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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study of molecular clock mechanisms in psychiatric disorders is gaining significant interest due to data suggesting that a misalignment between the endogenous circadian system and the sleep-wake cycle might contribute to the clinical status of patients suffering from a variety of psychiatric disorders. Sleep disturbances in major depressive disorder (MDD) are characterized by increased sleep latency, poorer sleep efficiency reduced latency to the first rapid eye movement (REM) sleep episode, and early-morning awakening, but there is little data to indicate a role of circadian clock genes in MDD. There is also relatively little information regarding the role of clock genes in anxiety. In contrast, a significant amount of evidence gathered in bipolar disorder (BPD) patients suggests a circadian rhythm disorder, namely an advanced circadian rhythm and state-dependent alterations of REM sleep latency. Most research on the role of clock genes in BPD has focused on polymorphisms of CLOCK, but the lithium target GSK3 may also play a significant role. A circadian phase shift is also theorized to contribute to the pathophysiology of winter seasonal affective disorder (SAD). Certain allelic combinations of NPAS2, PER3, and BMAL1 appear to contribute to the risk of SAD. In chronic schizophrenia, disturbances of sleep including insomnia and reduced sleep efficiency have been observed. Genetic studies have found associations with CLOCK, PER1, PER3, and TIMELESS. Sleep and circadian changes associated with dementia due to Alzheimer's disease suggest a functional change in the circadian master clock, which is supported by postmortem studies of clock gene expression in the brain.
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PMID:The role of circadian clock genes in mental disorders. 1796 70

Recent concerns have been raised regarding whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) might increase suicidal tendencies and intense debate-rages over the pros and cons of their use. Although systematic reviews and population-based studies have been conducted, a consensus on this association remains to be established. Subsequently, the concept of so-called 'activation syndrome' associated with antidepressants has been accepted without its adequate verification. In the present report, we present our experience of seven cases considered of having 'activation syndrome' brought on by antidepressants, and examine its clinical relevance to bipolar spectrum disorder (Ghaemi, et al., 2001) both symptomatologically and diagnostically. Five patients, diagnosed as having major depressive disorder according to the diagnostic manual (DSM-IV), met the criteria of bipolar spectrum disorder and suffered from activation syndrome following the administration of SSRIs, mainly paroxetine. Similarly, hypomania developed in all five cases with depression; the diagnostic criteria of a hypomanic episode were not met. In the remaining two patients, who were both diagnosed with bipolar disorder, one showed irritability and insomnia through imipramine use, and the another developed a hypomanic and/or a mixed state after the co-administration of fluvoxamine and trazodone. From the results of our examination, 'bipolarity', which is the pivotal factor of bipolar spectrum, might exist behind the phenomenon recognized as activation syndrome, and be revealed by antidepressant treatment, just like manic switching. Moreover, the various problems encountered in the current practice of treating mood disorders, including unipolar-bipolar dichotomy, manic switching by antidepressants, and narrow criteria for a mixed episode, were pointed out a new through this concept of activation syndrome. Actually, the understanding of activation syndrome clinically leads to the prevention of suicidal behavior and the careful use of antidepressants for bipolar (spectrum) disorder, but we must be prudent when applying this concept, since it has not yet been established.
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PMID:[Clinical relevance of antidepressant-induced activation syndrome: from a perspective of bipolar spectrum disorder]. 1796 91

Although most treatment research on bipolar disorder has focused on mania, depressive episodes occur more frequently among patients with bipolar disorder. Here, we report the results of 2 identically designed, 8-week, multicenter, randomized, double-blind, placebo-controlled studies (CN138-096 and CN138-146) to evaluate the efficacy and safety of aripiprazole monotherapy in outpatients with bipolar I disorder experiencing a major depressive episode without psychotic features. Patients were randomized to placebo or aripiprazole (initiated at 10 mg/d, then flexibly dosed at 5-30 mg/d based on clinical effect and tolerability). The primary end point was mean change from baseline to Week 8 (last observation carried forward) in the Montgomery-Asberg Depression Rating Scale total score. In Studies 1 and 2, respectively, 186 and 187 patients were randomized to aripiprazole, and 188 and 188 to placebo. Although statistically significant differences were observed during Weeks 1 to 6, aripiprazole did not achieve statistical significance versus placebo at Week 8 in either study in the change in Montgomery-Asberg Depression Rating Scale total (primary end point). In addition, despite early statistical separation on the Clinical Global Impressions Bipolar Version Severity of Illness-Depression score (key secondary end point), aripiprazole was not superior to placebo at end point. Aripiprazole was associated with a higher incidence of akathisia, insomnia, nausea, fatigue, restlessness, and dry mouth versus placebo. More patients discontinued with aripiprazole versus placebo in Study 1 (46.8% vs 35.1%) and Study 2 (41.2% vs 29.8%). Aripiprazole monotherapy-as dosed in this study design-was not significantly more effective than placebo in the treatment of bipolar depression at end point (Week 8).
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PMID:Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. 1820 35

In this review, the authors detail our current understanding of the crucial role that sleep and its disturbances play in bipolar disorder. Multiple lines of evidence suggest that impaired sleep can induce and predict manic episodes. Similarly, treatment of sleep disturbance may serve as both a target of treatment and a measure of response in mania. The depressive phase of bipolar illness is marked by sleep disturbance that may be amenable to somatic therapies that target sleep and circadian rhythms. Residual insomnia in the euthymic period may represent a vulnerability to affective relapse in susceptible patients. Given the importance of sleep in all phases of bipolar disorder, appropriate evaluation and management of sleep disturbance in patients with bipolar illness is further detailed.
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PMID:Sleep disturbance in bipolar disorder: therapeutic implications. 1848 32

When taking antipsychotic medications, children and adolescents seem to have a higher risk than adults for experiencing adverse events such as extrapyramidal symptoms, prolactin elevation, sedation, weight gain, and metabolic effects. Side effects may be predicted by the pharmacologic binding profiles of antipsychotics to certain neuroreceptors. Data from 7 recently completed randomized placebo-controlled trials in adolescent schizophrenia and pediatric bipolar disorder that included a total of 1480 patients extend prior results and provide numbers-needed-to-harm as a clinically useful measure of risk. Results from these pediatric studies indicate that adverse effect profiles differ among commonly used antipsychotics. However, more detailed data are needed, as information is lacking regarding carryover or withdrawal effects from prior medications and regarding the masking of effects by adjunctive treatments used to treat agitation, insomnia, or extrapyramidal symptoms and akathisia in these studies. Moreover, randomized head-to-head trials and large-scale studies that investigate predictors of adverse effects as well as the safety and efficacy of interventions aimed at preventing and reversing negative effects of antipsychotics with relevant impact on psychological, psychiatric, and physical functioning are lacking. When choosing an antipsychotic treatment, patients and their families should be included in a careful risk-benefit assessment. Consideration of adverse effects, as well as dietary and lifestyle counseling, should be part of any antipsychotic treatment initiation and continuation. Routine, proactive monitoring of side effects is essential to optimize patient outcomes. In all treatment decisions, the benefits of improving often severe and debilitating manic, psychotic, and aggressive symptomatology must be balanced against the varying risks of adverse effects associated with specific antipsychotic agents in child and adolescent patients.
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PMID:Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents. 1853 66

Research and treatment have traditionally adopted a 'disorder-focused' approach by targeting one specific disorder, aiming to understanding its cause, maintenance and treatment. The aim of the present study was to contribute to the burgeoning interest in examining common, or 'transdiagnostic,' processes across disorders. Three candidate transdiagnostic processes involved in emotion regulation - rumination, worry, and automatic negative thoughts - were examined in euthymic bipolar I disorder (n=21) and insomnia (n=19), and a non-clinical control group (n=20). Rumination and worry were endorsed to a larger degree by the bipolar and insomnia groups compared to the control group. However, while the bipolar group had more negative automatic thoughts than the control group, there were no significant differences in negative automatic thoughts between the bipolar and insomnia groups or the insomnia and control groups. These results suggested that rumination and worry, but not negative automatic thoughts, might be common across bipolar disorder and insomnia. However, these findings no longer remained significant when current symptoms of anxiety and depression were controlled for. Prospective and experimental studies are needed to test the extent to which these processes contribute to the etiology or maintenance of insomnia and bipolar disorder.
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PMID:Transdiagnostic emotion regulation processes in bipolar disorder and insomnia. 1868 36

Modafinil is a wake-promoting agent that is pharmacologically different from other stimulants. It has been investigated in healthy volunteers, and in individuals with clinical disorders associated with excessive sleepiness, fatigue, impaired cognition and other symptoms. This review examines the use of modafinil in clinical practice based on the results of randomized, double-blind, placebo-controlled clinical trials available in the English language in the MEDLINE database. In sleep-deprived individuals, modafinil improves mood, fatigue, sleepiness and cognition to a similar extent as caffeine but has a longer duration of action. Evidence for improved cognition in non-sleep-deprived healthy volunteers is controversial.Modafinil improves excessive sleepiness and illness severity in all three disorders for which it has been approved by the US FDA, i.e. narcolepsy, shift-work sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure (CPAP). However, its effects on safety on the job and on morbidities associated with these disorders have not been ascertained. Continued use of CPAP in obstructive sleep apnoea is essential. Modafinil does not benefit cataplexy.In very small, short-term trials, modafinil improved excessive sleepiness in patients with myotonic dystrophy. It was efficacious in fairly large studies of attention deficit hyperactivity disorder (ADHD) in children and adolescents, and was as efficacious as methylphenidate in a small trial, but has not been approved by the FDA, in part because of its serious dermatological toxicity. In a trial of 21 non-concurrent subjects, with 2-week treatment periods, modafinil was as effective as dexamfetamine in adult ADHD. Modafinil was helpful for depressive symptoms in bipolar disorder in a trial that excluded patients with stimulant-induced mania. A single dose of modafinil may hasten recovery from general anaesthesia after day surgery. A single dose of modafinil improved the ability of emergency room physicians to attend didactic lectures after a night shift, but did not improve their ability to drive home and caused sleep disturbances subsequently.Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo.Trials of modafinil for excessive sleepiness in Parkinson's disease, cocaine addiction and cognition in chronic fatigue syndrome provided inconsistent results; all studies had extremely small sample sizes. Modafinil cannot be recommended for these conditions until definitive data become available.Modafinil induces and inhibits several cytochrome P450 isoenzymes and has the potential for interacting with drugs from all classes. The modafinil dose should be reduced in the elderly and in patients with hepatic disease. Caution is needed in patients with severe renal insufficiency because of substantial increases in levels of modafinil acid. Common adverse events with modafinil include insomnia, headache, nausea, nervousness and hypertension. Decreased appetite, weight loss and serious dermatological have been reported with greater frequency in children and adolescents, probably due to the higher doses (based on bodyweight) used. Modafinil may have some abuse/addictive potential although no cases have been reported to date.
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PMID:Approved and investigational uses of modafinil : an evidence-based review. 1872 34

Variations in voltage-dependent calcium channel L-type, alpha 1C subunit (CACNA1C) gene have been associated with bipolar disorder in a recent meta-analysis of genome-wide association studies [Ferreira et al., 2008]. The impact of these variations on other psychiatric disorders has not been yet investigated. Caucasian non-Hispanic participants in the STAR*D study of treatment for depression for whom DNA was available (N = 1213) were genotyped at two single-nucleotide polymorphisms (SNPs) (rs10848635 and rs1006737) in the CACNA1C gene. We examined putative phenotypic indicators of bipolarity among patients with major depression and elements of longitudinal course suggestive of latent bipolarity. We also considered remission and depression severity following citalopram treatment. The rs10848635 risk allele was significantly associated with lower levels of baseline agitation (P = 0.03; beta = -0.09). The rs1006737 risk allele was significantly associated with lesser baseline depression severity (P = 0.04; beta = -0.4) and decreased likelihood of insomnia (P = 0.047; beta = -0.22). Both markers were associated with an increased risk of citalopram-emergent suicidality (rs10848635: OR = 1.29, P = 0.04; rs1006737: OR = 1.34, P = 0.02). In this exploratory analysis, treatment-emergent suicidality was associated with two risk alleles in a putative bipolar liability gene.
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PMID:Phenotypic effects of a bipolar liability gene among individuals with major depressive disorder. 1938 2

Depression is a family of complex and multifactorial illnesses that are characterized by disruptions in the functioning of a number of physiological, neuroendocrine and behavioral processes. Of these, sleep disturbance and circadian rhythm abnormalities constitute the most prevalent signs of depressive illness. Difficulty in falling asleep, decreases in total sleep time and sleep efficiency, early morning awakenings, and rapid eye movement sleep alterations are all commonly seen in depressed patients. Advances or delays in the phase of circadian rhythms have been documented in patients with major depressive disorder (MDD), bipolar disorder and patients with seasonal affective disorder (SAD). The disturbances in the amplitude and rhythm of melatonin secretion that occur in patients with depression resemble those seen in subjects with chronobiological disorders. The finding that insomnia and circadian rhythm abnormalities are prominent features in depression suggests that a close link exists between melatonin secretion disturbance and depressed mood. This inference has been further strengthened by the finding that agomelatine, a recently introduced melatonergic agent with a novel mechanism of action, has beneficial effects in patients with MDD, bipolar disorder or SAD. Among agomelatine's characteristics are a rapid onset of action and a pronounced effectiveness for improving sleep efficiency and correcting circadian rhythm abnormalities. Disruptions in melatonin secretion or availability may be the common factor, which underlies depressive disorder and its prominent signs and symptoms such as sleep and circadian rhythm abnormalities.
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PMID:Bidirectional communication between sleep and circadian rhythms and its implications for depression: lessons from agomelatine. 1945 2

Despite the high prevalence of insomnia in the primary care setting, only a small proportion of patients report sleep problems to their physician. Evidence shows that treatment of insomnia can ameliorate the high socioeconomic burden associated with the disorder, as well as improve patient outcomes in coexistent diseases such as depression, bipolar disorder, rheumatoid arthritis, and fibromyalgia. The first strategy for improving diagnosis of insomnia is heightened awareness of the condition. As the first point of contact for most patients, primary care physicians are in a unique position to improve rates of detection and treatment. All patients should be screened for sleep disorders with such questions as "How is your sleep?" "Do you have trouble getting to sleep or staying asleep?" and "Do you get drowsy during the day or at inappropriate times?" Medical history and physical examination may also reveal possible coexistent psychiatric and medical illnesses that put patients at higher risk for insomnia, as well as suggest involvement of prescription and nonprescription medications and environmental factors that contribute to insomnia. Diagnostic tools such as the Epworth Sleepiness Scale and the Sleep Hygiene Self-Test can aid patients and physicians in recognizing sleep problems, assessing their severity, and measuring improvement after treatment.
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PMID:Practical diagnostic strategies and tools for insomnia. 1966 87


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