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Insomnia and depression are often intertwined, creating a challenging cycle that can significantly impact one’s overall well-being.

The inability to obtain restorative sleep not only exacerbates the symptoms of depression but can also contribute to the development and persistence of depressive disorders. 

In the search for effective solutions, medicine provides various interventions tailored to address both insomnia and depression concurrently.

This article explores the relationship between insomnia and depression, exploring how these conditions influence each other. 

Moreover, it examines the approaches within the medical field, aiming to shed light on pharmacological and therapeutic strategies designed to break the cycle and promote not only better sleep but also mental health and emotional resilience. 

How Are Insomnia and Depression Related?

The connection between insomnia and depression is more than just symptom overlap; it’s a two-way street where each condition influences the other. 

Depression, a complex mood disorder, is closely tied to sleep disturbances. Research reveals that depression is linked to specific sleep issues, such as a reduction in restorative slow-wave sleep. 

Research indicates that a significant number—up to 90%—of individuals dealing with depression grapple with insomnia, hypersomnia, or consistently short sleep duration (6 hours or less).

This close relationship highlights a mutual impact on mental well-being.

Analyzing the overlap of sleep and psychiatric disorders, a meta-analysis found that those with both sleep problems and depression often experience increased sleep latency, elevated rapid eye movement (REM) sleep, more mid cycle awakenings, decreased slow-wave sleep, and shorter REM latency.

Conversely, while a sleep disorder itself may not cause depression, insufficient sleep worsens depressive symptoms.

Whether due to a medical condition, a diagnosed sleep disorder, or personal challenges, lack of sleep significantly exacerbates depression. 

According to John Hopkins Medicine, individuals with insomnia face a tenfold higher risk of developing depression compared to those with restful nights.

This reciprocal link emphasizes how depression disrupts sleep and disrupted sleep, in turn, fuels depression.

Navigating Treatment Priorities: Insomnia or Depression?

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Determining whether to address insomnia or depression first in the treatment process is a nuanced decision guided by individual needs. 

According to Dr. David A. Merrill, an adult and geriatric psychiatrist, and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center, the approach often centers on tackling what the patient perceives as the primary concern.

In many cases, if depression takes the forefront, doctors may initially prescribe antidepressants. Improvements in mood often correlate with enhanced sleep.

It’s a sequential approach where alleviating the mood disorder positively influences sleep patterns.

However, the interplay between insomnia and depression introduces an intriguing consideration. Recent evidence highlights that treating insomnia may yield improvements in depression severity. 

A meta-analysis of 23 studies, published in 2018, revealed that insomnia treatment is associated with substantial decreases in depression symptoms, emphasizing the potential benefits of concurrently addressing both conditions. 

This dual-focused strategy acknowledges the relationship between sleep and mood, emphasizing the potential benefits of a holistic treatment approach that targets both aspects simultaneously.

Treating Depression-Related Insomnia With Medications

The treatment of depression-related insomnia often involves the use of FDA-approved hypnotic medications.

These medications fall into several categories:

1. Benzodiazepines

Benzodiazepines, a class of medications commonly used to address insomnia, have been found to increase sleep time and improve sleep quality. 

A research article published in 2007 by Ramakrishnan and Scheid indicates that these medications achieve this by reducing sleep-onset latency, minimizing the time it takes to fall asleep, and decreasing wakefulness after sleep onset. 

Additionally, benzodiazepines enhance sleep efficiency, ensuring a more consolidated and restful sleep experience.

Despite their effectiveness, it’s important to note that benzodiazepines have a higher potential for dependency, and patients often develop rapid tolerance to their sedative effects.

Additionally, studies have indicated that benzodiazepines may lead to psychomotor retardation, memory impairment, paradoxical inhibition (increased excitement, irritability, and impulsivity), depression, and teratogenic effects in pregnant women. 

Caution is advised in elderly patients due to the potential for cognitive impairment, delirium, falls, and fractures.

2. Non-benzodiazepines (Z drugs)

Non-benzodiazepines, also known as Z drugs, are developed to minimize adverse effects and abuse potential. In a meta-analysis of 13 studies, involving more than 4000 subjects, Z drugs have shown statistically significant reductions in sleep latency compared to placebo.

A research review, published in 2022 by four insomnia experts, indicated common side effects of non-benzodiazepines (Z drugs), such as headache and dizziness.

These medications, classified as pregnancy category C drugs, should also be used cautiously in pregnant women due to potential effects on balance and the increased risk of falls. 

3. Melatonin Agonists

Medications like ramelteon, which mimics the natural hormone melatonin, are also commonly prescribed for the treatment of depression-related insomnia. These medications regulate the sleep-wake cycle in people who have trouble falling asleep. 

Generally, melatonin agonists have a favorable side effect profile, avoiding cognitive or psychomotor effects.

They are not linked to balance issues, reducing the risk of falls. However, some users may experience common side effects such as headache, nausea, and dizziness, which are generally mild and transient.

4. DORAs (Dual Orexin Receptor Antagonists)

A newer class of insomnia medications, DORAs block signals in the brain that stimulate wakefulness. This class of drugs suggests a potential alternative for those avoiding habit-forming medication. 

DORAs don’t appear to cause tolerance, withdrawal symptoms, or rebound insomnia upon discontinuation, making them a promising option. 

While generally considered safe, DORAs may cause daytime drowsiness the next day, particularly if a full night’s sleep is not achieved. People with narcolepsy are cautioned against taking DORAs as they can increase daytime sleepiness. 

Best Medications for Depression-Related Insomnia 

Let’s explore some of the best drugs in the above-mentioned categories for the treatment of depression-related insomnia. 

1. Estazolam (Prosom)

Estazolam (ProSom), a benzodiazepine, is prescribed to address insomnia by slowing down brain activity to promote sleep.

Typically used for short-term treatment, usually lasting 7-10 days, estazolam’s prescription duration is limited due to its potential for dependence and addiction. 

Estazolam is available in tablet form and its prolonged use can lead to withdrawal symptoms upon abrupt discontinuation. 

Research conducted by Pierce and Shu in the USA clinical population proved estazolam to be efficacious in treating situational insomnia and significantly enhancing sleep in patients with insomnia associated with moderately severe anxiety or depression. 

They established that estazolam, particularly in doses of 1.0 mg and 2.0 mg, significantly improves various sleep parameters, including sleep latency, total sleep time, number of nocturnal awakenings, depth of sleep, and overall sleep quality in adults with chronic insomnia. 

Long-term studies affirm estazolam’s sustained effectiveness as a hypnotic for at least six weeks of continuous nightly use, without significant tolerance. 

2. Eszopiclone (Lunesta)

Eszopiclone (Lunesta), a non-benzodiazepine (non-BZD) hypnotic agent, is approved for the long-term treatment of insomnia. This drug is available in 1-3 mg dosages with a duration of action lasting up to 7 hours. 

Due to its longer half-life, eszopiclone is recommended for use only in patients who can dedicate at least seven to eight hours of sleep before the planned time of awakening. 

Known for its rapid absorption, eszopiclone reaches its peak concentration in about an hour. Importantly, its absorption is slowed when taken with or immediately after a heavy meal, leading to a subsequent decrease in its impact on sleep onset.

Eszopiclone has shown efficacy in a six-month, double-blind, placebo-controlled study involving approximately 800 patients.

The study demonstrated the drug’s effectiveness in treating insomnia, as evidenced by improved sleep latency, total sleep time, and wake time after sleep onset. 

Rosner and colleagues conducted a comprehensive review of research studies up till 2018, evaluating the efficacy and safety of eszopiclone in treating insomnia, and comparing it to both placebo and active control.

The findings suggest that eszopiclone is an effective medication with moderate effects on both sleep onset and maintenance. 

When used as recommended, there was minimal to no evidence of harm. However, caution is advised, particularly for elderly individuals with cognitive and motor impairments, as well as those at an increased risk of using eszopiclone in a manner not recommended.

3. Zolpidem tartrate 

Zolpidem tartrate, a non-benzodiazepine, holds the distinction of being the first developed Z drug.

Zolpidem has a usual prescribed dosage ranging from 5-10mg and a duration of action spanning 7-8 hours, which is why it should not be taken if the person does not have time for a full night’s sleep. 

Available in various formulations, including immediate- and modified-release tablets (Ambien and Ambien CR), sublingual tablets (Edluar and Intermezzo), and an oral spray (ZolpiMist), this medication is typically taken on an empty stomach once a night, right before bedtime, for optimal efficacy.

Moreover, zolpidem demonstrates no withdrawal effects and minimal rebound insomnia, along with little or no tolerance during extended use.

A qualitative review conducted by Nowell and colleagues, encompassing 22 studies, explored the efficacy of benzodiazepines and zolpidem tartrate in the treatment of chronic insomnia. 

This comprehensive analysis, based on a homogeneous sample of studies involving 1894 patients treated for an average duration of 7 days, concluded that both benzodiazepines and zolpidem reliably improved commonly measured sleep parameters in patients with chronic insomnia.

Reaffirming these findings, a systematic review in 2021 by Edinoff and colleagues emphasized the effectiveness of zolpidem in treating insomnia, particularly when used in conjunction with cognitive-behavioral therapy.

Their research expanded on the existing evidence, highlighting the role of Zolpidem as a helpful drug in managing insomnia.

4. Zaleplon (Sonata, Pfizer)

Zaleplon (Sonata, Pfizer) emerged as the second non-benzodiazepine (BZD) to enter the market, offering a unique profile characterized by rapid onset of action and a notably shorter duration of up to 4 hours.

This distinctive pharmacological feature makes it particularly advantageous for individuals experiencing middle-of-the-night awakenings.

With a dosage ranging from 5 to 20 mg, Zaleplon presents an effective option for improving sleep without inducing rebound effects, especially in outpatients grappling with insomnia.

A randomized, double-blind, placebo-controlled study, as reported in the Journal of Clinical Sleep Medicine, involved 37 adults with insomnia subjected to experimental awakenings four hours after bedtime.

The study aimed to evaluate the efficacy of Zaleplon 10 mg and Zolpidem 10 mg. 

The results indicated that both Zaleplon and Zolpidem effectively reduced sleep latency and extended sleep duration when administered during nighttime awakenings.

Notably, Zaleplon exhibited a shorter duration of residual sedation compared to Zolpidem.

Research on Zaleplon’s efficacy extended to a study involving HIV+ patients with comorbid insomnia and depression. Over a 6-week period, 20 individuals with asymptomatic seropositive HIV received Zaleplon. 

Assessments using the Insomnia Severity Index, Epworth Sleepiness Scale, and Quick Inventory of Depression revealed improvements in insomnia, correlated with reduced depressive symptoms and beneficial metabolomic changes.

This underscores Zaleplon’s potential as a valuable intervention in addressing insomnia within the context of depression.

5. Ramelteon (Rozerem)

Ramelteon, marketed as Rozerem and recognized as the first melatonin receptor agonist approved by the Food and Drug Administration (FDA), serves as a prescription treatment for insomnia marked by challenges in initiating sleep.

It is crucial to note that Ramelteon is not intended for individuals struggling with sleep maintenance difficulties.

With a recommended adult dose of 8 mg taken within 30 minutes before bedtime, Ramelteon has a rapid absorption rate, but experiences delayed and reduced absorption when consumed with food. 

Many studies have confirmed that ramelteon has shown promise in addressing depression-related insomnia.

An exploratory study conducted in 2019 focused on assessing the impact and safety of Ramelteon (8 mg/day) coadministered with antidepressants in patients suffering from insomnia and major depressive disorder. 

This open-label investigation, spanning 8 weeks, involved outpatients aged 20 to  65 years with sleep-onset insomnia and major depressive disorder, already on stable antidepressant medication.

The findings from this exploratory study suggest that ramelteon may offer efficacy and well-tolerance in alleviating sleep-onset insomnia within individuals concurrently experiencing depression.

Additionally, a separate 12-week open-label study supported the notion that Ramelteon stands as an effective and generally well-tolerated intervention for insomnia symptoms in a community sample of adults dealing with Generalized Anxiety Disorder (GAD) as well.

6. Lemborexant (Davigo)

Lemborexant, marketed as Dayvigo, has been designated for the treatment of insomnia, specifically targeting improved sleep onset and maintenance in adults.

Presented in tablet form, the suggested dosage of lemborexant is 5 mg, to be taken just before bedtime, with the option to increase to 10 mg if necessary.

It is crucial not to exceed the maximum recommended clinical dose of 10 mg.

Unlike some other sleep medications, lemborexant does not necessitate tapering, allowing for abrupt discontinuation without the occurrence of rebound insomnia or withdrawal symptoms.

For optimal effectiveness, lemborexant should be consumed only if the patient can allocate at least seven hours for uninterrupted sleep, and it is most effective when taken on an empty stomach, particularly for sleep onset.

However, the advantages of lemborexant come with a significant cost, averaging around $290 for a 30-day supply of either 5 mg or 10 mg tablets.

Despite the financial consideration, Studies have consistently shown the safety and efficacy of lemborexant, especially over a one-year period with consistent use.

An independent 2017 study, sponsored by the makers of lemborexant, involved 291 participants diagnosed with insomnia.

It revealed that lemborexant facilitated faster sleep onset and longer sleep duration compared to a placebo over 15 nights.

Moreover, a 2019 randomized clinical trial by Rosenberg and colleagues, focused on adults over 55 years.

The results revealed that lemborexant significantly reduced the time to sleep onset by about 20 minutes, outperforming zolpidem extended-release which just reduced sleep onset by 7.5 minutes. 

Additionally, lemborexant displayed a modest improvement over zolpidem in minimizing waking after sleep onset, providing an additional seven to nine minutes of uninterrupted sleep before the first awakening.

7. Daridorexant (Quviviq)

Daridorexant is a medication categorized as an orexin antagonist, specifically designed for the treatment of insomnia. Administered orally, it comes in daily doses ranging from 25 to 50 mg. 

The recommended timing for daridorexant is once a day, no sooner than 30 minutes before bedtime.

While it can be taken with or without food, its onset of action is expedited when taken on an empty stomach.

Expect a prompt onset of drowsiness after taking daridorexant, lasting for a considerable duration. It is advised to plan bedtime immediately after consumption, allowing for a minimum of 7 hours of uninterrupted sleep. 

If the ability to stay asleep for the required duration is compromised, taking daridorexant is not recommended.

Early wake-ups post-daridorexant intake may lead to drowsiness, impairing activities requiring alertness, such as driving.

Typically, improvements in sleep patterns are noticeable within 7 to 10 days of initiating daridorexant.

In clinical trials, the 50 mg dose of daridorexant demonstrated enhanced sleep onset and maintenance, reflected in both objective measures and self-reported outcomes. 

Adverse events were infrequent and included effects like sleepiness, fatigue, dizziness, and falls, with a prevalence similar to that of a placebo.

The positive impact and tolerability of daridorexant were sustained over a 12-month period, presenting a favorable safety profile compared to other insomnia medications. 

In another clinical trial led by Yves Dauvilliers and team in 2020, involving 359 participants under the age of 65 experiencing insomnia, daridorexant demonstrated efficacy in reducing wake time after sleep onset.

The impact of the medication was dose-dependent, with varying effectiveness observed based on the doses administered to participants.

Discontinuing Sleep Medications

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Image Credit: discovermagazine.com

Deciding to discontinue sleep medications is a significant step that necessitates a careful and gradual process. 

While it’s not obligatory to cease sleep medications when exploring alternative approaches, those considering discontinuation, especially after prolonged use, should approach it gradually and under the guidance of a healthcare professional.

Despite modern sleep medications being designed to minimize physical dependence, psychological reliance can still be a factor.

Abruptly halting these medications may lead to a couple of restless nights, mainly attributed to withdrawal effects rather than the underlying insomnia. 

This discomfort often tempts individuals to swiftly resume medication. To facilitate a smoother discontinuation, a recommended strategy involves a slow reduction in dosage, such as a 25% decrease per week. 

This gradual tapering minimizes disruptions to sleep quality, making the transition more manageable. The cumulative effect of these measured steps allows individuals to discontinue medications altogether over time.

Other Treatment Options for Depression-Related Insomnia 

Non-medicinal treatment options for depression-related insomnia can be beneficial in managing sleep difficulties associated with depression.

Here are some strategies:

1. Cognitive Behavioral Therapy for Insomnia (CBT-I): 

CBT-I is a structured program that helps individuals identify and change thoughts and behaviors that contribute to insomnia. It addresses negative thought patterns and establishes healthy sleep habits.

2. Sleep Hygiene Practices: 

Maintain a consistent sleep schedule by going to bed and waking up at the same time every day. Create a relaxing bedtime routine to signal the body that it’s time to wind down. 

Ensure the sleep environment is comfortable, dark, and quiet. Limit exposure to screens (phones, tablets, computers) before bedtime, as the blue light can interfere with melatonin production.

3. Light Therapy: 

Exposure to natural light during the day, especially in the morning, can help regulate the sleep-wake cycle.

Light therapy boxes emitting bright light can be beneficial, particularly for those with seasonal affective disorder (SAD).

4. Exercise: 

Regular physical activity has been shown to improve sleep quality and reduce symptoms of depression.

Engage in moderate exercise, such as walking, biking, or swimming, but avoid vigorous exercise close to bedtime.

5. Relaxation Techniques:

Practice deep breathing exercises or progressive muscle relaxation to reduce anxiety and promote relaxation before bedtime.

Mindfulness meditation and yoga can also effectively calm the mind and body.

6. Limit Stimulants and Naps: 

Avoid consuming caffeine and nicotine close to bedtime, as they are stimulants that can interfere with sleep.

While short naps can be beneficial, long or irregular napping during the day can disrupt nighttime sleep. If you need to nap, keep it brief and earlier in the day.

7. Maintain a Healthy Diet: 

Ensure a balanced diet, and avoid heavy or spicy meals close to bedtime. Some individuals find that a light snack before bed can be helpful.

8. Establish a Wind-Down Period: 

Allow time to unwind before bedtime by engaging in relaxing activities such as reading, listening to calming music, or taking a warm bath.

9. Mind-Body Interventions: 

Practices such as acupuncture and biofeedback have shown promise in managing insomnia associated with depression.

Conclusion

Dealing with both insomnia and depression involves understanding how these conditions interact. Medications are vital tools for managing these challenges, providing relief to those facing the complex interplay of mental health issues. 

Whether it’s traditional antidepressants or medications tailored for sleep problems, there’s a range of options.

However, choosing the right path should be based on an individualized approach, considering each person’s symptoms and potential medication side effects. 

Combining medications with other strategies like lifestyle changes and complementary therapies forms a well-rounded plan to tackle both insomnia and depression.

FAQ’s:

1. Can I stop taking sleep medications suddenly?

It’s generally not recommended to stop sleep medications abruptly. Gradual discontinuation under medical supervision is advisable to manage potential withdrawal effects.

2. How long does it take for sleep medications to show results?

The effectiveness of sleep medications can vary. Some provide immediate relief, while others may take time, around 4-6 weeks, to build up in the system. 

3. How can I improve my sleep without medications?

Implementing good sleep hygiene practices, maintaining a consistent sleep schedule, and addressing stressors through relaxation techniques are non-pharmacological ways to enhance sleep quality.

4. Is it safe to combine different medications for insomnia and depression?

Combining medications should only be done under the supervision of a healthcare professional. It’s essential to consider potential interactions and side effects.

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