The pharmaceutical industry has never quite got it right with mother’s little helpers. The first sleeping pills were barbiturates – and highly addictive. These hypnotics were then replaced by the extraordinarily successful benzodiazepines, such as Valium, marketed as the non-addictive sleeping pills until they, also, were found to cause dependency. Indeed, the EC Committee for Proprietary Medicinal Products has recently recommended fairly stiff restrictions on seven hypnotics/tranquillisers, including Valium, following a sleeping pill study that showed evidence of increased tolerance over time.
So, enter the latest class of sleeping pills with names like Sonata (zaleplon), Ambien (zolpidem) and Lunesta (eszopiclone, formerly known as Estorra) – all names wonderfully redolent of a blissful siesta. In mid-December, the US Food and Drug Administration approved Lunesta as the first sleeping pill that could be used long term (for more than 10 days).
Ambien belongs to a class of drugs called the imidazopyridines, Zaleplon is a pyrazolopyrimidine and Lunesta is a pyrrolopyrazine derivative of the cyclopyrrolone class. These so-called ‘Z’ drugs operate much like the benzodiazepines, by binding to receptors in the brain that assist in the activity of GABA neurotransmitters, which are thought to help induce sleep.
However, unlike the benzos, which bind all three such receptors, the Zs bind to only a single subtype of GABA receptor. It is speculated that it is this selective binding that allows these new hypnotics to more closely mimic natural sleep. The Z drugs reportedly maintain deep (stages 3 and 4) sleep – unlike the benzos, which reduce the time spent in deep sleep.
The challenge with a sleeping pill is to create a product that lasts for the duration of a normal night’s sleep – and no longer.
In theory, Ambien, the current bestseller, will keep the user asleep throughout the night and then, as the drug wears off, allow him to awaken refreshed. In contrast, the benzos either wore off in the middle of the night, or left the patient in a stupor during the day.
Now, the drug companies are set to launch a new batch of drugs like Indiplon, a drug so short-acting that it can help someone get to sleep quickly at any time of the night.
As with the benzos, these drugs are claimed to have less potential for addiction than the earlier classes of hypnotics. Yet, Ambien, Sonata and Lunesta are schedule-IV controlled substances, the same classification as the benzodiazepines. Furthermore, the evidence is mounting that they share the same potential for dependence as the benzos, too (see box). In addition, these drugs can cause memory loss, and behavioural changes such as less inhibition, more aggressiveness and uncharacteristic extroversion – effects similar to drunkenness.
Some people using these drugs have also experienced abnormal thinking such as loss of identity, hallucinations, worsening of depression and even thoughts of suicide. These reactions are exacerbated if the patient is also taking selective serotonin reuptake inhibitors (SSRIs) like Prozac, the side-effects of which include loss of concentration, aggravated depression, manic reactions and an increased tendency for suicidal thoughts.
The prescribing information for Ambien also admits that it can cause hypertension and tachycardia, angina, sudden falls, heart attacks, confusion, agitation, sleepiness, difficulty concentrating or coordinating, dizziness and, believe it or not, insomnia.
Perhaps most worrying, these new drugs can cause a type of memory loss where the user has no recollection of what has happened for several hours after taking the medication. This is a particular problem if a person has taken the drug to sleep on a plane and awakens before its effects have worn off – so much so that the drug industry has dubbed it ‘traveller’s amnesia’.
If you do decide to take a Z sleeping pill rather than a natural alternative (see WDDTY vol 15 no 2, page 6), make sure you don’t take it with: SSRI antidepressants; antifungals such as ketoconazole or fluconazole; certain medicines for HIV/AIDS, such as ritonavir; St John’s wort or kava-kava; antihistamines; melatonin; drugs to relieve anxiety or pain; antipsychotics; or drugs for Parkinson’s disease and other movement disorders.
Despite the more selective nature of drugs like Ambien, they can still lead to ‘rebound insomnia’ on stopping them, so that you are even less likely to get a good night’s sleep after taking them than you were in the first place.