Posttraumatic stress disorder (PTSD) is a mental health condition that may develop in response to a traumatic event, such as that experienced by a soldier during active combat duty. In 2009, more than 495,000 veterans within the VA health care system were treated for PTSD—nearly triple the number a decade earlier.1 Core symptoms of PTSD include alterations in arousal and reactivity, avoidant behaviors, negative alterations in mood and cognition, and intrusive thoughts and nightmares. All of the symptoms can be debilitating. First-line pharmacotherapy options that target these core symptoms include selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).2
The anxiolytic and sedative effects of benzodiazepines may provide quick relief from many of the secondary symptoms of PTSD, including sleep disturbances, irritability, and panic attacks. However, benzodiazepines potentially interfere with the extinction of conditioned fear—a goal integral to certain types of psychotherapy, such as exposure therapy.3,4 In addition, the systematic review and meta-analysis by Guina and colleagues revealed that benzodiazepines are ineffective in the treatment of PTSD.5 The majority of the evaluated studies that used PTSD-specific measures (eg, Clinician-Administered PTSD Scale [CAPS]) found increased PTSD severity and worse prognosis with use of these medications.5 In 2010, the VA and the DoD released a joint guideline for PTSD management.2 According to the guideline, benzodiazepines cause harm when used in PTSD and are relatively contraindicated in combat veterans because of the higher incidence of comorbid substance use disorders (SUDs) in these veterans relative to the general population.2,6
Opioid use also has been linked to poor functional and clinical outcomes in veterans with PTSD. Among patients being treated for opioid use disorder, those with PTSD were less likely to endorse employment as a main source of income and had a higher incidence of recent attempted suicide.7 In a large retrospective cohort study, Operation Iraqi Freedom and Operation Enduring Freedom veterans with PTSD who were prescribed opioids were more likely to present to the emergency department (ED) and to be hospitalized for overdoses and injuries.8
Despite the risks of benzodiazepine and opioid use in this patient population, these medications are still often prescribed to veterans with PTSD for symptomatic relief. In fiscal year 2009, across the VHA system 37% of veterans diagnosed with PTSD were prescribed a benzodiazepine, 69% of the time by a mental health provider.9 Among Iraq and Afghanistan veterans, those with PTSD were significantly more likely to be prescribed an opioid for diagnosed pain—relative to those with a mental health disorder other than PTSD and those without a mental health disorder.8 Thus, there seems to be a disconnect between guideline recommendations and current practice.
The authors conducted a study to assess the potential risk of hospitalization for veterans with PTSD prescribed first-line pharmacotherapy and those also prescribed concurrent benzodiazepine and/or opioid therapy since the release of the PTSD guideline in 2010.2
Methods
In this retrospective cohort study, conducted at the Southern Arizona VA Health Care System (SAVAHCS), the authors analyzed electronic medical record data from November 1, 2009 to August 1, 2015. Study inclusion criteria were veteran, aged 18 to 89 years, diagnosis of PTSD (International Classification of Diseases, Ninth Revision, Clinical Modification code 309.81), and SSRI or SNRI newly prescribed between November 1, 2010 and August 1, 2013.
Any veteran prescribed at least one 30-day or longer supply of any benzodiazepine or opioid within 1 year before the SSRI/SNRI initial prescription date was excluded from the study. Also excluded was any patient treated for PTSD at a facility outside SAVAHCS or whose 2-year evaluation period extended past August 1, 2015.
Study Groups
An outpatient prescription was determined to be the initial SSRI/SNRI prescription for a patient who received less than a 30-day cumulative supply of any SSRI or SNRI within 1 year before that prescription date. Citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, paroxetine, sertraline, venlafaxine, vilazodone, and vortioxetine were the prespecified SSRI/SNRIs included in the study.
Patients who received at least 1 outpatient prescription for any benzodiazepine (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI and benzodiazepine therapy. Alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, oxazepam, temazepam, and triazolam were the prespecified benzodiazepines included in the study.
Patients who received at least 1 outpatient prescription for any opioid (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI and opioid therapy. Codeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, oxymorphone, pentazocine, propoxyphene, and tramadol were the prespecified opioids included in this study.
Patients who received at least 1 outpatient prescription for any benzodiazepine and any opioid (minimum 30-day supply) within 1 year after the initial SSRI/SNRI prescription date were determined to be on concurrent SSRI/SNRI, benzodiazepine, and opioid therapy.
The index date was defined as the first date of prescription overlap. If there was no benzodiazepine or opioid prescription within 1 year after the initial SSRI/SNRI prescription date, the patient was categorized as being on SSRI/SNRI monotherapy, and the index date was the date of the initial SSRI/SNRI prescription. For each patient, hospitalization data from the 2-year period after the index date were evaluated.