Late-Stage Lyme Disease and Psychiatric Illness: Final Verdict?

Lyme neuroborreliosis (LN), a late-stage manifestation of Lyme disease, is not associated with an increased risk of developing serious psychiatric illness, results of a large, population-based study suggest.

Nevertheless, a higher percentage of patients with LN received anxiolytic, hypnotic, sedative, and/or antidepressant medications within the first year after LN diagnosis — although the levels at which these medications were prescribed returned to the levels prescribed to the comparison cohort after the first year.

The findings "suggest that most symptoms associated with the diagnosis [of LN] subside within a short period," lead author Malte M. Tetens, BMSc, a research assistant at Infektionsmedicinsk Afdeling, Rigshospitalet, Copenhagen, Denmark, told Medscape Medical News.

"Whereas highlighting risks associated with disease is indisputably important, reassurance when diseases are not that deleterious is just as important; and, based on our study, we must conclude that there is no evidence to suggest that patients with Lyme neuroborreliosis are at increased risk of psychiatric disease," he said.

The study was published online October 7 in JAMA Psychiatry.

Ongoing Concern

Tetens said the study was "prompted by studies suggesting that Lyme neuroborreliosis might be the cause of psychiatric disorders, and although these studies have some flaws, patients diagnosed with Lyme neuroborreliosis still worry about the association."

No nationwide population-based cohort study incorporating long-term follow-up data has investigated the potential association between LN and the risk of developing psychiatric diseases.

Tetens said his team "felt obliged to use an established cohort to study whether Lyme neuroborreliosis is associated with psychiatric disorders, as our study design provides results that are more reliable than previously published."

To investigate the question, the researchers compared data on Danish residents (n = 2897) who were diagnosed with LN (ie, they had received a positive result on the Borrelia burgdorferi intrathecal antibody test) for the first time between January 1, 1995, and December 31, 2015, with data on an age- and sex-matched cohort (n = 16,460) of individuals who had not been diagnosed with LN.

For both groups, the median age was 45.7 years (interquartile range, 11.5 – 62.0 years); 56.8% were male. The two groups did not differ with regard to the percentage of participants whose Charlson comorbidity index score was >1.

In comparing the LN cohort to the non-LN cohort, the researchers found no increase in the overall risk of developing psychiatric disease (hazard ratio, 1.1; 95% CI, 0.9 – 1.2).

Similarly, during the first year, there were no differences between the LN and the comparison cohorts with respect to subcategories of psychiatric disease, such as psychoactive substance use, mood affective disorders, anxiety, obsessive-compulsive disorders, severe stress reactions, or adjustment disorders.

A sensitivity analysis that excluded participants not born in Denmark yielded the same results.

The researchers calculated the proportion of each group who had some type of hospital contact during the period beginning 10 years prior to study inclusion to 15 years following study inclusion, and there was no difference between the cohorts (10.9% vs 10.2%).

However, there were notable differences during the first year after study inclusion between the LN cohort and the comparison cohort with respect to prescriptions for psychotropic medications.

Psycholeptic	16.5% vs 9.9%; difference, 6.6% (5.2% – 8.0%)
Anxiolytic	7.2% vs 4.7%; difference, 2.6% (1.6% – 3.5%)
Hypnotic and sedative	11.0% vs 5.3%; difference, 5.7% (4.5% – 6.8%)
Antidepressant	11.4% vs 6.0%; difference, 5.4% (4.3% – 6.6%)

There were no differences in prescriptions between the two cohorts for any of these medications after 1 year.

"It is important to emphasize that many questions remain unanswered, [and] absence of evidence is not evidence of absence," Tetens commented.

"Further, our study focuses on patients with Lyme neuroborreliosis and was not designed to evaluate the posttreatment Lyme disease syndrome," he added.

Although the study cannot "finally conclude" whether neuropsychiatric sequelae occur in association with LN, the study "suggests that it is not an overwhelming problem," said Tetens.

However, he added, the short-term affective symptoms of LN warrant further investigation to assess the association between the disease and the receipt of prescribed psychiatric medications.

A World of Difference

Commenting on the study for Medscape Medical News, Michael P. Koster, MD, director, Division of Pediatric Infectious Diseases, and associate medical director, Department of Epidemiology and Infection Control, Rhode Island and Hasbro Children's Hospitals, Providence, Rhode Island, described the study as a "very nice country-wide, case-matched cohort study with an amazing registry powered to help answer the question of lingering neuropsychiatric symptoms in patients who have been diagnosed with neuroborreliosis."

Koster, who is also an associate professor of pediatrics at the Alpert Medical School of Brown University in Providence and was not involved with the study, said that the "postinfectious syndrome is a difficult disease process to manage, as it can be very nonspecific, outside of the actual date of infection, and can vary widely between patients."

He added that it "takes a caring physician to understand this syndrome and to help the patient overcome the postinfectious issues, such as pain from radiculopathy, sleep disturbances, arthralgias, depression, and mental fogginess."

Often, "transdisciplinary care between an infectious disease expert, psychiatry, and possibly a pain specialist can make a world of difference for a patient suffering the consequences of a postinfectious process," he noted.

He emphasized that a "caring and compassionate demeanor from the treating physician could mean the difference between supportive care vs unwarranted and harmful further antibiotic treatment."

Clinicians should be "be willing to reach out to mental health providers in their area for support in the treatment of sequelae from these types of infections," said Koster.

The study was sponsored by a grant from the Danish Council for Independent Research. Tetens reports no relevant financial relationships. Disclosures for the other authors are listed in the original article. Koster reports no relevant financial relationships.

JAMA Psychiatry. Published online October 7, 2020. Abstract

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