Laird Harrison

March 21, 2017

SAN DIEGO — The risk for revision after total hip or total knee replacement is reduced in patients taking preoperative selective serotonin reuptake inhibitors (SSRIs), a new study suggests.

"We found a pretty strong protective effect for people using antidepressants," said Hilal Maradit Kremers, MD, from the Mayo Clinic in Rochester, Minnesota.

Depression is common in patients undergoing total hip or knee replacement. Previous studies have shown that it is associated with poor patient-reported orthopedic outcomes, higher complication rates, longer hospital stays, and increased costs, she reported.

"We got interested in this because we were looking at a whole bunch of comorbidities, particularly the risk of aseptic loosening," she explained. "When we looked at the whole list of comorbidities, depression came out very strong."

Dr Maradit Kremers presented the study findings here at the American Academy of Orthopaedic Surgeons 2017 Annual Meeting.

To examine the roles SSRIs and depression play, she and her colleagues reviewed the records of 20,091 patients 18 years and older who underwent total hip or total knee replacement from 2002 to 2009.

There was some overlap between the 1290 (6.4%) patients with a diagnosis of depression and the 1563 (7.8%) who were taking an SSRI, she noted.

High Risk

Patients with depression had an elevated risk for joint infection (hazard ratio [HR], 1.9), an elevated long-term risk for revision (HR, 2.2), and an elevated risk for revision related to aseptic loosening (HR, 2.6).

In contrast, the rate of revision surgery, including that related to aseptic loosening, was almost 60% lower in patients taking perioperative SSRIs than in those who were not. And the risk for infection was about 33% lower, although the difference was not statistically significant.

It is not clear how depression increases the risk for complications or how SSRIs reduce that risk, Dr Maradit Kremers said.

It is possible that, because hospital records on depression and SSRI use might be incomplete, the association is not real. For example, people might use SSRIs at home but not mention that to the surgical team.

But it is also possible that depression and surgery complications have common risk factors, such as socioeconomic status, nutritional status, sleep, and obesity.

Or it might be that people who are depressed are less concerned with their overall health, whereas people taking SSRIs are more concerned, and might, for example, avoid tobacco. However, the researchers analyzed their data and did not find any evidence of health-related behaviors having an effect on outcomes, Dr Maradit Kremers reported.

It could also be that depression-induced immunologic changes increase the risk for infection and other problems in arthroplasty patients. Likewise, SSRIs might have biochemical effects that somehow improve the success of arthroplasty.

But previous studies have suggested the opposite, showing that SSRIs can increase the risk of bleeding and, in patients with osteoporosis, can increase the risk for fracture.

The data from this retrospective study might provide some reassurance that patients don't have to be taken off SSRIs before knee or hip replacement, Dr Maradit Kremers noted.

The issue of depression also came up in an arthroplasty study presented at the meeting by investigator Brian Werner, MD, from the University of Virginia in Charlottesville.

Infection After Surgery

Dr Werner and his team found that depression was one of the main risk factors for infection in their study of the association between comorbidities and total knee replacement.

Although studies have reported that rates of infection are low in arthroscopy patients — ranging from 0.04% to 0.42% — the consequences can be serious, leading to readmission, surgical treatment, and long-term antibiotic use.

Because Dr Werner and his colleagues could not find any studies that identified the most significant factors associated with infection, they conducted their own analysis.

The team searched the PearlDriver database to identify patients who had undergone arthroscopy. Patients who underwent concomitant open or more complex arthroscopy procedures, such as anterior cruciate ligament repair, and those who had a history of knee infection or who had undergone a previous procedure for knee infection were excluded from the study cohort.

Ultimately, their analysis involved 100,399 patients who were insured by Humana and 629,842 who were covered by Medicare.

Depression, they discovered, was one of the most significant risk factors for infection.

Table. Significant Risk Factors for Infection

  Humana Population Medicare Population
Variable Odds Ratio P Value Odds Ratio P Value
Depression 2.02 <.0001 1.73 .0001
Hypercoagulable disorder 2.76 <.0001 1.58 .0001
Hemodialysis 1.93 .003 1.36 .003
Chronic kidney disease 1.65 .003 1.32 <.0001
Inflammatory arthritis 1.61 <.0001 1.60 <.0001
Congestive heart failure 1.47 .002 1.18 .002
Tobacco use 1.34 .003 1.48 <.0001
Congestive heart failure 1.47 .002 1.18 .002
Age <65 years 1.27 .010 1.43 <.0001
Body mass index ≥40 kg/m² 1.26 .046 1.74 <.0001


This information can help surgeons "have a conversation with the patient" about the risks associated with the procedure, said Dr Werner. However, he told Medscape Medical News, "it's not a reason to withhold knee arthroscopy from someone."

Knowing the risk factors for infection might help surgeons decide which patients to treat with antibiotic prophylaxis, said session moderator Robert Gallo, MD, from Penn State Health in Hershey, Pennsylvania. "I personally use it for everyone," he told Medscape Medical News.

After the presentation, a member of the audience asked about the association between depression and infection. "I've always had a theory that it's a symptom, like a headache; it could be caused by many things," he said.

"I agree completely," said Dr Werner. "I don't think it's the depression that's causing the infection, obviously."

Many knee and hip replacement teams don't screen patients for depression, said Dr Maradit Kremers. They are more likely to focus on risk factors like cardiovascular disease and cancer, she explained.

However, they sometimes refer people considering total knee or hip replacement to other healthcare providers for assistance with weight loss or smoking cessation, she pointed out.

"I don't know if the management of depression will be part of perioperative care in the future," Dr Maradit Kremers said, "but I hope so."

Dr Werner and Dr Maradit Kremers have disclosed no relevant financial relationships. Dr Gallo reports financial relationships with B. Braun Aesculap and Smith & Nephew.

American Academy of Orthopaedic Surgeons (AAOS) 2017 Annual Meeting: Abstracts 237 and P128. Presented March 15, 2017.


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