High Risk Antibiotics
Fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin) are broad-spectrum antibiotics that kill bacteria by inhibiting DNA gyrase and topoisomerase IV—enzymes required for bacterial DNA replication and repair. Because of their potency, tissue penetration, and adverse-effect profile, regulators such as the FDA recommend reserving fluoroquinolones for situations where benefits clearly outweigh risks, particularly when safer alternatives are available.
A major concern with fluoroquinolones is their neurologic and psychiatric side-effect profile. Mechanistic literature describes CNS excitation, including GABA-A receptor inhibition/antagonism (reducing inhibitory signaling) and effects that can increase excitatory neurotransmission, sometimes discussed alongside NMDA-related mechanisms. Clinically and in regulatory safety communications, reported CNS effects include anxiety, agitation, insomnia, confusion or delirium, hallucinations, depression, suicidal thoughts, and seizures in some individuals, with guidance to discontinue the drug if serious CNS or psychiatric symptoms occur.
Doxycycline is a tetracycline-class antibiotic commonly prescribed for acne, respiratory infections, tick-borne illnesses, and malaria prophylaxis. Its antibacterial action is inhibition of bacterial protein synthesis via binding to the 30S ribosomal subunit. Although often perceived as a relatively “routine” antibiotic, official labeling and post-marketing data include CNS and psychiatric adverse reactions in some users, such as anxiety, depression, insomnia, abnormal dreams, hallucinations, and suicidal ideation.
In discussions relevant to PFS/PSSD/PAS, doxycycline is sometimes approached cautiously because some individuals report destabilizing reactions. One proposed (but debated) explanation is possible serotonin-system involvement, including arguments by psychiatrist David Healy that doxycycline may have serotonin-reuptake–inhibiting properties and can provoke SSRI-like activation in susceptible people. Separately, published clinical literature describes severe mood and behavioral reactions temporally associated with doxycycline, including a BMJ Case Reports series of suicidal ideation that improved after discontinuation in some cases. These observations do not establish causation, but they contribute to concern among individuals who are sensitive to CNS-active medications.
(2) https://pmc.ncbi.nlm.nih.gov/articles/PMC10957204/
(3) https://davidhealy.org/doxycycline-and-stephen-oneill/
(4) https://pubmed.ncbi.nlm.nih.gov/24347450/
(5) https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/205931s006%2C208253s004lbl.pdf
Crash Anecdotes (Community Reports):
https://ncmedsoc.org/do-you-know-what-floxing-is-could-it-be-deadly-to-your-patients/
https://www.reddit.com/r/PSSD/comments/10jfcnv/did_doxycycline_antibiotic_crash_you_or_help_you/
https://www.reddit.com/r/PSSD/comments/16pfrhe/doxycycline_is_causing_me_anxiety_is_it_safe_to/
https://www.reddit.com/r/PSSD/comments/18jzuv3/crash_from_doxycycline/
How to Interpret This Page
This page summarizes anecdotal reports and community observations, not medical evidence. “Risk” here refers to how frequently severe or prolonged symptom worsening is reported, not to proven causation or population-wide probability. Individual responses vary widely, and absence of issues in some users does not rule out significant reactions in others.
Risk Signal Based on User Reports
Reports of Severe and Sometimes Lasting Worsening (for PFS/PSSD/PAS):
Among individuals who already have PFS/PSSD/PAS, both fluoroquinolones and doxycycline are frequently discussed in community reports as preceding symptom worsening, sometimes described as prolonged. For fluoroquinolones, concern centers on well-documented CNS toxicity and GABA-related mechanisms; for doxycycline, reports focus on mood, anxiety, sleep, and behavioral destabilization in a subset of users. Because outcomes appear variable and can be severe in some cases, many in these communities consider avoiding these antibiotics—when clinically appropriate alternatives exist—a more conservative strategy.
For individuals without these conditions, these antibiotics are widely prescribed and often effective, but there are still reports of significant CNS or psychiatric adverse effects in a minority of users. Given the uncertainty, individual susceptibility, and potential severity described in some reports, some people judge careful risk–benefit assessment and consideration of alternative antibiotic classes (when appropriate) to be prudent.
Evidence basis: Regulatory safety communications; pharmacologic and mechanistic literature; case reports; anecdotal reports (online forums, self-reports); no controlled studies examining PFS/PSSD/PAS-specific outcomes.
