Impact of Lithium and Diphenhydramine (Benadryl) on Sleep Architecture
Diphenhydramine has minimal to no beneficial effect on sleep architecture and should not be relied upon for improving sleep quality, while lithium significantly alters sleep architecture by suppressing REM sleep and increasing slow-wave sleep, though these changes may be therapeutically relevant in mood disorders.
Diphenhydramine (Benadryl) Effects on Sleep Architecture
Limited Evidence for Sleep Architecture Improvement
Diphenhydramine shows minimal effect on sleep architecture and daytime functioning, with evidence suggesting it may decrease sleep latency but does not consistently reduce nighttime awakenings 1.
One study in 50 children (including 7 with atopic dermatitis) suggested that sleep latency and numbers of nocturnal awakenings were decreased with diphenhydramine compared with placebo 1.
However, a more recent study of healthy children found that nighttime awakenings were not decreased by administration of diphenhydramine, contradicting earlier findings 1.
Clinical Limitations and Tolerance Development
Children and adults can develop tolerance to the sedating properties of antihistamines, despite the persistence of antimuscarinic and anticholinergic side effects 1.
The improvement in nocturnal symptoms is most likely due to the sedative effect rather than any restorative impact on sleep architecture 1.
At best, sedating antihistamines improve global sleep assessments in only 26% of children with eczema, demonstrating limited efficacy 1.
Safety Concerns
The FDA label warns of marked drowsiness, potential for excitability (especially in children), and cautions against use with other sedatives or alcohol 2.
Due to the relative lack of efficacy and safety data, plus potential for rebound insomnia, over-the-counter antihistamines like Benadryl are not recommended for treatment of chronic insomnia 1.
Lithium Effects on Sleep Architecture
REM Sleep Suppression
Lithium carbonate significantly decreases REM sleep percentage and increases REM sleep latency in both normal and depressed subjects 3.
In normal subjects receiving lithium for two weeks, total sleep time did not vary, but REM sleep decreased and REM sleep latency increased 3.
Plasma lithium levels were negatively correlated with REM sleep percentage and positively correlated with REM sleep latency, indicating a dose-dependent relationship 3.
REM activity per minute of sleep (an index of REM intensity) decreased in depressed subjects on lithium therapy 3.
Slow-Wave Sleep Enhancement
In depressed subjects on both short-term and long-term lithium therapy, stages 3 and 4 (slow-wave sleep) increased 3.
This increase in restorative slow-wave sleep may be therapeutically relevant for patients with mood disorders, who often exhibit abnormal sleep architecture 3.
Circadian Rhythm Effects
Short-term therapy with lithium caused small but significant delays in the sleep-wake circadian rhythm 3.
These effects are of particular interest given that circadian disturbances may account for polygraphic sleep abnormalities found in affective disorders 3.
Adverse Effects Related to Sleep
The FDA label for lithium lists somnolence, psychomotor retardation, confusion, and stupor as potential adverse reactions, though these do not appear directly related to serum lithium levels 4.
EEG changes include diffuse slowing, widening of frequency spectrum, and disorganization of background rhythm 4.
Clinical Algorithm for Decision-Making
When Diphenhydramine is Considered:
Avoid for chronic insomnia or sleep architecture improvement - evidence does not support efficacy 1.
May consider for acute, short-term sedation only - recognizing tolerance develops rapidly 1.
Screen for contraindications: chronic bronchitis, glaucoma, enlarged prostate, concurrent sedative use 2.
Monitor for anticholinergic side effects that persist despite tolerance to sedation 1.
When Lithium is Prescribed:
Expect REM sleep suppression and increased slow-wave sleep - these are consistent effects 3.
Monitor serum lithium levels - sleep architecture changes correlate with plasma levels 3.
Recognize potential therapeutic benefit - increased slow-wave sleep may help correct sleep abnormalities in mood disorders 3.
Watch for excessive somnolence or confusion - these may indicate toxicity even at therapeutic levels 4.
Key Clinical Pitfalls
Do not prescribe diphenhydramine expecting improvement in sleep architecture - it provides sedation without restorative sleep benefits 1.
Avoid combining diphenhydramine with other sedatives - marked drowsiness and impaired function can occur 2.
Do not overlook lithium's sleep effects when managing mood disorder patients - REM suppression and slow-wave sleep enhancement are consistent findings that may contribute to therapeutic efficacy 3.
Remember that tolerance to antihistamine sedation develops while side effects persist, making long-term use problematic 1.