Sleep Disorders and Medication - Dr. Jonathan Haverkampf

Sleep Disorders and Medication

Dr Jonathan Haverkampf, M.D.

Sleep problems affect many people. Especially in our complex and fast paced world remaining thoughts or emotions from the day can occupy us at night. Dealing with stress effectively, such as prioritizing the activities in one’s life in line with one’s values and interests, can improve sleep considerably. The mental health diagnostic manual DSM-IV defines insomnia as difficulty initiating sleep or maintaining sleep.

Several mental health conditions can also cause sleeplessness. Major depression, PTSD, trauma, anxiety, bipolar disorders, psychosis and many more can cause insomnia. Many organic diseases can also cause insomnia, as can sleep apnea and chronic pain syndromes. In some cases, where no other reason can be found, an idiopathic insomnia may itself be a mental health problem.

The first step is to identify whether there is a sleep problem that requires treatment. People who sleep seven to eight hours usually do not have a problem with lack of sleep. In the case of paradoxical insomnia, although one believes to have a sleep problem, electrophysiological measurements show no sign of a sleep disturbance.

The second step is to identify if there is inadequate sleep hygiene. If there are behaviors that are not conducive to good sleep, they should be addressed first. Some behaviors increase arousal, such as consuming caffeine or nicotine in the evening or at night. Various drugs, legal and illegal, can affect one’s sleep greatly. Intense thoughts or emotions can also disturb one’s sleep, as do day-time naps or significant irregularities in the daily sleep-wake schedule.

Treatment of insomnia should also always include psychotherapy. It can help reduce the worries about and consequences of sleeplessness, and thereby break the vicious cycle of insomnia. Feeling less anxious about the ability to get a goodnight’s sleep often improves one’s sleep. Cognitive therapy, CBT, but also psychodynamic approaches can be helpful.

There are several over-the-counter sleep aids available, often with questionable effectiveness. Nonprescription drugs, such as sedating antihistamines, protein precursors, and a host of other substances can work in individual cases, but they are often not strong enough even in cases of moderate insomnia. L-Tryptophan has been withdrawn from the market after it was linked to outbreaks of eosinophilia. Melatonin may help some individuals, although the placebo should not be underestimated.

Most hypnotics are approved by the U.S. Food and Drug Administration (FDA) only for short-term use. The z-drugs zolpidem (Stilnoct®, Ambien®, Ambien CR®, Intermezzo®, Stilnox® and eszopiclone (Lunesta®), as well as the melatonin-receptor agonist ramelteon (Rozerem®) are exceptions. The z-drugs are by their function related to the benzodiazepines and are also considered potentially addictive if taken regularly. This means that if they are stopped one’s sleep might be worse for a while. There could also be an additional increase in anxiety and, at least theoretically, panic attacks. Benzodiazepines and z-drugs should not be used while driving a car or operating heavy machinery, and the longer lasting ones can lead to a hangover in the morning and drowsiness during the day.

If the insomnia has lasted for a while and is expected to reoccur for at least a couple of weeks, sleep inducing antidepressants should be considered first choice. Mirtazapine (Remeron®) is often a good option, which in clinical experience is more sleep inducing at lower doses (15mg) than at higher doses (45mg). Second-generation antipsychotics, such as Olanzapine (Zyprexa®) are also used, but it seems there should be some other symptom or reason that justifies their use because of the potentially more serious die-effects. If the insomnia is combined with some types of obsessive thoughts or even Tourette’s syndrome, for example, sleep inducing second-generation antipsychotics may be a logical choice.

Psychotherapeutic treatment of insomnia is discussed in my other articles, but medication as a supportive measure seems warranted in some cases, especially if a modern antidepressant can help the patient maintain a job or a relationship, while using therapy to explore the reasons of the sleep disturbance.

Listed below are some substances that are used to treat insomnia.

We will start with the group of benzodiazepines and then move on to the pharmacologically closely related z-drugs, which should usually be preferred to the former, if they are used at all.

Benzodiazepines

The most commonly used class of hypnotics for insomnia are the benzodiazepines. Benzodiazepines are not significantly better for insomnia than antidepressants. [1] While they have an important role in anxiety and panic attacks, especially in the time interval until an antidepressant works, their role in the treatment of insomnia should only occur in niche cases, and only over a short internal. The z-drugs, which also work on the benzodiazepine receptor should be preferred, if at all necessary. In clinical practice, the risk for dependency seems higher if the benzodiazepines are used as sleeping pills than if they are used in acute anxiety attacks.

Benzodiazepines all bind unselectively to the GABA-A receptor. There is some indication that certain benzodiazepines (hypnotic benzodiazepines) have significantly higher activity at the α1 subunit of the GABA-A receptor compared to other benzodiazepines (for example, triazolam and temazepam have significantly higher activity at the α1 subunit compared to alprazolam and diazepam, making them superior sedative-hypnotics – alprazolam and diazepam, in turn, have higher activity at the α2 subunit compared to triazolam and temazepam, making them superior anxiolytic agents). Modulation of the α1 subunit is associated with sedation, motor impairment, respiratory depression, amnesia, ataxia, and reinforcing behavior (drug-seeking behavior). Modulation of the α2 subunit is associated with anxiolytic activity and disinhibition. For this reason, certain benzodiazepines may be better suited to treat insomnia than others.

Triazolam (Halcion®)
Temazepam (Restoril®)
[Alprazolam (Xanax®)]

and others may be useful as an insomnia medication that stays in the system longer. For instance, they have been effectively used to treat sleep problems such as sleepwalking and night terrors. However, these drugs may cause sleepiness during the day and can also cause tolerance.

Chronic use

With chronic use, the sleep inducing effect of the benzodiazepines often goes away, while the risk of tolerance increases quite quickly if they are used as hypnotics. Chronic users of hypnotic medications have more regular nighttime awakenings than patients suffering from insomnia who are not taking hypnotic medications. [2] Hypnotics should be prescribed for only a few days at the lowest effective dose and avoided altogether wherever possible, especially in the elderly. [3] Between 1993 and 2010, the prescribing of benzodiazepines to individuals with sleep disorders has decreased from 24% to 11% in the US, coinciding with the first release of nonbenzodiazepines. [4]

Common Side Effects

The benzodiazepine and nonbenzodiazepine hypnotic medications have a number of side-effects such as day time fatigue, changes in reaction time potentially leading to motor vehicle crashes and other accidents, cognitive impairments and falls and fractures. Elderly people are more sensitive to these side-effects. [5]

Some benzodiazepines have demonstrated effectiveness in sleep maintenance in the short term but in the longer-term benzodiazepines can lead to tolerance, physical dependence, benzodiazepine withdrawal syndrome upon discontinuation, and long-term worsening of sleep, especially after consistent usage over long periods of time. Benzodiazepines, while inducing unconsciousness, actually worsen sleep as—like alcohol—they promote light sleep while decreasing time spent in deep sleep. [6] A further problem is, with regular use of short-acting sleep aids for insomnia, daytime rebound anxiety can emerge. [7]

Although there is little evidence for benefit of benzodiazepines in insomnia compared to other treatments and evidence of major harm, prescriptions have continued to increase. [8] This is likely due to their addictive nature, both due to misuse and because—through their rapid action, tolerance and withdrawal—they can “trick” insomniacs into thinking they are helping with sleep. There is a general awareness that long-term use of benzodiazepines for insomnia in most people is inappropriate and that a gradual withdrawal is usually beneficial due to the adverse effects associated with the long-term use of benzodiazepines and is recommended whenever possible. [9]

Z-Drugs

Zolpidem (Ambien®, Intermezzo®)

They often work quite well, but some patients wake up in the middle of the night. Zolpidem is now available in an extended release version, Ambien CR®. This helps prolong the effect of the medication. The FDA has approved a prescription oral spray called Zolpimist®, which contains zolpidem, for the short-term treatment of insomnia brought on by difficulty falling asleep.

Eszopiclone (Lunesta®)

Studies show people sleep an average of seven to eight hours. Because of the risk of impairment, the next day, the FDA recommends the starting dose of Lunesta® be no more than 1 mg.

Zaleplon (Sonata®)

Zaleplon stays active in the body for the shortest amount of time. That means patients can try to fall asleep on their own. Then, if they are still not asleep at 2 a.m., they can take it without feeling drowsy in the morning. However, if one tends to wake during the night, this might not be the best choice.

Melatonin-receptor agonist

Ramelteon (Rozerem®)

This is a sleep medication that works differently than the others. It works by targeting the sleep-wake cycle, not by depressing the central nervous system. It is prescribed for people who have difficulty falling asleep. Rozerem® can be prescribed for long-term use, and the drug has so far shown no evidence of abuse or dependence.

Antidepressants

Mirtazapine (Remeron®)
Doxepine (Silenor®)

This tricyclic antidepressant is approved for use in people who have trouble staying asleep. Silenor® may help with sleep maintenance by blocking histamine receptors. Dosage is based on health, age, and response to therapy. Caution is required with all the tricyclic antidepressants as they can prolong the QT interval and have a number of other potentially severe side-effects.

Trazodone (Desyrel®)

Antipsychotics

Certain antipsychotic drugs like Olanzapin (Zyprexa®) also have a sedative effect and they are sometimes used in slow doses as sleep medication. However, because of the rare but potentially severe side-effects of neuroleptics, even in the second generation, they should not be used as sleep medication without any other rational for using them.

Over-the-Counter Sleep Aids

Most of these sleeping pills are antihistamines. They generally work well but can cause some drowsiness the next day. They are generally considered safe enough to be sold without a prescription. However, if combined with other drugs that also contain antihistamines, like cold or allergy medications, one could inadvertently take too much.

Sleep medication can have a number of side-effects. In 2007, the FDA issued warnings for prescription sleep drugs, alerting patients that they can cause rare allergic reactions and complex sleep-related behaviors, including “sleep driving.” Medication should in the case of a sleeping disorder always be the last option. Better sleep hygiene and psychotherapy/counselling should come long before it and be the first choice. No sleeping pill can take away worries about the job or one’s relationship or correct for drinking coffee in the evening or sleeping next to one’s laptop.

References

[1] Buscemi, N.; Vandermeer, B.; Friesen, C.; Bialy, L.; Tubman, M.; Ospina, M.; Klassen, T. P.; Witmans, M. (2007). “The Efficacy and Safety of Drug Treatments for Chronic Insomnia in Adults: A Meta-analysis of RCTs”. Journal of General Internal Medicine. 22 (9): 1335–1350. doi:10.1007/s11606-007-0251-z. PMC 2219774Freely accessible. PMID 17619935.

[2] Ohayon, M. M.; Caulet, M. (1995). “Insomnia and psychotropic drug consumption”. Progress in neuro-psychopharmacology & biological psychiatry. 19 (3): 421–431. doi:10.1016/0278-5846(94)00023-B. PMID 7624493.

[3] “What’s wrong with prescribing hypnotics?”. Drug and therapeutics bulletin. 42 (12): 89–93. 2004. doi:10.1136/dtb.2004.421289. PMID 15587763.

[4] Kaufmann, Christopher N.; Spira, Adam P.; Alexander, G. Caleb; Rutkow, Lainie; Mojtabai, Ramin (2015). “Trends in prescribing of sedative-hypnotic medications in the USA: 1993–2010”. Pharmacoepidemiology and Drug Safety. 25: 637–45. doi:10.1002/pds.3951. ISSN 1099-1557. PMID 26711081.

[5] Glass, J.; Lanctôt, K. L.; Herrmann, N.; Sproule, B. A.; Busto, U. E. (2005). “Sedative hypnotics in older people with insomnia: Meta-analysis of risks and benefits”. BMJ. 331 (7526): 1169. doi:10.1136/bmj.38623.768588.47. PMC 1285093Freely accessible. PMID 16284208.

[6] Tsoi, W. F. (1991). “Insomnia: Drug treatment”. Annals of the Academy of Medicine, Singapore. 20 (2): 269–272. PMID 1679317.

[7] Montplaisir, J. (2000). “Treatment of primary insomnia”. Canadian Medical Association Journal. 163 (4): 389–391. PMC 80369Freely accessible. PMID 10976252.

[8] Carlstedt, Roland A. (13 December 2009). Handbook of Integrative Clinical Psychology, Psychiatry, and Behavioral Medicine: Perspectives, Practices, and Research. Springer. pp. 128–130. ISBN 0-8261-1094-0.

[9] Authier, N.; Boucher, A.; Lamaison, D.; Llorca, P. M.; Descotes, J.; Eschalier, A. (2009). “Second Meeting of the French CEIP (Centres d’Évaluation et d’Information sur la Pharmacodépendance). Part II: Benzodiazepine Withdrawal”. Thérapie. 64 (6): 365–370. doi:10.2515/therapie/2009051. PMID 20025839.

Dr Jonathan Haverkampf, M.D. MLA (Harvard) LL.M. trained in medicine, psychiatry and psychotherapy and works in private practice for psychotherapy, counselling and psychiatric medication in Dublin, Ireland. The author can be reached by email at jonathanhaverkampf@gmail.com or on the websites www.jonathanhaverkampf.com and www.jonathanhaverkampf.ie.

This article is solely a basis for academic discussion and no medical advice can be given in this article, nor should anything herein be construed as advice. Always consult a professional if you believe you might suffer from a physical or mental health condition. Trademarks belong to their respective owners. No checks have been made.