1. Medications and Effects on Sleep Architecture & EEG
Roxanne Valentino, MD, FAAN, FAASM
TSS 2017 Annual Conference
Outpatient neuro- new cognitive evals every week.
EPIDEMIC of AD- 5 million in the US, 15 mil projected by 2050.
35 million now worldwide, 100 mil projected by 2050.

2. Conflicts of Interest
None to disclose

3. Objectives
Review common medications and drugs that affect sleep architecture
Review medications that can produce specific effects on EEG during PSG recordings
Review medications that can produce specific effects on EOG and EMG during PSG recordings

4. Hypnotics alcohol melatonin antihistamines benzodiazepines
bon-benzodiazepines
buspirone
rameltion & tazimelteon
suvorexant
rameltion (Rozerem), tazimelteon (Hetlioz), suvorexant (Belsomra)

5. Alcohol Increases spindles
Increases SWS, decreases REM in first part of the night, then can see REM-rebound
Worsens OSA and NREM parasomnias
Case in lab where I saw increased spindles and patient was not on a benzo, only zolpidem. Went back and looked at H&P, and patient was a problem drinker.

6. Melatonin Neurohormone primarily produced by the pineal gland
Generally works in hrs
Decreases SOL
+/- increase of SE (may decrease WASO)
Stronger effects in DSPS than insomnia
Stronger effects during the daytime
Note different formulations of melatonin now available, but most studies were from 10+ yrs ago.
SOL decreases in normal sleepers and primary sleep disorders, not necessarily secondary sleep disorders.

7. diphenhydramine (Benadryl)
Antihistamines
Most ↓ SL
REM suppression
diphenhydramine (Benadryl)
hydroxyzine
cyproheptadine
meclizine
promethazine
loratadine
cetirizine
fexofenadine
Non-selective H1 (central and peripheral).
Selective peripheral H1: Claritin, Zyrtec, Allegra.
H2: Pepcid, Zantac *do not decrease SL).
*Nasal sprays also do not decrease SL on MSLT.

8. Benzodiazepines Increased beta Increased spindles
Major decrease in SWS
Mild decrease in REM sleep (without REM rebound)
Discontinuation effect→ rebound insomnia
*dose-dependent*
Decreased SL on MSLT
diazepam flurazepam triazolam temazepam alprazolam lorazapam clonazepam oxazepam clorazepate chlordiazepoxide
Oxazepam (Serax), clorazepate (Tranxene), chlordiazepoxide (Tranxene)

9. Non-benzodiazepine Hypnotics
Decrease SOL
Increase SE
Tend to increase N2 and can decrease REM a little
*more true at higher doses*
zaleplon zolpidem eszopiclone
Various preparations of zolpidem.
Don’t typically increase spindles like BZs do.

10. Others Buspirone Ramelteon and Tasimelteon Suvorexant
No significant effects
Ramelteon and Tasimelteon
No significant effects (other than potentially ↓ SOL)
Suvorexant

11. Antidepressants ***ALL decrease REM except for nefazodone***
Monoamine oxidase inhibitors (MAOIs)
Rarely used anymore
Tricyclic antidepressants (TCAs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
Others
Bupropion, mirtazepine, trazodone, nefazodone
***ALL decrease REM except for nefazodone***
Skip MAOIs
Characteristics of different classes differ.
Decreased REM includes increase in REM latency and also decreased % of TST.

12. TCAs SSRIs PLMS Eye movements in NREM Pseudo-RBD PLMS
amitriptyline
nortriptyline
doxepin
imipramine
protriptyline
PLMS
Eye movements in NREM
Pseudo-RBD
fluoxetine
sertraline
paroxetine
citalopram
escitalopram

13. SSRI Eyes
Example of SSRI effect

14. SNRIs Bupropion PLMS Eye movements in NREM Pseudo-RBD No PLMS
venlafaxine
desfenlafaxine
duloxetine
No PLMS
No eye movements in NREM sleep
No pseudo-RBD

15. Trazodone/ Mirtazepine Nefazodone
PLMS
No Eye movements in NREM
Pseudo-RBD
No PLMS
Did not find evidence of eye movements in NREM
No pseudo-RBD

16. RBD

17. RBD tracing with extra EMG leads

18. PLMS + - Eye movts ? Pseudo-RBD TCA SSRI SNRI Bupropion Mirtazepine
Trazodone
PLMS + -
Eye movts ?
Pseudo-RBD

19. Stimulants cocaine amphetamine methylphenidate modafinil & armodafinil
caffeine
nicotine

20. Cocaine/Amphetamines
Decreased amount of sleep (insomnia)
Increased REM latency, decreased REM overall
Discontinuation associated with unpleasant dreams
Considerations regarding discontinuation prior to MSLT
REM-rebound during initial abstinence in studies

21. Methylphenidate
Complex differences based on pharmacokinetics, including specific preparations and timing of doses
Exacerbation of sleepwalking (most stimulants)
BID dosing may not increase SOL much or at all. TID dosing increases SOL.
CR forms.
Some studies- improvement in SE with stimulants during the day??

22. Modafinil and Armodafinil
Some patients can have insomnia
No major changes in polysomnography
Insomnia- about 5%.

23. OTC agents Caffeine Nicotine Dose and time-specific
Increased SOL, decreased TST, decreased REM and NREM
Nicotine
Increased SOL, decreased TST, decreased REM
Patch may help sleep in smokers who are quitting
Nicotine effects are true for “normals” in studies. Smokers- different.

24. Antipsychotics Typicals vs Atypicals Schizophrenia: PLMS Pseudo-RBD
Decreased REM latency & increased REM overall ??
Decreased SWS in some studies
PLMS
Pseudo-RBD

25. As if that is not enough…. Welcome to 2017

26. Marijuana Different effects with different preparations?
Decreased SOL, Increased SWS, Decreased REM
Tolerance to sleep effects with chronic use
Sleep problems very common in chronic users who discontinue use
*Unpleasant dreams, Insomnia
Common for individuals to look to alcohol or other sedatives to ease symptoms
THC sedating vs some preparations of medical marijuana- alerting?
Smoking vs oral does not seem to make a difference

27. Opiates Potent REM suppression initially, but then tolerance
Other PSG parameters variable
Worsening of OSA
Cause of CSA

28. Take-Home Points Be aware of medication effects in the sleep lab.
Help to be a sleuth!
Help to raise attention to adverse effects on sleep measures that may occur with some medications/substances. These details can help patients!

29. Questions?