Insomnia evaluation

Eplivanserin (39) is a 5-HT2A antagonist initially developed for a broader spectrum of psychiatric disorders but that has been tested recently for insomnia. Within this latter indication, phase II studies showed benefits in sleep maintenance, but not in induction [9]. Compound 39 is currently in phase III, to assess the efficacy for the treatment of sleep maintenance insomnia, evaluating both sleep and daytime functioning [96]. 

Seidel WF, Dement WC. Sleepiness in insomnia evaluation and treatment. Sleep 1982 5(suppl) 182-190. 

Viens M, De Koninck J, Mercier P, St-Onge M, Lorrain D (2003) Trait anxiety and sleep-onset insomnia evaluation of treatment using anxiety management training. J Psychosom Res 54 31-37... 

Light therapy is an alternative treatment for depression associated with seasonal (e.g., winter) exacerbations. Possible side effects include eye strain, headache, insomnia, and hypo-mania.16,17 Also, potentially vulnerable patients, such as those with photosensitivity or a history of skin cancer, should be evaluated carefully prior to therapy.16... 

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. 

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

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. 

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. 

Currently the safety and efficacy of 20 is being evaluated in a Phase II study. The program is focused on the evaluation of the sleep induction and maintenance in insomnia patients but also will attempt to demonstrate orexin antagonists effects on improved sleep and side effect profiles compared to current GABAa receptor modulators. 

Pimavanserin tartrate (40, ACP-103) is a 5-HT2A receptor inverse agonist currently in phase II clinical development as an antipsychotic agent and for insomnia, focused on sleep maintenance, evaluating slow-wave-sleep at doses of 5 and 20 mg [97,98]. 

The use of benzodiazepines should be avoided. There are other safer pharmacological alternatives. Benzodiazepine withdrawal may play a role in the occurrence of delirium in the elderly. Other withdrawal symptoms include tremor, agitation, insomnia and seizures (Turnheim 2003). Thus, when there is long-term use of benzodiazepines abrupt discontinuation might be difficult. Discontinuation should however not be withheld but done slowly and step-wise. If benzodiazepines are used in the elderly, short-acting benzodiazepines such as oxazepam are preferred, because they do not accumulate in the elderly to the same extent (Kompoliti and Goetz 1998). If short-acting benzodiazepines are used they should be prescribed with caution, at low doses, and for short periods. As with all pharmacotherapy the effects should be evaluated. Benzodiazepines are sometimes used as a behavioural control. One should always ask if this use is for the benefit of staff or the benefit of the patient. The presence of staff may be sufficient for behavioural control. 

Let us assume that Mr. Z does indeed have leukemia. For many conditions claimed by plaintiffs, especially those that are highly subjective in nature (headaches, nausea, intermittent skin rashes, insomnia, muscle pain), a similarly objective diagnosis may not be possible this creates many problems in causation evaluation which we shall not try to cope with here. But to evaluate the likelihood that Mr. Z s leukemia was caused by one or more water contaminants, it will be necessary to determine whether there is evidence in the scientific literature that is sufficient to establish a causal link (in the sense, for example, described by lARC and discussed in Chapter 6) between exposure to any one of those contaminants and leukemia. This evaluation is referred to as an analysis of general causation. Thus, it is directed at the question of whether one or more of the chemicals to which Mr. Z was exposed is known, in a general sense, to be a cause of leukemia. If benzene is, for example, one of the chemicals found in Mr. Z s well, and it can be established that he consumed water containing benzene, then we could conclude that general causation is established. 

Psychiatric/Physical disorder Because sleep disturbances may be the presenting manifestation of a physical or psychiatric disorder, initiate symptomatic treatment of insomnia only after a careful evaluation of the patient. 

Duration of therapy Because sleep disturbances may be the presenting manifestation of a physical or psychiatric disorder, initiate symptomatic treatment of insomnia only after careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the need for evaluation of a primary psychiatric or medical illness. Do not prescribe zaleplon in quantities exceeding a 1-month supply. 

Evaluate the patient for reversal of deficiency symptoms (anorexia, ataxia, fatigue, hyporeflexia, insomnia, irritability, loss of positional sense, pallor, and palpitations on exertion) a therapeutic response to treatment usually occurs within 48 hr... 

Evaluate the patient for therapeutic response to insomnia, a decrease in number of nocturnal awakenings and an increase in length of sleep... 

Assessing the effectiveness of a new drug candidate can be complex and often difficult. This is because some diseases or symptoms do not follow a predictable path. For example, acute conditions such as influenza or insomnia may resolve without intervention, while chronic conditions such as multiple sclerosis or arthritis follow a varying course of progression. Depending on age, treatment, and other risk factors, heart attacks and strokes may produce variable mortality rates. Additional difficulty is introduced by subjective evaluation, which can be influenced by the expectations of patients and physicians. Some of these issues can be addressed in controlled clinical trials. 

Kripke DF, Hauri P, Roth T. Sleep evaluation in chronic insomnia during short-and long-term use of two benzodiazepines, flurazepam and midazolam. Sleep Res 1987 16 99. 

Insomnia is a common comorbid condition with depression, and frequently is made worse by antidepressants, particularly the SSRIs. When insomnia persists despite adequate evaluation and attempts to reduce it by other approaches, it is often necessary to use a concomitant sedative-hypnotic, especially a short-acting nonbenzodiazepine with rapid onset such as zaleplon or zolpidem. At times a benzodiazepine sedative hypnotic such as triazolam or temazepam may be necessary. If anxiety persists during the day and cannot be otherwise managed, it may be necessary to add an anxiolytic benzodiazepine such as alprazolam or clonazepam. Use of sedative-hypnotics and anxiolytics should be short-term whenever possible. 

In recent years, natural products such as melatonin and herbs such as valerian have become popular over-the-counter remedies for insomnia. There are no comprehensive evaluations of safety and efficacy of these products. Beyond questions of safety and efficacy, there is no consensus on what their doses should be. Nevertheless, these products continue to be used widely by some patients. 

Long-term insomnia is insomnia that lasts for more than 3 weeks no specific stressor may be identifiable. A more complete medical evaluation is necessary in these patients, but most do not need an all-night sleep study. 

The symptoms of jitters, insomnia, tremors, and agitation are common in those consuming caffeine and in those with depression or the other illnesses for which these drugs are prescribed. Combining caffeine with antidepressants may exaggerate the symptoms and make it difficult for the physician to arrive at an accurate diagnosis or evaluate the drug s effectiveness. 

Sleep disorders are common, and are generally underdiagnosed. The two major complaints related to sleep are insomnia ( I can t sleep ) and excessive daytime sleepiness (EDS, I can t stay awake ). EDS is a relatively nonspecific symptom. It can be the end result of any factor that causes sleep disruption, and it can be caused by primary or intrinsic sleep disorders. Insomnia of any cause can result in sleep deprivation and subsequent EDS. The most common cause of EDS in the general population is self-imposed sleep deprivation, or insufficient sleep syndrome. By contrast, the most common causes of EDS seen in a sleep center are primary (intrinsic) disorders of EDS. The American Academy of Sleep Medicine (AASM, formerly the American Sleep Disorders Association) classification of sleep disorders includes over 80 diagnoses that are associated with EDS, but the majority of patients evaluated at sleep centers have sleep apnea, narcolepsy, idiopathic hypersomnia, or periodic limb movements of sleep. 

The MSLT is the most common method of objectively measuring daytime sleepiness in sleep laboratories. This test has been standardized into a form that reliably measures sleepiness in various populations. The MSLT has been used to evaluate levels of sleepiness (1) in conditions of sleep deprivation, reduction, fragmentation, and extension (2) in suspected narcoleptic patients (3) in patients with various disorders of excessive daytime sleepiness (4) in patients with insomnia and (5) in the posttreatment condition of patients with sleep disorders associated with daytime sleepiness. Further work is needed to compare subjective measures of sleepiness and newer performance measures with the MSLT. 

Scharf MB, Roth T, Vogel GW, Walsh JK. A multicenter, placebo-controlled study evaluating zolpidem in the treatment of chronic insomnia. J Clin Psychiatry 1994 55(5) 192-199. 

Subsequently, several authors have tested SRT, either alone or as one component in multifactorial interventions. The majority of the studies evaluating SRT alone have focused on elderly populations. As sleep becomes fragmented, daytime alertness is reduced, and insomnia vulnerability increases with aging. Older adults often spend more time in bed to cope with these changes. Although this response is adaptive in the short term, it may also perpetuate/exacerbate sleep difficulties. The use of SRT is, therefore, very relevant for this segment of the pop-... 

Two meta-analyses on the efficacy of nonpharmacological interventions for insomnia have shown that SRT produces, along with stimulus control therapy, among the largest effect sizes on sleep onset latency and wake after sleep onset variables (3,4). However, SRT alone has been evaluated in significantly fewer studies than other interventions. Furthermore, results from meta-analyses have also shown that SRT produces a reduction of TST, particularly at posttreatment, with a rebound/gain at short-term follow-ups. Three treatment studies of late-life insomnia have directly compared the relative efficacy of SRT to other nonphar-... 

Riedel BW, Lichstein KL. Strategies for evaluating adherence to sleep restriction treatment for insomnia. Behav Res Ther 2001 39 201-212. 

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