Abstract
Deep transcranial magnetic stimulation (dTMS) is an Food and Drug Administration-approved treatment for treatment-resistant depression (TRD). Our study aims to examine the impact of baseline insomnia severity on mood outcomes of dTMS and the impact of dTMS on comorbid insomnia in patients with treatment-resistant depression using a retrospective analysis. Twenty-five patients with treatment-resistant depression who underwent dTMS were divided into two groups: “low insomnia” and “high insomnia,” depending on Insomnia Severity Index scores at baseline. Significant improvements in depression and anxiety from baseline to final dTMS session were noted in both groups. Baseline insomnia severity was not associated with poorer treatment outcomes after dTMS. Final insomnia scores of the two groups were not significantly different, suggesting dTMS alleviated insomnia symptoms in patients with treatment-resistant depression. Further research incorporating a prospective study design in a multicenter setting is warranted to replicate these findings and elucidate the mechanistic action of dTMS on insomnia outcomes.
Citation:
Chopra A, Singal P, Kodya S. Impact of deep transcranial magnetic stimulation on insomnia outcomes in patients with treatment-resistant depression: a retrospective study. J Clin Sleep Med. 2024;20(5):813–815.
Keywords: deep TMS, insomnia, treatment-resistant depression
INTRODUCTION
Insomnia, usually considered a symptom of depression, shares a bidirectional relationship with major depressive disorder. Patients with major depressive disorder with residual insomnia are at increased risk for recurrent depressive episodes and increased suicidality.1 Furthermore, insomnia is a recognized risk factor for developing treatment-resistant depression (TRD), characterized by failure of at least two adequate trials of antidepressant medications.2 Compared to treatment-responsive depression, TRD is associated with increased morbidity, higher chronicity, higher recurrence, and increased economic costs.3 Higher symptom severity leads to poorer treatment outcomes in TRD, leaving 72% of patients with refractory insomnia.4 Further exploration into developing effective treatments addressing insomnia outcomes in patients with TRD is needed.
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique employing magnetic field-induced electrical signals to selectively increase or decrease cortical activity in brain regions by modulating the frequency, intertrain intervals, number of pulses, and type and shape of the TMS coil.5 rTMS offers an efficacious and safe intervention for patients with TRD.5 The Food and Drug Administration approved the deep TMS (dTMS) H-1 coil, which provides deeper cortical penetration (up to 4–6 cm), compared to standard rTMS using the figure of eight coils (which provides 2–2.5 cm cortical penetration), for the management of major depressive disorder in 2013.6 To our knowledge, ours is the first report on insomnia outcomes in TRD patients receiving dTMS. We aim to assess the impact of dTMS on outcomes of insomnia and examine the impact of baseline insomnia severity on mood outcomes in patients with TRD using standardized rating scales for depression, anxiety, and insomnia.
METHODS
Institutional review board approval was obtained to perform a retrospective analysis of insomnia, mood, and anxiety outcomes in patients with TRD (> 3 adequate antidepressant trials) lasting 6 months or longer undergoing dTMS at our center. We reviewed electronic medical records of patients ages 18–75 years with TRD, consecutively referred to our center for dTMS treatment over 10 months. Patients with pregnancy, bipolar depression, active psychosis, or active substance use (within the last 3 months of study enrollment) were excluded. Patients (n = 25) who underwent a full treatment course of dTMS (32–36 sessions) administered for at least 6–8 weeks were included. Treatments targeted the dorsolateral prefrontal cortex daily for the first 4 weeks followed by tapering of dTMS sessions in subsequent weeks. Fourteen of these patients (56%) with motor threshold > 55% received theta burst stimulation instead of standard rTMS to prevent stimulation-related side effects. The standard dTMS administered 1980 pulses/session at 18 Hz frequency for 18 minutes per session (total 32–26 sessions). As a standard of care, patients with TRD receiving dTMS were serially monitored for mood, anxiety, and insomnia outcomes at baseline and every week using scales including the Patient Health Questionnaire,7 Generalized Anxiety Disorder 7-item scale,8 and Insomnia Severity Index (ISI).9 Based on baseline ISI scores, TRD patients were grouped into “low insomnia” (ISI score ≤ 14) and “high insomnia” (ISI score > 14). The dTMS treatment team made no psychotropic medication changes. Although data from the standards of care assessments were collected prospectively, the data was analyzed as a retrospective study. Independent and paired t tests were utilized for statistical analysis.
RESULTS
The electronic medical records of the first 25 patients meeting the criteria for TRD (17 females and 8 males) referred to our center for dTMS were used for analyses. We compared 13 patients with a mean age of 50.38 ± 13.7 years who were categorized as “high insomnia” to 12 patients with a mean age of 53.23 ± 14.3 years as “low insomnia” based on ISI scores. Using independent sample t tests, no significant differences were found between baseline depression and anxiety scores of patients with low insomnia and high insomnia on the Patient Health Questionnaire [t(23) = 1.3372, P = .1942] and Generalized Anxiety Disorder 7-item scale [t(23) = 0.3582, P = .7235]. The baseline ISI scores of patients with low insomnia and high insomniawere significantly different [t(23) = 8.9617, P < .0001] (Table 1).
Table 1.
Baseline and postintervention characteristics of patients with treatment-resistant depression with “high” and “low” insomnia.
| Group | PHQ-9 Score* Mean (SD) | P **** | GAD-7 Score** Mean (SD) | P **** | ISI Score*** Mean (SD) | P **** |
|---|---|---|---|---|---|---|
| Total patients n = 25 (male 8, female 17) | ||||||
| Baseline | 17.32 (3.6) | < .0001 | 9.36 (5.8) | .001 | 14.20 (6.9) | < .0001 |
| Postintervention | 7.52 (5.9) | 5.64 (3.9) | 8.36 (5.8) | |||
| “High insomnia” (ISI score > 14) n = 13 (male 4, female 9) | ||||||
| Baseline | 18.23 (3.2) | < .0001 | 9.77 (6.5) | .018 | 20.00 (3.7) | < .0001 |
| Postintervention | 8.08 (7.1) | 5.62 (5.7) | 10.54 (6.3) | |||
| “Low insomnia” (ISI score ≤ 14) n = 12 (male 4, female 8) | ||||||
| Baseline | 16.33 (3.8) | < .0001 | 8.92 (5.2) | .036 | 7.92 (2.9) | .243 |
| Postintervention | 6.91 (4.6) | 5.42 (4.3) | 6.33 (4.6) |
PHQ-9 score and severity: minimal 0–4; mild 5–9; moderate 10–14; moderately severe 15–19; severe 20–27.
GAD-7 score and severity: minimal 0–4; mild 5–9; moderate 10–14; severe 15–21.
ISI score and severity: minimal 0–7; mild 8–14; moderate 15–21; severe 22–28.
P value < .05 considered significant.
GAD-7 = Generalized Anxiety Disorder 7-item scale, ISI = Insomnia Severity Index, PHQ-9 = Patient Health Questionnaire; SD = standard deviation.
Theta burst stimulation was used in 46.2% (n = 6) of the “high insomnia” group and in 66.7% (n = 8) of the “low insomnia” group. Patients receiving theta burst TMS were administered dTMS at 80%–90% of motor threshold, compared to 120% of motor threshold in the standard dTMS. To evaluate for interactions based on TMS delivery type, two sample t tests were performed comparing the changes in the baseline to final scores. Standard dTMS (n = 11) vs theta burst stimulation (n = 14) did not contribute to significant between-group differences on the Patient Health Questionnaire [t(23) = 0.6052, P = .5510], Generalized Anxiety Disorder 7-item scale [t(23) = 0.2199, P = .8279], or ISI [t(23) = 0.7019, P = .4898] postintervention. A noteworthy finding is that both groups had patients with final Patient Health Questionnaire scores of 4 or less, which suggests a remission of their depression [“high insomnia” 38.5% (n = 5) and “low insomnia” 41.7% (n = 5)]. No seizures or treatment discontinuation were reported in patients with TRD with either “high” or “low” insomnia symptoms during dTMS treatment.
DISCUSSION
We examined the effects of dTMS targeting the left dorsolateral prefrontal cortex on insomnia outcomes in 25 patients with TRD using standard and theta burst stimulation.
In our retrospective analysis, 80% of all patients and 92.3% of “high insomnia” patients showed significant improvement in insomnia symptom severity postintervention. Since the final insomnia scores of both the “low insomnia” and “high insomnia” groups were comparable, we concluded that dTMS alleviated insomnia symptoms regardless of baseline score differences, and baseline insomnia severity did not predict dTMS outcomes for depression. Additionally, dTMS significantly reduced anxiety symptoms, suggesting its potential as a multimodal intervention for patients with TRD with comorbid insomnia and anxiety. Our findings concur with previous studies done in similar cohorts reporting comparable improvements in insomnia using left10/bilateral rTMS,11 respectively, at the dorsolateral prefrontal cortex.
Our results suggest that dTMS holds promise to improve insomnia outcomes in patients with TRD. However, the study’s limitations, including its small sample size, lack of data on the possible effects of psychotropic drugs on insomnia, and retrospective design warrant caution in interpreting the results. Larger, multicenter, sham-controlled studies with objective sleep measurement tools are essential to establish dTMS efficacy and mechanistic action in addressing insomnia in TRD patients.
DISCLOSURE STATEMENT
All authors have seen and approved the manuscript. Institution where work was performed: Psychiatry & Behavioral Health Institute, Allegheny Health Network, Pittsburgh, PA. The authors report no conflicts of interest.
ABBREVIATIONS
- dTMS
deep transcranial magnetic stimulation
- ISI
Insomnia Severity Index
- rTMS
repetitive transcranial magnetic stimulation
- TMS
transcranial magnetic stimulation
- TRD
treatment-resistant depression
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