He took amoxicillin to cure pneumonia, but heard God's call in the middle of the night.

"come on, from now on, you will take on a special mission." The moonlight was so bright that Victor seemed to hear the call of God in the haze. He felt more and more wrong, as if an invisible force was dragging him into the abyss. "am I terminally ill? Lord, bless me." He prayed to himself again and again, and after a long time, he gradually fell asleep.

Victor has had pneumonia for a while. That night, after taking the doctor's amoxicillin clavulanic acid (amoxicillin-clavulanic acid), he lay down tired, hoping to wake up the next day feeling better. He had never taken antibiotics before, and this time it was a completely helpless move, but unexpectedly it made him feel as if he had gone to the end of the world.

Early the next morning, Victor was surprised to find that he had not been taken away by God. "I seem to have had a strange dream." He didn't take it too seriously last night, but soon he found that he was still coughing and a little out of breath, and the medicine he took yesterday didn't seem to work. He had to go to the hospital again, and the doctor thought clarithromycin might work, so he asked Victor to stop the medicine he had prescribed and take the new one.

After two days, the family found that Victor seemed to be a different person. Although pneumonia has not yet recovered, he is full of vitality all over his body. He always walks around, seems to be unable to relax for a moment, and becomes a talker. "I have seen God, and I heard him talking to me!" Victor excitedly recounted his magical experience to his family. And the next second, he may be inexplicably furious.

The family was at a loss about the situation and had to take Victor to the hospital. After learning the situation, the doctor recommended Victor to go to the psychiatric emergency department of the University of Geneva Hospital, thinking that the doctors there might be more experienced in the situation.

After learning the whole story, emergency psychiatrists found that Victor's symptoms were consistent with the onset of mania. In view of this, the doctors told Victor to stop taking clarithromycin immediately and prescribed lorazepam (lorazepam), which relieves anxiety and insomnia.

That day, Victor failed to go home and spent the night in the emergency department. Fortunately, the next day, his strange symptoms alleviated a lot, but he still talked a lot. After the evaluation, the doctor concluded that Victor's symptoms had alleviated to hypomania and could go home. However, because Victor's pneumonia was not cured, the doctor re-prescribed amoxicillin clavulanic acid, but in a smaller dose than before.

At this point, Victor's magical experience came to an end for the time being. He had no previous history of mental illness, but he developed a variety of abnormal mental symptoms soon after taking antibiotics, and the symptoms alleviated quickly after withdrawal, which lasted only 36 hours. Judging from the whole incident, doctors believe that antibiotics should have caused Victor's manic symptoms.

Antibiotics and mania

Although it may be difficult to associate antibiotics with mental problems, this phenomenon was documented as early as 1954, only 26 years after Fleming discovered the magical effects of penicillin. Doctors at the time found that patients with tuberculosis became hyperactive, talkative and difficult to fall asleep after taking isoniazid (iproniazid), similar to Victor.

In these reports, the most frequent antibiotics were clarithromycin (Macrolides), ciprofloxacin (ciprofloxacin) and ofloxacin (ofloxacin) in Quinolones (interfering with bacterial DNA synthesis), and isoniazid (isoniazid), an anti-tuberculosis drug, which inhibits cell wall synthesis of Mycobacterium tuberculosis. By 2017, some scholars had collected more research reports and found that the drugs with the highest frequency of antibiotic mania reported were generally consistent with those summarized by predecessors.

But why do antibiotics strangely make people manic?

An unsolved riddle

A popular guess is that antibiotics can interact with neurotransmitters in our central nervous system. For example, γ-aminobutyric acid (GABA) is the most common inhibitory neurotransmitter in the central nervous system. It has been found that quinolones can bind to GABA receptors to form competitive inhibition, so that GABA can not bind to the receptor, while isoniazid can inhibit the activity of glutamate decarboxylase, thus inhibit the conversion of glutamine to GABA and reduce the concentration of GABA, while clarithromycin seems to inhibit the activity of GABA receptor. All of these mechanisms can lead to overexcitation of neurons.

In addition, there are some other conjectures, such as antibiotics may cause mitochondrial dysfunction, bipolar disorder and other problems; antibiotics may change the composition of gastrointestinal microbial community, and then interfere with the intestinal brain axis; and so on. In addition, clarithromycin can inhibit the activity of cytochrome P450 3A4, which is very important for human body to metabolize drugs. If it is inhibited, it may lead to drug accumulation in the body, increase the concentration, form positive feedback and enhance other side effects of drugs.

After putting forward all kinds of possible explanations from a scientific point of view, the doctor also came up with a bold (magical) conjecture: maybe it was because the little girl's family was so anxious that they kept asking her if her hallucinations had disappeared. So after recovering, the little girl took it as a game and played the adults. We don't seem to be able to rule out the possibility of this situation.

Multifaceted antibiotics

It is estimated that the global use of antibiotics increased by 46% from 2000 to 2018. In contrast, reports of cases of antibiotic mania are still rare, and many data are incomplete, so the above conjecture has not been fully verified so far. It is also impossible to estimate the incidence of such symptoms, or to determine which antibiotics are most likely to cause such symptoms, because the "high-risk" antibiotics summed up by scholars are themselves the most commonly used antibiotics, and more reports are normal. Even so, antibiotic mania is so rare that most people don't need to worry about it when taking antibiotics.

Interestingly, some antibiotics seem to be effective in treating affective disorders, such as studies showing that tetracycline (tetracycline) can stabilize mood, while dimecycline (demeclocycline) can help some people fight mania.

After leaving the hospital, Victor took amoxicillin clavulanic acid again in accordance with the doctor's advice, only to encounter the previous problem again that night, and the doctor's prescription of lorazepam did not have much effect. The next day, after consulting his family doctor, Victor stopped the antibiotics again. A week after he was discharged from the hospital, he was back to his former self, but he was still a little excited and talked a little more than before. After another evaluation, the doctor thought that Victor had returned to normal.

How will Victor choose the next time he needs antibiotics?

(most of Vic is an alias in this article)