Insomnia is the most prevalent sleep disturbance linked to mental illness and is characterized by difficulty falling asleep, staying asleep, or waking up early and not being able to return to sleep [1]. Insomnia results in reduced sleep duration and poor sleep quality, and it may present as a symptom of major depressive disorder (MDD) or as a side effect of its treatments [2]. MDD is identified as a primary cause of long-term insomnia in both clinical settings and population studies [3]. Insomnia often precedes the manifestation of a new or recurrent depressive episode, with many reporting that their insomnia occurred either before (40%) or simultaneously with (22%) other depressive symptoms [4]. The potential of insomnia to serve as an early indicator of MDD underscores the importance of understanding its role in the evolution of depression [5].

Insomnia influences the trajectory of MDD, exacerbating both the severity and duration of depressive episodes [6]. Poor sleep quality prior to treatment is indicative of a reduced response to therapeutic interventions [7]. For instance, women who experienced significant mood improvements during interpersonal therapy had better sleep quality prior to treatment compared to those who did not exhibit depression alleviation. Additionally, poor sleep quality has been linked to diminished responses to combined pharmacological and psychological treatments for depression [8]. Insomnia is also associated with increased suicidal attempts, with individuals at heightened suicide risk showing higher incidences of poor sleep quality and insomnia [9]. In one study, the severity of insomnia was determined to be a predictor of suicide within the subsequent year [10]. Additionally, insomnia remains the most prevalent residual symptom following MDD treatment. Considering the detrimental effects of insomnia on MDD, addressing and treating insomnia and poor sleep quality during MDD management are crucial. Moreover, targeted treatment for insomnia may also ameliorate other depressive symptoms [11].

The recommended initial treatment for insomnia is cognitive behavioral therapy for insomnia (CBT-I) [12]. However, access to CBT-I is often limited and it can be costly. Pharmacotherapies generally fall short in treating insomnia due to their daytime side effects, limited effectiveness, metabolic side effects, and the potential for drug tolerance [13]. Hence, alternative treatments are essential. One such alternative is repetitive transcranial magnetic stimulation (rTMS), which modifies brain activity by applying magnetic stimulation to targeted brain regions via a TMS device [14]. Approved by the Food and Drug Administration for MDD treatment in 2008, rTMS is now employed for various psychiatric disorders [15]. The impact of rTMS on sleep is not yet fully understood; however, it is thought to affect sleep by modulating altered cortical states and enhancing slow-wave activity [16]. Research has shown that rTMS effectively treats both primary and comorbid insomnia [17]. rTMS is typically administered once daily, with a recommended total of 30–40 sessions for MDD treatment [18]. However, immediate intervention is imperative for managing suicide risk. Since insomnia has been linked to elevated suicide risk, prompt treatment is vital. Advances in TMS protocols now incorporate multiple sessions per day, termed accelerated TMS (aTMS), which accelerates the treatment process [19].

aTMS has shown effectiveness in treating treatment-resistant depression (TRD) [20]. However, the effects of aTMS on insomnia severity and sleep quality, particularly regarding the improvement of depressive symptoms, have not been fully explored. In this study, we aimed to assess insomnia severity and sleep quality before and after aTMS treatment in patients with TRD.

Our study utilized a retrospective design. The inclusion criteria included: patients diagnosed with MDD who had not responded to at least two antidepressants at adequate doses and durations, patients undergoing antidepressant treatment at a stable dose for a minimum of 4 weeks, individuals with a primary diagnosis of MDD, those aged between 18–65 years, and patients whose files included sleep scale assessments. The exclusion criteria included patients with another primary psychiatric illness besides MDD, and those who experienced any changes in antidepressant or other psychiatric treatments during the aTMS treatment period.

TRD patients were routinely receiving aTMS at the Selçuk University Faculty of Medicine TMS unit. Some patients also had sleep scales in addition to depression scales. The Selçuk University Psychiatry Clinic specializes in the treatment of sleep disorders. Sleep parameters are typically monitored throughout the treatment of patients receiving various interventions. Out of 58 TRD patient files available from individuals who underwent aTMS between May 2023 and May 2024, 30 were excluded for not meeting the criteria: 5 files lacked sleep scales, 21 had changes in antidepressant doses within the last 4 weeks, and 4 were diagnosed with a primary psychiatric condition other than MDD. The study proceeded with the files of 28 patients who fulfilled the inclusion and exclusion criteria. Insomnia severity was evaluated using the Insomnia Severity Index (ISI), and sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The ISI and PSQI were administered both before and immediately following aTMS.

To our knowledge, this study is the inaugural investigation into the effects of aTMS on sleep parameters. We analyzed the ISI and PSQI data from 28 patients with TRD. Results demonstrate a significant reduction in insomnia severity and an improvement in sleep quality post-aTMS.

Insomnia and poor sleep quality are linked to suboptimal responses to depression treatment [24] and can also lead to the recurrence of depression as a residual symptom [25]. In this study, a considerable number of TRD patients suffered from clinical insomnia and poor sleep quality, with only five showing no signs of insomnia. A PSQI score above 5 suggests poor sleep quality, and our patients exhibited scores approximately 2.5 times above this threshold. Each PSQI sub-dimension is rated from 0 to 3, with higher scores indicating poorer sleep quality. The most affected PSQI subscale was subjective sleep quality, nearing a score of 3. These significantly poor sleep scores (both ISI and PSQI, including the PSQI sub-scores) likely contributed to the patients’ treatment resistance.

TMS has demonstrated positive effects on sleep issues [26]. Nonetheless, the impact of aTMS on sleep parameters in patients with TRD remains insufficiently explored. In our investigation, we observed a significant reduction in ISI, PSQI, and PSQI sub-scores following aTMS treatment. The effect size of aTMS on both ISI and PSQI was substantial. These results indicate that aTMS can alleviate insomnia severity and enhance sleep quality within a mere two weeks. Such improvement might also aid in alleviating depressive symptoms and hastening the resolution of suicidal ideation. Among the PSQI sub-dimensions, sleep duration showed the least change, likely because measurements were taken immediately post-aTMS, suggesting that aTMS might not immediately affect sleep duration. The marked improvement in sleep quality suggests that aTMS primarily enhances sleep quality.

It is widely acknowledged that insomnia and poor sleep quality exacerbate the severity of depression and elevate the risk of suicide [27]. The prompt reduction in insomnia severity and enhancement of sleep quality within just two weeks through aTMS might appear ambitious. However, previous research has documented considerable improvements in depressive symptoms within one to two weeks of initiating aTMS [28-30]. It is plausible that these improvements are facilitated by diminished insomnia or enhanced sleep quality. A significant ambiguity regarding aTMS remains its lack of a clear definition and standardized protocol. Typically, aTMS involves the administration of iTBS to the L-DLPFC multiple times daily [31]. In our study, we conducted five iTBS sessions targeting the L-DLPFC daily. Activation of the L-DLPFC may mitigate rumination [32], a pivotal contributor to insomnia. This brain region tends to be underactive in patients with depression and has extensive connections with other mood-regulating areas, such as the insula, anterior cingulate, and amygdala [33]. Rumination is recognized as a major contributing factor to the development of insomnia [34]. Hence, aTMS stimulation of the L-DLPFC may have mitigated rumination, alleviated insomnia severity, and enhanced sleep quality.

This study has several limitations. Firstly, it employs a retrospective design. Secondly, the findings may not extend to all patients with TRD. Thirdly, our assessments did not utilize objective sleep measures, such as polysomnography or actigraphy. Future research, through large-scale, randomized, controlled, double-blind studies, is required to further evaluate the effects of aTMS on insomnia severity and sleep quality.

In conclusion, aTMS significantly reduced insomnia severity and improved sleep quality in patients with TRD within just two weeks. These findings suggest that aTMS may provide a promising therapeutic approach for managing insomnia in patients with TRD.