Effects of Common Analgesic Medications on Sleep: A Topical Review
Findings from a recent review highlight the impact of common analgesic medications on sleep patterns in people with chronic pain.
Many people with chronic pain also have problems with sleep. Although commonly thought to be a unidirectional issue (ie, chronic pain causes sleep problems), impaired sleep can both cause and exacerbate pain. Depression, another common comorbid condition with chronic pain, can also cause sleep problems, can be secondary to sleep issues and also cause and exacerbate pain.
Based on these issues, clinicians should try to avoid treatments that might worsen sleep for patients with chronic pain. It is a common belief that any medication that is sedating is also beneficial for sleep, but more important is how the sedating medication affects sleep architecture. A recent review examined how commonly used analgesics affect sleep architecture.1 In the slides below, find results and important takeaways for clinicians.
Sleep architecture describes the stages of the sleep cycle—non-rapid-eye movement (NREM) sleep followed by rapid eye movement (REM) sleep. NREM sleep consists of 3 stages: N1 (transition from wakefulness to sleep), N2 (predominant stage, comprises approximately 50% of total sleep time), and N3 (deepest stage with the highest arousal threshold).
The average human sleep cycle lasts approximately 90 minutes. Neurotransmitter levels differ between the stages. The amount of N3 sleep appears to be important in pain experience with reduced amounts associated with a lowered pain threshold and increased pain. Lower levels of N2 sleep also appear to be associated with more pain.
The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen on sleep architecture have been explored in a limited number of studies. While NSAIDs and acetaminophen may have some effect on sleep architecture with a reduction in restorative sleep, the effect seems to be minimal.
Opioids have been found to decrease N3 and REM sleep in healthy volunteers and also in patients with fibromyalgia and osteoarthritis. Chronic opioid use can reduce endogenous opioid production and weaken the opioid system’s regulation of sleep cycles, which may underlie sleep problems associated with use of drugs in this class.
Serotonin-norepinephrine reuptake inhibitors (SNRIs), including duloxetine and venlafaxine, and the tricyclic antidepressants (TCAs; amitriptyline was used in most studies) can reduce REM sleep. The medications do not appear to reduce total sleep time or NREM sleep and actually increase N2 sleep. TCAs appear to maintain N3 sleep, which appears to more than offset any effect of the reduction in REM sleep. The non-TCA antidepressants may reduce deep sleep.
Studies have reported mixed results with gabapentinoids. Several have shown increased N3 sleep and total sleep time, and some have reported a reduction in N2 sleep or increase in REM sleep.
Although benzodiazepines are not analgesics, their effects on sleep architecture are notable as they are among the most commonly prescribed medications for sleep. Benzodiazepines increase N2 sleep but decrease N3 and REM sleep. Extended use of benzodiazepines can lower pain thresholds and interfere with the analgesic effects of opioids during concomitant use making it problematic to prescribe both for patients with chronic pain.2
Conclusions: Of all the commonly used analgesics, opioids appear most likely to negatively impact sleep, suggesting that the belief that the sedating effects equate with sleep benefits is incorrect. Opioids can cause respiratory depression, an additional reason to avoid prescribing them for patients diagnosed with sleep disorders, such as sleep apnea.
Conclusions: TCAs and gabapentinoids appear to be beneficial for sleep among those with chronic pain, in addition to their analgesic effects, especially for neuropathic pain conditions. TCAs are also effective for the treatment of the comorbid depression experienced by many people with chronic pain.
Although the benefits of the SNRI medications for sleep are less clear, the class is effective for neuropathic pain and depression and associated with fewer adverse events than TCAs.
Caveats:
- Follow-up in most of the studies performed on the effects of analgesics on sleep architecture has been relatively short, providing little information on their long-term effects. This is an important consideration as many patients with chronic pain take analgesic medications for extended periods of time.
- There are many theories as to how analgesic drugs affect sleep, however, based on current knowledge about sleep and its regulation, more studies are needed to determine their precise effects.
Reference:
1. Antila H, Lilius TO, Palada V, et al. Effects of commonly used analgesics on sleep architecture: a topical review. Pain. 2024;165:1664-1673.
2. de Mendonça FMR, de Mendonça GPRR, Souza LC, et al. Benzodiazepines and sleep architecture: a systematic review. CNS Neurol Disord Drug Targets. 2023;22:172-179.
