Benzodiazepines Linked to Post-ICU Depression

Janis Kelly

April 22, 2009

April 22, 2009 — Intensive care unit (ICU) patients with adult respiratory-distress syndrome (ARDS) and other forms of acute lung injury (ALI) may need sedation to endure the stress of mechanical ventilation, but the benzodiazepine doses often used in this situation may be setting patients up for clinical depression after discharge.

In a study published in the May issue of Critical Care Medicine, David W. Dowdy, MD, PhD, and colleagues, from the Johns Hopkins University School of Medicine, in Baltimore, Maryland, identified several factors associated with symptoms of depression 6 months after ICU admission for ALI. These included a high level of organ failure, high benzodiazepine doses, and admission to a surgical (vs medical or trauma) ICU.

"The hope is that as we learn more about the effect of variations in ICU care, we'll be able to predict which patients are most susceptible to depression, prevent some depression by changing ICU practices, and make sure patients receive adequate mental health monitoring after discharge," said coauthor O. Joseph Bienvenu, MD, PhD.

Researchers have long theorized that a health problem devastating enough to send someone to an ICU might trigger depression, but only some ICU patients become depressed. The Hopkins researchers wondered whether the root causes might be more complex. "So we asked ourselves, could certain aspects of critical illness and ICU care swing patients toward depression?" Dr. Bienvenu said.

The researchers conducted a prospective cohort study of 160 patients who survived at least 6 months after ALI diagnosis and admission in 13 ICUs located at 4 teaching hospitals in Baltimore, Maryland, including 4 ICUs at Johns Hopkins Hospital. The investigators found that 26% of the patients had a positive score for depression at 6 months post-ALI.

Dose Effect Not Seen With Other Sedatives

Compared with other ALI survivors, those with depression were more likely to have suffered greater severity of organ failure and to have received a daily dose of 75 mg or more of a benzodiazepine.

"Surgical ICU admission was statistically significant, but we are not sure what to make of that, since it involved a very small number of patients," Dr. Bienvenu told Medscape Psychiatry.

Dr. Bienvenu said that because more severe organ failure may lead to a longer physical recovery period after ICU discharge, patients' depression might be explained, in part, by a slow recovery. However, he and his colleagues are not sure how to explain the association between depression and ICU benzodiazepine dose.

The dose received may just reflect how agitated patients were in the ICU, with very distressed individuals getting higher doses, but this relationship has not been seen with other types of sedatives.

"High doses of benzodiazepines alone may somehow cause depressive symptoms," Dr. Bienvenu suggested. He pointed out that benzodiazepines are also associated with worse posttraumatic stress disorder (PTSD) scores after ICU stays.

In related work, a small randomized, controlled trial comparing sedation with the anesthetic agent isoflurane vs midazolam, reported by Peter Sackey, MD, and colleagues, from the Karolinska Institute, in Stockholm, Sweden, found fewer delusional memories or hallucinations from the ICU after isoflurane than after the more commonly used benzodiazepine (Sackey P et al. Crit Care Med. 2008;3:801-806).

"Benzodiazepines do make people delusional, and that might contribute to post-ICU psychological morbidity," said Dr. Dowdy. "PTSD symptoms appear to be related to being really sick and having delirious experiences in the ICU. It looks like depressive symptoms are not as persistent after ICU treatment as PTSD symptoms."

Filling in Memory Gap Helps Prevent Depression

Christina Jones, PhD, from St. Helens and Knowsley Hospitals, in London, the United Kingdom, who has conducted extensive studies of PTSD symptoms after critical care, told Medscape Psychiatry that the study "shows that the sedation regime in the ICU is associated with depression during recovery. Our own study on PTSD showed a similar association but modulated by a history of previous psychological problems. A careful patient history taken from the family and general practitioner would help identify patients already at risk."

"Recognition of possible psychological consequences early in the patients’ recovery, normalizing their experiences, and filling in gaps in the illness experience can do much to help patients make sense of what has happened to them," Dr. Jones said

According to Dr. Jones, the fragmentary nature of memories from critical illness coupled with possible recall of delusional experiences such as hallucinations means that patients struggle to understand why they feel the way they do, both physically and psychologically.

"It is important to ask them what they recall from their illness and if necessary find someone who can put their memories into context. There is an increasing use of ICU diaries, which are a daily record of the patients’ stay, written by healthcare staff and the families, which have been shown in a small, randomized trial to reduce depression.

"We have just finished a large randomized controlled study of the use of diaries with PTSD and also found a positive result. This would support the idea that understanding what happened in the ICU helps to reduce the impact of delusional memories and underlines the importance to patients of filling in the gaps."

Both researchers pointed to the need for more research on sedation regimens, not only to shorten the ICU stay but also to look at longer-term psychological and cognitive consequences.

"No matter what caused the post-ICU depressive symptoms, clinicians can expect these patients to respond to typical treatments for depression," Dr. Bienvenu added.

The study was supported by the US National Institutes of Health and the Canadian Institutes of Health Research.

Crit Care Med. 2009;37:1702-1707. Abstract

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