Less Sleepy with clarithromycin antibiotic!


Senior Member
I took Clarithromycin for an infected wound and I'm feeling stimulated and less sleepy.

GABA A receptor antagonism is a well known side effect of this drug, so it may explain my reaction!

Lynn Marie Trotti, MD, MSc,1,* Prabhjyot Saini, MSc,1 Donald L. Bliwise, PhD,1 Amanda A. Freeman, PhD,1 Andrew Jenkins, PhD,2 and David B. Rye, MD, PhD1

Some central hypersomnolence syndromes are associated with a positive allosteric modulator of GABA-A receptors in cerebrospinal fluid. Negative allosteric modulators of GABA-A receptors, including clarithromycin, have been reported to reduce sleepiness in these patients. We sought to systematically assess the effects of clarithromycin on objective vigilance and subjective sleepiness.

This was a five-week, randomized, placebo-controlled, double-blind, crossover trial of clarithromycin 500 mg with breakfast and lunch, in patients with hypersomnolence syndromes (excluding narcolepsy with cataplexy) and evidence for abnormal cerebrospinal fluid potentiation of GABA-A receptors. The study occurred at a university-affiliated medical center. The primary outcome measure was median reaction time on the psychomotor vigilance task (PVT) at week 2 in each condition. Secondary outcomes included the Epworth Sleepiness Scale, Stanford Sleepiness Scale, Functional Outcomes of Sleep, Pittsburgh Sleep Quality Index, the SF-36, and additional PVT measures.

Twenty-three patients began treatment. Three patients dropped out, and final analyses were performed on twenty complete cases. Median reaction time was not significantly different between clarithromycin and placebo.

Subjective measures of sleepiness were significantly improved on clarithromycin versus placebo. Altered taste perception occurred, but was the only side effect more common on clarithromycin than placebo. No serious adverse events occurred.


Subjective sleepiness, but not psychomotor vigilance, improved during a two-week course of clarithromycin.

Although additional studies are needed, this suggests that clarithromycin may be a reasonable treatment option in patients with treatment-refractory hypersomnolence.


Senior Member
other antibiotics can have GABA A antagonism effect as well:

Psychiatric Adverse Effects of Antibiotics (psychiatrictimes.com)


Beta-lactams include penicillins, cephalosporins, and carbapenems. Generally, they are considered broad spectrum antibiotic agents that may act as GABA-A antagonists in a dose dependent fashion to produce neurotoxicity. The beta-lactam ring is structurally similar to the GABA antagonist bicuculline. CNS effects include seizures, encephalopathy, tremors, hyperactivity, and excitability.


Macrolides, including clarithromycin, azithromycin, and erythromycin, are used to treat respiratory infections, peptic ulcer disease caused by Helicobacter pylori, sexually transmitted diseases, and mycobacterium avium complex. Of all the macrolides, clarithromycin has been associated with the most CNS adverse effects.

Neurotoxicity associated with clarithromycin can manifest as mania, delirium, acute psychosis, and even hallucinations. It is also one of the most common causative agents of antibiomania, referring to antibiotics that can cause mania.6 A few case reports of clarithromycin-induced psychiatric manifestations in children describe a different clinical picture with symptoms that range from hypomania and aggression to insomnia and even hypersomnia.7 Visual hallucinations have been reported in patients taking clarithromycin in the setting of end-stage renal disease.8

Although rare, there are case reports of azithromycin causing psychosis, delirium, and hallucinations in elderly patients who did not have an underlying psychiatric disorder.

It may be that the CNS effects of macrolides are due to GABA-A antagonism because of their ability to produce epileptogenic activity.7 Other theories include drug interactions and accumulation of clarithromycin’s active metabolite, as macrolides are substrates of CYP3A4 (clarithromycin and erythromycin are also CYP3A4 inhibitors).


Fluoroquinolones are among the most frequently reported causes of antibiotic-induced neuropsychiatric reactions. Based on a recent study, fluoroquinolones may be more commonly associated with delirium and psychosis than previously thought.9 Like macrolides, it is suspected that GABA-A antagonism causes proconvulsant activity, leading to adverse CNS effects.6 Additionally, fluoroquinolones have been reported to affect N-methyl-d-aspartate (NMDA) receptors in vitro, but further studies are needed to fully elucidate its mechanism.

The most common neuropsychiatric-related adverse effects from fluoroquinolones are excitatory effects, including insomnia, dizziness, headache, nervousness, and restlessness, which usually resolve upon discontinuation. Fluoroquinolone antibiotics can also cause more serious reactions. They have a black-box warning for potentially disabling and irreversible adverse effects including CNS events.

Seizures and status epilepticus can occur due to GABA-A inhibition. Therefore, fluoroquinolones should be used with caution in patients with a history of epilepsy. Encephalopathy, antibiomania, delirium, hallucinations, and acute psychosis are among the other neurotoxic manifestations associated with fluoroquinolones.