Depression is the most common psychiatric disorder that women experience during pregnancy, with estimated prevalence rates as high as 10% worldwide.1 Numerous studies have identified a range of adverse fetal and maternal outcomes associated with untreated depression in pregnancy. In infants, premature delivery, small birth size and weight, and low Apgar scores have been observed, and these children also have a greater risk for subsequent mental disorders. In mothers, depression in pregnancy is closely associated with postpartum depression risk.1

However, treating depression with established therapies during pregnancy presents several challenges. For example, selective serotonin reuptake inhibitors may increase the risk for neonatal pulmonary hypertension, cardiovascular malformations, and fetal death, so patients often decline to use them.1 While psychotherapy may be useful in pregnant women with mild depression, it is largely ineffective for moderate to severe depression due to the length of time required to achieve symptom improvement.1

Noninvasive brain stimulation techniques, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have emerged as an additional effective treatment option for depression.2,3 tDCS may be particularly advantageous because of its low cost, ease of use, minimal side effects, and lack of seizure risk compared with rTMS. Findings from several studies indicate that tDCS is generally safe and has similar efficacy in depression as psychotherapy and pharmacotherapy.1

“The rationale behind using tDCS is based on the understanding that modified neuronal activity in the left and right [prefrontal dorsolateral cortex] DLPFC including the pathophysiologic models of left hypofrontality and interhemispheric imbalance contributes to the development of depressive disorders,” according to a systematic review published online in Brain Sciences.1 “tDCS is supposed to modulate prefrontal dysfunction by changing local neural activity and activity in remote areas via neural networks.”

Because the effects of tDCS are limited to the brain and are not systemic, this modality could prove to be especially useful for treating depression in pregnancy. The review authors explored the available evidence pertaining to the use of tDCS to treat depression in pregnant women and found a dearth of studies on the topic.

One case study focused on a pregnant patient with depression who received tDCS daily for 10 days. At follow-up, her scores on the Hamilton Depression Scale (HAMD) and the Hamilton Anxiety Rating Scale (HAMA) had decreased from 18 to 6 points and 32 to 5 points, respectively, indicating remission.4

In a case study regarding tDCS as an intervention for auditory hallucinations in a pregnant patient with schizophrenia, twice-daily tDCS for 10 days was associated with a 41% reduction in depressive symptoms as assessed with the Calgary Depression Scale in Schizophrenia (CDSS).5

A single-center pilot study (DRKS00008537)1 is currently recruiting participants to examine the effects of tDCS on depression in pregnant women; preliminary results are promising.6

The results of a recently completed Canadian multicenter randomized controlled trial (RCT) investigating tDCS for depression in pregnancy (NCT02116127) will be reported in the near future.7

To further discuss the potential role of tDCS as a treatment option for depression during pregnancy, Psychiatry Advisor interviewed one of the authors of the 2018 review and the single-center pilot study, Urich Palm, MD, senior physician in the department of psychiatry and psychotherapy at Ludwig Maximilian University (LMU) of Munich in Germany, and head of clinical trials at LMU’s Transcranial Brain Stimulation and Neuroplasticity Research Group; and Ryan Vidrine, MD, assistant professor, department of psychiatry at the University of California, San Francisco.

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Psychiatry Advisor: What does the evidence suggest thus far about the use of tDCS for depression in pregnancy?

Dr Palm: While evidence is emerging from single case reports and congress proceedings, suggesting an improvement of depression symptoms, we do not yet have evidence from larger or randomized clinical trials. We will have to wait for the publication from the Canadian research group conducting the first RCT to see if active tDCS is biologically superior to sham treatment or improvement is only driven by the tDCS procedure itself and caregiving.7

Dr Vidrine: There is currently insufficient evidence to suggest a clear clinical role for tDCS. Based on the available data, we suspect that it is likely to be a safe option, but whether or not it is efficacious or any better than other available treatments will require large-scale RCTs.

This study serves as an important prompt to suggest a greater role for noninvasive brain stimulation in depression in general, particularly in more vulnerable populations, such as pregnant women. It is an exciting time, and this is an exciting question to consider, but it still remains just a question. Even as small positive studies arise, we need to see if they can be replicated, especially in real-world clinical populations.

Psychiatry Advisor: For which patients might tDCS be most appropriate in pregnancy?  

Dr Palm: It is likely that this intervention may be useful for patients with a history of recurrent depression prior to pregnancy. In these patients, pharmacologic treatment could be replaced by tDCS to maintain remission or to treat a relapse when medication has been discontinued before a planned pregnancy due to fear of teratogenic effects. However, at the moment, it is not recommended to replace an ongoing medication with tDCS when pregnancy is diagnosed by chance.

Dr Vidrine: In the future, this could prove to be an appropriate treatment in patients with depression, anxiety, or even other disorders — especially patients who have contraindications to medications or struggle to tolerate medications. It may also be an option to enhance various forms of psychotherapy. We just don’t have the clinical trial data yet to [support the clinical use of tDCS in pregnant women].

Currently, both electroconvulsive therapy (ECT) and TMS are already US Food and Drug Administration (FDA)-approved for depression, with large-scale study data going back >10 years that supports their efficacy, and they are often covered by insurance. Both treatments are thought to be quite safe in pregnant women, and TMS particularly may have a bigger role, as it is easily done in an outpatient setting without anesthesia or cognitive side effects.

Psychiatry Advisor: What should be the focus of future research in this area?   

Dr Palm: First, we need to prove the superiority of active stimulation over sham stimulation in placebo-controlled trials. Then we could think of establishing standardized treatment regimens consisting of multimodal interventions, such as brain stimulation plus manualized short-term psychotherapy and counseling with an obstetrician, social worker, and midwife, for example.

Dr Vidrine: The focus should be on large-scale, prospective RCTs for specific mental health disorders, such as depression, panic disorder, and obsessive compulsive disorder. If efficacy is determined, tDCS should be investigated head-to-head against other treatments with known efficacy, such as cognitive behavioral therapy, ECT, TMS, and medications.

References

1. Kurzeck AK, Kirsch B, Weidinger E, Padberg F, Palm U. Transcranial direct current stimulation (tDCS) for depression during pregnancy: scientific evidence and what is being said in the media—a systematic review. Brain Sci. 2018;8(8):155.

2. Lefaucheur JP, André-Obadia N, Antal A, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014;125(11):2150-2206.

3. Lefaucheur JP, Antal A, Ayache SS, et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017;128(1):56-92.

4. Sreeraj VS, Bose A, Shanbhag V, Narayanaswamy JC, Venkatasubramanian G, Benegal V. Monotherapy with tDCS for treatment of depressive episode during pregnancy: a case report. Brain Stimul. 2016;9(3):457-458.

5. Strube W, Kirsch B, Padberg F, Hasan A, Palm U. Transcranial direct current stimulation as monotherapy for the treatment of auditory hallucinations during pregnancy. J Clin Psychopharmacol. 2016;36(5):534-535.

6. Palm U, Kirsch B, Leitner B, Popovic D, Padberg F. P017 Transcranial direct current stimulation (tDCS) for the treatment of depression during pregnancy: A pilot study. Clin Neurophysiol. 2017;128(3):e17-e18.

7. Vigod S, Dennis CL, Daskalakis Z, et al. Transcranial direct current stimulation (tDCS) for treatment of major depression during pregnancy: Study protocol for a pilot randomized controlled trial. Trials. 2014;15:366.