Patient Care

Hospitalization Risk With Benzodiazepine and Opioid Use in Veterans With Posttraumatic Stress Disorder

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References

Discussion

In 2013, Hawkins and colleagues evaluated hospitalization risk in veterans treated for PTSD within the Northwest VISN 20 between 2004 and 2010.11 Compared with patients treated with only an SSRI or SNRI, those treated with 1 of those medications and a benzodiazepine were at significantly higher risk for overall hospitalization (AHR, 1.79; 95% CI, 1.38-2.32; P < .001) and mental health hospitalization (AHR, 1.87; 95% CI, 1.37-2.53; P < .001). Furthermore, those prescribed a benzodiazepine and an opioid along with an SSRI or SNRI were at higher risk for overall hospitalization (AHR, 2.98; 95% CI, 2.22-4.00; P < .001), mental health hospitalization (AHR, 2.00; 95% CI, 1.35-2.98; P < .01), medical/surgical hospitalization (AHR, 4.86; 95% CI, 3.30-7.14; P < .001), and ED visits (AHR, 2.01; 95% CI, 1.53-2.65; P < .001).

Findings from the present study, which covered a period after the newest PTSD guideline was released,support findings reported by Hawkins and colleagues in their retrospective cohort study covering an earlier period.2,11 In the present study, compared with the monotherapy group, the SSRI/SNRI and benzodiazepine therapy group and the SSRI/SNRI, benzodiazepine, and opioid therapy group were at higher risk for both overall hospitalization and mental health hospitalization within 2 years. However, in a subset of PTSD patients prescribed opioids along with first-line pharmacotherapy, this study found that overall, mental health, and medical/surgical hospitalizations were significantly increased as well. Furthermore, this study found 2-year mortality was significantly higher for the SSRI/SNRI, benzodiazepine, and opioid therapy group than for the SSRI/SNRI monotherapy group.

Adjusted hazard ratios were higher in the present study than those in the study by Hawkins and colleagues,but CIs were wider as well.11 These differences may be attributable to the relatively smaller sample size of the present study and may explain why the HR was higher for the SSRI/SNRI and opioid therapy group than for the SSRI/SNRI, benzodiazepine, and opioid therapy group.

Nevertheless, these results support the growing body of evidence establishing the many risks for AEs when benzodiazepines and opioids are prescribed in the setting of PTSD. Unfortunately, it seems that, against clear guideline recommendations and literature findings, these medications still are being prescribed to this vulnerable, high-risk population.

In the last few months of 2013, the VA health care system launched 2 important medication safety initiatives. The Psychotropic Drug Safety Initiative (PDSI) was established as a quality improvement initiative for evidence-based provision of psychotropic medications. One PDSI metric in particular focused on reducing the proportion of veterans with PTSD being treated with benzodiazepines. The Opioid Safety Initiative (OSI) came as a response to a dramatic increase in the number of fatal overdoses related to prescription opioids—an increase linked to an unprecedented jump in opioid use for nonmalignant pain. As the present study’s inclusion cutoff date of August 1, 2013, preceded the debut of both PDSI and OSI, the benzodiazepine and opioid prescription rates reported here might be higher than those currently being found under the 2 initiatives.

Limitations

This study had several limitations that might affect the interpretation or generalizability of findings. Requiring at least a 30-day supply for prescription eligibility was an attempt to focus on chronic use of medications rather than on, for example, onetime supplies of opioids for dental procedures. However, prescription fill history was not assessed. Therefore, patients could have been included in certain study groups even if their SSRI, SNRI, benzodiazepine, or opioid prescription was not refilled. Furthermore, only VA medical records were used; non-VA prescriptions were not captured.

In addition, this study was limited to patients who at bare minimum were prescribed an SSRI or an SNRI. Some patients may have been prescribed a benzodiazepine and/or an opioid but were not on appropriate first-line pharmacotherapy for PTSD. These patients were excluded from the study, and their relative hospitalization risk went unexplored. Therefore, the magnitude of the issue at hand might have been underestimated.

Although psychotherapy is a first-line treatment option for PTSD, the study did not assess the potential impact of psychotherapy on outcomes or the groups’ relative proportions of patients undergoing psychotherapy. It is unknown whether the groups were equivalent at baseline in regards to psychotherapy participation rates.

This study did not characterize the specific reasons for hospitalization beyond whether it was for a mental health or a medical/surgical issue; thus, no distinction was made between hospitalizations for an elective procedure and hospitalizations for a drug overdose or an injury. Investigators could characterize admission diagnoses to better assess whether hospitalizations are truly associated with study medications or whether patients are being hospitalized for unrelated reasons. In addition, they could elucidate the true nature of hospitalization risk associated with SSRI/SNRI, benzodiazepine, and opioid use by comparing admission diagnoses made before and after initiation of these pharmacologic therapies.

This study also could not assess outcomes for patients who presented to the ED but were not admitted. If the hospital’s floor and ED beds were at full capacity, some patients might have been transferred to an outside facility. However, this scenario is not common at SAVAHCS, where the study was conducted.

Although some comorbid conditions were noted, the study did not evaluate whether its patients had a compelling indication for benzodiazepines in particular. Opioid use is very limited to the treatment of pain, and the majority of the patients on opioid therapy in this study had a diagnosed pain syndrome.

Because of the study’s sample size and power limitations, patients were eligible to be included in a concurrent therapy group if a benzodiazepine, an opioid, or both were added no later than 1 year after SSRI/SNRI initiation. This gap of up to 1 year might have introduced some variability in exposure to risk from earlier prescribed medications. However, sensitivity analyses were performed with multiple constructed Weibull models of time to hospitalization based on subsets with varying overlapping medication gaps. Analyses revealed relatively stable HRs, suggesting that potential bias did not occur.

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