We have a regular conference on the consultation-liaison service called the Clinical Problems in Consult Psychiatry (CPCP). At the most recent meeting, resident psychiatrist Dr. Ki Won Nam reviewed the topic of sleep disturbance in patients who’ve suffered traumatic brain injury (TBI).
Dr. Nam reviewed the Baumann article below . He also sent along another article about the effect of sleep medications on cognitive recovery and TBI . Traumatic brain injury (TBI) is a major cause of death and disability worldwide, and distressingly common in children and young adults. About 1.6 million people suffer TBI annually in the U.S. alone, accounting for 52,000 deaths and the toll reaches 80,000 patients suffering from irreversible neurological impairment. The Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury defines TBI “as an alteration in brain function, or other evidence of brain pathology, caused by an external force.” Common causes of TBI include motor vehicle accidents, falls, violence, and sports accidents.
Background on TBI
The two main types of traumatic brain damage are primary, which refers to external forces such as direct impact and penetrating objects, and secondary brain damage, including free radical generation, neurotransmitter release, and calcium-mediated damage among others. An important contributor to fatal outcome after TBI is increased intracranial pressure, signs of which include but are not limited to dilated pupils, coma, and respiratory depression.
Neurologic function can continue to improve over two or more years after the injury, although it’s fastest in the first 6 months. Residual symptoms are common including impaired consciousness, hyposmia (reduced sense of smell), cognitive deficits, seizures, psychiatric disorders, and sleep-wake disturbances (SWD).
And conversely, SWD can worsen neurological adverse outcomes. Sustained attention is impaired in patients who have TBI and suffer SWD. Obstructive sleep apnea can make this worse. Patients with mild TBI with SWD are more likely to suffer from depressive symptoms, irritability, and headaches.
Posttraumatic SWD is understudied and the studies which do exist tend to have methodological shortcomings. However, SWD after TBI are common, and in one study occurred in up to 72% of the population. In most cases excessive daytime sleepiness and fatigue were the most common sort of SWD. This was found in studies using a number of validated scales including the Epworth Sleepiness Scale (see resource list below). Insomnia tends to be less common.
Pathophysiology of Posttraumatic SWD
The pathophysiology of postraumatic SWD is essentially unknown, but are probably due to many causes. damage to the human brain injures many brain areas that control neurological and psychiatric functions. Interestingly, lower levels of the wake-promoting neurotransmitter hypocretin (orexin, which is produced by the posterior hypothalamus) have been found after acute TBI. Both primary and secondary damage might account for this. This may be part of the explanation for the excessive daytime sleepiness often seen in TBI patients. Another study showed lower levels of melatonin production correlating with subjective complaints of sleep problems and symptoms of depression and anxiety.
Sleep Medications and TBI
Although we didn’t review the Larson and colleagues article, the bottom line seems to be that benzodiazepines (e.g., Ativan, Xanax, Valium, Klonopin) should be avoided because they tend to be associated with cognitive impairment and interference with recovery. Other GABA agonists like Ambien probably ought to be avoided for the same reasons. Trazodone, an older antidepressant, may be less likely to result in cognitive impairment. Melatonin is an endogenous neurohumeral agent made in the pineal gland under hypothalamic control. Research tends to support the view that melatonin agonists might be preferred in the TBI population, particularly because of its benign side effect profile, and because sleep latency tends to be decreased and sleep time modestly improved with the use of these agents.
By way of review of the CPCP purpose and structure:
Clinical Problems in Consultation Psychiatry (CPCP):
A weekly case conference held Wednesdays from 8:00 a.m. to approximately 8:45 a.m. Each week, a case is selected from the Daily Review Rounds Records to illustrate a clinical problem for the next week’s meeting. The residents are assigned dates when they rotate. The medical students are welcome and even encouraged to participate as well.
This is a practical way to approach teaching the Practice-Based Learning & Improvement Core Competency. This helps develop the habit of reflecting on and analyzing one’s practice performance; locating and applying scientific evidence to the care of patients; critically appraising the medical literature; using the computer to support learning and patient care; facilitating the education of other health care professionals. This is applying principles of evidence-based medicine (EBM) to clinical practice.
- Evidence-based medicine is a systematic approach to use up to date information in the practice of medicine
- Skills are needed to integrate the available evidence with clinical experience and patient concerns
- Application and evaluation of EBM skills will provide a frame-work for life-long learning.
Self-evaluation is vital to the successful practice of EBM:
- Am I asking answerable clinical questions?
- Am I searching the literature?
- Am I becoming more efficient in my searches?
- Am I integrating my critical appraisals into my practice?
The assigned resident is responsible for searching the literature and selecting one or two teaching papers for the conference. Presentations will begin with a review of the case, followed by a summary of the references with subsequent round table discussion.
Circulate copies of 2-4 pertinent articles to team members including psychiatric nurses and faculty. A copy machine is available in the departmental administration office. Consult staff can also assist with obtaining copies.
Presentations begin with a 5-minute summary of the case with discussion of both psychiatric and medical aspects of evaluation and management. The remaining time is spent summarizing the pertinent data in the articles. Residents and medical students are encouraged to use the case conference material as preparation for submitting a case report or letter to the editor.
1. Baumann, C. R. (2012). “Traumatic Brain Injury and Disturbed Sleep and Wakefulness.” Neuromolecular medicine.
Traumatic brain injury is a frequent condition worldwide, and sleep-wake disturbances often complicate the course after the injuring event. Current evidence suggests that the most common sleep-wake disturbances following traumatic brain injury include excessive daytime sleepiness and posttraumatic hypersomnia, that is, increased sleep need per 24 h. The neuromolecular basis of posttraumatic sleep pressure enhancement is not entirely clear. First neuropathological and clinical studies suggest that impaired hypocretin (orexin) signalling might contribute to sleepiness, but direct or indirect traumatic injury also to other sleep-wake modulating systems in the brainstem and the mesencephalon is likely. Posttraumatic insomnia may be less common than posttraumatic sleepiness, but studies on its frequency revealed conflicting results. Furthermore, insomnia is often associated with psychiatric comorbidities, and some patients with posttraumatic disruption of their circadian rhythm may be misdiagnosed as insomnia patients. The pathophysiology of posttraumatic circadian sleep disorders remains elusive; however, there is some evidence that reduced evening melatonin production due to traumatic brain damage may cause disruption of circadian regulation of sleep and wakefulness.
2. Larson, E. B. and F. S. Zollman (2010). “The effect of sleep medications on cognitive recovery from traumatic brain injury.” The Journal of head trauma rehabilitation 25(1): 61-67.
OBJECTIVE: To summarize the literature on the available pharmacotherapy for insomnia and the adverse cognitive effects of those options in persons with traumatic brain injury (TBI). DESIGN: Ovid/MEDLINE databases were searched by using the following key words: “brain injury,” “sleep initiation and maintenance disorders,” “hypnotics and sedatives,” “benzodiazepines,” “trazodone,” and “neuronal plasticity.” RESULTS: The reviewed literature consistently reported that benzodiazepines and atypical gamma-aminobutyric acid (GABA) agonists result in cognitive impairment when plasma levels are at their peak. Evidence of residual effects on cognition was reported for benzodiazepines but was seen less often in atypical GABA agonists. However, evidence has also been presented that GABA agonists have adverse effects on neuroplasticity, raising concerns about their use in patients recovering from TBI. CONCLUSIONS: Use of benzodiazepines in TBI has been discouraged and some authors also advocate caution in prescribing atypical GABA agonists. Alternate treatments including trazodone and a newer class of agents, melatonin agonists, are highlighted, along with the limited data available addressing the use of these medications in TBI. Finally, suggestions are offered for further research, especially on topic related to neural plasticity and functional recovery.