Sleep Problems Can Guide Antidepressant Selection

From Psychiatric Times, 22/05/2019

There’s a paradox with antidepressants. Even as they improve mood they can worsen sleep, and poor sleep is both a symptom and a cause of depression. It’s a common problem, but one that can be avoided by selecting the right antidepressant. Nikhil Rao, MD, has identified antidepressants that work well with specific sleep disorders, including insomnia, restless legs syndrome (RLS), and obstructive sleep apnea.

Antidepressants and insomnia

A sedating antidepressant makes sense for patients with insomnia and depression, but just as important is how that antidepressant affects sleep quality. Mirtazapine and trazodone are two antidepressants that help patients fall asleep and improve their sleep architecture. However, mirtazapine’s sedative effects are greater in the lower dose range (15 mg and below), which may not treat depression. Trazodone also has limitations. Its sedative effects tend to wear off over time, and it comes with risks including daytime fatigue, reduced recovery rates in depression (a paradoxical phenomenon seen in adolescents), and dry mouth─which itself may interfere with sleep.

Some atypical antipsychotics have sedative effects, particularly quetiapine (Seroquel). Quetiapine carries too many risks to recommend it for primary insomnia, but it is appropriate for antidepressant augmentation (150 to 300 mg qhs). Quetiapine is not just sedating. It also improves the deep, restorative phase of sleep.

The SSRIs can cause insomnia and worsen sleep quality, but bupropion is surprisingly more favorable for sleep. Although it is activating in the daytime, bupropion causes no more insomnia than the SSRIs and has neutral or positive effects on sleep architecture. Most of the tricyclics have similar problems as the SSRIs. Two exceptions are amitriptyline and doxepin. These sedating tricyclics can help with sleep initiation, but they do not improve sleep architecture.

One hypnotic that Dr Rao warned against is diphenhydramine, the sedative ingredient in many over-the-counter sleep aids from Benadryl to Tylenol PM. The problem is that diphenhydramine worsens cognition in the short term and raises the risk of dementia with chronic use. Its anticholinergic and histaminergic mechanism is the likely culprit here. Hydroxyzine (Vistaril) has similar effects and probably carries similar risks. Dr Rao pointed out another limitation of diphenhydramine: its sedative effects tend to wear off after 3 weeks.

Antidepressants in restless legs syndrome

RLS is common in two conditions that often co-occur with depression: ADHD and PTSD. Although serotonergic antidepressants can cause RLS, bupropion appears to treat it, according to a randomized controlled trial. Another medication to watch for in patients with RLS is mirtazapine. Although it is often used for insomnia, in some studies the risk of RLS is greater with mirtazapine than with other antidepressants.6

Finally, there is an FDA-approved treatment for RLS that can treat depression as well: pramipexole. In small, positive controlled trials in both bipolar and unipolar depression, this dopaminergic agonist worked as monotherapy and as augmentation. The dose for depression (1 to 2 mg qhs) is higher than the typical RLS dose (0.125 to 1 mg qhs).

Obstructive sleep apnea is the only sleep disorder in which SSRIs may have an advantage. Most apneas occur during REM sleep, and SSRIs suppress this phase of sleep. SSRIs may also improve sleep apnea through direct effects on smooth muscle in the upper airway. These theoretical advantages translated into clinical benefits in a handful of studies. The same cannot be said for mirtazapine. That antidepressant was once thought to improve sleep apnea, through smooth muscle effects, but the theory did not hold up in practice. The risk of weight gain associated with mirtazapine also makes it less desirable in this population.

Sleep apnea is more common in overweight, middle-aged men with thick necks, but another type of patient is breaking this stereotype. Newer studieshave identified alarming rates of obstructive sleep apnea (40% to 75%) in PTSD. These patients tend to be young and thin, so how can they have sleep apnea? The exact cause is unknown but may be related to the effects of PTSD on autonomic hyperarousal and pharyngeal smooth muscle.

Although insomnia is common in patients with obstructive sleep apnea, hypnotics─particularly benzodiazepines─can suppress breathing and worsen hypoxia in these cases. Dr Rao recommends clonidine for insomnia in apneic patients. Besides its sedative effects, clonidine decreases the apnea-hypoxia index, a key outcome measure in obstructive sleep apnea. Clonidine reduces nightmares in PTSD and also improves a nocturnal impairment often seen in depression: sleep fragmentation.

The bottom line

No single antidepressant is best for sleep, but each has properties that can help or harm depending on the patient’s sleep disorder. Selecting the right one can improve daytime functioning and lead to a fuller recovery.

Restless Legs: Why behavioural issues may be linked to your child's sleep

He's a boy. He gets distracted easily. He's emotionally sensitive.

These are the excuses Courtney Waltz would tell herself when she tried to understand her son, Shane, and his behavior.

Too often, she would see his sweet nature disappear as he would get frustrated and melt down.

One day, his teacher sent home a video she took during nap time on her phone. The video showed Shane repeatedly moving his legs and then hitting himself on the head as he slept.

"It kinda freaked me out," Waltz said. "After I saw that, I started to pay a little more attention to what was going on at night, and it wasn't normal."

Waltz took Shane to the doctor and explained what she was seeing night after night.

"He was kicking himself awake, there were periods of time where he just did not stop moving," she said.

Dr. Ameet Daftary, a sleep specialist, ordered a sleep study. It revealed sleep fragmentation, restlessness during sleep and a lot of leg movement.

Dr. Daftary diagnosed Shane with restless leg syndrome after reviewing the study and listening to Shane describe how his legs moved.

"He did not have sleep apnea. But what is interesting is he... complained about leg pain which is not something that a lot of 5-year-olds actually do, so that really helped us get to his diagnosis."

Shane told him his legs felt itchy and that scratching didn't help.

Dr. Daftary said the syndrome often runs in families and a majority of patients report having at least one affected first-degree relative.

Shane now shares the diagnosis with his father.

"My legs get tired, and they get sore. I feel like something has bitten me; for some reason they are itching all over the place," Shane said.

Dr. Daftary said restless leg syndrome is more common in men than women.

"It's an irresistible urge to move the legs. It's present in about two to six percent of the population of children and much higher in adults. It can be expressed as creepy crawlies in the legs, ouchies, owies, hot and cold sensations, my legs can't stop, even growing leg pains. These are all the common terms that children use to describe their symptoms," Dr. Daftary said.

He said the movement disrupts sleep and that impacts what happens during the day at work and school. Shane feels it.

"I try to focus on my work, and then I feel tired," Shane said.

Doctors said behavior issues are frequently reported in children with sleep disorders.

"That can manifest with just moodiness, crankiness, irritability, but it can also be in the form of attention deficit problems and sometimes school under performance. The teachers don't know that the child is not sleeping well," Dr. Daftary said. "Poor sleep quality is...a big deal because many children have actively growing brains all the way up to age 21, and so you have poor sleep quality during the phase when your brain is actively developing. We do know that several studies that have shown sub-optimal cognitive performance in these children as compared to children who don't have sleep disturbances. You could potentially permanently be setting these kids up for some kind of sub-optimal performance for the rest of their lives," he said.

Once Waltz learned that some of Shane's disruptive behaviors were linked to sleep, she felt she could be a more compassionate mother and focus on the fix.

"A lot of the issues that he was having hyperactivity and then oversensitivity. He would bump his knee and then it would become this gigantic meltdown. It turns out that was all because of the sleep. I thought this was a personality thing and it was, he was severely sleep deprived," Waltz said.

Doctors said it's common for patients diagnosed with restless leg syndrome to have abnormal iron levels and adding iron can alleviate symptoms.

"We can actually treat with iron supplementation, which tends to be very effective," Dr. Daftary said. "It works in almost 80 percent of children."

Shane first took oral iron supplements, and now he gets iron infusions.

"He is one of the class patients where as long as his iron levels are maintained adequately, his symptoms go away," Dr. Daftary said. "Shane had sleep walking. Shane had poor sleep quality. Shane had a lot of leg discomfort, bed wetting, all of these were significant factors impacting his quality of life. All of these factors significantly improved once we started treating him."

The doctor said parents play a key role in getting a diagnosis, adding sleep is not a standard screening question pediatricians will ask during a well-child visit. "Unless the family brings this up, this may actually be a significant quality of life issue that may not be addressed," he said.

Nights and days now are much better for Shane. With treatment, his iron levels are stabilizing, and Waltz wishes she would have sought help sooner.

"My suggestion would be, if you are seeing something that doesn't feel right, or doesn't seem right, you need to talk to somebody," she said. "I can own that I let this go for too long."


What Is Augmentation?

Restless legs syndrome (RLS) augmentation is a formidable foe. It describes a not-uncommon phenomenon in which—after weeks, months, or years of a patient’s RLS (also known by the newer name of Willis-Ekbom disease) being well controlled by a dopamine drug—the symptoms become more intense, take less time to occur when at rest, manifest earlier in the day, return more quickly after taking therapeutic medication, and may spread to other parts of the body.

This article, written by Dr. Mark Buchfuhrer, is one of the best we have read!