction of the zopiclone,  a study by Gaillot (1987) measured zopiclone plasma levels in seniors. When compared to non-seniors,  plasma levels were higher by  168% and the plasma  half-life of the drug increased from 5.1 hours to 8.1 hours. In seniors, not only does the drug stay around longer, it also reaches more than double the blood level. Gaillot (1987) explains that this double whammy is a result of the extensive hepatic (liver) metabolism of the drug. Reduced liver metabolism in seniors causes the difference. The real effect of this is morning sedation and grogginess through the day after. 

zopiclone impairs driving for up to 11 hours after taking it

Caffeine is the GABA counterpart, so going for coffee is a perfectly natural instict

A study by Leufkens in 2009 compared the effects of zopiclone, temazepam and a placebo on the driving ability of the elderly and found that zopiclone impairs the driving ability for 11 hours after it is taken. This poses a hazard for the typical senior who sleeps at 11 o’clock and drives at 9:00 the next morning to go to  Tim Horton’s .. because he needs that cup of doubledouble. He/she  is more likely to have driving impairment this much later. 

glutamate is excitatory, GABA is inhibitory

Zopiclones evil twin makes it more addicting. Part of zopiclones action is through its active metabolite, desmethylzopiclone, which is even more powerful than the parent compound. Although the hypnotic (sleep inducing) activity of the drug is from the unchanged parent drug, the active metabolite desmethylzopiclone inhibits NMDA (N-methyl-D-asparate) in the brain as well as blocking nicotinic acetylcholine receptors. NMDA is an excitatory neurotransmitter  and has been studied in the breeding of “Doogie Mice”. These mice learn very quickly ( the reference is to Doogie Howser, MD) since their NMDA receptors are stimulated. NMDA is responsible for learning and remembering new information. Suppression of NMDA activity by the zopiclone metabolite leads to degradation of these learning skills. Is it possible that zopiclone makes you dumber?  Blocking of the nicotinic acetylcholine receptors causes anti-chollinergic side effects such as dry mouth, loss of balance and bladder infections. Most seniors already suffer from these conditions.

doogie mice are smarter from NMDA receptor stimulation
One of the main side effects of zopiclone is a disturbance  of motor coordination. This is a result of three effects:  the blocking of the nicotinic acetylcholine receptors by desmethylzopiclone causes dizziness. Secondly, the prolonged grogginess is from the extended half-life.  Thirdly, the inhibition of GABA transmission affects body balance through a mechanism called the sway effect.  A study by Mets (2010) measured the impairment of body balance and concluded that the elderly patients on zopiclone are more likely to fall, leading to possible fractures. Combined with increased incidence  of osteoporosis in the elderly (especially in female seniors),  the sway effect makes zopiclone more dangerous.

In North America, every 18 seconds, a senior is admitted in the hospital due to a fall

How long do all these negative effects last? More bad news. A study by Puustinen (2014)  measured cognitive and psychomotor impairment in elderly patients who have been taking zopiclone and found that the problem persists for six months after the drug is stopped. 

female seniors are more likely to have osteoporosis

What to do? 

Do not stop your zopiclone suddenly. Talk to your physician. There is complete list of drugs that are not recommended for the elderly. It was first published by Dr. Mark Beers in 1991 and in this list, there are recommended alternative prescription drugs. Called The Beers List, it recommends low dose trazodone and low dose doxepin as alternatives.  Please do not ask your doctor for his beer list, that is another thing entirely.

The Beers List, not the beer list

Marigold Compounding Pharmacy can work with your doctor to successfully navigate the withdrawal from the drug so that the cessation symptoms are reduced.  Sometimes described as the wash in-wash out method, it involves compounding dilutions of the zopiclone (as little as 5% increments) over a period of ten to twenty weeks. This is available with a prescription order from you doctor and can be compounded by Marigold Compounding Pharmacy.

learn progressive muscle relaxation

Non-drug therapy is also recommended by Dr. Beers. Some considerations are sleep hygiene techniques, meditation, Traditional Chinese Medicine, homeopathic medicine,  teas,  progressive muscle relaxation, magnesium and medicinal herbs. In combination, these strategies have been found successful in restoring sleep.
magnesium helps sleep and is a common deficiency

Gaillot J, Le Roux Y, Houghton GW, Dreyfus JF. Critical factors for
pharmacokinetics of zopiclone in the elderly and in patients with liver and renal
insufficiency. Sleep. 1987;10 Suppl 1:7-21. PubMed PMID: 3438645.

Verbeeck RK. Pharmacokinetics and dosage adjustment in patients with hepatic
dysfunction. Eur J Clin Pharmacol. 2008 Dec;64(12):1147-61. doi:
10.1007/s00228-008-0553-z. Epub 2008 Sep 2. Review. PubMed PMID: 18762933.

Leufkens TR, Vermeeren A. Highway driving in the elderly the morning after
bedtime use of hypnotics: a comparison between temazepam 20 mg, zopiclone 7.5 mg,
and placebo. J Clin Psychopharmacol. 2009 Oct;29(5):432-8. doi:
10.1097/JCP.0b013e3181b57b43. PubMed PMID: 19745642.
Puustinen J, Lähteenmäki R, Polo-Kantola P, Salo P, Vahlberg T, Lyles A,
Neuvonen PJ, Partinen M, Räihä I, Kivelä SL. Effect of withdrawal from long-term 
use of temazepam, zopiclone or zolpidem as hypnotic agents on cognition in older 
adults. Eur J Clin Pharmacol. 2014 Mar;70(3):319-29. doi: 10.1007/s00228-013-1613-6. Epub 2013 Dec 12. PubMed PMID: 24337417.

Mets MA, Volkerts ER, Olivier B, Verster JC. Effect of hypnotic drugs on body 
balance and standing steadiness. Sleep Med Rev. 2010 Aug;14(4):259-67. doi:
10.1016/j.smrv.2009.10.008. Epub 2010 Feb 18. PubMed PMID: 20171127