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diabetes Ptsd And Sleep Disorders
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DenDowhy
Sleep and Anxiety: Focus on PTSD and Generalized Anxiety Disorder: Posttraumatic Stress Disorder
Authors and Disclosures
[*] References
Posttraumatic Stress Disorder
Sleep disturbance is a core feature of PTSD, as reflected in its inclusion in 2 of the 3 major symptom clusters in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR®): difficulty falling asleep as a hyperarousal symptom and nightmares as a reexperiencing symptom.[7] Sleep disturbance is highly prevalent among patients with PTSD; 70% to 91% of individuals with civilian- or combat-related PTSD experience some sleep disruption.[8-11] For example, 91% of 116 Vietnam veterans with PTSD seen in a Veterans Administration clinic reported sleep disturbance (distinct from nightmares), with 73% experiencing recurrent dreams and nightmares and 39% avoiding sleep because of anticipation of troubling thoughts or nightmares.[11]
The development of sleep disturbance following trauma exposure appears to be a marker and a potential risk factor for the subsequent development of PTSD.[12] In one study, PTSD developed by 6-month follow-up in almost three fourths of individuals (72%) reporting sleep disturbance in the month following trauma exposure.[13] Disturbed sleep among individuals with PTSD is associated with a number of measures of poorer clinical status, including depression and suicidality,[14] poorer overall quality of life and functioning,[15] poorer health functioning and somatic symptoms,[16,17] and increased rates of alcohol and substance use.[18,19] Sleep disturbances appear to both worsen and prolong the PTSD syndrome,[20] which is consistent with preclinical data demonstrating that sleep deprivation leads to impaired extinction learning in fear-conditioned rats.[21]
Although a number of agents and psychosocial interventions have been tested and used for the treatment of PTSD, there is relatively little systematic controlled data specifically addressing the treatment of associated sleep disturbance. Treatment with selective serotonin reuptake inhibitors (SSRIs) has been associated with small but significant overall improvement in sleep disturbance in large randomized, controlled trials of patients with PTSD[22,23]; however, sleep disturbance is also noted after the administration of these agents.[24,25] These medications can have a number of adverse effects on sleep, including increased arousals and decreased rapid eye movement (REM) sleep and total sleep time.[26,27] Other sedating antidepressants, such as amitriptyline or mirtazapine, show weak results for the treatment of PTSD symptoms, and studies that suggested benefit were small and had methodologic limitations, including significant dropout rates.[28,29] Although a consensus treatment guideline[30] and survey data[31] suggest that trazodone may be beneficial for patients with PTSD, there is no controlled study of its application in affected individuals.
Benzodiazepines are commonly administered to patients with PTSD,[32] although there are relatively few systematic data addressing their use in this patient population. However, in a small randomized, controlled trial, alprazolam did not have substantial benefit for PTSD or for nightmares, although it did improve anxiety.[33] In a small single-blind, placebo-controlled crossover study, clonazepam did not demonstrate significant benefit in any sleep parameters, including nightmares, although there were some modest, nonsignificant improvements in sleep latency and maintenance.[34] Further, although the findings need to be understood in the context of the small number of patients examined, data from 2 studies[35,36] suggest that although benzodiazepines administered to individuals who have been recently traumatized may have a salutary acute effect on reducing anxiety and insomnia, their use is associated with an increased risk for PTSD at up to a 6-month follow-up. The use of benzodiazepines is also constrained by their potential for abuse and dependence and because they may worsen depression, which is of particular relevance given the high comorbidity rate of substance abuse and depression in individuals with PTSD. Further, patients with combat-related PTSD have experienced severe withdrawal symptoms, including disinhibition and rage with even gradual withdrawal of alprazolam.[37]
Prazosin, an alpha-1 adrenergic antagonist antihypertensive, has demonstrated efficacy in double-blind, randomized, controlled trials in civilian- and combat-related PTSD for nightmares, sleep disturbance, and overall PTSD symptomatology.[38,39] Although this agent was generally well tolerated in those trials, it can be associated with orthostatic hypotension, particularly early in treatment. Atypical antipsychotic medications are being used as adjunctive therapy and, occasionally, as monotherapy for PTSD and other mood and anxiety disorders. For instance, in a double-blind, placebo-controlled study of olanzapine augmentation of SSRI in patients with persistent symptomatology despite antidepressant treatment alone, there was significant improvement in sleep disturbance as well as in other symptoms of PTSD in combat veterans.[40] Of note, however, the average weight gain for olanzapine-treated patients in this study was more than 13 pounds. Quetiapine also demonstrated benefit for sleep-related symptoms in patients with PTSD in a 6-week open-label adjunctive study.[41] The potential salutary effects on sleep and PTSD associated with the use of atypical antipsychotic drugs, however, need to be weighed against their potential to cause significant weight gain, diabetes, and other manifestations of metabolic syndrome, as well as extrapyramidal effects.
Although cyproheptadine, a 5HT2 and H1 receptor antagonist used to treat symptomatic allergies, showed benefit for the treatment of nightmares in individuals with PTSD in a number of open reports,[42,43] it was ineffective for nightmares or PTSD in a double-blind, randomized, controlled trial, and in fact appeared to exacerbate sleep disturbance and other PTSD symptoms.[44] A retrospective report suggested that the anticonvulsant gabapentin was effective in enhancing sleep duration and decreasing nightmares when used adjunctively with antidepressants for individuals with PTSD,[45] although there has been no subsequent systematic study of this issue. The hypnotic zolpidem reduced sleep disturbance, including nightmares, in an open series of patients with combat-related PTSD, although effects on other PTSD symptoms were not reported.[46] Eszopiclone was recently reported to improve both PTSD symptomatology and sleep disturbance when administered as monotherapy or augmentation therapy for PTSD in a double-blind, randomized, controlled crossover study.[47]
Exposure-based cognitive behavioral therapy (CBT) has been demonstrated effective in numerous studies for the treatment of PTSD.[29] A specific form of CBT called imagery rehearsal therapy, which targets chronic nightmares, has demonstrated efficacy in a randomized controlled study for reducing nightmares, insomnia, and overall PTSD symptoms in affected individuals.[48] Although CBT is clearly effective, its use can be limited by patients' willingness and ability to participate in the necessary interventions, as well as by problems with the broad dissemination of these treatments.
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