OTC medicines casebook: Insomnia
Alan Nathan looks at a complex condition that affects many people...
In the Casebook Pharmacy, the counter assistant has referred a woman asking for 'sleeping pills' to the pharmacist, Eve. This is how the conversation between them went.
Eve: “Hello, how can I help you?”
Woman: “I’ve got a problem sleeping and I wonder if you can give me anything for it?”
Eve: “Can you tell me a bit more about the problem?”
Woman: “Well, for the past few weeks I've been getting off to sleep okay, but I keep waking up during the night. Sometimes I lie there for a couple of hours with thoughts going through my mind and I just can’t switch them off. And now I'm so tired during the day I can't concentrate and it's affecting my job.”
Eve: “Is there anything worrying you?”
Woman: “Quite a lot actually…I'm going through a divorce.”
Eve: “Have you seen your GP because what you describe sounds like it could be due to depression or anxiety caused by your situation? Your GP might be able to prescribe you something for it.”
Woman: “But I don't want to take antidepressants or anything like that. Isn’t there something I can buy from you? I've read about herbal medicines for sleep problems. How about those?”
1. What exactly is insomnia?
2. How should a pharmacist respond to a person asking for something for insomnia?
3. What licensed OTC medicines for insomnia are available?
4. What herbal products are available?
1. Insomnia has been defined as “a symptom complex consisting of difficulty falling asleep or staying asleep, or of non-refreshing sleep, in combination with some kind of daytime sequelae. The symptom complex can be secondary to another disorder or it can be an independent disorder.”1
Three types of insomnia are recognised:
• Primary: insomnia for at least a month that is not caused by an underlying psychological or physical condition, or a drug. It can be caused by problems with the sleep environment, irregular sleep routine, or negative conditioning to sleep. It accounts for about one-third of incidences of chronic insomnia. 2
• Secondary insomnia secondary to an underlying psychological or physical condition or drug. For causes, see Table 1.3
• Circadian rhythm sleep disorders: insomnia due to a mismatch between the sleep–wake schedule required of the person and their circadian sleep–wake pattern. They are usually transient but may be recurrent. Common causes are jet-lag and shift work.4
Insomnia is also categorised according to duration of symptoms:
· transient: lasting for 2–3 days
· short-term: lasting for more than a few days but less than 3 weeks
· long–term: insomnia most nights for 3 weeks or longer.
2. When advice or treatment for insomnia or poor quality sleep is requested, wherever possible any underlying physical, emotional or psychological cause, or personal problems causing anxiety, should be identified and treated or dealt with. This will often require referral to a doctor or appropriate agency.
Pharmacists can consider recommending short-term OTC treatment of a few days, and no more than 10 as an absolute maximum, for insomnia due to identified minor and short-lived problems, such as jet lag, a change in work shift patterns, or anxiety or unhappiness due to bereavement or stress.
Pharmacists should carefully monitor sales of OTC sleep aids. Customers requesting them repeatedly should be referred, as there may be an underlying cause that needs investigation and treatment. The medicines are likely to become progressively less effective the longer they are taken, and there is a high risk of dependency developing. For longer-term sleeping problems with no identifiable reasons, advice should be given to aid sleep without the use of drugs, as set out in Panel 1.
3. OTC drug treatments include two sedating antihistamines – diphenhydramine hydrochloride and promethazine hydrochloride – both of which are licensed for treatment of temporary sleep disturbance. Their effectiveness as hypnotics may be due to their antimuscarinic actions, but it has also been proposed that sedation is due to the blockade of central H1-receptors.
Diphenhydramine is a potent antihistamine with a high incidence of sedation and antimuscarinic effects. Maximum sedation is achieved one to three hours after administration, and duration of sedation is between three and six hours. From psychomotor tests it appears that mental alertness and cognitive ability are not impaired beyond the length of time that drowsiness lasts. The optimum dose appears to be 50 mg; higher doses do not increase efï¬cacy but do increase the potential for side-effects.
Promethazine hydrochloride is a phenothiazine derivative with marked sedative properties. It is long-acting, with action reported to last between four and 12 hours. Residual drowsiness the next morning therefore seems more likely than with diphenhydramine.
4. Herbal sleep aid products
A number of herbal products are available for the relief of restlessness and promotion of relaxation and sleep. As is generally the case with herbal medicines, most are mixtures of several constituents.
The constituents occurring most frequently are:
Valerian (Valeriana ofï¬cinalis, Valerianaceae) contains valerenic acid, which has been shown to inhibit the enzyme system responsible for the metabolism of gamma-aminobutyric acid (GABA). Increased levels of GABA are associated with a decrease in CNS activity. The results of a systematic review indicated that valerian had some beneficial effects as a hypnotic, but that evidence was sparse and limited. Valerian appears to be safe in use.5
Passionï¬‚ower (Passiï¬‚ora incarnata, Passiï¬‚oraceae) contains maltol and ethylmaltol, which have been shown to cause sedation and to increase the length of sleeping induced by hexobarbital in laboratory tests on mice. Passionï¬‚ower also contains constituents which cause CNS stimulation, but the sedative effects appear to predominate. No adverse effects of the herb have been reported.
Hops (Humulus lupulus, Cannabinaceae) contain the compound 2-methyl-3-buten-2-ol, which has been shown to possess narcotic properties in mice, and the plant is reported to exhibit hypnotic and sedative actions in humans.6 Hops have been claimed to improve sleep disturbance when taken in association with valerian. Hops are thought to be non-toxic in small doses, but their sedative action may potentiate the effects of other sedative therapy and alcohol.
Wild lettuce (Lactuca virosa, Asteraceae/Compositae) has been reported to have mild sedative, analgesic and hypnotic properties, but this has not been scientiï¬cally demonstrated in humans.
Two natural physiological supplements – tryptophan and melatonin - are available as sleep aids. Tryptophan is an essential amino-acid that acts as an immediate metabolic precursor of the neurotransmitter serotonin, which regulates mood and emotion. It has been indicated in the treatment of sleep disorders because it acts as a precursor for melatonin, a neurohormone responsible for regulating sleep cycles. It has the advantage of not limiting cognitive performance or interfering with arousal from sleep, as some hypnotics do.
Melatonin is also popular as a sleep aid. There are potential problems of interaction between tryptophan and melatonin with antidepressants, particularly SSRIs, which can significantly increase serotonin levels and can lead to serotonin syndrome, characterised by agitation, confusion, delirium, tachycardia and diaphoresis.
See potential causes of secondary insomnia in February's edition of ICP.
Panel 1: Advice to aid sleep without the use of drugs
· Wind down and relax towards the end of the evening. Do not do anything mentally stimulating within 90 minutes of bedtime. Gentle exercise, such as a short walk, just before bedtime, often helps.
· Do not sleep or doze during the evening. Do not go to bed until you feel tired and ready for sleep.
· Do not eat a large meal or have tea or coffee for several hours before going to bed. Do not drink alcohol; it may cause drowsiness but its effect is short-lived. A milky drink is often relaxing.
· Make sure that the bedroom and bed are warm and comfortable.
· Once you have put the light out, just relax, perhaps thinking of something pleasant. Try to put any worries aside. Do not try to force yourself to sleep, let it come naturally.
· Aim to get up at the same time every day until a sleep pattern is restored.
· If you have not fallen asleep after 20 minutes, get up and do something relaxing and go back to bed when you feel sleepy. Do the same if you wake in the middle of the night and cannot get back to sleep.
· Remember that if you have naps during the day you will need to sleep less at night.
· Many people need much less than eight hours sleep per night.
1. American Psychiatric Task Force on DSM-IV. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 4th ed. Washington, DC: American Psychiatric Association; 1994.
2. PsychNet-UK (2003) Primary insomnia. PsychNet-UK. (www.psychnet-uk.com
3. NICE. Clinical Knowledge Summaries. 2015. https://cks.nice.org.uk/insomnia#!topicsummary
4. PsychNet-UK (2003) Circadian rhythm sleep disorder. PsychNet-UK. (www.psychnet-uk.com)
5. C Stevinson, E Ernst. Valerian for insomnia: a systematic review of randomized clinical trials. Sleep Medicine 2000;1: 91-99.