apnea (OSA) along with excessive daytime sleepiness (EDS) is termed as
obstructive sleep apnea syndrome (OSAS) or obstructive sleep apnea-hypopnea
syndrome (OSAHS). There are repeated episodes of collapse of upper airway (UA)
The cardinal clinical
symptoms of sleep apnea are snoring and significant obesity. Another common
symptom is large neck circumference (>42 cm in men).
The occurrence of OSA
is 3 percent to 7 percent in males and about 2 percent to 5 percent in females.
The morbidity percentage in obese individuals is 78.
The prevalence of OSA
increases with advancing age and the primary risk factor is obesity.
The criterion of
diagnosis for OSA is either an apnea-hypopnea index (AHI) of more than five
events per hour along with excessive daytime sleepiness or an AHI greater than
15 events per hour irrespective of symptoms.
Peppard et al conducted
a study to assess the relationship between hypertension and obstructive sleep
apnea. They observed that OSA was a risk factor for hypertension and with
continuous positive airway pressure (CPAP), high blood pressure can be treated.
Marin et al prospective
research found that untreated OSA increased the odds by 2.87 for a fatal and
3.17 for a nonfatal cardiovascular event.
It was also observed
that OSA might lead to insulin resistance and diabetes.
The treatment for
obstructive sleep apnea (OSA) includes pharmacologic and non- pharmacologic
modalities. Continuous positive airway pressure (CPAP) is the most sought after
treating option for OSA. It is effective in creating a pneumatic splint and
maintaining patency of airway and thus eliminates apnea and hypopnea episodes.
Other therapies are
oral appliances, drug therapy, weight loss and surgery. Reduction of risk
factors, rectifying the underlying metabolic ailments, treating the
repercussions and preventing the episodes of hypopnes and apnea constitute the
goals of the treatment.
obstructive sleep apnea by increasing rapid eye movement (REM) sleep latency
while decreasing the overall amount of time spent in REM sleep.
Smith and his
colleagues and Brownell et al have studied the effect of Protriptyline as a REM
sleep suppressant. Smith et al revealed that there was a reduction in snoring
and apnea-hypopnea index (AHI) while, oxygen saturation and daytime somnolence
The muscle tone of the
upper airway can be increased by selective serotonin reuptake inhibitors
(SSRIs). Hanzel et al conducted a study that revealed reduction in and
apnea-hypopnea index (AHI) from 57 to 34 events per hour with both protriptyline
and fluoxetine but no reduction was noticed in AHI during REM sleep.
Prasad et al combined
fluoxetine with ondansetron, which yielded small reductions in AHI during
non-REM and REM sleep after 28 days of treatment.
Nicotine products not
only stimulate respiration but also increase the activity of the muscles
responsible for dilating the upper airway. Gothe et al reported that the use of
nicotine gum (2 or 4 mg) at bedtime eliminated obstructive apneas in the first
2 hours of sleep.
Methylxanthine such as
oral theophylline and IV aminophylline work by inhibiting the adenosine
receptors and stimulates the ventilator drive.
Mulloy and McNicholas
evaluated oral theophylline for 4 weeks in 12 patients with OSA. They reported
a small yet statistically significant decrease in AHI (from 49 to 40 episodes
per hour) as did Hein et al in a similar study (from 9.2 to 6.7 episodes per
Allergic rhinitis is
known to cause nasal obstruction and deteriorates the obstructive sleep apnea.
Inhaled nasal corticosteroids can improve the patency of airway.
Kiely et al
investigated the use of intranasal fluticasone in 23 snorers with rhinitis for
4 weeks. Further evaluation of the subpopulation of 13 patients with AHI values
above 10 episodes per hour resulted in an observed drop in AHI from 30.3 to
23.3 with the use of inhaled nasal fluticasone.
The use of oral
leukotriene antagonists such as intranasal budesonide and oral montelukast has
been successful in treating sleep-disordered breathing in children.
Goldbart et al studied
daily montelukast therapy (4 or 5 mg) in 24 children with OSA for 16 weeks.
They reported a significant reduction in respiratory disturbance index (RDI)
and adenoid size.
decongestants act on the arterioles of the mucosa of nose and result in
vasoconstriction by stimulating alpha-adrenergic receptors.
Braver and Block
evaluated the use of oxymetazoline in 20 OSA patients, but found it to have no
benefit when used as monotherapy.
It is seen that
patients with hypothyroidism often suffer from obstructive sleep apnea. This
could either be due to reduction in ventilator drive or weight gain.
therapy may improve the situation. However, the evidences are quite
Menopause or cessation
of menstruation is regarded as a risk factor for sleep-disordered breathing and
snoring. The effects of medroxyprogesterone, estrogen and combination therapy
with progesterone and estrogen on obstructive sleep apnea are also beneficial
in hypercapnia-associated disorders.
such as armodafinil and modafinil have been clinically investigated as
adjunctive therapy for obstructive sleep apnea. The adverse effects are
dizziness, nausea, headache and insomnia.
In clinical trials
wake-promoting agents to improve sleepiness relates with OSA.
Sleep apnea can be
treated by additional therapies such as agents for acromegaly, testosterone,
antihypertensives, glutamate antagonists, physostigmine, acetazolamide, opiate
antagonists, tumor necrosis factor (TNF)-alpha agonists, and carbon dioxide
Except for physostigmine,
TNF-alpha antagonists, carbon dioxide inhalation and agents for acromegaly
other miscellaneous agents have not proved to be effective in lowering OSA
A pilot study of
TNF-alpha agonists did demonstrate reduced AHI and reduced sleepiness, but
further studies would be required to establish their benefit in OSA.
mirtazapine and donepezil are also beneficial in treating obstructive sleep
apnea. Donepezil is a reversible inhibitor of acetylcholinesterase enzyme, and
is known to improve saturation of oxygen in Alzheimer's patients.
double-blind, placebo-controlled study of donepezil in OSA patients found an
improvement in AHI, oxygen saturation, and REM sleep. The study failed to find
improvement in sleep efficiency or EPSS.
With increasing doses
of mirtazapine, significant decrease in collapse of upper-airway has been
noticed. However, the associated side effects are sedation and weight gain.
apnea can be worsened by CNS depressants such as barbiturates, older sleep
agents, benzodiazepines, opiates and alcohol. These agents can adversely affect
the ventilation control during sleep and make the upper airway easily
Other harmful drugs
such as sildenafil, an erectile dysfunction medication and propranolol, a
beta-blocker should also be avoided in OSA.
It was thus concluded
that clinical trials have failed to reveal noteworthy benefit in pharmacologic
treatment of OSA. Continuous positive
airway pressure (CPAP) still on remains a better choice in comparison to drug
The researchers said
that further pharmacologic therapies should be formulated for treating daytime
sleepiness and fatigue related to obstructive sleep apnea.
Pharmacotherapy Options in the Treatment of
Obstructive Sleep Apnea; Kimberly Tackett et al; US Pharm. 2012;37(7):23-26.