This blog was prompted when I learned of a family that had been riddled with chronic fatigue syndrome (ME/CFS), one of whose members began experiencing psychotic symptoms, and ultimately, full psychotic episodes after being given fludrocortisone. Her severe illness had resulted in her existing in a sensory-deprived environment in which she had little social contact.
This person’s story prompted a dive into the intersection between hallucinations and psychosis, and post-infectious diseases like long COVID and chronic fatigue syndrome (ME/CFS); i.e. could her symptoms have been post-infectious in nature? Neither this person nor her family had any history of mental illness.
The outcome was surprising – the data clearly shows that while the risk is low, infections clearly do increase the risk of coming down with these symptoms. Plus, it turns out that the stimuli overload often experienced by severely ill, which results in them living in low stimuli environments, presents another risk factor.
All in all, the data suggests that at least some people with ME/CFS, long COVID and other post-infectious diseases must be experiencing hallucinations and psychosis as a result of their illness. Hence this blog and the poll at the end of it.
The Link Between Infections and Psychosis
A 2021 paper, “Viral respiratory infections and psychosis: A review of the literature and the implications of COVID-19“, demonstrated the effects viruses can have on “neuropsychiatric” symptoms. Many of these symptoms (seizures, attention deficit disorder, cognitive issues, uncontrolled anger, migraine, eating disorders, impaired sleep, easy fatiguability, depression, anxiety, other psychiatric issues) are common in ME/CFS and, in fact, ME/CFS has often been referred to as a “neuropsychiatric disorder”. While that’s clearly not a complete description of the disease, it does demonstrate that many of the symptoms of ME/CFS seem to be brain-related.
The 2021 paper indicated that reports of infections triggering neuropsychiatric symptoms date back at least to the 1385 German flu pandemic. Indeed, careful reports of past pandemics have always noted a wide variety of symptoms including depression, insomnia, and psychosis. Karl Menninger’s 1919 detailed case series documented the psychotic symptoms triggered by the Spanish flu. (It also found that the psychotic symptoms usually resolved themselves within 5 years.)
You don’t need a pandemic, though, to understand that infections increase the risk of psychosis. Studies indicate that children born to a mother who had the flu during pregnancy have an increased risk of schizophrenia. Viral infections in neonates, children, and adolescents have all been associated with an increased risk of schizophrenia later in life. The effects of infection on the central nervous system appear to be greatest when they occur during critical neurodevelopmental windows such as childhood and adolescence.
The Coronavirus Connection
The coronaviruses are no stranger to these phenomena. Several coronaviruses prior to SARS-CoV-2 were associated with an increased risk of psychotic disorders. Papers published early in the pandemic predicted that the SARS CoV-2 coronavirus’s neuroinvasive properties, plus its ability to trigger a massive inflammatory response, would cause it to produce psychosis in some cases – and it has.
Numerous case reports of people suddenly experiencing hallucinations or psychosis after coming down with COVID-19 have shown up. One young woman with no history of psychosis began acting erratically, told others that it was time for her to die, and complained of seeing and feeling bugs in her hair. She responded well to olanzapine and apparently recovered.
Another young man with no psychiatric history experienced an acute onset of psychotic symptoms (visual and auditory hallucinations, delusions of persecution, and lack of insight) after being affected. He made a gradual recovery and returned to work 12 weeks later.
Shortly after having been hospitalized for COVID-19, another man with no history of psychiatric illness began experiencing visual, visceral, and auditory hallucinations (hearing the voice of God talking to him, feeling demons inside his body), delusional ideas (the apocalypse will come soon, he was on a special mission from God), etc. He had a good response to antipsychotic treatment and was discharged with a diagnosis of acute and transient psychotic disorder.
Another 26-year-old woman with, again, no history of psychiatric disorders, presented with severe psychotic symptoms just days after she had apparently recovered from a mild COVID-19 infection. Her symptoms persisted for approximately two months, after which she was able to discontinue lithium and quetiapine and return to full-time work.
The coronavirus pandemic has, thankfully, spurred the first detailed, large-scale examinations of the effects of infection on psychosis. Larger studies have confirmed that while the risk is low, COVID-19 infection increases the risk of long-term psychotic disorders. While the rates of common psychiatric disorders increased immediately after the infection in one study, they returned to normal 1-2 months later. Other, more severe neurological problems, however, such as psychotic disorders (as well as dementia, epilepsy, and cognitive issues) remained elevated two years later.
The Effects of Sensory Deprivation and Isolation
The sensory deprivation that people with severe ME/CFS can face presents a risk factor for hallucinations. People with severe ME/CFS who are intolerant of sounds and lights live in a world that their brains are poorly adapted to. Our brain is adapted to reacting to stimuli – lots of it – and when those stimuli disappear, it is literally at a loss as to what to do.
After ME/CFS put Dan Moricoli into a coma-like state for months, he found that – particularly when he was under stress – his speech would become alarmingly slurred and his arms would suddenly flap around, sometimes even hitting him in the face. His neurologist believed that the lack of stimulation over time he’d experienced had caused his nervous system to crack up. (Despite his severe symptoms, Dan completely recovered from ME/CFS).
Dan’s reactions to stress bore some similarities to the inability of Whitney Dafoe’s brain to tolerate even the smallest stimuli. He reported:
“I couldn’t tolerate any colors or patterns on them (shirts). I also became sensitive to text like logos or labels on things because it is impossible not to read text that you see; it is something we do instinctually at this age. Reading required more mental energy than I had and caused a mental crash. “
While very severe patients like Whitney must be protected from even low levels of stimuli, it should be noted that it doesn’t take long even for a healthy person kept in those conditions to begin to experience some pretty strange events.
Take Richard Alati’s case. His room was kept in darkness, and few sounds were allowed to intrude, leaving him totally isolated. Alati was not a severely ill ME/CFS patient. He was a professional poker player who’d bet $100,000 that he could survive 30 days alone and in darkness in a small room with a refrigerator and bathroom. He made it 20 days – he’d begun experiencing hallucinations on the 3rd day.
In 2008, clinical psychologist Ian Robbins isolated six healthy people for 48 hours in soundproofed rooms in a former nuclear bunker. The results were predictable – lacking their normal sensory inputs, their brains went a bit crazy. Some suffered from anxiety, extreme emotions, paranoia, and a significant deterioration in their mental functioning. Bizarre hallucinations showed up: people saw thousands of empty oyster shells; zebras; tiny cars, fighter planes buzzing around the room, etc.
An autoimmune reactions can produce psychosis. Studies indicate that people with multiple sclerosis and lupus have higher frequencies of neuropsychiatric symptoms, including psychosis. Autoimmune encephalitis (AE), for instance, produces inflammation in the brain that produces neurologic and/or psychiatric symptoms. If a neuropsychiatric form of lupus has been distinguished, one wonders why a more neuropsychiatric form of ME/CFS or long COVID would not exist as well.
Anyone wondering about the ability of an autoimmune reaction to produce dramatic, off-the-charts psychotic symptoms should read Susannah Callahan’s book “Brain on Fire: My Month of Madness“.
Callahan was a young, healthy, news reporter in New York City who came perilously close to being permanently locked in a psychiatric word. MRI, CT and viral assessments were negative, but an alert doctor who did a brain biopsy found that massive numbers of microglial cells were attacking her nerves. She was eventually diagnosed with a recently discovered disease – anti-NMDA receptor autoimmune encephalitis – and was given massive doses of steroids, followed by plasmapheresis and IVIG. She returned to complete health a year later.
Odd drug reactions are another potential source of psychosis. Case studies of drug-induced psychosis, in fact, are so prevalent that it almost seems like any drug could produce psychosis in the wrong person.
Fludrocortisone and then later methylphenidate appears to have triggered/exacerbated the psychotic symptoms the young woman with ME/CFS referenced at the beginning of this blog experienced.
Recent reports of drug-induced psychosis include a single dose of ibuprofen that produced tunnel vision and altered consciousness, a rapid zolpidem withdrawal that resulted in hallucinations, and an anticancer drug letrozole that produced hallucinations, a monoclonal antibody (dupilumab) that triggered visual hallucinations, disorientation, cognitive decline, and behavioral changes.
One case report suggested that ingesting large amounts of Coricidin HBP Cough & Cold tablets (Triple-C) (to get high) resulted in psychosis and hallucinations in one person. Clarithromycin apparently caused closed-eye hallucinations in one woman. The list goes on and on… the antiviral acyclovir, the anticonvulsant Lyrica, the antibiotic linezolid, and pseudoephedrine.
Most of these cases are very rare and only occur when the right central nervous system meets the wrong drug. Some drugs, though, can produce hallucinations more regularly. Amantadine, for instance, produced hallucinations in 24% of Parkinson’s patients. The triazole class of antifungal drugs appear to be fairly adept at producing hallucinations and putting patients in a “predelirium” state.
As a whole, antibiotics appear more adept at causing hallucinations than other classes of drugs. Of the rather notorious fluoroquinolone antibiotics, levofloxacin reportedly has a greater tendency to cause “psychosis, auditory, and visual hallucinations”. The antibiotics most frequently associated with hallucinations, though, appear to be cephalosporins and sulfa drugs.
The effect is more common in patients taking multiple medications. “Just why antibiotics cause hallucinations is uncertain,” said Dr. Fraunfelder, “but numerous patient reports document disturbing hallucinations or vivid nightmares associated with taking antibiotics.
Some commonly used drugs in ME/CFS/FM including fludrocortisone, propranolol, atenolol, Eszopiclone, Zolpidem, aspirin, and oxycodone have been reported to trigger hallucinations or other psychotic episodes in small numbers of people.
- Can infections produce psychotic episodes? That was the question that came to mind when I learned of a young woman with severe ME/CFS who began experiencing hallucinations and severe psychotic episodes.
- It turns out that not only does infection have a long history of inducing hallucinations and psychotic episodes in some but the sensory-deprived environments that people with very severe ME/CFS can find themselves in present another risk factor.
- Psychosis can present itself in a variety of ways including hallucination (seeing, hearing, feeling things that aren’t there), delusions (unable to separate fact from fiction), jagged, illogical thought patterns, extreme paranoia and anxiety and others.
- Coronavirus-induced psychosis was predicted and numerous case reports and studies indicate that it has happened. Studies suggest that while the rates of milder psychiatric illnesses such as mood disorders return to normal after two years, the rates of more serious illnesses such as psychosis remain elevated.
- Because our brains were developed to constantly interact with stimuli depriving them of that stimuli leaves them at a loss. Putting even healthy people in an environment devoid of stimuli can rather quickly produce a bizarre variety of hallucinations.
- So many drugs have been reported to induce at least temporary hallucinations and other forms of psychosis that one wonders if any drug is completely exempt from this. Case studies of psychosis from such innocuous drugs as ibuprofen and cold and flu tablets have been published. Some commonly used drugs in ME/CFS/FM including fludrocortisone, propranolol, atenolol, Eszopiclone, Zolpidem, aspirin, and oxycodone have been reported to trigger hallucinations or other psychotic episodes in small numbers of people.
- Many different factors – reduced oxygenation of the brain, direct invasion by a virus, a breach of the blood-brain barrier by immune cells or cytokines, immune dysregulation that results in low-level inflammation – have been posited to trigger psychosis.
- The MOOD Stratification EU research group which focuses on neuroendocrine-immune causes of psychosis believes that immune testing will quickly lead to more personalized and effective treatments for psychosis.
- If you’ve experienced psychosis or personally know someone with ME/CFS, long COVID and/or related diseases please take the Infection, ME/CFS, Long COVID and psychosis poll found at the bottom of the blog. All entries are anonymous.
An inflammatory model of psychosis has been developed. Reduced oxygenation of the brain – surely a possibility in ME/CFS – could cause a brain disease (encephalopathy) that produces neuropsychiatric symptoms. Direct invasion of the CNS by a virus, or a breach of the blood-brain barrier by immune cells or cytokines from the periphery, could produce an inflammatory state in the brain that destabilizes the microglia. Jarred Younger is currently assessing whether immune cells from the body have made it into the brain in ME/CFS.
An infection and immune activation that causes hypothalamic-pituitary-adrenal (HPA) axis dysregulation (cortisol elevation, problems with dopamine and glutamate neurotransmission) has also been linked to psychosis.
The “MOOD Stratification” EU research program posits that T-cells’ failure to rein in low-grade inflammation triggers an inappropriate stress response that throws the limbic system out of whack. The white matter changes that occur in the brain, in turn, produce mood disorders and the like. This state leaves one prone to post-infectious illnesses and autoimmune disorders.
Besides antipsychotics, one review suggested trying anti-histamine drugs to combat neuroinflammation. That was interesting given that the one medication that really helped Whitney Dafoe – Abilify – came out of a search for better antihistamines.
Recent rodent studies suggest that Abilify may also “impact insulin, energy sensing, and inflammatory pathways” in the hypothalamus. If Abilify is impacting neuroinflammation, hopefully more effective “Abilifys” are on the horizon as efforts to find more effective neuroinflammation busters have ramped up in several central nervous system diseases.
The MOOD Stratification research group believes that personalized treatments based upon each person’s immune signatures are not far off. They present fictive cases of four patients experiencing some familiar symptoms (severe fatigue, loss of energy, irritability, sleeping problems, and difficulties with concentrating). They contrasted the treatment options these patients would likely have received in 2016 (SSRI, lithium, amitriptyline, electroconvulsive therapy) and then looked forward to personalized treatments they might receive in 2024.
Immunological testing revealed that an SSRI was appropriate for one, an SSRI plus an anti-inflammatory agent (e.g. anti-TNF) and a T cell enforcing therapy (e.g. low dose IL-2 therapy) looked like it would work for another, an SSRI and an anti-inflammatory agent (e.g. low dose aspirin) was given to the third person, and the last was given an SSRI, lithium, and anti-inflammatory therapy, e.g. anti-TNF.
Health Rising’s ME/CFS and Long-COVID Hallucination and Psychosis Poll
A number of factors – infection, sensory deprivation, isolation, a drug reaction, and infection-induced autoimmunity – could increase the risk of hallucinations and psychosis in post-infectious diseases.
Psychosis, ME/CFS, and Long-COVID Poll
If you’ve experienced these symptoms or personally know someone who has, please take the poll. Please note that your responses are completely confidential.