Background and objective
Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic health condition affecting
mostly women of childbearing age, and significantly impacting their health and quality
of life. It is currently poorly understood with no approved licensed treatments. The
aim of this systematic review was to contextualize the symptom burden of POTS, and
review factors associated with this burden that may guide future treatments. The specific
questions were (1) How does symptom burden in POTS compare to the burden in other
long term conditions (LTCs), (2) Which factors are associated with POTS symptom burden,
and (3) Which interventions show promise in reducing symptom burden in POTS.
Databases and data treatment
Electronic databases (CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science,
APA PsycArticles, OpenGrey) were searched from inception to January 2022 for observational
studies reporting on the association between any biological, psychological or social
factors and symptom burden, and randomized controlled trials reporting on interventions
for symptom burden in adults with POTS. Two reviewers independently conducted eligibility
screening, data extraction and quality assessment. A narrative synthesis was undertaken.
5159 entries were screened for eligibility. Twenty-nine studies were included (1372
participants with POTS of a total sample size of 2314, 17 High-, 12 Medium-quality),
seventeen were observational and twelve were randomized controlled experimental and
intervention trials. Overall methodological quality of the evidence was medium-high
but heterogeneity was high and sample sizes modest, allowing moderately robust conclusions.
Orthostatic symptom burden was higher in POTS than other LTCs. Serum activity against
adrenergic α1 receptors, physical functioning, depression, catastrophizing, prolonged
cognitive stress testing and anxiety were significantly associated with symptom burden
in medium-high quality studies. Preliminary medium-high quality evidence from predominantly
proof-of-concept (n = 11) studies and one 3-month 2 × 2 factorial design trial suggest that compression
garments, propranolol, pyridostigmine, desmopressin, and bisoprolol may hold promise
in reducing symptom burden. Directions for future research include investigating associated
factors over time, the development of complex interventions which address both biological
and psychosocial factors associated with symptom burden, and effectiveness trials
of these interventions.
POTS symptom burden is high, particularly in relation to orthostatic intolerance when
compared to other long-term conditions (LTCs). Despite this burden, there are no effectiveness
randomized controlled trials of treatment to reduce symptoms in POTS. This review
provides a starting point to understanding researched biological and psychosocial
factors associated with this burden. There was however inconsistency in the measurement
of symptom burden, lowering the confidence of cross-study inferences. A coherent definition
of POTS symptom range, severity and impact along with a validated and reliable POTS-specific
instrument is currently lacking. A standardized questionnaire to assess POTS symptom
burden as a core outcome measure will help clarify future research and clinical practice.