Treatment of insomnia

Benzodiazepines, for example diazepam Enhance GABA activity Anxiety, insomnia 

Beta blockers, for example Rednce somatic symptoms of Anxiety 

Zolpidem and zopiclone Enhance GABA activity Insomnia 

Beta blockers (for example propranolol and oxprenolol) have a place in the treatment of some anxiety states. Although they do not affect psychological symptoms, such as worry, tension and fear, they are useful for patients with predominantly somatic symptoms such as palpitations and tremor treatment of these symptoms may prevent the onset of worry and fear. 

Beta blockers are used to treat arrhythmia, angina and hypertension and are discussed more fully in Chapter 4. 

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The definition of desired therapeutic and side effects in the case of the benzodiazepines very much depends on the clinical problem in question. The sedative and hypnotic actions are desired effects in the treatment of insomnia, but undesired effects in the treatment of anxiety disorders. Effects that are usually undesired include daytime drowsiness, potentiation of the sedative effects of ethanol, and anterograde amnesia. They are mediated via the benzodiazepine site of GABAa receptors, since they can be antagonized with flumazenil. 

A condition following treatment of insomnia, when on cessation of medication, the insomnia reoccurs and is... 

Several novel approaches to the treatment of insomnia have attracted much attention among researchers. 

The two selective GABA j receptor agonists currently marketed in the United States, zaleplon and Zolpidem, are a pyrazolopyrimidine and a imidaz-opyridine, respectively. Both of these drugs are approved only for the shortterm treatment of insomnia. 

BP 2.94) or (5) (Sch 50971) induce significant increases of slow-wave sleep or induce sedation in animal models [10, 33]. Potent and selective brain-penetrating H3 agonists could provide a new therapeutic option for the treatment of insomnia. 

O Insomnia is most frequently a symptom or manifestation of an underlying disorder (secondary insomnia) but may occur in the absence of contributing factors (primary insomnia). Early treatment of insomnia may prevent the development of psychopathologic complications. 

The increasing popularity of sedating antidepressants for the treatment of insomnia resulted in trazodone being the most prescribed drug in 2002.39 Other common antidepressants also... 

Antihistamines such as diphenhydramine are known for their sedating properties and are frequently used over-the-counter medications (usual doses 25-50 mg) for difficulty sleeping. Diphenhydramine is approved by the FDA for the treatment of insomnia and can be effective at reducing sleep latency and increasing sleep time.43 However, diphenhydramine produces undesirable anticholinergic effects and carryover sedation that limit its use. As with TCAs and BZDRAs, diphenhydramine should be used with caution in the elderly. Valerian root is an herbal sleep remedy that has inconsistent effects on sleep but may reduce sleep latency and efficiency at commonly used doses of 400 to 900 mg valerian extract. Ramelteon, a new melatonin receptor agonist, is indicated for insomnia characterized by difficulty with sleep onset. The recommended dose is 8 mg at bedtime. Ramelteon is not a controlled substance and thus may be a viable option for patients with a history of substance abuse. 

Kudo Y, Kurihara M. Clinical evaluation of diphenhydramine hydrochloride for the treatment of insomnia in psychiatric patients. J Clin Pharmacol 1990 30 1041-1048. 

Walsh JK, Schweitzer PK. Ten-year trends in the pharmacological treatment of insomnia. Sleep 1999 22 371-375. 

In contrast, another meta-analysis undertaken by Brzezinski et al., using 17 different studies involving 284 subjects, most of whom were older, concluded that melatonin is effective in increasing sleep efficiency and reducing sleep onset time (Brzezinski et al. 2005). Based on this meta-analysis the use of melatonin in the treatment of insomnia, particularly in aged individuals with nocturnal melatonin deficiency, was proposed. 

Gaboxadol (9) is a selective extrasynaptic GABA receptor agonist in late-stage investigation for the treatment of insomnia. The action of this compound was extensively reviewed in Chebib et al. [13] and updated in Wafford et al. [23]. Nevertheless, the sponsor companies Merck Co., Inc., and H. Lundbeck A/S announced in March 2007 that the results from recently completed clinical studies do not support further development and announced the discontinuation of their joint development program for gaboxadol. 

Pruvanserin hydrochloride (41, EMR-62218/LY-2422347) is a 5-HT2A antagonist in phase II for the treatment of insomnia [99]. Safety and tolerability studies of 5 and 15 mg compared with placebo are ongoing and completion was expected in November 2006. 

Volinanserin (42, MDL-100907) is a selective 5-HT2A antagonist discontinued for schizophrenia and is currently undergoing phase II clinical trials for the treatment of insomnia. However, no data has been reported recently for this indication. 

HT2A ligands for the treatment of insomnia. Bioorganic el Medicinal Chemistry Letters, 15, 3665—3669. 

Thalidomide was synthesized in Germany and became available in late 1957. It was prescribed for the treatment of insomnia and nausea in pregnant women. 

Alcohol. It may seem odd to list alcohol among the treatments for insomnia, bnt it has long been among the most common self-administered treatments for insomnia. Alcohol usually does help the person fall asleep, but it is otherwise an extremely poor treatment for insomnia. It can lead to fragmented sleep later in the night, not to mention the potential for hangover and tolerance. In fact, with repeated use, alcohol itself can produce insomnia. Even without taking the social and medical consequences of frequent alcohol use into account, alcohol has no place in the treatment of insomnia. 

The development of tolerance is a major drawback to the use of benzodiazepines in the long-term treatment of insomnia. Whereas tolerance to the hypnotic effects of benzodiazepines permits them to be used without excessive sedation when treating anxiety disorders, this is counterproductive when attempting to treat insomnia. Patients often find themselves requiring higher doses to obtain the same sedative-hypnotic effect initially accomplished by lower doses. For this reason, careful consideration must be given before benzodiazepines are used to treat chronic insomnia. 

Ramelteon (Rozerem). Recently approved by the FDA for treatment of insomnia in the US, ramelteon acts via a completely novel mechanism of action, that is, stimulating so-called melatonin Ti and T2 receptors in the brain s suprachiasmatic nucleus (SCN). The SCN is regarded as the body s master clock that regulates the sleep-wake cycle and other circadian rhythms. The effects of ramelteon in some respects mimic those of melatonin. Ramelteon, in clinical trials, administered at bedtime doses of 8 mg, outperformed placebo with respect to several indices of sleep disturbance (see Table 9.4). 

Acute Phase Treatment. Hypnotic medications are useful for short-term treatment of insomnia, but they should always be accompanied by behavioral and psychoeducational treatments, including a review of good sleep hygiene practices. It may also include more aggressive measures such as relaxation training, sleep restriction therapy, and stimulus control therapy. 

Jindal RD, Buysse DJ, Thase ME. Maintenance treatment of insomnia What can we learn from the depression literature Am J Psychiatry 2004 161 19-24. 

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