Cases That Test Your Skills

The paranoid business executive

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References

Another possible mechanism of antibiotic-induced CNS excitability is through the glutamatergic system. Cycloserine, an antitubercular agent, is an N-methyl-D-aspartate receptor (NMDA) partial agonist and has reported neuropsychiatric adverse effects.12 It has been proposed that quinolones may also have NMDA agonist activity.

The prostaglandin hypothesis suggests that a decrease in GABA may increase concentrations of steroid hormones in the rat CNS.13 Steroids have been implicated in the breakdown of prostaglandin E1 (PGE1).13 A disruption in steroid regulation may prevent PGE1 breakdown. Lithium’s antimanic properties are thought to be caused at least in part by limiting prostaglandin production.14 Thus, a shift in PGE1 may lead to mood dysregulation.

Bipolar disorder has been linked with mitochondrial function abnormalities.15 Antibiotics that target ribosomal RNA may disrupt normal mitochondrial function and increase risk for mania precipitation.15 However, amoxicillin exerts its antibiotic effects through binding to penicillin-binding proteins, which leads to inhibition of the cell wall biosynthesis.

Lastly, research into the microbiome has elucidated the gut-brain axis. In animal studies, the microbiome has been found to play a role in immunity, cognitive function, and behavior. Dysbiosis in the microbiome is currently being investigated for its role in schizophrenia and bipolar disorder.16 Both the microbiome and changes in mitochondrial function are thought to develop over time, so while these are plausible explanations, an onset within 4 days of antibiotic initiation is likely too short of an exposure time to produce these changes.

The most likely causes of Mr. R’s manic episode were clomiphene or amoxicillin-clavulanate, and the time course seems to indicate the antibiotic was the most likely culprit. Table 2 lists things to consider if you suspect your patient may be experiencing antibiomania.

Clinical considerations when you suspect antibiomania

Continue to: TREATMENT Stable on olanzapine

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