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PubMed1990

Sleep disorders and their management. Special considerations in the elderly.

Complaints of insomnia and disordered sleep are pervasive among the elderly, and reduced total sleep time and changes in sleep architecture are considered to be normal in the aging process. Additionally, numerous medical and psychiatric disorders that are highly prevalent in the geriatric population are known to affect sleep adversely. Epidemiologic data indicate that at least 5 million older adults suffer severe disorders of sleep and that most people with severe insomnia receive no treatment for this troubling symptom. However, although the elderly comprise only about 12 percent of the American population, between 35 and 40 percent of all prescriptions for sedative hypnotics are written for people over the age of 60. Moreover, approximately 23 percent of Americans over age 85 reside in long-term care facilities, and institutionalization is an important risk factor for disordered sleep and for sedative hypnotic prescription. Consequently, the evaluation of any sedative hypnotic agent must include substantial assessment of efficacy, safety, and tolerance in geriatric patients.

Aged↗

PubMed1996

Fatal insomnia in a case of familial Creutzfeldt-Jakob disease with the codon 200(Lys) mutation.

Fatal familial insomnia (FFI) has been exclusively associated with a pathogenic mutation at codon 178 in the PRNP gene coupled with methionine (Met) at codon 129. We now describe a subject with familial Creutzfeldt-Jakob disease, heterozygous for the pathogenic lysine (Lys) mutation at codon 200 and homozygous for Met at codon 129 of the PRNP gene, who was affected by severe insomnia. At autopsy the patient had significant involvement of the thalamus, as previously described in subjects affected by FFI with the codon 178 mutation. This case demonstrates the wide variability of the clinical expressions in patients with the codon 200 mutation, that may include insomnia and thalamic pathology.

Amyloid↗

PubMed2005

Randomized study on the efficacy of cognitive-behavioral therapy for insomnia secondary to breast cancer, part I: Sleep and psychological effects.

PURPOSE: Chronic insomnia is highly prevalent in cancer patients. Cognitive-behavioral therapy (CBT) is considered the treatment of choice for chronic primary insomnia. However, no randomized controlled study has been conducted on its efficacy for insomnia secondary to cancer. Using a randomized controlled design, this study conducted among breast cancer survivors evaluated the effect of CBT on sleep, assessed both subjectively and objectively, and on hypnotic medication use, psychological distress, and quality of life. PATIENTS AND METHODS: Fifty-seven women with insomnia caused or aggravated by breast cancer were randomly assigned to CBT (n = 27) or a waiting-list control condition (n = 30). The treatment consisted of eight weekly sessions administered in a group and combined the use of stimulus control, sleep restriction, cognitive therapy, sleep hygiene, and fatigue management. Follow-up evaluations were carried out 3, 6, and 12 months after the treatment. RESULTS: Participants who received the insomnia treatment had significantly better subjective sleep indices (daily sleep diary, Insomnia Severity Index), a lower frequency of medicated nights, lower levels of depression and anxiety, and greater global quality of life at post-treatment compared with participants of the control group after their waiting period. Results were more equivocal on polysomnographic indices. Therapeutic effects were well maintained up to 12 months after the intervention and generally were clinically significant. CONCLUSION: This study supports the efficacy of CBT for insomnia secondary to breast cancer.

Aged↗

PubMed2005

Stress, insomnia, and chronic idiopathic urticaria--a case-control study.

BACKGROUND AND PURPOSE: There is growing evidence that stress might play a crucial role in the pathogenesis of urticaria. This study examined the association between chronic idiopathic urticaria and stress from major life events and explored the validity of the biopsychosocial model of stress as it relates to urticaria. METHODS: A total of 75 consecutive cases with chronic idiopathic urticaria and 133 controls with tinea pedis who visited a dermatologic clinic for treatment were recruited for participation in this study. Subjects in both groups were assessed with a semi-structured questionnaire to determine the number and subjective weighting of major life events, somatic symptoms, insomnia, irregularity of daily life, perceived family support, ego-function, positive coping, and negative coping. Structural equation modeling was used to examine the influence of biologic, psychologic, and social factors on the development of urticaria. Cluster analysis was used to classify subjects according to risk of developing urticaria. RESULTS: In the 6 months preceding disease onset, patients with chronic idiopathic urticaria had significantly more life events, higher subjective weighting of impacts from life events, more somatic symptoms, more severe insomnia, less family support, more negative coping tendencies, and were younger in age. Good ego-function, coping strategies and family support were associated with decreased frequency of urticaria. CONCLUSIONS: Stress is an important risk factor for the development of chronic idiopathic urticaria while positive coping tendencies and good family support appear to have preventative effects. Insomnia might be the most important psychosomatic symptom that is a predisposing factor for chronic urticaria.

Adaptation, Psychological↗

PubMed2006

What predicts patients' perceptions of improvement in insomnia?

Although there has been considerable research into the effectiveness of individual cognitive behavioral treatment for chronic insomnia, less is known about patients' perceptions of what constitutes actual improvement. This study utilized 70 outpatients (mean age = 49.7 years, SD = 12.0) with insomnia who completed a 6-week cognitive behavioral group for sleep. Participants completed a number of primary (Pittsburgh Sleep Quality Index) and secondary measures (the Dysfunctional Beliefs about Sleep Scale, Insomnia Severity Index, Beck Depression Inventory, Penn State Worry Questionnaire) at pre- and post-treatment. Perceived improvement was measured using the Clinical Global Improvement Scale (CGI). Results were analyzed using a combination of Logistic Regression analysis and receiver operating curve characteristic analysis (ROC). Results demonstrated that sleep quality and sleep duration were the most sensitive primary measures, or best predicted perceived improvement, whereas sleep efficiency was the most specific primary measure, or best predicted perceived lack of improvement (defined as only mild improvement). Of the secondary measures, results showed that daytime impairment was the most sensitive predictor of perceived improvement and that mood was the most specific predictor of perceived lack of improvement. Implications of these findings are that sleep quality, sleep duration, and sleep efficiency may offer different types of information and the choice of measure for predicting global improvement in insomnia will depend on the needs of the researcher/clinician.

Adult↗

PubMed2005

The restless legs syndrome.

The restless legs syndrome (RLS) is one of the commonest neurological sensorimotor disorders at least in the Western countries and is often associated with periodic limb movements (PLM) during sleep leading to severe insomnia. However, it remains largely underdiagnosed and its underlying pathogenesis is presently unknown. Women are more affected than men and early-onset disease is associated with familial cases. A genetic origin has been suggested but the mode of inheritance is unknown. Secondary causes of RLS may share a common underlying pathophysiology implicating iron deficiency or misuse. The excellent response to dopaminegic drugs points to a central role of dopamine in the pathophysiology of RLS. Iron may also represent a primary factor in the development of RLS, as suggested by recent pathological and brain imaging studies. However, the way dopamine and iron, and probably other compounds, interact to generate the circadian pattern in the occurrence of RLS and PLM symptoms remains unknown. The same is also the case for the level of interaction of the two compounds within the central nervous system (CNS). Recent electrophysiological and animals studies suggest that complex spinal mechanisms are involved in the generation of RLS and PLM symptomatology. Dopamine modulation of spinal reflexes through dopamine D3 receptors was recently highlighted in animal models. The present review suggests that RLS is a complex disorder that may result from a complex dysfunction of interacting neuronal networks at one or several levels of the CNS and involving numerous neurotransmitter systems.

Animals↗

PubMed2006

Severe hot flashes are associated with chronic insomnia.

BACKGROUND: Because hot flashes can occur during the night, their presence has been frequently associated with insomnia in women with symptoms of menopause. However, many factors other than hot flashes or menopause can be responsible for insomnia, and several factors associated with insomnia in the general population are also commonly observed in perimenopausal and postmenopausal women who have hot flashes. METHODS: A random sample of 3243 subjects (aged > or =18 years) representative of the California population was interviewed by telephone. Included were 982 women aged 35 to 65 years. Women were divided into 3 groups according to menopausal status: premenopause (57.2%), perimenopause (22.3%), and postmenopause (20.5%). Hot flashes were counted if they were present for at least 3 days per week during the last month and were classified as mild, moderate, or severe according to their effect on daily functioning. Chronic insomnia was defined as global sleep dissatisfaction, difficulty initiating sleep, difficulty maintaining sleep, or nonrestorative sleep, for at least 6 months. Diagnoses of insomnia were assessed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, classification. RESULTS: Prevalence of hot flashes was 12.5% in premenopause, 79.0% in perimenopause, and 39.3% in postmenopause. Prevalence of chronic insomnia was reported as 36.5% in premenopause, 56.6% in perimenopause, and 50.7% in postmenopause (P<.001). Prevalence of symptoms of chronic insomnia increased with the severity of hot flashes, reaching more than 80% in perimenopausal women and postmenopausal women who had severe hot flashes. In multivariate analyses, severe hot flashes were significantly associated with symptoms and a diagnosis of chronic insomnia. Poor health, chronic pain, and sleep apnea were other significant factors associated with chronic insomnia. CONCLUSIONS: Severe hot flashes are strongly associated with chronic insomnia in midlife women. The presence of hot flashes should be systematically investigated in women with insomnia. Treating hot flashes could improve sleep quality and minimize the deleterious consequences of chronic insomnia.

Adult↗

PubMed2000

Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects.

OBJECTIVE: Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Thirty individuals with major depressive disorder. INTERVENTIONS: Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo. OUTCOME MEASURES: Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures. RESULTS: During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness. CONCLUSIONS: Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings.

Adolescent↗

PubMed1979

Effects of loxapine on the sleep of chronic schizophrenics.

The sleep patterns of four male chronic schizophrenic patients were monitored throughout the various phases of a 1-year therapeutic trial with loxapine succinate, a newly developed neuroleptic. Compared with the initial drug-free baseline, the early drug period was characterized by an increase in REM percentage, REM density, and REM activity. During the drug maintenance period, the increase in REM phasic events was accompanied by an increase in total sleep. Severe insomnia was noted during the initial period of drug withdrawal. The absence of time lag between changes in drug administration schedule and the associated alterations in sleep patterns was in contrast with the time latency of the therapeutic response. This neuroleptic on sleep and on psychopathology are mediated by different mechanisms.

Adult↗

PubMed1995

Single photon emission tomography (SPET) imaging of dopamine D2 receptors in the course of dopamine replacement therapy in patients with nocturnal myoclonus syndrome (NMS).

Single photon emission tomography (SPET) permits the in vivo measurements of regional cerebral radioactivity in the human brain following the administration of compounds labeled with photon-emitting isotopes. According to our SPET findings of a reduced binding of [123I]labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) (a highly selective CNS D2 dopamine receptor ligand) to D2 dopamine receptors in striatal structures in untreated patients with nocturnal myoclonus syndrome (NMS) it seemed to be of interest to investigate whether there are changes in D2 receptor binding under dopamine replacement therapy or not. We studied the uptake and distribution of [123I]IBZM before and in the course of dopamine replacement therapy in four patients with severe insomnia caused by a nocturnal myoclonus syndrome (NMS). We found an increase of the IBZM binding to D2 receptors in the course of treatment, which was associated with an improvement of sleep quality. Reasons for this are discussed. The [123I]IBZM SPET technique in conclusion offers an intersting tool for in vivo investigations of functional changes in the dopaminergic neurotransmitter system in longitudinal studies.

Aged↗

PubMed2003

Restless Leg Syndrome and Periodic Limb Movements of Sleep.

Restless leg syndrome is one of the most common causes of severe insomnia, and is easily diagnosed by patient history alone. Formal sleep studies are rarely, if ever, indicated. The only routine laboratory study indicated is a serum ferritin level. The majority of patients with restless leg syndrome obtain substantial relief with a variety of medications. Although the majority of restless leg syndrome patients demonstrate periodic limb movements on polysomnographic study, the true clinical significance, if any, of periodic limb movements identified by polysomnographic study in the absence of restless leg syndrome symptoms remains to be determined.

Journal Article↗

PubMed2000

The diagnosis of primary insomnia and treatment alternatives.

This review provides information about the diagnosis and treatment of primary insomnia. Several treatment strategies are reviewed including the use of hypnotics, naturopathic remedies and behavioral interventions. We suggest that nonpharmacologic interventions are likely to be the most safe and effective.

Antidepressive Agents↗

PubMed1995

Treatment of delayed sleep phase syndrome.

Delayed sleep phase syndrome (DSPS) is a common but little reported cause of severe insomnia. Affected individuals complain of difficulty falling asleep and difficulty awaking at socially acceptable hours. It results from a dysregulation of the circadian sleep-wake cycle. DSPS presents in clinically heterogenous ways as modulated by motivation, psychopathology, drug status, and treatment compliance factors. Patients respond variably to the range of possible treatments. Bright light treatment potentially corrects the circadian abnormality of DSPS. Other treatments reported to relieve some DSPS patients include schedule shifts, drugs, and vitamin and hormone treatments. The safety and efficacy of light treatment have not been conventionally defined, but available information suggests that it is ophthalmologically safe. At present, DSPS must be managed empirically by various methods.

Adolescent↗

PubMed1989

The detoxification of high dose heroin addicts in Pakistan.

Treatment services in Pakistan have been swamped by the recent appearance and rapid growth of heroin abuse, and there is an urgent need to initiate and strengthen effective responses. This paper presents the results of an exercise in national monitoring of heroin detoxification services in Pakistan. The study also offers the first systematic description of the withdrawal response of heroin addicts dependent upon doses greatly in excess of those reported in developed countries. The trial was conducted at four major treatment centres and looks at three of the most widely used detoxification procedures in Pakistan (symptomatic treatment only, opium reduction plus symptomatic treatment and clonidine). Data are presented on 118 addicts receiving inpatient detoxification from heroin. The results indicate that all three detoxification methods reduced peak levels of withdrawal symptoms to acceptable levels, and that all produced a return to baseline levels of symptomatology within 10 days or less. The three most persistent symptoms were aches and pains, restlessness and insomnia. Several differences were found between treatments, notably with regard to the number of drugs required to modify the withdrawal response. The implications of these and other results are discussed.

Adolescent↗

PubMed2005

Long-term outcome after discontinuation of benzodiazepines for insomnia: a survival analysis of relapse.

Discontinuation of benzodiazepine (BZD) treatment for insomnia can be a difficult task. Cognitive-behavior therapy (CBT) for insomnia, combined with a supervised medication taper, can facilitate withdrawal but there is limited evidence on long-term outcome after discontinuation. The objective of this study was to examine medication-free survival time and predictors of relapse (i.e., resumed BZD hypnotics) over a 2-year period in 47 older adults (mean age 62.1 years) with persistent insomnia and prolonged BZD use (average duration of 18.9 years), who had successfully discontinued BZD following CBT for insomnia, a supervised medication taper program, or a combined approach. The Kaplan-Meier product-limit method was used to estimate survival time, defined as time between end-of-treatment and relapse or end of follow-up. By the end of the 24-month follow-up, 42.6% of the samples had resumed BZD use. Participants in the Combined (33.3%) and Taper (30.8%) groups relapsed significantly less than their counterparts from the CBT group (69.2%). Survival rates at 3 months were 61.5% (CBT), 100% (Taper), and 80.9% (Combined). At 12 months, they were 38.5%, 83.3%, and 70.8%, respectively; and, at 24 months, they were 28.9%, 64.8% and 64.9%, respectively. Mean survival time was significantly longer for both the Taper (18.6 months, SE = 2.1) and Combined groups (12.6 months, SE = 1.4), relative to the CBT group (8.5 months, SE = 1.8). Significant predictors of relapse included treatment condition, end of treatment insomnia severity, and psychological distress. In conclusion, there is a substantial relapse rate following BZD discontinuation among prolonged users. CBT booster sessions might enhance compliance with CBT and prove useful in preventing relapse.

Aged↗

PubMed2002

Development of an adjective checklist to measure five FACES of fatigue and sleepiness. Data from a national survey of insomniacs.

Development and initial validation of the FACES of fatigue and sleepiness adjective checklist. An initial item pool of 65 adjectives, descriptive of fatigue, sleepiness and related deprivation states, was developed and administered to 372 individuals referred by their family physicians for psychiatric investigation and treatment of severe insomnia. Participants attended one of six Canadian university-affiliated sleep clinics where they completed a psychiatric assessment and a 766-item questionnaire, including a number of standard indices of sleep-related behavior and symptoms, medical history, sleep hygiene, psychosocial well-being and psychopathology. Principal-components and item analyses were undertaken to refine the initial 65-item pool to a smaller 50-item set, consisting of five subscales: Fatigue, Anergy, Consciousness, Energized and Sleepiness. Coefficient alpha was calculated and indicated high internal consistency reliability for all subscales. Convergent and discriminant validity were also evaluated by calculating correlations between FACES subscales and a number of independent indices. The resulting five-scale FACES questionnaire appears to offer a promising self-report instrument for the measurement of fatigue and related subjective experiences.

Adult↗

PubMed1989

Morvan's fibrillary chorea. A case with possible manganese poisoning.

The clinical picture of Morvan's fibrillary chorea includes a. spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin (multiplets), b. autonomic dysregulation with profuse hyperhidrosis, and c. central nervous system involvement as shown by severe insomnia and hallucinosis. A case featuring all these symptoms is presented. Whereas known causative factors range from gold or mercury poisoning to autoimmune disorders, the presented case is the first one in which chronic manganese intoxication (occupational exposure) seems to be implicated. Manganese has been found to inhibit acetylcholine esterase, and, as a consequence, may produce peripheral and central cholinergic hyperactivity.

Aged↗

PubMed2003

The primary restless legs syndrome pathogenesis depends on the dysfunction of EEG alpha activity.

A dopaminergic drug - lisuride exhibited increase in alpha, decrease in beta and slow activities on brain function measured by computerized EEG. It was postulated that reverse EEG changes might play role in the pathogenesis of RLS. During transition from wakefulness to sleep stage 1 changes in alpha activity initiate long-lasting alpha arousal responses and they continue increasingly at sleep stage 2. This dysfunction is probably due to a genetic vulnerability of EEG alpha rhythm and disinhibits the diencephalospinal dopamine system, mostly during sleep but also during wakefulness. The disinhibition produces background for activation of PLMs, disturbing sensations in brainstem and urge to move, motor restlessness at cerebral cortex, generally for legs. All lead to severe insomnia. In RLS patients, forced deviations from alpha to theta or beta activity are unsuitable and resting EEGs reflect a dopamine receptor-specific 'individual sensitivity.' This vulnerability is alleviated after lisuride with suitable CEEG changes.

Brain↗