TY - JOUR
AU - Strohl, Kingman P
AB - Nightmares are an intrinsic component of several disorders including post-traumatic stress disorder (PTSD), rapid eye movement (REM) sleep behavior disorder and night terrors [1] and afflict some 2%–6% of adults [2–4]. The prevalence is higher in veterans who have suffered combat-related trauma [5]. Pickworth et al. [6] suggested that amplified central nervous system α1-adrenergic receptor stimulation heightened reactivity during sleep and thus constituted the basis of nightmares in PTSD. We observed patients on risperidone had fewer complaints about nightmares. We report a series of seven patients in whom low-dose risperidone proved effective in attenuating nightmares that emerged as part of their primary PTSD [1]. The pharmacological rationale for trying risperidone was based on prior case series illustrating its success in treating nightmares. Pharmacological agents affecting the neurotransmitters norepinephrine, serotonin, and dopamine are associated with patient reports of nightmares. A possible association exists between reports of nightmares and agents affecting the neurotransmitters acetylcholine, GABA, and histamine. Given its multiple receptor binding profile, risperidone acts as an antagonist at the following receptors: D2, 5-HT2A, Alpha 1, Alpha 2, H1 (moderate affinity). Thus, its action to alleviate nightmares may be multifactorial regarding receptors. In this case, series veterans treated with risperidone filled out the Nightmare Distress Questionnaire (NDQ) at each visit; one of the physicians who treated a veteran with risperidone successfully ablated his nightmares subsequently leading to the case series. We monitored veterans treated with risperidone for nightmares, the sample only includes veterans prescribed risperidone to treat nightmare disorder, no other medications were utilized to treat nightmares. All veterans met the criteria for nightmare disorder as defined by the ICSD [7]; remission was designated as a score of 0 on the nightmare distress questionnaire; as veterans who scored zero were no longer reporting anxiety dreams and were deemed in remission. Individuals who scored 21 met the ICSD criteria for nightmare disorder. Unfortunately, we have no data regarding the frequency of nightmares as no question in the Nightmare Distress Questionnaire quantifies the frequency of nightmares. A linear mixed-effects model was estimated predicting nightmare distress questionnaire scores with time, dose, the interaction of time and dose, and a random intercept for each subject. This modeling approach was selected given the unbalanced groups and missing observations. Differences in questionnaire scores over time were assessed as model contrasts, averaging over levels of dose. All analyses were performed in R 3.5.1 using the lme4 and emmeans packages. There was an initial prompt decrease in symptoms as the NDQ scores at 4 weeks exhibited a trend toward baseline. At 12 weeks, 30% of the sample had an NDQ score of 0 (Figure 1). Figure 1. Open in new tabDownload slide Legends shown are a mean ± SD of NDQ values at baseline, 4, 8, and 12 weeks. Test for trends (p < 0.01). Figure 1. Open in new tabDownload slide Legends shown are a mean ± SD of NDQ values at baseline, 4, 8, and 12 weeks. Test for trends (p < 0.01). In 30% of the veterans in this case series, nightmares resolved over 12 weeks of risperidone in the low-dose range (0.5–2 mg HS). In an earlier case series (n = 4), risperidone doses 1–3 mg/d were reported to attenuate nightmares [8]. Risperidone improves REM density acutely [9], and this may explain is transient short-term therapeutic benefit for nightmares. However, more than 12 weeks, not all improved. This could be tachyphylaxis. Thus, long-term efficacy would require confirmation by a randomized controlled trial. Low-dose risperidone was generally well-tolerated and effective in resolving PTSD-related nightmares more than 12 weeks. There is increasing awareness that nightmares per se increase distress and elevate suicide risk [10, 11] Conflict of interest statement. None declared. Work Performed: Louis Stokes VA Medical Center, 10701 East Blvd, Cleveland, Ohio 44106. References 1. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders DSM-5 . Washington, DC : American Psychiatric Publishing, Inc. ; 2013 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 2. Belicki K , et al. Predisposition for nightmares: a study of hypnotic ability, vividness of imagery, and absorption . J Clin Psychol. 1986 ; 42 ( 5 ): 714 – 718 . Google Scholar Crossref Search ADS PubMed WorldCat 3. Bixler EO , et al. Prevalence of sleep disorders in the Los Angeles metropolitan area . Am J Psychiatry. 1979 ; 136 ( 10 ): 1257 – 1262 . Google Scholar Crossref Search ADS PubMed WorldCat 4. Ohayon MM , et al. Prevalence of nightmares and their relationship to psychopathology and daytime functioning in insomnia subjects . Sleep. 1997 ; 20 ( 5 ): 340 – 348 . Google Scholar Crossref Search ADS PubMed WorldCat 5. Neylan TC , et al. Sleep disturbances in the Vietnam generation: findings from a nationally representative sample of male Vietnam veterans . Am J Psychiatry. 1998 ; 155 ( 7 ): 929 – 933 . Google Scholar Crossref Search ADS PubMed WorldCat 6. Pickworth WB , et al. Sleep suppression induced by intravenous and intraventricular infusions of methoxamine in the dog . Exp Neurol. 1977 ; 57 ( 3 ): 999 – 1011 . Google Scholar Crossref Search ADS PubMed WorldCat 7. American Academy of Sleep Medicine . International Classification of Sleep Disorders . 3rd ed. Darien : American Academy of Sleep Medicine ; 2014 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 8. Detweiler MB , et al. Risperidone for post-traumatic combat nightmares: a report of four cases . Consult Pharm. 2011 ; 26 ( 12 ): 920 – 928 . Google Scholar Crossref Search ADS PubMed WorldCat 9. Giménez S , et al. Effects of olanzapine, risperidone and haloperidol on sleep after a single oral morning dose in healthy volunteers . Psychopharmacology (Berl). 2007 ; 190 ( 4 ): 507 – 516 . Google Scholar Crossref Search ADS PubMed WorldCat 10. Sandman N , et al. Nightmares as predictors of suicide: an extension study including war veterans . Sci Rep. 2017 ; 7 : 44756 . Google Scholar Crossref Search ADS PubMed WorldCat 11. Perlis ML , et al. Nocturnal wakefulness as a previously unrecognized risk factor for suicide . J Clin Psychiatry. 2016 ; 77 ( 6 ): e726 – e733 . Google Scholar Crossref Search ADS PubMed WorldCat Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US. Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2019.
TI - Low-dose risperidone diminishes the intensity and frequency of nightmares in post-traumatic stress disorder
JO - SLEEP
DO - 10.1093/sleep/zsz144
DA - 2019-10-09
UR - https://www.deepdyve.com/lp/oxford-university-press/low-dose-risperidone-diminishes-the-intensity-and-frequency-of-lADo4WNsIN
VL - 42
IS - 10
DP - DeepDyve
ER -