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Medications and Sleep

A 32-year-old woman is being evaluated for loud snoring and fatigue. Her medical problems includedepression and hypertension.Hermedications include fluoxetine,metoprolol, and lisinopril. The patientis also taking pramipexole for restless legs syndrome and clonazepam for insomnia. Lights out was at thepatient’s usual bedtime of 10:00 PM. The sleep architecture is summarized in Table P14-1.

ABLE P14-1 Sleep Architecture

leep Architecture Total Night Normal Range

otal recording time (min) 450 (425–462)

otal sleep time (min) 380 (394–457)

leep efficiency (%) 84 (90–100)

leep latency (min) 35.0 (0–19)

EM latency (min) 200.0 (69–88)

leep Stages

wake (WASO): (min) 35.0 %TST (0–26) min

tage N1: (min) 24.0 6.3 (3–6) (%)

tage N2: (min) 275.5 72.5 (46–62) (%)

tage N3: (min) 20.5 5.4 (10–21) (%)

tage R: (min) 60.0 15.8 (21–31) (%)

, Minutes; REM, rapid eye movement; TST, total sleep time; WASO, wake after sleep onset.

QUESTIONS

1. What is abnormal about the sleep architecture?

2. Which of the patient’s medication ismost likely to increase the rapid eyemovement (REM) latency?

3. Which of the medications have been associated with disturbing dreams?

4. Which of the patient’s medications may affect the amount of stage N3?

5. What medications may have decreased the amount of REM sleep?

ANSWERS

1. Answer: REM latency is very prolonged. The sleep latency is prolonged, and the total sleep time(TST) is decreased. The amount of stageN3 is decreased, and stageN2 is increased. The amount ofREM sleep is also mildly decreased.

2. Answer: Fluoxetine

Discussion: Nearly all antidepressants may increase REM latency (Table P14-2).1–3 The limiteddata on bupropion is conflicting. Nefazodone may decrease REM latency. Mirtazapine is said tohave minimal effect on the REM latency. Both depression and nonsedating antidepressants tendto increase sleep latency and decrease TST. Mirtazapine, trazodone, and nefazodone are sedating

TABLE P14-2 Effects of Antidepressant Medications on Sleep

Continuity Stage N3 REM Sleep (%TST) REM Latency

TCAs Decreased(increased if sedating)

Unchanged Decreased Increased

SSRIs Decreased Unchanged Decreased Increased

Bupropion Unchanged or decreased Unchanged ?Conflicting data ? Conflicting data

Venlafaxine Decreased Unchanged Decreased Increased

Nefazodone Increased Unchanged Increased? Decreased

Mirtazapine Increased Increased? Unchanged No change

Trazodone Increased Increased Decreased Increased

Adapted fromGursky JT, Krahn LE: The effects of antidepressants on sleep: a review,Harvard Rev Psychiatry 8:298-306, 2000.REM, Rapid eyemovement;SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; TST, total sleep time.

79PATIENT 14 MEDICATIONS AND SLEEP

antidepressants, which may reduce the sleep latency. Mirtazapine and trazodone are often used inlow doses at bedtime to improve the sleep in patients taking other antidepressants. Nefazodonemayalso improve sleep quality. Data about bupropion is conflicting, with one study showing a decrease,and another reported an increase in REM latency. The first-night effect (sleep in a new environ-ment) or ethanol consumption near bedtime may also prolong REM latency.

3. Answer: Both metoprolol (a beta blocker) and pramipexole may cause disturbing dreams.

Discussion: Pramipexole is commonly associated with nightmares (up to 11% in some reports).1,2

See Fundamentals 8 for other medications associated with nightmares.

4. Answer: Clonazepam

Discussion:Benzodiazepines tend to decrease the amount of stageN3 and increase stageN2. Theymay also cause small decreases in REM sleep. Clonazepam is a benzodiazepine with a long durationof action and is sometimes used off-label as a hypnotic, especially in patients with anxiety. Note thatin this patient, sleep latency remained prolonged. The nonbenzodiazepine benzodiazepine receptoragonists zolpidem, zaleplon, and eszopiclone do not reduce the amount of stage N3 sleep.

5. Answer: Fluoxetine, possibly clonazepam

Discussion:Most antidepressants reduce the amount of REM sleep.3 Exceptions include mirtaza-pine, which has little effect on REM sleep, and nefazodone, whichmay actually increase the amountof REM sleep (see Table P14-2). Nefazodone is rarely used today due to concerns about liver tox-icity and the availability of many alternative medications. Benzodiazepines may cause mild reduc-tions in the amount of REM sleep (as a percentage of TST).

CLINICAL PEARLS

1. Medications are a common etiology of abnormal sleep architecture. It is essential to knowwhatmedicationsthe patient has been taking, whatmedicationswere recently stopped, and if a hypnoticwas taken at bedtimebefore the sleep study.

2. Most antidepressants prolong the REM latency. Exceptions include mirtazapine (no change) and nefazo-done (decrease). Data about bupropion is conflicting.

3. Benzodiazepines tend to reduce stage N3 and increase stage N2. They may also induce a mild reduction inthe amount REM sleep. Nonbenzodiazepine benzodiazepine receptor agonists do not decrease stage N3.

4. A number of medications may cause nightmares, including beta-blockers, varenicline, and pramipexole.

REFERENCES

1. Schweitzer P, Dodson ER: Effects of drugs on sleep. In Avidan A, Barkoukis T, editors: Review of sleep medicine, ed 3,Philadelphia, 2012, Saunders, pp 272–291.

2. Roux FJ, Kryger MH: Medication effects on sleep, Clin Chest Med 31(2):397–405, 2010.3. Gursky JT, Krahn LE: The effects of antidepressants on sleep: a review, Harvard Rev Psychiat 8:298–306, 2000.