|
1
|
Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder. CNS Drugs 2022; 36:721-737. [PMID: 35688992 DOI: 10.1007/s40263-022-00929-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/16/2022] [Indexed: 11/03/2022]
Abstract
Posttraumatic stress disorder (PTSD) can be a chronic and disabling condition. Post-traumatic nightmares (PTNs) form a core component of PTSD and are highly prevalent in this patient population. Nightmares in PTSD have been associated with significant distress, functional impairment, poor health outcomes, and decreased quality of life. Nightmares in PTSD are also an independent risk factor for suicide. Nightmare cessation can lead to improved quality of life, fewer hospital admissions, lower healthcare costs, and reduced all-cause mortality. Effective treatment of nightmares is critical and often leads to improvement of other PTSD symptomatology. However, approved pharmacological agents for the treatment of PTSD have modest effects on sleep and nightmares, and may cause adverse effects. No pharmacological agent has been approved specifically for the treatment of PTNs, but multiple agents have been studied. This current narrative review aimed to critically appraise proven as well as novel pharmacological agents used in the treatment of PTNs. Evidence of varying quality exists for the use of prazosin, doxazosin, clonidine, tricyclic antidepressants, trazodone, mirtazapine, atypical antipsychotics (especially risperidone, olanzapine and quetiapine), gabapentin, topiramate, and cyproheptadine. Evidence does not support the use of venlafaxine, β-blockers, benzodiazepines, or sedative hypnotics. Novel agents such as ramelteon, cannabinoids, ketamine, psychedelic agents, and trihexyphenidyl have shown promising results. Large randomized controlled trials (RCTs) are needed to evaluate the use of these novel agents. Future research directions are identified to optimize the treatment of nightmares in patients with PTSD.
Collapse
|
|
2
|
Simon KC, Whitehurst LN, Zhang J, Mednick SC. Zolpidem Maintains Memories for Negative Emotions Across a Night of Sleep. AFFECTIVE SCIENCE 2022; 3:389-399. [PMID: 35791418 PMCID: PMC9249708 DOI: 10.1007/s42761-021-00079-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 09/01/2021] [Indexed: 11/27/2022]
Abstract
Zolpidem, a common medication for sleep complaints, also shows secondary, unexpected memory benefits. We previously found that zolpidem prior to a nap enhanced negative, highly arousing picture memory. As zolpidem is typically administered at night, how it affects overnight emotional memory processing is relevant. We used a double-blind, placebo-controlled, within-subject, cross-over design to investigate if zolpidem boosted negative compared to neutral picture memory. Subjects learned both pictures sets in the morning. That evening, subjects were administered zolpidem or placebo and slept in the lab. Recognition was tested that evening and the following morning. We found that zolpidem maintained negative picture memory compared to forgetting in the placebo condition. Furthermore, zolpidem increased slow-wave sleep time, decreased rapid eye movement sleep time, and increased the fast spindle range in NREM. Our results suggest that zolpidem may enhance negative memory longevity and salience. These findings raise concerns for zolpidem administration to certain clinical populations.
Collapse
Affiliation(s)
- Katharine C. Simon
- Department of Cognitive Science, University of California, Irvine, 2201 Social & Behavioral Sciences Gateway, Irvine, CA 92697 USA
| | | | - Jing Zhang
- Department of Cognitive Science, University of California, Irvine, 2201 Social & Behavioral Sciences Gateway, Irvine, CA 92697 USA
| | - Sara C. Mednick
- Department of Cognitive Science, University of California, Irvine, 2201 Social & Behavioral Sciences Gateway, Irvine, CA 92697 USA
| |
Collapse
|
|
3
|
Brownlow JA, Miller KE, Gehrman PR. Treatment of Sleep Comorbidities in Posttraumatic Stress Disorder. ACTA ACUST UNITED AC 2021; 7:301-316. [PMID: 33552844 DOI: 10.1007/s40501-020-00222-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Purpose of the review Sleep disturbances, insomnia and recurrent nightmares in particular, are among the most frequently endorsed symptoms of posttraumatic stress disorder (PTSD). The present review provides a summary of the prevalence estimates and methodological challenges presented by sleep disturbances in PTSD, highlights the recent evidence for empirically supported psychotherapeutic and pharmacological interventions for comorbid sleep disturbances implicated in PTSD, and provides a summary of recent findings on integrated and sequential treatment approaches to ameliorate comorbid sleep disturbances in PTSD. Recent Findings Insomnia, recurrent nightmares, and other sleep disorders are commonly endorsed among individuals with PTSD; however, several methodological challenges contribute to the varying prevalence estimates. Targeted sleep-focused therapeutic interventions can improve sleep symptoms and mitigate daytime PTSD symptoms. Recently, attention has focused on the role of integrated and sequential approaches, suggesting that comprehensively treating sleep disturbances in PTSD is likely to require novel treatment modalities. Summary Evidence is growing on the development, course, and treatment of comorbid sleep disturbances in PTSD. Further, interventions targeting sleep disturbances in PTSD show promise in reducing symptoms. However, longitudinal investigations and additional rigorous controlled trials with diverse populations are needed to identify key features associated with treatment response in order to alleviate symptoms.
Collapse
Affiliation(s)
- Janeese A Brownlow
- Department of Psychology, College of Health & Behavioral Sciences, Delaware State University, Dover, Delaware, USA.,Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Katherine E Miller
- Mental Illness Research, Education, and Clinical Center, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
| | - Philip R Gehrman
- Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.,Mental Illness Research, Education, and Clinical Center, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
4
|
Hassinger AB, Bletnisky N, Dudekula R, El-Solh AA. Selecting a pharmacotherapy regimen for patients with chronic insomnia. Expert Opin Pharmacother 2020; 21:1035-1043. [PMID: 32202451 DOI: 10.1080/14656566.2020.1743265] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
INTRODUCTION Chronic insomnia, whether it is primary or in combination with another medical or psychiatric disorder, is a prevalent condition associated with significant morbidity, reduced productivity, increased risk of accidents, and poor quality of life. Pharmacologic and behavioral treatments have equivalent efficacy with each having its own advantages and limitations. AREAS COVERED The purpose of this perspective is to delineate the limitations encountered in implementing cognitive behavioral therapy (CBT) and to review the pharmacological treatments designed to target the different phenotypes of insomnia. The discussions address how to choose the optimal medication or combination thereof based on patients' characteristics, available medications, and the presence of comorbid conditions. Selective nonbenzodiazepine sedative 'Z-drug' hypnotics, melatonin receptor agonist-ramelteon, and low-dose doxepin are the agents of choice for treatment of primary and comorbid insomnia. EXPERT OPINION A pharmacological intervention should be offered if cognitive behavioral therapy for insomnia is not available or has failed to achieve its goals. Increasing evidence of the significant adverse consequences of long-term benzodiazepines should limit the prescription of these agents to specific conditions. Testing novel dosing regimens with a combination of hypnotic classes augmented with CBT deserve further investigation.
Collapse
Affiliation(s)
- Amanda B Hassinger
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, NY, USA.,VA Western New York Healthcare System , Buffalo, NY, USA
| | - Nikolas Bletnisky
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, NY, USA.,VA Western New York Healthcare System , Buffalo, NY, USA
| | - Rizwan Dudekula
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, NY, USA.,VA Western New York Healthcare System , Buffalo, NY, USA
| | - Ali A El-Solh
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, NY, USA.,VA Western New York Healthcare System , Buffalo, NY, USA.,Department of Epidemiology and Environmental Health, Research and Development, School of Public Health, University at Buffalo , Buffalo, NY, USA
| |
Collapse
|
|
5
|
Dowd SM, Zalta AK, Burgess HJ, Adkins EC, Valdespino-Hayden Z, Pollack MH. Double-blind randomized controlled study of the efficacy, safety and tolerability of eszopiclone vs placebo for the treatment of patients with post-traumatic stress disorder and insomnia. World J Psychiatry 2020; 10:21-28. [PMID: 32257848 PMCID: PMC7099286 DOI: 10.5498/wjp.v10.i3.21] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 02/10/2020] [Accepted: 02/23/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Sleep disturbance is a core feature of post-traumatic stress disorder (PTSD). Given the relationship between sleep disturbance and PTSD, there has been a relative paucity of studies examining the potential therapeutic impact of using pharmacotherapy to target sleep disturbance in patients with PTSD. Eszopiclone (ESZ) is a non-benzodiazepine y-aminobutyric acid-A receptor agonist indicated for the treatment of sleep and may affect sleep in patients with PTSD.
AIM To evaluate the efficacy of ESZ vs placebo (PBO) for patients with PTSD and insomnia.
METHODS The study was a 12-wk, double blind, randomized controlled trial with 3 mg of ESZ (n = 13) or PBO (n = 12).
RESULTS Patients in both arms experienced significant improvement in PTSD symptoms as assessed by the Clinician-Administered PTSD Scale for DSM-IV (CAPS): ESZ (t11 = -3.12, P = 0.005) and PBO (t11 = -3.5, P = 0.002) and by self-report with the Short PTSD Rating Interview (ESZ t11 = -3.38, P = 0.003 and PBO t11 = -4.48, P = 0.0005). There were no significant differences between treatments on the CAPS (t22 = -0.13, P = 0.70) or the Short PTSD Rating Interview (t22 = -0.58, P = 0.56). Similarly, both treated groups improved on sleep measures as assessed by the Pittsburgh Sleep Quality Index with PTSD Addendum (PSQI) and on total sleep time (TST) and sleep latency assessed by actigraphy with no significant differences between groups (PSQI t22 = -0.24, P = 0.81; total sleep time t10 = 0.13, P = 0.90 and sleep latency t10 = 0.68, P = 0.50). There was a significant correlation between improvement in sleep and overall improvement in PTSD as measured by change scores on the PSQI and CAPS, r(8) = 0.79, P = 0.01 for ESZ treated subjects, but not for those treated with PBO r(9) = 0.16, P = 0.69. Adverse events of ESZ were consistent with the known profile of the medication including dysgeusia (30%, mild), sedation (20%, mild) and headache (20%, moderate to severe).
CONCLUSION Results do not support the hypothesis of a specific positive effect of ESZ compared to PBO for measures of PTSD and associated sleep disturbance.
Collapse
Affiliation(s)
- Sheila M Dowd
- Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL 60601, United States
| | - Alyson K Zalta
- Department of Psychological Science, University of California Irvine, Irvine, CA 92697, United States
| | - Helen J Burgess
- Sleep and Circadian Research Laboratory, Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, United States
| | - Elizabeth C Adkins
- Center for Behavioral Intervention Technologies | Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States
| | | | - Mark H Pollack
- Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL 60601, United States
| |
Collapse
|
|
6
|
Akinnusi M, El Solh AA. Drug treatment strategies for insomnia in patients with post-traumatic stress disorder. Expert Opin Pharmacother 2019; 20:691-699. [PMID: 30794468 DOI: 10.1080/14656566.2019.1574745] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Insomnia is among the most reported sleep disturbances in patients with post-traumatic stress disorder (PTSD). The pervasiveness of this disorder among trauma-inflicted civilians and military personnel has been associated with reduced quality of life, impaired psychosocial functioning including cognitive impairments, negative mood swings, cardiovascular complications, and increased utilization of medical services. AREAS COVERED This review describes the current state of science with respect to the impact of the most dispensed pharmacological interventions for posttraumatic insomnia. At the present, there are no established treatment algorithms for PTSD-related insomnia. Pharmacotherapy offers an alternative treatment modality for patients with PTSD who fail or decline cognitive behavioral therapy (CBT). Selection of a hypnotic/sedative agent should be based on the patient's history, precipitating and perpetuating factors of insomnia, side effect profile, and potential medication-related interactions. Antipsychotics and benzodiazepines appear ineffective or are associated with significant harm in treating PTSD-related insomnia. EXPERT OPINION In the absence of randomized controlled trials, prescription patterns have been guided by anecdotal reports and expert opinion. Due to the complexity and multifactorial etiology of insomnia in PTSD, clinical investigations should examine available pharmacologic agents in comparative trials or in combination with CBT or complementary therapies to assess both short-term and long-term sleep outcomes in this population.
Collapse
Affiliation(s)
- Morohunfolu Akinnusi
- a Department of Medicine , StrongTower Behavioral HealthCare , Marietta , GA , USA
| | - Ali A El Solh
- b Department of Medicine , VA Western New York Healthcare System , Buffalo , NY , USA.,c Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine , State University of New York at Buffalo , USA.,d Department of Epidemiology and Environmental Health , State University of New York at Buffalo School of Medicine and Biomedical Sciences and School of Public Health and Health Professions , USA
| |
Collapse
|
|
7
|
Sleep Disorders in Patients With Posttraumatic Stress Disorder. Chest 2018; 154:427-439. [PMID: 29684315 DOI: 10.1016/j.chest.2018.04.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Revised: 03/27/2018] [Accepted: 04/03/2018] [Indexed: 02/05/2023] Open
Abstract
A growing body of evidence supports a bidirectional relationship between posttraumatic stress disorder (PTSD) and sleep disturbances. Fragmented sleep induced by sleep-related breathing disorders, insomnia, and nightmares impacts recovery and treatment outcomes and worsens PTSD symptoms. Despite recent attention, management of these disorders has been unrewarding in the setting of PTSD. This review summarizes the evidence for empirically supported treatments of these sleep ailments, including psychotherapeutic and pharmacologic interventions, as it relates to PTSD. Recent advances in positive airway pressure technology have made treatment of OSA more acceptable; however, adherence to CPAP therapy presents a substantial challenge. Concomitant insomnia, which engenders psychiatric and medical conditions, including depression, suicide, and alcohol and substance abuse, can be managed with cognitive behavioral therapy. Hypnotic agents are considered an alternative therapy, but concerns about adverse events and lack of high-level evidence supporting their efficacy in PTSD treatment have limited their use to resistant cases or as adjuncts to behavioral therapy when the response is less than desirable. Intrusion of nightmares can complicate PTSD treatment and exert serious strain on social, occupational, and marital relations. Imagery rehearsal therapy has shown significant reduction in nightmare intensity and frequency. The success of noradrenergic blocking agents has not been consistent among studies, with one-half reporting treatment failure. An integrated stepped care approach that includes components of both behavioral and pharmacologic interventions customized to patients' sleep-maladaptive behaviors may offer a solution to delivering accessible, effective, and efficient services for individuals with PTSD.
Collapse
|
|
8
|
Detweiler MB, Pagadala B, Candelario J, Boyle JS, Detweiler JG, Lutgens BW. Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center. J Clin Med 2016; 5:jcm5120117. [PMID: 27999253 PMCID: PMC5184790 DOI: 10.3390/jcm5120117] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 10/28/2016] [Accepted: 12/09/2016] [Indexed: 11/17/2022] Open
Abstract
The effectiveness of medications for PTSD in general has been well studied, but the effectiveness of medicatio.ns prescribed specifically for post-traumatic stress disorder (PTSD) nightmares is less well known. This retrospective chart review examined the efficacy of various medications used in actual treatment of PTSD nightmares at one Veteran Affairs Hospital. Records at the Salem, VA Veterans Affairs Medical Center (VAMC) were examined from 2009 to 2013 to check for the efficacy of actual treatments used in comparis.on with treatments suggested in three main review articles. The final sample consisted of 327 patients and 478 separate medication trials involving 21 individual medications plus 13 different medication combinations. The three most frequently utilized medications were prazosin (107 trials), risperidone (81 trials), and quetiapine (72 trials). Five medications had 20 or more trials with successful results (partial to full nightmare cessation) in >50% of trials: risperidone (77%, 1.0–6.0 mg), clonidine (63%, 0.1–2.0 mg), quetiapine (50%, 12.5–800.0 mg), mirtazapine (50%; 7.5–30.0 mg), and terazosin (64%, 50.0–300.0 mg). Notably, olanzapine (2.5–10.0) was successful (full remission) in all five prescription trials in five separate patients. Based on the clinical results, the use of risperidone, clonidine, terazosin, and olanzapine warrants additional investigation in clinically controlled trials as medications prescribed specifically for PTSD nightmares.
Collapse
Affiliation(s)
- Mark B Detweiler
- Staff Psychiatrist, Veterans Affairs Medical Center, Salem, VA 24153, USA.
- Department Psychiatry, Edward via College of Osteopathic Medicine, Blacksburg, VA 24060, USA.
- Virginia Tech-Carilion Clinic Psychiatry Residency Program, Roanoke, VA 24014, USA.
- Geriatric Research Group, Veterans Affairs Medical Center, Salem, VA 24153, USA.
| | | | - Joseph Candelario
- Geriatric Research Group, Veterans Affairs Medical Center, Salem, VA 24153, USA.
- Emergency Department, Veterans Affairs Medical Center, Salem, VA 24153, USA.
| | - Jennifer S Boyle
- Attending Physician, Veterans Affairs Medical Ce.nter, Syracuse, NY 13210, USA.
| | - Jonna G Detweiler
- Geriatric Research Group, Veterans Affairs Medical Center, Salem, VA 24153, USA.
| | - Brian W Lutgens
- Geriatric Research Group, Veterans Affairs Medical Center, Salem, VA 24153, USA.
| |
Collapse
|
|
9
|
Koffel E, Khawaja IS, Germain A. Sleep Disturbances in Posttraumatic Stress Disorder: Updated Review and Implications for Treatment. Psychiatr Ann 2016; 46:173-176. [PMID: 27773950 DOI: 10.3928/00485713-20160125-01] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Sleep disturbances are common in adults with PTSD and range from insomnia and nightmares to periodic leg movements and disruptive nocturnal behaviors. Together these findings suggest profound disturbances in rapid eye movement (REM) and non-REM (NREM) sleep, although there is a lack of consensus regarding a distinct profile of objective sleep disturbances associated with PTSD. Prospective, longitudinal studies have established that sleep disturbances represent a risk factor for the development and course of PTSD, suggesting that sleep is an important neurobiological mechanism in the etiology and maintenance of this disorder. This research highlights the importance of early identification and treatment of sleep disturbances in at-risk and trauma exposed populations. A number of psychological and pharmacological treatments are effective at treating sleep disturbances in PTSD. Additional research is needed to further develop clinical guidelines informing when and how to integrate sleep-specific treatment with PTSD focused clinical care.
Collapse
Affiliation(s)
- Erin Koffel
- Center for Chronic Disease Outcomes Research, Minneapolis VA Health Care System; Department of Psychiatry, University of Minnesota Medical School
| | - Imran S Khawaja
- Minnesota Regional Sleep Disorders Center, Hennepin County Medical Center; Department of Neurology, University of Minnesota School of Medicine
| | - Anne Germain
- Department of Psychiatry, University of Pittsburgh School of Medicine
| |
Collapse
|
|
10
|
Asnis GM, Thomas M, Henderson MA. Pharmacotherapy Treatment Options for Insomnia: A Primer for Clinicians. Int J Mol Sci 2015; 17:ijms17010050. [PMID: 26729104 PMCID: PMC4730295 DOI: 10.3390/ijms17010050] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2015] [Revised: 12/22/2015] [Accepted: 12/22/2015] [Indexed: 01/08/2023] Open
Abstract
Insomnia is a prevalent disorder with deleterious effects such as decreased quality of life, and a predisposition to a number of psychiatric disorders. Fortunately, numerous approved hypnotic treatments are available. This report reviews the state of the art of pharmacotherapy with a reference to cognitive behavioral therapy for insomnia (CBT-I) as well. It provides the clinician with a guide to all the Food and Drug Administration (FDA) approved hypnotics (benzodiazepines, nonbenzodiazepines, ramelteon, low dose sinequan, and suvorexant) including potential side effects. Frequently, chronic insomnia lasts longer than 2 years. Cognizant of this and as a result of longer-term studies, the FDA has approved all hypnotics since 2005 without restricting the duration of use. Our manuscript also reviews off-label hypnotics (sedating antidepressants, atypical antipsychotics, anticonvulsants and antihistamines) which in reality, are more often prescribed than approved hypnotics. The choice of which hypnotic to choose is discussed partially being based on which segment of sleep is disturbed and whether co-morbid illnesses exist. Lastly, we discuss recent label changes required by the FDA inserting a warning about “sleep-related complex behaviors”, e.g., sleep-driving for all hypnotics. In addition, we discuss FDA mandated dose reductions for most zolpidem preparations in women due to high zolpidem levels in the morning hours potentially causing daytime carry-over effects.
Collapse
Affiliation(s)
- Gregory M Asnis
- Albert Einstein College of Medicine/Montefiore Medical Center, Department of Psychiatry & Behavioral Science, Bronx, NY 10467, USA.
- The Anxiety and Depression Clinic, Bronx, NY 10570, USA.
| | - Manju Thomas
- The Anxiety and Depression Clinic, Bronx, NY 10570, USA.
| | | |
Collapse
|
|
11
|
Abstract
Sleep disturbances are among the most commonly endorsed symptoms of post-traumatic stress disorder (PTSD). Treatment modalities that are effective for the waking symptoms of PTSD may have limited efficacy for post-traumatic sleep problems. The aim of this review is to summarize the evidence for empirically supported and/or utilized psychotherapeutic and pharmacological treatments for post-traumatic nightmares and insomnia. While there are few controlled studies of the applicability of general sleep-focused interventions to the management of the sleep disturbances in PTSD, evidence is growing to support several psychotherapeutic and pharmacological treatments. Future investigations should include trials that combine treatments focused on sleep with treatments effective in managing the waking symptoms of PTSD.
Collapse
|
|
12
|
Abstract
Sleep disturbances are very common in patients suffering from post-traumatic stress disorder (PTSD) and can have various negative sequelae, including worsening of perceived levels of stress, depression, and suicidal ideation. Although PTSD treatment can lead to improved sleep in some patients, there are a number of patients whose sleep disturbances do not remit even after treatment and can persist long after the original trauma. There are various non-pharmacological and pharmacological treatment modalities that have been studied. Non-pharmacological therapies include image rehearsal therapy (IRT), cognitive behavioral therapy for insomnia (CBTI), prolonged exposure (PE), and eye-movement desensitization and reprocessing (EMDR). Pharmacological studies include alpha-1-adrenergic receptor antagonists, alpha-adrenergic agonists, selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) monoamine oxidase inhibitors (MAOIs), other antidepressants, atypical antipsychotics, benzodiazepines, sedative hypnotics, and antiepileptics. The therapies with the most evidence to support their use are Image Rehearsal Therapy (IRT) and the alpha-1-adrenergic receptor antagonist, prazosin.
Collapse
Affiliation(s)
- Megan Tomas
- Student Pharmacist, Class of 2015, Notre Dame of Maryland University
| |
Collapse
|
|
13
|
Abstract
Insomnia is a common condition that affects one's ability to sleep comfortably and consequently to work effectively. Its etiology is multifactorial and involves plethora of risk factors. Consequences can vary from mild sleepiness to more sever psychiatric disturbances and ischemic stroke. Despite several diagnostic criteria it is poorly diagnosed and less often treated. Benzodiazepines formed the mainline therapy for many years till the advent of newer nonbenzodiazepine group of drugs including zolpidem. Zolpidem is an imidazo-pyridine compound that enhances the GABA(A) receptor function by interaction with Omega-1 receptor subtype. Its pharmacokinetic profile allows the patients to use it later in the night when having trouble falling asleep without any residual cognitive impairment the next morning. It has rapid onset of action, improves total sleep duration, and reduces night-time awakenings. Its adverse effect profile is satisfactory as it appears to have low addiction potential. This review will focus on the current role of zolpidem in the management of insomnia.
Collapse
Affiliation(s)
- Amit Dang
- Department of Pharmacology, Goa Medical College, Goa, India.
| | | | | |
Collapse
|
|
14
|
Treating nightmares and insomnia in posttraumatic stress disorder: a review of current evidence. Neuropharmacology 2011; 62:576-85. [PMID: 21396945 DOI: 10.1016/j.neuropharm.2011.02.029] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2010] [Revised: 02/27/2011] [Accepted: 02/28/2011] [Indexed: 11/22/2022]
Abstract
Emerging evidence supports the notion of disrupted sleep as a core component of Posttraumatic Stress Disorder (PTSD). Effective treatments for nighttime PTSD symptoms are critical because sleep disruption may be mechanistically linked to development and maintenance of PTSD and is associated with significant distress, functional impairment, and poor health. This review aimed to describe the state of science with respect to the impact of the latest behavioral and pharmacological interventions on posttraumatic nightmares and insomnia. Published studies that examined evidence for therapeutic effects upon sleep were included. Some behavioral and pharmacological interventions show promise, especially for nightmares, but there is a need for controlled trials that include valid sleep measures and are designed to identify treatment mechanisms. Our ability to treat PTSD-related sleep disturbances may be improved by moving away from considering sleep symptoms in isolation and instead conducting integrative studies that examine sequential or combined behavioral and/or pharmacological treatments targeting both the daytime and nighttime aspects of PTSD. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
Collapse
|
|
15
|
Abstract
Nightmares, distressing dreams that primarily arise from REM sleep, are prevalent among the general population and even more so among clinical populations. The frequency of nightmares and related nightmare distress are linked to both sleep disturbance and waking psychopathology. Based on the extant evidence, nightmares appear to be particularly relevant to posttraumatic stress disorder, and may even be implicated in its pathophysiology. Significant advances in treatment have occurred in recent years, with effective pharmacological and psychosocial interventions now available. Despite the progress that has been made, however, more consistent assessment methods and more rigorous study designs are needed to fully understand the causes and consequences of nightmares.
Collapse
Affiliation(s)
- Brant Hasler
- University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, PA
| | | |
Collapse
|
|
16
|
Bandelow B, Zohar J, Hollander E, Kasper S, Möller HJ, Zohar J, Hollander E, Kasper S, Möller HJ, Bandelow B, Allgulander C, Ayuso-Gutierrez J, Baldwin DS, Buenvicius R, Cassano G, Fineberg N, Gabriels L, Hindmarch I, Kaiya H, Klein DF, Lader M, Lecrubier Y, Lépine JP, Liebowitz MR, Lopez-Ibor JJ, Marazziti D, Miguel EC, Oh KS, Preter M, Rupprecht R, Sato M, Starcevic V, Stein DJ, van Ameringen M, Vega J. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders - first revision. World J Biol Psychiatry 2009; 9:248-312. [PMID: 18949648 DOI: 10.1080/15622970802465807] [Citation(s) in RCA: 428] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.
Collapse
Affiliation(s)
- Borwin Bandelow
- Department of Psychiatry and Psychotherapy, University of Gottingen, Gottingen, Germany.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
17
|
Miller LJ. Prazosin for the Treatment of Posttraumatic Stress Disorder Sleep Disturbances. Pharmacotherapy 2008; 28:656-66. [DOI: 10.1592/phco.28.5.656] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
|
|
18
|
van Liempt S, Vermetten E, Geuze E, Westenberg H. Pharmacotherapeutic treatment of nightmares and insomnia in posttraumatic stress disorder: an overview of the literature. Ann N Y Acad Sci 2006; 1071:502-7. [PMID: 16891608 DOI: 10.1196/annals.1364.053] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Sleep disturbances are hallmark symptoms of posttraumatic stress disorder (PTSD). Where the subjective experience of nightmares and insomnia in PTSD patients is very real indeed and demands treatment, objective research findings on disordered sleep architecture in PTSD are inconclusive and inconsistent. After reviewing the literature an insufficient number of controlled studies are published to formulate evidence-based guidelines. Several studies have methodological limitations, such as small group sizes and heterogenic samples. Large randomized controlled trials (RCTs) need to be conducted in order to further develop adequate therapeutic interventions. Objective parameters for insomnia and nightmares need to be identified for understanding underlying mechanisms of disturbed sleep in PTSD, and for evaluating therapy.
Collapse
Affiliation(s)
- Saskia van Liempt
- Rudolf Magnus Institute of Neurosciences and Department of Military Psychiatry, Central Military Hospital, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | | | | | | |
Collapse
|
|
19
|
Maher MJ, Rego SA, Asnis GM. Sleep disturbances in patients with post-traumatic stress disorder: epidemiology, impact and approaches to management. CNS Drugs 2006; 20:567-90. [PMID: 16800716 DOI: 10.2165/00023210-200620070-00003] [Citation(s) in RCA: 213] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Subjective reports of sleep disturbance indicate that 70-91% of patients with post-traumatic stress disorder (PTSD) have difficulty falling or staying asleep. Nightmares are reported by 19-71% of patients, depending on the severity of their PTSD and their exposure to physical aggression. Objective measures of sleep disturbance are inconsistent, with some studies that used these measures indicating poor sleep and others finding no differences compared with non-PTSD controls. Future research in this area may benefit from examining measures of instability in the microstructure of sleep. Additionally, recent findings suggest that sleep disordered breathing (SDB) and sleep movement disorders are more common in patients with PTSD than in the general population and that these disorders may contribute to the brief awakenings, insomnia and daytime fatigue in patients with PTSD. Overall, sleep problems have an impact on the development and symptom severity of PTSD and on the quality of life and functioning of patients. In terms of treatments, SSRIs are commonly used to treat PTSD, and evidence suggests that they have a small but significant positive effect on sleep disruption. Studies of serotonin-potentiating non-SSRIs suggest that nefazodone and trazodone lead to significant reductions in insomnia and nightmares, whereas cyproheptadine may exacerbate sleep problems in patients with PTSD. Prazosin, a centrally acting alpha1-adrenoceptor antagonist, has led to large reductions in nightmares and insomnia in small studies of patients with PTSD. Augmentation of SSRIs with olanzapine, an atypical antipsychotic, may be effective for treatment-resistant nightmares and insomnia, although adverse effects can be significant. Additional medications, including zolpidem, buspirone, gabapentin and mirtazapine, have been found to improve sleep in patients with PTSD. Large randomised, placebo-controlled trials are needed to confirm the above findings. In contrast, evidence suggests that benzodiazepines, TCAs and MAOIs are not useful for the treatment of PTSD-related sleep disorders, and their adverse effect profiles make further studies unlikely. Cognitive behavioural interventions for sleep disruption in patients with PTSD include strategies targeting insomnia and imagery rehearsal therapy (IRT) for nightmares. One large randomised controlled trial of group IRT demonstrated significant reductions in nightmares and insomnia. Similarly, uncontrolled studies combining IRT and insomnia strategies have demonstrated good outcomes. Uncontrolled studies of continuous positive airway pressure for SDB in patients with PTSD show that this treatment led to significant decreases in nightmares, insomnia and PTSD symptoms. Controlled studies are needed to confirm these promising findings.
Collapse
Affiliation(s)
- Michael J Maher
- Department of Psychiatry and Behavioral Sciences, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York 10467, USA
| | | | | |
Collapse
|
|
20
|
van Liempt S, Vermetten E, Geuze E, Westenberg HGM. Pharmacotherapy for disordered sleep in post-traumatic stress disorder: a systematic review. Int Clin Psychopharmacol 2006; 21:193-202. [PMID: 16687990 DOI: 10.1097/00004850-200607000-00001] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Sleep disorders, such as insomnia and nightmares, are common problems in post-traumatic stress disorder (PTSD), exert a strong negative influence on the quality of life and are a great challenge for clinical psychiatry. Several studies have reported on the efficacy of drugs for the treatment of PTSD-related sleep disorders. These studies have not been systematically reviewed. This is the first review on the effectiveness of sleep medication in PTSD. We performed a Medline, EMBASE and Cochrane Library Indexed search, using the keywords: PTSD, pharmacotherapy, therapy, sleep, nightmares, insomnia and review. From this database, English-language, human subject, data driven papers published after 1980 were selected. Forty eight articles are discussed. Open-label and case studies suggest efficacy for some antidepressants, anticonvulsants and atypical antipsychotics. Only a few placebo-controlled studies have been published. They show promising results for the atypical antipsychotic olanzapine, and the alpha1-adrenoceptor antagonist prazosin. In comparison to the incidence and impact of sleep complaints in PTSD, the pharmacotherapeutic armamentarium for PTSD-related sleep complaints remains poorly investigated. Some recent studies show promising results, especially for alpha1-adrenoceptor and 5-HT2 receptor antagonists. However, randomized controlled trials with larger populations need to be conducted.
Collapse
Affiliation(s)
- Saskia van Liempt
- Department of Military Psychiatry, Central Military Hospital, Utrecht, The Netherlands
| | | | | | | |
Collapse
|
|
21
|
Connor KM, Stein DJ. Clinical Considerations at Each Stage of Evaluation and Treatment of Trauma Survivors and PTSD. Psychiatr Ann 2005. [DOI: 10.3928/00485713-20051101-05] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
|
|
22
|
Davidson J, Bernik M, Connor KM, Friedman MJ, Jobson KO, Kim Y, Lecrubier Y, Ma H, Njenga F, Stein DJ, Zohar J. A New Treatment Algorithm for Posttraumatic Stress Disorder. Psychiatr Ann 2005. [DOI: 10.3928/00485713-20051101-04] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
|
|
23
|
Abstract
The mainstay of treatment for chronic posttraumatic stress disorder (PTSD) is a combination of psychotherapy and medication treatments. The first-line medications for PTSD are antidepressants, with two selective serotonin reuptake inhibitors (sertraline and paroxetine) currently Food and Drug Administration-indicated for PTSD. However, many patients do not have an adequate response to antidepressants, therefore, combinations with other antidepressants or with other classes of psychotropic medication are often utilized to enhance the therapeutic response. Other agents that have been used include mood stabilizers, anti-adrenergics, anxiolytics, and atypical antipsychotics. The heterogeneity of symptom clusters in PTSD as well as the complex psychiatric comorbidities (eg, with depression or substance abuse) further support the notion that combinations of medications may be needed. To date, there is a paucity of data to support specific strategies for augmenting antidepressants in PTSD. This review will address representative existing studies and discuss several potential pharmacologic strategies for patients suffering from treatment-refractory PTSD.
Collapse
Affiliation(s)
- Mark B Hamner
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, USA.
| | | | | |
Collapse
|
|
24
|
|