At Mid City TMS, many patients seeking help for Depression describe a frustrating and exhausting pattern: persistent insomnia despite multiple medications. Difficulty falling asleep, staying asleep, or waking up too early is not just common in Major Depressive Disorder (MDD) — it is often one of the most stubborn and impairing symptoms.
A recent large-scale study published in the Journal of Affective Disorders provides important insight into how sleep medications are used in patients with Depression — and, importantly, how often that use becomes long-term. When viewed alongside what we know about the biology of Depression and sleep, the findings highlight a pattern worth understanding: medications alone are often not enough to restore healthy sleep, and may not address the underlying problem.
This is where treatments that directly target brain function, such as Transcranial Magnetic Stimulation (TMS), may play an important role.
What the Study Examined
The study analyzed a large, real-world population of 78,383 patients with Depression, making it one of the most robust analyses of sleep medication depression in this population. To be included, participants had to have a recent diagnosis of Depression, a new prescription for a hypnotic (sleep medication), and no hypnotic prescriptions in the prior 12 months. This design allowed researchers to specifically examine what happens after patients with Depression are newly started on sleep medications.
The average participant was 39.4 years old, 58.4% were women, and over 90% were already receiving specialized psychiatric care. This is particularly significant because it reflects a group already receiving relatively high-level mental health treatment, yet still requiring pharmacologic help with sleep.
Which Sleep Medications Were Prescribed?
Researchers analyzed several commonly prescribed classes of sleep medications, including Z-drugs (such as zolpidem), benzodiazepine hypnotics, propiomazine, and melatonin. In addition to dedicated sleep medications, many patients were also prescribed broader sedating medications: antihistamines (35.1%), antidepressants with sedating properties (23.3%), antipsychotics (7.4%), and Z-drugs (51.0%). This distribution reflects how frequently clinicians rely on multiple medication classes when trying to manage sleep in patients with Depression.
Long-Term Use of Sleep Meds Is More Common Than Expected
The central finding of the study was how frequently patients transitioned to long-term use of sleep medications, defined as at least 180 daily doses across three or more prescription fills, with at least one fill in the second half of the year.
The results were striking: 30% of patients — nearly 23,500 individuals — transitioned to long-term use of sleep meds within just one year.
These medications are typically prescribed with the intention of short-term relief. Yet nearly one in three patients continued using them chronically. For anyone starting a sleep medication while being treated for Depression, this is important context to have.
Who Is Most Likely to Become a Long-Term User?
The study identified several predictors of long-term use of sleep meds. The single strongest was the number of prior antidepressant trials. Patients with one prior trial had a meaningfully elevated risk; those with three or more prior trials had more than triple the risk, and nearly half of that group became long-term users. This suggests that patients with more treatment-resistant Depression are substantially more likely to develop chronic reliance on sleep medications.
Age also played a significant role. Long-term use of sleep meds increased from 21.8% among patients aged 18 to 29, to 44.9% among those aged 70 and older. Other predictors included psychostimulant use, sedating antipsychotic use, and a history of substance use disorder — pointing to a subgroup of patients with more complex neurobiological profiles and greater vulnerability to chronic sleep dysfunction.
Switching Medications May Not Help
One of the more notable findings is that long-term use rates were similar across different medication classes: benzodiazepines at 22.0%, Z-drugs at 22.2%, propiomazine at 20.6%, and melatonin at 22.6%. Switching between medication classes did not appear to meaningfully reduce the likelihood of long-term use.
The study also documented a prescribing shift over time — long-term benzodiazepine use decreased significantly while long-term melatonin use rose dramatically. This reflects a broader move toward medications perceived as safer. But even with melatonin, long-term use of sleep meds still occurred at similar rates, reinforcing the idea that medication choice alone does not resolve the underlying problem.
What These Findings Suggest About Depression and Sleep
Taken together, the data point to several important conclusions. Sleep dysfunction in Depression is persistent, patients do not simply begin sleeping better once medication starts. Instead, many continue to struggle and remain on treatment long-term. And patients with multiple failed antidepressant trials are the most likely to develop that chronic use, suggesting that sleep disturbance is closely tied to underlying brain dysfunction rather than being a separate or secondary issue.
As the study authors noted, further research is needed to evaluate the long-term safety and effectiveness of hypnotic treatments in Depression across different drug classes and patient subgroups.
Where TMS Fits In
While this study focuses on medication use rather than TMS, it provides useful context for understanding why brain-based treatments can be valuable for patients who are not finding adequate relief through medication.
Transcranial Magnetic Stimulation works by stimulating the dorsolateral prefrontal cortex (DLPFC) — a region involved in mood regulation, stress response, and cognitive control. This area is also connected to networks that regulate arousal, circadian rhythm, and the sleep-wake cycle. By improving function in these circuits, TMS may help reduce hyperarousal, stabilize mood, and support more natural, restorative sleep, rather than simply sedating the brain.
For patients with treatment-resistant Depression, this distinction matters. The question worth asking is not only which sleep medication to try next, but why the brain is struggling to regulate sleep in the first place. For many patients, the answer is rooted in dysregulated brain circuits, and addressing those circuits directly may offer more durable relief.
At Mid City TMS, we take an approach that focuses on treating the underlying mechanisms of Depression rather than managing symptoms in isolation. For patients dealing with persistent Depression and ongoing sleep difficulties, TMS offers a non-invasive, evidence-based option that may help restore both mood and the brain’s capacity to regulate sleep more naturally.
Contact us today to learn how Mid City TMS can help, or read our blog for more on Depression treatments and the latest research.
Sources
- Nygren, Adam, et al. “Factors Associated with Long-Term Hypnotics Use in Depression.” Journal of Affective Disorders, vol. 403, 2026, 121415. ISSN 0165-0327.