More Sleep Research

Psychiatry Clin Neurosci. 2004 Apr;58(2):138-144.

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Clonidine effects on all-night human sleep: Opposite action of low- and medium-dose clonidine on human NREM-REM sleep proportion.

Miyazaki S, Uchida S, Mukai J, Nishihara K.

Department of Neuropsychiatry, Tokyo Medical and Dental University and Department of Sleep Disorders Research, Tokyo Institute of Psychiatry, Tokyo, Japan.

Norepinephrine (NE) is considered to play a permissive role in the occurrence of rapid eye movement (REM) sleep. Clonidine is an NE alpha-2-receptor agonist, which has been considered to act mainly on the autoreceptors of presynaptic noradrenergic neurons to reduce their release of NE. However, previous studies of clonidine effects on REM sleep have produced controversial results and the effects of clonidine remain uncertain. To clarify the pharmacological effects of clonidine on human sleep, the sleep electroencephalograms (EEG) recorded from 15 young normal subjects after a single administration of either a low (25 micro g) or medium (150 micro g) dose of clonidine were examined, and fast Fourier transformation (FFT) spectral analyses of the C3-A2 EEG were performed. Low-dose clonidine significantly increased the amount of REM sleep and decreased the amount of non-REM (NREM) sleep during the second one-third of the drug nights compared to the corresponding hours of baseline night recordings. In contrast, medium-dose clonidine significantly decreased REM and increased NREM on drug nights compared to baseline nights in the entire night. The opposite actions of low and medium doses of clonidine on NREM-REM proportion may indicate that low-dose clonidine mainly affects the alpha-2-receptors on locus coeruleus-NE neurons presynaptically, reducing the release of NE, whereas medium-dose clonidine acts more post-synaptically.

PMID: 15009817 [PubMed - as supplied by publisher]

Analysis: This is an interesting study because it shows how important it is to avoid thinking in strict mechanistic terms when prescribing medication. All too often, we think of the mechanism of action of a drug as something that is always the same. Experience shows that medications affect different people differently. This study shows that different doses of the same medication can affect the same person in different ways, depending on the dose.

Sometimes patients come back to their doctor after having gotten a prescription, and report an unexpected outcome. Sometimes the doctor says, “that can’t happen.” This leads to all kinds of misunderstanding and hard feelings. This study shows one mechanism for possible unexpected results.

It is important for doctors and patients to understand that, in the case of an unexpected outcome, you start out the analysis by recognizing what happened. After making the pertinent observations, you draw a hypothesis, then test the hypothesis if clinically appropriate. To start out be saying “that can’t happen” is an unproductive strategy: you don’t start with a conclusion, you start with observation.