When Interpretation of Results Misses the Bull’s-eye

by Timothy J. Sellati, Ph.D., Chief Scientific Officer, GLA

New Danish study published in JAMA Psychiatry misses the mark on the link between Lyme disease and psychiatric disorders

The Infectious Disease Society of America, the American Academy of Neurology, and the American Academy of Rheumatology recently proposed draft Lyme disease guidelines^[1] wherein they failed to recognize the causal association between Lyme disease and psychiatric illnesses. However, some studies and physicians’ experiences treating Lyme patients reveal clear connections between this most prevalent tick-borne disease, caused by the bacterial spirochete Borrelia burgdorferi, and specific psychiatric disorders.^[2-4]

Previous research demonstrated a low prevalence of mental illness before infection with B. burgdorferi and the more significant presence of psychiatric illnesses and comorbidities post-infection. A new Danish study published by Malte M. Tetens, BMsc and colleagues in JAMA Psychiatry made essentially the same observations, as evidenced by increased treatment with psychiatric medications, but failed to draw the same conclusion – that there is a link between Lyme disease and psychiatric disorders.^[5]

Tetens’ group studied patients between 1995 and 2015 in whom the presence of Lyme neuroborreliosis (LNB) was diagnosed based on antibodies against B. burgdorferi in cerebrospinal fluid. Based on the risk of psychiatric disorders, use of psychiatric hospitals, and receipt of psychiatric medication LNB patients were compared to individuals without the disease. The authors concluded that LNB was not linked to an increased risk of psychiatric disorders or hospitalizations. But they did find that psychiatric medications were dispensed at a significantly higher rate within the first year for patients with a diagnosis of LNB than for the control subjects.

In this cohort of 2,879 LNB patients studied, there was no long-term association with a hospital-based psychiatric diagnosis, hospital contact, or medication treatment. The descriptor “long-term” is important and absent from the author’s overall conclusion drawn from their results. From my perspective, it is not entirely correct to say there was no increased risk for a psychiatric disorder when the use of psychiatric medication by LNB patients was statistically higher the year after diagnosis of LNB.

In fact, we do not know whether additional psychiatric diagnoses were made in these LNB patients after their first year of disease. This is because many of these patients would have been followed up after the hospital diagnosis by community-based physicians – not through a hospital outpatient clinic. The Danish Registers do not provide information about community doctor diagnoses – only those made by hospital physicians. Given that psychiatric medication use was increased during the first year after hospital-based diagnosis of LNB, it is likely that the community doctors may have continued prescribing medications for psychiatric purposes to some of these patients.

Clearly, there are more questions to be answered.

Medications used more by LNB than non-LNB patients included psycholeptics (drugs that have calming effects), anxiolytics (drugs that have anti-anxiety effects), hypnotics and sedatives, stimulants, and antidepressants. The authors suggest their increased use may reflect an attempt to manage pain. While this is likely true for some of the medications prescribed, other medications that do not alleviate pain were prescribed for purely psychiatric purposes to alleviate symptoms commonly experienced by Lyme patients, such as mood, anxiety, and sleep disturbances. Thus, the more accurate summary of this study’s findings would be that there may be no sustained psychiatric problems requiring hospitalization associated with a LNB diagnosis. We cannot know whether there was an increase in community-based psychiatric disorder diagnoses and treatment during the first year or after. Clearly, there are more questions to be answered.

Future studies should investigate 1) the reasons for prescription of psychiatric medication during the first year of illness (to mitigate neuropathic pain or other reasons), 2) the prevalence of cognitive disorders and/or suicidal behaviors, and 3) the full spectrum of Lyme disease manifestations, not just neuropathologies. It also would be informative to have a community-based follow-up after hospital LNB diagnosis using standardized psychiatric measures.

Overall, this is a valuable study that supports the general conclusion that patients with confirmed LNB do well in the long-term and do not suffer from an increased risk of psychiatric disorders requiring hospitalization. However, it would be important for clinicians to be aware that during the first year after LNB diagnosis, psychiatric symptoms may emerge that require psychiatric medications. Finally, this study does not specifically investigate the relationship between Lyme disease, depression, and suicidality.

Recognizing the importance of this latter question, GLA has funded a Danish population study that uses medical information on all residents born after 1977 (~2.44 million people) to determine whether Lyme disease is a risk factor for mental disorders, particularly depression and suicide. Data will be mined from registries indicating the cause of death, the national patient registry, the Danish psychiatric central register, and national registry that tracks education, occupation, marital/cohabitation status, divorces, childbirths, unemployment, and family loss. Numbers of hospitalizations and prescription use including antibiotics and psychiatric medications will also be determined. Additionally, subgroup analysis on siblings without mental illness will be conducted as a control group. This study will be the largest population study ever to examine psychiatric disorders, depression and suicidality in Lyme patients with and without LNB.

REFERENCES

^[1]https://www.idsociety.org/globalassets/idsa/practice-guidelines/lyme/draft-lyme-disease-guidelines.pdf
^[2]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165408/
^[3]https://pubmed.ncbi.nlm.nih.gov/7943444/
^[4]https://pubmed.ncbi.nlm.nih.gov/8335653/
^[5]https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2771016