Insomnia and Its Implications

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

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The Failures of Standard Medicine in addressing sleep disorders, insomnia, and safe and effective treatment of these disorders

A 1993 survey of physician education in sleep and sleep disorders in U.S. medical schools (Rosen RC et al, Sleep 1993;16:249-54), found that on average, only 2 hours were devoted to undergraduate teaching of sleep and sleep disorders, and 7 percent of medical schools undertook no sleep medicine teaching whatsoever. A recreation of this survey took place in 2011 (Urquhart DS et al, Archives of Disease in Childhood 2012;97:90-91), and a median of 2.5 hours was devoted to undergraduate premedical sleep teaching, with 13 percent of medical schools offering no sleep teaching whatsoever (see link to the British Medical Journal below). The authors stated: "Despite a key role for sleep and sleep disorders in human disease and behaviour, there is a paucity of undergraduate teaching in this subject area."

A study published in the British Medical Journal (BMJ Open 2012-000850) and reviewed in the New York Times, Sunday March 25, 2012 (The Case for Sleep Medicine), revealed that commonly prescribed sleeping pills are associated with a fourfold increased risk of death, even for those taking fewer than 18 doses per year, and a significantly increased risk of cancer among those taking high doses. The authors state: "Agreement is beginning to build that alternatives to sleeping pills for the treatment of insomnia may be warranted." The drugs studied include benzodiazepines (e.g. temazepam/Restoril), non-benzodiazepine hypnotics such as zolpidem (Ambien, Intermezzo), eszopiclone (Lunesta), and zaleplon (Sonata), barbituates, and sedative antihistamines (e.g. doxylamine/Unison). The BMJ Open editor in chief, Dr. Trish Groves, stated: "Although the authors have not been able to prove that sleeping pills cause premature death, their analyses have ruled out a wide range of other possible causative factors. So these findings raise important concerns and questions about the safety of sedatives and sleeping pills."

As far back as 2003, concern had grown for the dangers of chronic use of sleep medications, with Dr. John WG Tiller MD PhD, a professor of psychiatry at The University of Melbourne, in Australia, writing that "in general, hypnotics (such as Ambien, Lunesta et al) should only be prescribed if the duration of use is likely to be less than four weeks, and preferably less than one or two weeks".

Dr. Tiller stated that abundant evidence supported a safer approach to treatment of insomnia, addressing underlying health problems and discussing an "exit strategy" for patients, with adoption of a more conservative and holistic approach to resolving sleep problems. Dr. Tiller noted that commonly prescribed hypnotic medications come with a significant incidence of adverse health effects with chronic use, as well as drug dependency and difficulty with withdrawal. Dr. Tiller also discussed the adverse effects of other types of sleep medication, such as benzodiazepines, with daytime drowsiness, forgetfulness (amnesic effects), and difficulty with drug withdrawal and dependency, sedative antihistamines, with anticholinergic effects, confusion, and rapid development of tolerance, leading to increased dosage and tissue accumulation, and negative effects on the heart, and antipsychotic medication, with an array of toxicities. Dr. Tiller recommended in 2003 that prescribing Medical Doctors explain to their patients why short-term use is important, and discuss "alternatives" to pharmacological control of insomnia. Unfortunately, what is still not realized, or admitted, is that safe and effective conservative therapies in a holistic protocol are not an 'alternative', but rather something that should be tried first, before becoming dependent on chronic use of problematic and perhaps dangerous drugs to treat insomnia. These therapies are also sensible to incorporate into the treatment protocol to both reduce the use of problematic sleep drugs, to avoid the weakening of effect of these drugs with overuse, and to perhaps help correct the underlying cause of insomnia and arrive at a point where there is no longer any dependency on treatment to obtain restful sleep.

The U.S. FDA issued a requirement on January 10, 2013 that pharmaceuticals cut the recommended dosage in half for the most popular sleeping medications Ambien, Zolpimist, Lunesta et al, for women, and issued a recommendation that dosages for men be lowered as well. In approving the newest sleep medication, Suvorexant, an inhibitor of hypothalamic orexin, the FDA insisted on guidelines calling for a low dosage as well, half the dosage that the pharmaceutical company said would be needed. These non-benzodiazepine hypnotic drugs showed in challenging studies that women eliminate the drug more slowly than men, and an estimated 15 percent of women taking the normal 10 milligram dose will have a level of the drug in circulation 8 hours after taking the pill that could impair function, such as driving, as well as attention and focus at work. The 2013 label warning changed by the U.S. FDA sated that patients "should not drive or engage in other activities that require complete mental awareness the day after taking the drug because zolpidem levels can remain high enough the next day to impair these activities". If the purpose in taking a sleep medication is to perform better the next day, these newer hypnotics such as Ambien obviously fail in this regard. Whether or not there is adherence by the patient, or their prescribing doctor, to this guideline is still in question, as most patients may increase the dose if it is not effective, and adherence to treatment dosage guidelines would require that the patients are aware of these risks. Of course, many patients do recognize that their mental function is still impaired the next morning, and hence seek other types of sleep aids. Correcting the underlying homeostatic imbalance responsible for dysfunctional sleep should always be the ultimate goal with troublesome insomnia, even if medication such as zolpidem is used when needed. For Medical Doctors to discourage this goal, and dismiss Complementary and Integrative Medicine (CIM) use for their patients is not sensible.

These sleeping medications already come with a risk of adverse side effects that include headache, dizziness, altered thought patterns, impaired judgement, memory impairment, delusions, impulsive or uninhibited social behavior, increased appetite, decreased libido, diminished motor coordination, and rebound insomnia when stopping the medication after chronic use. In addition, the number of reported instances of sleepwalking behavior, sometimes elaborate, such as cooking and driving, have raised alarm among physicians, and resulted in an Australian FDA black box warning in 2008. In addition, warnings that the elderly are often more sensitive to non-benzodiazepine hypnotics, potentially causing falls and adverse cognitive and behavioral effects, have been issued. These newer sleep medications are agonists at selective GABA receptors, altering this important mood regulatory neurotransmitter function by increasing the affinity for GABA at certain types of receptors, and potentially impairing the GABA potential bioavailability at others. The subsequent impairment of mood regulation and inhibition has led to warnings by the U.S. Drug Enforcement Administration that zolpidem (Ambien) has rapidly replaced other sedatives as the most common date-rape drug. To counter the rising use of sleep medications that affect attention span and mental focus, we have seen an enormous increase in the prescription of medications to treat attention deficit and hyperactivity disorder (ADHD), usually with almost no diagnostic workup. These drugs, in the amphetamine class, now are used to increase focus and energy at work or school, in effect completing a drug cycle of sedation and stimulation that would be alarming to the public if it involved illicit drug use.

There is also increasing concern of the combination of common sleep medication with a number of other medications, and the potential for health risk in this scenario. Often, sleep medication is prescribed due to insomnia that is caused by other medication, and alterations of neural control of the sleep cycle, as well as the breathing mechanism, from combinations of drugs, are seldom considered in assessment of chronic insomnia. The Mayo Clinic reports that "many prescription drugs may interfere with sleep, including some antidepressants, heart and blood pressure medications, allergy medications, stimulants (such as Ritalin for ADHD) and corticosteroids." Corticosteroids are commonly found in asthma medications, topical creams for skin disorders, pain and arthritis medication, and drugs to treat autoimmune disorders.

The potential for insomnia secondary to common prescription drug use is high, and is usually countered by addition of a sleeping pill. In addition, many over-the-counter drugs contain antihistamines and stimulants that interfere with sleep, and affect neurological function. Most sleep medications come with warnings that these drugs should not be taken with alcohol or other medications as this could significantly suppress the central nervous or respiratory systems, slowing and stopping breathing, yet studies show that the incidence of alcohol consumption before sleep in chronic insomnia is high. The most popular sleep medication, zolpidem (Ambien), lists potential side effects as breathing difficulties, suppression of deep REM sleep, and short-term memory difficulties. Opioid pain medications, beta-blockers for hypertension, and anti-arrhythmic cardiac drugs are also well known to cause respiratory depression. A study of chronic insomnia at the Maimonides Sleep Arts and Sciences clinic in Albuquerque, New Mexico, published in the December, 2012 issue of Sleep, studied respiratory patterns in 20 men and women with chronic insomnia, most of whom were taking sleep medication. None of the study participants suffered from sleep apnea or a sleep-disordered breathing syndrome, yet almost all awakenings by these patients were preceded by an abnormal respiratory process which led to the awakening. The study director, Dr. Barry Sanders of the non-profit Sleep and Human Health Institute, showed that respiratory dysfunction may be integral to most awakenings in chronic insomnia. The Sleep and Human Health Institute is currently studying the relationship between psychiatric medications and disorders and chronic insomnia in patients using a prescription medication to help them sleep. Such studies have not been conducted in the past, with a strong reluctance to link concurrent drug prescription to chronic insomnia disorders. This first small study is prompting larger university research institutes to further explore respiratory dysfunction and awakenings, and the role of prescription medications, including drugs prescribed to relieve insomnia, as the cause of such events.

Like most medications and surgical options in allopathic medicine, sleep medication is sometimes necessary, but the failure to support safer and healthier remedies to insomnia and sleep disorders, to adequately diagnose these problems, and the comorbid conditions that often cause them, is a matter of grave concern for patients, and a growing cadre of physicians. Integrative approaches, utilizing individualized protocols with herbal and nutrient medicine, acupuncture, cognitive and behavioral modification, and techniques of sleep hygiene, as well as seriously addressing underlying health problems with Complementary Medicine, provide the patient with the ability to regain health and not continue with a dependence on sleeping medications that often provide meager benefits and need for increased dosages over time. While a more thorough treatment protocol is more work in the short term, the promise of a better quality of life and non-dependence on drugs or therapy in the future is worth the effort.

A number of neurohormonal chemicals have been discovered that explain the links between sleep arousal, Metabolic Syndrome, obesity, and anxiety. Orexin and nesfatin-1 are both chemical messengers produced in the hypothalamus, and originally discovered with a relation to control of appetite and obesity, but now are revealed as having many functions as neurohormones. Orexin, also called hypocretin, regulates arousal, wakefulness and appetite, and was discovered in 1998 as experts in narcolepsy looked for the key to this pathology of constant wakefulness. The name orexin comes from the Greek orexis, or appetite. Orexin plays a major role in integration of metabolic, circadian and factors that determine the need for sleep. Orexin strongly interacts with acetylcholine, histamine, adrenalin (norepinephrine) and dopamine. Nesfatin-1 is a neurohormonal peptide that was also discovered as integral to appetite control and obesity, but plays a profound role in regulation of insulin, metabolism, autonomic regulation, stress response, and sleep. Nesfatin-1 is co-expressed with melanin, and is associated with immunoreactivity as well, as well as chronic adaptive stress response. Studies have shown that levels of nesfatin-1 are highly correlated inversely with severity of sleep apnea. Such research has already resulted in a pharmaceutical drug to antagonize orexin receptors, Belsomra, or Suvorexant, and may soon develop a drug to act as a nesfatin-1 agonist as well. Restoration of the homeostasis of these sleep and arousal related neurohormones may be a healthier approach, if possible. Holistic medicine offers a number of protocols to restore this hypothalamic, circadian, metabolic, autonomic and cholinergic homeostasis. Acupuncture may play a role in this restorative protocol as well. A 2012 study at the Institutes of Brain Science, Fudan University, Shanghai, China, found that orexin A and hypocretin are involved in analgesic effects noted with specific electroacupuncture independent of opioid expression (PMID: 23173601). A research-based intelligently designed step-by-step treatment protocol, individualized to each patient, is possible with Traditional Chinese Medicine, or the treatment by a Licensed Acupuncturist and herbalist.

A jaded and controversial history of pharmacological insomnia treatment

In the past there has been frequent changes in pharmaceutical protocol for chronic insomnia. Opioids and barbituates dominated therapy for many decades, then benzodiazepine receptor agonists, and later benzodiazepines themselves were popularly prescribed. Valium, or diazepam, was a heavily prescribed benzodiazepine sedative hypnotic in the 1960s and 1970s that went out of favor when the adverse effects, addiction, and harsh withdrawal syndrome became well known. Diazepam was added to heroin and synthetic heroin (Demerol) sold recreationally during this period to increase addiction. Daytime sedation and cognitive changes resulted in all benzodiazepines and benzodiazepine receptor agonists going out of favor for the treatment of insomnia. In the 1970s a new sedative hypnotic drug was marketed and heavily prescribed for insomnia, methaqualone, or Quaaludes, Sopors, or as they become well known to the teenagers, Ludes. This drug had CNS effects, and quickly became a popular recreational drug that was devastating. Not only the sopoforic effects, but the complete release from sexual inhibition made this the party drug of choice until its manufacture was mostly discontinued, and the U.S. had to impose the strictest drug controls on sale and distribution. Despite similar problems in European countries, American pharmaceuticals were able to lobby and delay substance abuse controls of methaqualone for years in the U.S.

In the 1980s, a resumption of benzodiazepine prescriptions occurred, or as an alternative, sedative antihistamine medication (Sominex, Nytol, Tylenol PM, Unison), which also had negative CNS effects over time, as well as alarming symptoms of racing heart (tachycardia), dizziness, and daytime sedation. The problems with withdrawal syndromes, drug dependence, increase in depression, daytime drowsiness, memory loss, sleepwalking, and increases in urinary urgency and incontinence in the elderly led to an increased unpopularity of benzodiazepine hypnotics among the patient population. The most popularly prescribed benzodiazepine hypnotic for insomnia, flurazepam, or Dalmane, like diazepam and clorazepate, has active breakdown products that result in a clearance time for half the chemical of 11 days. This prolonged effect resulted in a buildup with nightly use, and was associated with falls, hip fractures and auto accidents for the elderly patients. A withdrawal syndrome with REM rebound also made the prescription of benzodiazepines hypnotics unpopular, often resulting in a period of insomnia followed by persistent anxiety that could last for some time. REM rebound, or episodes of prolonged REM sleep, sometimes even occurred during the same night as taking the medication, resulting in daytime memory impairment. The incidence of cardiac problems associated with antihistamine sedatives made these drugs unpopular as well, and led to some of the antihistamines being removed from the market before an outright ban by the FDA.

In the 1990s antidepressants were widely prescribed, and continue to be the drug of choice for many medical doctors, despite no randomized controlled human clinical trials demonstrating proof of efficacy. SSRIs (selective serotonin reuptake inhibitors) have a tendency to induce insomnia, and may worsen or induce nocturnal bruxism, another frequent underlying cause of insomnia. Benzodiazepine receptor agonists are still often prescribed, although most experts now agree that these should be used infrequently, and are appropriate only for transient and short-term insomnia, not chronic insomnia. Guidelines for use of sedative hypnotic drugs for chronic insomnia specify that alcohol use should be discouraged, that rebound insomnia often results when discontinuing the drug, and that noncontinuous use and the lowest effective dosage is recommended. The newest type of sleep medication, Ramelteon (Rozerem), is technically a melatonin receptor agonist, but does come with the same warnings as the non-benzodiazepine sedative hypnotics, mainly eventually triggering complex sleep activities, such as walking, driving, eating or making phone calls for which the patient later has no memory. These effects occur because these drugs affect a part of the brain that is involved in cognition of the waking state. Although Rozerem is the first sleep drug not classified as a controlled substance, common side effects of dizziness, drowsiness, fatique, tiredness and diarrhea have made it much less popular than Ambien among prescribing doctors. In addition, disruption of the menstrual cycle, decreased libido, mood changes, and problems with fertility sugggest that a drug that affects the melatonin receptors may alter the endocrine responses.

In 2014, a new type of drug to regulate sleep was fast-tracked for U.S. FDA approval, reportedly to treat a disorder called Non-24 Disorder, which only affects patients that are totally blind, and lose the diurnal rhythm that is so important to human health and function. Tasimelteon (Hetlioz) is a melatonin receptor agonist, and taken in a diurnal rhythm has shown the ability to increase nighttime sleep and decrease daytime sleep better than a placebo for most of the 104 totally blind patients with Non-24 Disorder. Unfortunately, a significant number of the study participants experienced dream-disturbed sleep, drowsiness, headaches, liver dysfunction, and increased infections, especially urinary tract infections and bronchitis. The drug was advertised highly, indicating that the pharmaceutical company that made it hopes that it will be prescribed off-label to patients who aren't blind, especially those that repeatedly see the advertisements and request this drug. The small number of study participants, and the short term of study of adverse effects, and long-term efficacy, leaves many unanswered questions concerning chemical enhancement of the melatonin receptors.

The potential for rebound insomnia syndromes after stopping medication

Rebound insomnia, or decreased sleep, or poor quality sleep, after stopping medication has been the cause of considerable concern among sleep experts. Only a few quality published studies have assessed this problem, though. A 1991 study of 11 healthy young men at Henry Ford Hospital, Sleep Disorders and Research Center, in Detroit, Michigan, demonstrating the concern even at this early date, showed that a 6-12 night prescription of triazolam 0.5 mg, followed by half the patients receiving a placebo for 2 nights, demonstrated that all healthy patients suddenly discontinuing the drug experienced diminished sleep and sleep quality compared to baseline. Subsequent studies showed that for a small percentage of patients, persistent rebound insomnia on sudden withdrawal that is worse than the original insomnia pattern, occurs for a variety of sleep medications, including zolpidem (Ambien), benzodiazepines, and eszopicione (Lunesta).

A study at the Sleep Research and Treatment Center at Pennsylvania State University (Anthony Kales et al) showed that results of 6 separate sleep studies indicated that "an intense form of rebound insomnia occurs after the withdrawal of only a single nightly dose of certain benzodiazepine hypnotic drugs that have been administered for short and intermediate as well as long periods." These researchers stated that prior studies had "reported that a worsening of sleep was associated with the abrupt withdrawal of nonbenzodiazepine hypnotic drugs that had been administered in multiple nightly doses over a long period." These studies showed that a number of common sleep medications create a rebound insomnia pattern with single, short-term, or long-term use. The effects were attributed to supersensitivity of the central nervous system. While these rebound effects have been attributed to patient apprehension and/or long half-life breakdown of key drug metabolites, these researchers postulated that a more likely scenario, based on more complex study, was that introduction of exogenous benzodiazepines decreased the production of natural benzodiazepine chemicals in the brain, resulting in impaired ability to naturally quiet the mind during sleep.

Such studies show that the array of effects potentially causing rebound insomnia are still poorly understood and that there is a lack of large human clinical studies to explore these effects. No studies of note have explored the potential for long-term rebound effects, which many patients now report, because the assumed cause of rebound insomnia was attributed to either patient apprehension, or slowed clearing of drug metabolites, not a longer change in endogenous production of sleep regulating chemicals, or effects on the nerve receptors. A single published research study in the last 10 years is found concerning persistent rebound insomnia syndrome. This study at McGill University Health Centre, Montreal, Quebec, Canada (PMID: 16456219), concluded that a number of rebound insomnia syndromes have been documented, including new onset, rebound, and supersensitivity syndromes, some associated with rebound panic disorder and anxiety. The researchers stated: "Chronic paroxetine (Paxil, Aropax, Seroxat, Pexeva, Sereupin) treatment may lead to 5-HT2 receptor down regulation, with desensitization of 5-HT1A and 5-HT2 receptors, which many contribute to tardive (persistent) rebound symptoms upon abrupt withdrawal...Cholinergic rebound may also occur and could explain tardive insomnia and anxiety in paroxetine withdrawal." This study review demonstrates that sleep medications may alter CNS receptor functions and lead to a persistent long-term insomnia rebound effect, perhaps varied in intensity depending upon other factors altering 5-HT (serotonin) and cholinergic metabolism.

This array of warnings, cautions, and potential problems has led many patients to seek a safer and less potentially harmful treatment for their insomnia. A number of herbal and nutrient aids to sleep have thus become more and more popular in the general population, and sleep clinics specializing in cognitive and behavioral therapies, as well as transcranial electrical stimulation are now well studied and being developed as safer methods of managing insomnia. The cost of these sleep clinics are a prohibitive factor, though, while the cost of a holistic protocol in Traditional Chinese Medicine (TCM) is relatively inexpensive. As stated, TCM has utilized a program of sleep hygiene, or regulation of the habits and environment that affect sleep, within the holistic treatment protocol for many centuries, while the use of electroacupuncture with microcurrent stimulation to the scalp and ear has been incorporated in the protocol for decades. Standard medicine seems to be inspired by the successes of Traditional Chinese Medicine and the acupuncture profession.

Probably the most popular hypnotic drug is simply alcohol. In studies of patients with chronic insomnia, more than 22 percent reported using alcohol to fall asleep. Unfortunately, chronic alcohol use for sleep can lead to dependence, diminished sleep quality and efficiency, and concurrent use with pharmaceutical medications for sleep can be fatal in excess. The combinations of alcohol, pain medication, antidepressants, and sedative hypnotics has led to a number of famous deaths, including the actor Heath Ledger. Alcohol dependency for sleep is highly discouraged by all experts, and combining alcohol with these sleep medications comes with numerous warnings . A safe and benign set of treatment protocols is available from the Complementary and Integrative Medicine physician, or Licensed Acupuncturist and herbalist that could replace the negative outcomes of the combination of alcohol and pharmaceutical medications to achieve sleep.

The patient that explores this realm of Integrative and Complementary Medicine (CIM) for treatment of insomnia soon discovers that much scientific evidence support these therapies in TCM, as well as public popularity and clinical evidence, but more importantly, research into these complementary treatments reveals that addressing the associated and underlying health problems may be the real key to overcoming chronic insomnia, and that insomnia may be a symptom of a more serious health problem or problems that need to be addressed. This is where assessment and consultation with a Complementary Medicine physician becomes valuable. The various herbal and nutrient medicines that are now popular all have their individual strong points and effects, and of course, not all of these insomnia remedies will work for 100 percent of patients, requiring some adjustment in therapy, but the key to a real treatment protocol is in the understanding and addressing of the underlying and associated health problems. This is where a knowledgeable Complementary Medicine physician, such as a Licensed Acupuncturist, can provide real value and help solve this problem once and for all.