US Pharm. 2018;43(11):21-25.
ABSTRACT: Occasional nightmares are fairly common, but nightmare disorder occurs in 2% to 6% of adults. Recurrent nightmares may be idiopathic, but they are often related to posttraumatic stress disorder (PTSD), underlying psychiatric disorders, or medication use. The American Academy of Sleep Medicine’s 2018 position paper provides guidance on nonpharmacologic and pharmacologic treatment. Behavioral intervention with imagery-rehearsal therapy is currently the only treatment strategy recommended for all patients with recurrent nightmares. Prazosin may be used to treat both PTSD-associated and idiopathic nightmare disorder. Antidepressants, anxiolytics, anticonvulsants, antipsychotics, and other agents have been studied, with mixed results.
Nightmares are vivid, disturbing, or frightening nocturnal episodes that often involve intense feelings of dread, humiliation, or failure. The International Classification of Sleep Disorders, Third Edition (ICSD-3), defines nightmare disorder as a parasomnia (i.e., abnormal or unusual nervous-system behavior during sleep) usually associated with rapid-eye-movement sleep. The minimal diagnostic criteria include recurrent episodes of awakenings from disturbed dreams, full alertness on awakening with clear recall of dream, and either delayed return to sleep or occurrence of the episode in the second half of the sleep period.1-3
Epidemiology and Etiology
Occasional nightmares are relatively common, but nightmare disorder affects between 2% and 6% of adults.1,3 It is more common in younger adults than in older adults. More women than men have nightmare disorder during young adulthood, but there is no difference in those aged 60 years and older.1,3 Although they can be idiopathic, recurrent nightmares are often related to posttraumatic stress disorder (PTSD) and other psychiatric disorders, and PTSD patients—up to 80% of whom experience nightmares—have been studied the most regarding nightmares.3 Medications that affect neurotransmitter levels in the central nervous system are also associated with nightmares (TABLE 1).4
In 2018, the American Academy of Sleep Medicine (AASM) published a position paper on the treatment of nightmare disorder that replaced their best-practice guide from 2010.3 Treatment options are designated recommended or not recommended if they are clearly useful or harmful based on clinical evidence. The may be used position is designated when evidence is less clear. The AASM further differentiates treatments for PTSD-associated nightmares and nightmares without a clear etiology (which is termed nightmare disorder).3 Although selection of therapy depends on the clinician and the patient’s access to resources, pharmacists should be aware of the various treatment options discussed in the position paper.
The only treatment strategy with enough evidence to be recommended in the AASM’s position paper is behavioral intervention with imagery-rehearsal therapy (IRT).3 IRT is based on the theory that nightmares are a learned behavior and can be replaced by a less disruptive behavior that will not ultimately affect sleep or daytime functioning. Patients are asked to recall the nightmare, write it down, alter its content to a positive outcome, and rehearse the rescripted dream for 10 to 20 minutes each day. Additional treatments that may be used for both PTSD-associated nightmares and nightmare disorder include cognitive behavioral therapy and exposure, relaxation, and rescripting therapies. Other behavioral strategies include hypnosis, lucid-dreaming therapy, eye-movement desensitization and reprocessing, and progressive deep-muscle relaxation techniques.3
Although no pharmacologic agent is recommended in the position paper, many of the medications discussed are designated may be used.3 TABLE 2 provides a detailed summary of these agents, along with available trial data. Prazosin remains the drug of choice and is the only one indicated for both nightmare types.3 Therefore, prazosin will be discussed first, followed by the remaining agents and drug classes in alphabetical order.
Prazosin: The 2010 AASM best-practice guide recommended prazosin for nightmare disorder; however, the current position paper has downgraded its classification to may be used based on a recent publication that did not find a statistical difference versus placebo.3,5 This trial had the largest patient population to date and was the first to show a lack of benefit with prazosin; however, the majority of patients in both groups were concurrently receiving an antidepressant.5-16 This is important because a prior trial noted a decreased response to prazosin in patients concurrently taking a selective serotonin reuptake inhibitor (SSRI).7 Further clarification of this possible interaction is needed.
Atypical Antipsychotics: In small studies, aripiprazole, olanzapine, and risperidone have been evaluated as adjunctive treatments for PTSD, and all of these agents have demonstrated some benefit for the associated nightmares. These medications, however, are limited by their adverse-effect profile.17-20
Benzodiazepines: Nitrazepam and triazolam were assessed in a single 3-day trial in which patients with disturbed sleep (nightmare type was not identified) reported a decrease in “unpleasant dreams.”21 Patients took just one dose of each medication, followed by a 1-day washout period. Clonazepam is currently not recommended because it was found to be ineffective for PTSD-associated nightmares in a randomized clinical trial.22
Clonidine: The two studies of clonidine conducted in PTSD patients had positive results; however, there were only 13 participants.23,24
Cyproheptadine: Three small trials of cyproheptadine in PTSD patients had conflicting data. Adverse effects may outweigh the benefit.25-27
Gabapentin: A single retrospective study of gabapentin in patients with PTSD showed a marked or moderate improvement in sleep, as well as a decreased frequency or intensity of nightmares.28
Nabilone: In a single open-label study, the majority of PTSD patients receiving nabilone experienced cessation of nightmares or a significant reduction in nightmare intensity. A smaller randomized trial also found a decreased incidence of PTSD-related nightmares.29,30
Phenelzine: Two studies of phenelzine in PTSD patients indicated a benefit. However, all patients in the larger study ultimately withdrew because the improvement in nightmare severity was negligible, was short-lived, or plateaued.31,32
SSRIs and Serotonin-Norepinephrine Reuptake Inhibitors: Of these agents, only fluvoxamine is designated may be used. Two small clinical studies of fluvoxamine showed benefit; however, in one study, many patients withdrew because of side effects.3,33,34 Venlafaxine has shown benefit for general PTSD symptoms, but not nightmares; therefore, it is not recommended.1,3
Topiramate: Despite positive results in several studies of PTSD-associated nightmares, topiramate use may be limited because of adverse effects.3,35-38
Trazodone: The only study to evaluate trazodone found it to be effective, but 19% of patients were unable to maintain an effective dose, and many experienced at least one side effect.39
Tricyclic Antidepressants (TCAs): One small case series in patients with PTSD suggested beneficial effects; however, findings were limited because TCA treatment was varied.40
The Pharmacist’s Role
Pharmacist awareness of nightmare disorder is becoming increasingly important. As the number of patients with PTSD continues to rise owing to war, mass shootings, and other traumatic events, the incidence of nightmare disorder will increase accordingly. Because patients may be hesitant or embarrassed to discuss nightmares with their primary care provider, pharmacists should learn to recognize the symptoms and common causes of nightmare disorder so that they can identify patients who may need referral for evaluation and treatment. Pharmacists should also be familiar with the pharmacologic agents that may be used to treat this condition so that they can appropriately counsel patients dealing with this disorder.
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