Insomnia is a common sleep disorder affecting up to 15% of adults.
While sedative medications are often prescribed, their long-term use can lead to dependence.
As an alternative, antidepressants are widely used in clinical practice despite limited evidence supporting their efficacy and safety for insomnia.
Key Facts:
- Insomnia affects up to 15% of adults, causing reduced quality of life and functioning.
- Sedative “hypnotic” medications effectively promote sleep short-term but risk dependence with longer-term use.
- Antidepressants are commonly prescribed for insomnia, though not approved for this use.
- Evidence supporting antidepressants for insomnia is limited to a few small short-term studies.
A recent Cochrane review analyzed all available studies on antidepressants for insomnia to assess the current level of evidence.
Source: Cochrane Database Syst Rev
What is Insomnia Disorder?
Insomnia disorder refers to a subjective feeling of unsatisfactory sleep that impairs daytime function.
Diagnostic criteria focus on complaints of:
- Difficulty falling or staying asleep
- Early morning waking
- Non-restorative sleep
Symptoms cause distress or daytime impairments in social, occupational, educational, or other facets of function.
About a third of adults report insomnia symptoms at least weekly, but estimates suggest 6-15% meet criteria for an insomnia disorder with associated disability.
Insomnia often initially manifests following an inciting event like added stress, change in environment or health conditions, but may evolve into a chronic standalone sleep disorder.
Acute insomnia generally remits once the initial trigger resolves, but the persistence of insomnia is influenced by conditioned arousal and learned sleep-preventing thought associations that are challenging to reverse.
Research has linked chronic insomnia to:
- Impaired daytime function: cognitive deficits, fatigue, mood changes
- Reduced quality of life and wellbeing
- Increased healthcare utilization
- Mental health issues like anxiety and depression
Therefore, insomnia warrants clinical attention. Treatment focuses on lessening suffering and improving daytime function.
Treatments for Insomnia (Overview)
Overall aims in treating insomnia disorder include:
- Improve ability to fall and stay asleep through the night
- Enhance sleep quality and duration
- Optimize daytime function and perceived well being
Recommended first-line treatment options:
Non-Pharmacological Interventions
- Sleep hygiene education – lifestyle, environment
- Cognitive behavioral therapy for insomnia (CBT-I) – cognitive, behavioral techniques
Pharmacological Interventions
- Prescription hypnotic medications
Various challenges complicate pharmacological management of chronic insomnia, especially long-term, including:
- Dependence, tolerance, adverse effects with hypnotics
- Access barriers to non-drug options like CBT-I
- Off-label use of sedating antidepressants without supporting evidence
This leads many to use medications off-label without clear evidence, like antidepressants.
Sedative Hypnotics for Insomnia: Benefits & Drawbacks
The most common pharmacologic treatments prescribed for insomnia are termed sedative “hypnotic” medications.
These include:
- Benzodiazepine receptor agonists (benzodiazepines)
- Melatonin receptor agonists (melatonin)
- Non-benzodiazepine GABA-A receptor agonists (“Z-drugs”)
These agents potentiate inhibitory neurotransmission via the neurotransmitter GABA, broadly suppressing brain activity to promote drowsiness and sleep onset.
Benefits
- Clearly effective for short-term treatment, usually 2-4 weeks
- Rapid onset of action
- Well-studied pharmacological profiles
Concerns with Long-Term Use
- Tolerance – decreased effects over time at same dose
- Withdrawal symptoms if stopped suddenly after physical dependence develops
- Impairments in memory and coordination
- Disruption of natural sleep architecture
- Only supposed to use short-term (2-4 weeks) but many use chronically
These concerns over long-term safety coupled with limited access to behavioral interventions leads many to consider off-label alternatives like antidepressants which have sedating properties.
Antidepressant Drugs for Insomnia Treatment
Antidepressants, particularly sedating tricyclic antidepressants (TCAs) and trazodone, are often tried off-label in insomnia despite lack of FDA approval and limited evidence supporting their efficacy.
Potential Benefits
- Long-term use for pain, depression provides some precedent
- Avoidance of dependence risks with benzodiazepines
- Anecdotal evidence of benefit
Proposed Mechanisms
- Antihistaminergic effects ↓ wakefulness signal
- Blockade of arousal-promoting receptors
- Augmentation of calming neurotransmission
However, the appropriateness of this practice has been questionable given the lack of high-quality evidence and risk of side effects with medications that act on complex neurologic pathways not fully understood.
Reviewing Evidence of Antidepressants for Insomnia
A systematic review and meta-analysis of randomized controlled trials on various antidepressants for insomnia was conducted by the reputable Cochrane Collaboration.
The review provides an unbiased assessment of the evidence base guiding practice, consistent with principles of evidence-based medicine.
Review Objectives:
Assess the clinical evidence on whether antidepressants are:
- Effective for subjectively and objectively improving sleep in insomnia
- Safe regarding adverse effects
- Well-tolerated regarding functions like daytime drowsiness
Review Methods:
- Systematic search of medical literature databases
- Identified randomized placebo-controlled trials in adults
- Included all types of antidepressants at any dose
- Grouped antidepressants into drug classes
Efficacy of Various Antidepressant Classes in Insomnia
In total, 23 RCTs with 2806 participants met inclusion criteria. Studies had limitations like small samples, short-term follow-up, and design issues complicating interpretation.
Key results for antidepressant drug classes:
Selective Serotonin Reuptake Inhibitors (SSRIs)
Examples: Fluoxetine, Paroxetine, Sertraline
- 3 small studies (n=135) vs placebo over 6-12 weeks → Mixed efficacy
- Paroxetine: Modest sleep improvements
- Fluoxetine: No difference from placebo
- Minimal data on adverse effects or long-term outcomes
- No differences when comparing 3 different SSRIs for insomnia
- Unclear differences vs the antidepressant nefazodone
Conclusion: Evidence does not support SSRI efficacy for insomnia
Tricyclic Antidepressants (TCAs)
Examples: Doxepin, Amitriptyline
- 6 studies of doxepin and trimipramine vs placebo over 4-12 weeks
- Low-dose doxepin (1-6 mg) showed:
- Improved sleep quality, efficiency, and duration
- Reduced night awakenings
- No increase in adverse effects
- No differences vs the sedative lormetazepam
Conclusion: Low-quality evidence supports short-term efficacy of low-dose doxepin
Other Antidepressants
Examples: Trazodone, Mirtazapine
- 7 small trials of trazodone vs placebo
- Some improvement in patient-reported but not objectively measured sleep
- Insufficient data on adverse effects or long-term efficacy
Conclusion: Evidence is low-quality and limited for efficacy of trazodone and other miscellaneous antidepressants
Takeaway: Antidepressants to Treat Insomnia
In summary, this high-quality systematic review revealed a limited evidence base with only equivocal data to support short-term use of some second-generation sedating antidepressants for insomnia disorder.
However, the widespread practice of off-label antidepressant prescribing is not adequately supported by current research.
There are also concerns over lack of evidence assessing adverse effects and withdrawal symptoms with longer-term use.
These findings indicate the need for further research in the form of large, rigorous controlled trials evaluating both the short and long-term risk/benefit ratio of antidepressant drug classes in treating insomnia disorder.
Study outcomes should focus on patient-centered measures like perceived sleep quality, sleep-related daytime function, and adverse effects leading to treatment discontinuation.
In the interim, these results do not support the prevalent practice of off-label antidepressant prescribing for insomnia, especially chronically.
Increased access to evidence-based non-pharmacologic approaches like CBT-I may help reduce this over-reliance on drugs lacking convincing evidence in this context.
Findings should ultimately inform updated evidence-based recommendations and guidelines regarding the judicious use of antidepressants to treat insomnia disorder when deemed clinically appropriate.
References
- Study: Antidepressants for insomnia in adults
- Authors: Everitt et al. (2018)
