Insomnia medications

A variety of factors can trigger insomnia. Medications, medical illness, pain, stress, schedule changes, depression, anxiety, and nighttime breathing problems all can produce insomnia. When insomnia has no clear cause, that is, it is not secondary to another condition, it is termed primary insomnia. The diagnostic criteria for primary insomnia are shown in Table 9.1. 

For patients with chronic insomnia, medical, psychiatric, and pharmacologic causes should be identified and managed." If treat-... 

In another randomized, double-blind, placebo-controlled trial, suvorexant showed significant improvements on the co-primary end points of sleep efficiency on night 1 and at the end of week 4 Suvorexant was found to be weU-tolerated with the most frequent side effects including dose-related increase in somnolence (drowsiness), dizziness (4.9%), abnormal dreams (4.9%), headaches (4.9%), upper respiratory tract infection (3.3%), and urinary tract infection (3.3%). Increased levels of alanine aminotransferase were also observed, all of which occurred in a dose-dependent manner. All reports of increased alanine aminotransferase were considered to be mild and resolved spontaneously. One patient reported hypnagogic hallucinations at a dose of 80 mg. There were no withdrawal effects or rebound insonmia. Thus, a clear advantage of suvorexant over previous insomnia medications is the low potential for addiction or dependence. ... 

Anxiety disorders and insomnia represent relatively common medical problems within the general population. These problems typically recur over a person s lifetime (3,4). Epidemiological studies in the United States indicate that the lifetime prevalence for significant anxiety disorders is about 15%. Anxiety disorders are serious medical problems affecting not only quaUty of life, but additionally may indirecdy result in considerable morbidity owing to association with depression, cardiovascular disease, suicidal behavior, and substance-related disorders. 

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

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

Time taken to fall asleep from full wakefulness. Used clinically as a measure of insomnia, and to determine the effectiveness of hypnotic medications. 

Benzodiazepines and other anxiolytics. Although benzodiazepines are widely used in the treatment of acute alcohol withdrawal, most nonmedical personnel involved in the treatment of alcoholism are opposed to the use of medications that can induce any variety of dependence to treat the anxiety, depression, and sleep disturbances that can persist for months following withdrawal. Researchers have debated the pros and cons of the use of benzodiazepines for the management of anxiety or insomnia in alcoholic patients and other substance abuse patients during the postwithdrawal period (Ciraulo and Nace 2000 Posternak and Mueller 2001). 

Note. Clonidine alone may not adequately treat insomnia, diarrhea, muscle aches, restlessness, irritability, or other withdrawal symptoms, which may require other medications. For this reason many programs use lower doses of clonidine than outlined in this table, in combination with oral... 

A dramatically different pattern is found in surveys of drug abuse treatment facilities. Substance abuse treatment centers have reported that more than 20% of patients use benzodiazepines weekly or more frequently, with 30%— 90% of opioid abusers reporting illicit use (Iguchi et al. 1993 Stitzer et al 1981). Methadone clinics reported that high proportions ofurine samples are positive for benzodiazepines (Darke et al. 2003 Dinwiddle et al. 1996 Ross and Darke 2000 Seivewright 2001 Strain et al. 1991 Williams et al. 1996). The reasons for the high rates of benzodiazepine use in opioid addicts include self-medication of insomnia, anxiety, and withdrawal symptoms, as well as attempts to boost the euphoric effects of opioids. 

Lejoyeux et al. 1998). Similar to opioid-dependent persons, these patients reported that they use benzodiazepines to self-medicate anxiety, insomnia, and alcohol withdrawal and, less commonly, to enhance the effects of ethanol. Approximately l6%-25% of patients presenting for treatment of anxiety disorders abuse alcohol (Kushner et al. 1990 Otto et al. 1992). Controversy exists concerning appropriate benzodiazepine prescribing in this population (Cir-aulo and Nace 2000 Posternak and Mueller 2001). 

Non-motor symptoms are due to multiple neurotransmitter abnormalities throughout the brain, and some symptoms may be aggravated by PD medications. Sleep disturbance can affect more than 70% of PD patients and includes insomnia, sleep... 

TABLE 38-2. Pharmacokinetics of Prescription Medications Used to Treat Insomnia... 

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. 

To determine the success of treatment, evaluate whether the treatment plan restored normal sleep patterns, reduced daytime sequelae, and improved quality of life without causing adverse effects. Schedule patients for follow-up within 3 weeks for insomnia and within 3 months for other sleep disorders. Perform a detailed clinical history to determine the patient s perception of treatment progress and symptoms along with medication effectiveness and side effects. 

Address other medical conditions that frequently coexist with insomnia and can worsen a patient s symptoms (e.g., psychiatric disorders, benign prostatic hypertrophy). 

Huang, W. F. Lai, I. C. (2005). Patterns of sleep - related medications prescribed to elderly outpatients with insomnia in Taiwan. Drugs Aging, 22( 11), 957-65. 

BZD effects on human sleep are well characterized (Mendelson 2001) (a) decreased sleep latency (b) decreased awakenings (c) increased stage II sleep (d) suppressed stage III and IV sleep (e) increased REM sleep latency (f) initial reduction and fragmentation of REM sleep. Discontinuation of BZD treatment after three to four weeks produces a rebound of REM sleep as well as slow-wave sleep (SWS). BZD and non-BZD compounds are pharmacological agents indicated in the management of anxiety, insomnia, and other conditions in which anxiety is the main symptom, and should be considered as symptomatic medications (Nishino et al. 2004). 

First, optimize current mood stabilizer or initiate mood-stabilizing medication lithium,0 valproate,0 or carba-mazepine0 Consider adding a benzodiazepine (lorazepam or clonazepam) for short-term adjunctive treatment of agitation or insomnia if needed Alternative medication treatment options carbam-azepine0 if patient does not respond or tolerate, consider atypical antipsychotic (e.g., olanzapine, quetiapine, risperidone) or oxcarbazepine. 

Transient (two to three nights) and short-term (less than 3 weeks) insomnia is common and is usually related to a precipitating factor. Chronic insomnia (greater than 1 month) may be related to medical or psychiatric disorders or medication, or it may be psychophysiologic. 

Common causes of insomnia are shown in Table 72-2. In patients with chronic disturbances, a diagnostic evaluation includes physical and mental status examinations, routine laboratory tests, and medication and substance abuse histories. 

Chronic insomnia calls for careful assessment for a medical cause, non-pharmacologic treatment, and careful use of sedative-hypnotics (intermittently to prevent tolerance and dependence). 

Patients with short-term or chronic insomnia should be evaluated after 1 week of therapy to assess for drug effectiveness, adverse events, and compliance with nonpharmacologic recommendations. Patients should be instructed to maintain a sleep diary, including a daily recording of awakenings, medications taken, naps, and an index of sleep quality. 

Insomnia is associated with severe daytime dysfunction and low performance, related to traffic accidents and work absenteeism [7], with increasing medical burden, attributable to both direct medical and indirect costs [8]. 

Although insomnia affects millions of people worldwide, few seek medical advice and only 14% report using sleep aids [9]. Nevertheless, the worldwide insomnia market was estimated at over 2.2 billion in 2004 and is forecast to grow at an annual rate of 10.2%, with the market predicted to approach 3.6 billion in 2009 [10],... 

Takeda s melatonin (MT1/MT2) receptor agonist ramelteon (11) was approved and launched in 2005 in the U.S., indicated for the treatment of primary insomnia characterized by difficulty with sleep onset. It is the first prescription medication for insomnia with a novel mechanism of action to reach the US market in 35 years. It is also the first and only prescription sleep medication that has not exhibited potential for abuse and dependence, and as such is not designated as a scheduled substance by the DEA. Moreover, ramelteon was also filed in late March 2007 in E.U. for primary insomnia. 

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