The 35-year-old woman’s eyes snapped open; her heart pounded. Her chest was tight, and she gasped for air as a terrible and familiar sense of panic spread through her. She checked the clock: 3 a.m. She tried the breathing exercises that she had to practice so often lately. They never really helped, but they distracted her from her terror. It had been a few months since she was able to get a good night’s sleep. And she was so very tired.
For much of her adult life, the woman struggled with anxiety and depression, but it never affected her sleep. Between talk therapy and antidepressants, she had it mostly under control. Then it flared that spring, around the time she started a new position at her company. Change was hard, her psychiatrist reminded her as she tried a couple of new medications to help get through the transition. Nothing seemed to help. She started having panic attacks that seemed to come on randomly, without any triggering stressors. Even at night. In the predawn hours, she would wake up in a pool of sweat, heart pounding. The days were no better. In addition to the fatigue from not sleeping, she was in a constant state of dread and anxiety. She couldn’t focus. She was an engineer, and thinking clearly was essential to her job.
She asked her psychiatrist week after week where this might be coming from. Certainly, there were stressors. In her new position, she had a continuing conflict with a colleague. And she had some medical problems. Two years earlier, a case of Covid had caused a flare-up of her Behcet’s disease, a rare autoimmune condition that had been quiet for the 13 years since her diagnosis. After months of debilitating joint pain and extreme stiffness, she agreed to start an immune-suppressing medication to tamp down the antibodies causing the disease. It helped with the pain, but suppressing her immune system put her at risk for tuberculosis — and sure enough, she tested positive for it a year after starting on the medication.
A chest X-ray did not show any sign of an active TB infection, and that was a relief. But unless she was treated, there was a good chance that her latent TB would become active. Four months on a drug called rifampin would kill the TB bacterium before that could happen. So that summer, she added it to her new regimen of medications. The drug turned her urine and tears an orange color, a side effect she had been warned about.
In the Grips of Anxiety
That spring and summer, her psychiatrist suggested a slew of medications: for sleep, for anxiety, even for bipolar disorder. But panic and dread remained her constant companions.
She requested and was granted a leave of absence from work and checked herself into the closest mental-health facility she could find. It was in Arizona, nearly seven hours away from her home in Los Alamos, N.M. Doctors there changed her antidepressants and had her in daily therapy sessions to help her develop strategies to manage the anxiety. Despite all this, she started having suicidal thoughts. When her insurance ran out after 30 days, the doctors were reluctant to discharge her, but she couldn’t pay to stay and didn’t think their treatments helped.
Her aunt lived in the next town over and was an important source of support, but she too was overwhelmed by the woman’s anxious days and panicked nights. Her brother lived in Seattle and invited her to stay with him and his family, so the woman’s aunt drove her there. But the change of scenery didn’t help. She felt supported by her family, but her depression deepened. She cried every day. Her world seemed dark. Her chest felt so tight that it seemed like work just to breathe. The suicidal thoughts were overwhelming, and she started to think more about how to end her life.
When she asked her aunt to take her to Switzerland, which has permissive laws around assisted suicide, her family insisted that she go to the nearby University of Washington Harborview Medical Center to be taken care of by the psychiatric teams there. In the emergency room, she was evaluated by the medicine team. When they didn’t find a cardiac cause of her chest pain, she was seen by a psychiatry resident and his attending doctor. One of them asked her if she was considering suicide. Not at that moment, she told them, but she did admit that she didn’t want to continue to live if she had to feel this way. She told the team she suspected that this sudden worsening of her anxiety and depression was caused by some undiagnosed physical disorder. She wondered about an endocrine issue and had read that Behcet’s could cause psychiatric symptoms. Could that be what was driving these terrible feelings?
She was admitted to the psychiatric unit for further evaluation. The team considered the possibility that her depression had a medical cause, but she’d had lots of tests looking for this in New Mexico and nothing was found. Still, they asked their rheumatologist to see her and help them understand if this debilitating mood change could be a result of her Behcet’s, which can cause neuropsychiatric symptoms. After seeing the patient and reviewing her records, the rheumatologist thought it unlikely. In her experience, neuropsychiatric forms of Behcet’s were characterized by an acute onset of psychosis or confusion, not the subacute worsening of existing anxiety and depression.
The Troublemaker
On her second day in the hospital, the pharmacologist, who was part of the team caring for her, asked a question: How long had she been on the rifampin? The past three and a half months, she told him. She was due to stop after she had completed four months of treatment for her latent TB.
The doctor looked thoughtful. Then he explained that rifampin ramps up the machinery in the liver that breaks down some drugs, including antidepressants. And increasing the speed with which a drug is eliminated will reduce its effectiveness. A dose of an antidepressant that might have worked well before starting rifampin will suddenly not be sufficient. The timing of the rifampin matched up well with the onset of the woman’s worsening psychiatric symptoms.
The team seemed surprised by this. They had not seen many people on rifampin, and they certainly didn’t know this about the drug. But they were reluctant to cut short the treatment. TB was at least as great a danger as depression and anxiety. So they increased the dose of her antidepressant instead, saying they would monitor her mood until she finished her course of the anti-TB treatment.
The next 10 days were brutal. She went to talk therapy. She worked with the therapists on improving her strategies for managing her anxiety and depression. But she didn’t feel better. When she stopped the rifampin, there was no instant change. But over the next week, the grip of anxiety began to loosen. The perpetual sensation of fight or flight eased, and she was able to see the possibility of recovery. While she didn’t feel completely herself, she no longer felt that everything was impossible. She was even able to imagine once again doing the things she loved.
Once at home, the patient looked on the internet to see what she could find out about this drug that had brought her down so low. She found a case report of a man on an antidepressant who had the same drastic worsening of anxiety, depression and insomnia when he took rifampin. That gave her a little hope, but she knew it would take a while to fully recover. The type of antidepressant she was taking could take weeks to start working. But over the next month, she did start to feel better. Almost like her old self.
Rifampin is derived from a bacterium called Amycolatopsis rifamycinica, whose antibacterial properties were first identified in 1957. This bacterium was named after the lead character in a popular French gangster movie called “Rififi,” which became a slang term for “trouble.” It turned out to be a very good name indeed. There are now over 800 medications that are known to be altered when administered with rifampin.
It has been a year since the patient was hospitalized. Her depression and anxiety are well controlled by her antidepressant, now that there isn’t another drug messing with its effectiveness. She hasn’t gone back to work yet. She’s not eager to go back to a job that gave her so much agita. She is taking her time, enjoying the opportunity to look around and figure out what’s next.
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