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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 1  |  Issue : 3  |  Page : 136-138

Possible replacement of augmenting medication in treatment-resistant depression by transcranial magnetic stimulation: a case report


Wayne State University, Detroit, MI, USA

Date of Submission07-Jul-2022
Date of Decision15-Aug-2022
Date of Acceptance22-Aug-2022
Date of Web Publication29-Sep-2022

Correspondence Address:
Anita Vaishampayan
Wayne State University, Detroit, MI, USA
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2773-2398.356523

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  Abstract 

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression. As the left prefrontal cortex activity is linked to depression, rTMS induces blood flow in the left dorsolateral prefrontal cortex. We used rTMS in a middle-aged male patient with depression who had discontinued psychostimulant medication over a 12-month period. He had been consistently taking dextroamphetamine-amphetamine extended release 30 mg once daily prior to the onset of rTMS treatment. The patient achieved depression remission through 39 sessions of high-frequency left dorsolateral prefrontal cortex rTMS treatments. We assessed disease progression using the Quick Inventory of Depressive Symptomatology, and we measured blood pressure before each session of rTMS. After tapering the dextroamphetamine-amphetamine extended release from 30 mg to 10 mg, the patient’s score on the Quick Inventory of Depressive Symptomatology increased slightly to 7 and then dropped to 0. The results indicate that interval rTMS can lower blood pressure and may be an alternative to adjunctive psychostimulants.

Keywords: augmenting medication; psychopharmacology; transcranial magnetic stimulation; treatment-resistant depression


How to cite this article:
Vaishampayan A, Saad B, Amarasinghe D, Carly B, Balon R, Nicholas M. Possible replacement of augmenting medication in treatment-resistant depression by transcranial magnetic stimulation: a case report. Brain Netw Modulation 2022;1:136-8

How to cite this URL:
Vaishampayan A, Saad B, Amarasinghe D, Carly B, Balon R, Nicholas M. Possible replacement of augmenting medication in treatment-resistant depression by transcranial magnetic stimulation: a case report. Brain Netw Modulation [serial online] 2022 [cited 2022 Dec 8];1:136-8. Available from: http://www.bnmjournal.com/text.asp?2022/1/3/136/356523


  Introduction Top


Repetitive transcranial magnetic stimulation (rTMS) is an effective acute and maintenance treatment for depression (Wilson et al., 2022). As depression is linked to a lack of activity in the left dorsolateral prefrontal cortex, rTMS induces blood flow in the left prefrontal cortex (Wilson et al., 2022). Psychostimulants may be prescribed as an adjunctive antidepressant treatment during rTMS therapy (Hunter et al., 2019). However, it is less well-known if there is a certain point during the rTMS treatment course at which adjunctive medications become less essential (Lefaucheur et al., 2020) and can be discontinued. In the presented case, this may be available.


  Case report Top


This was a 40-year-old White male with a history of recurrent severe major depressive disorder, generalized anxiety disorder, and sleep apnea. He was treated with duloxetine 60 mg twice a day, clonazepam 0.5 mg twice a day, and dextroamphetamine-amphetamine extended release 30 mg once daily with inadequate response. He was interested in novel treatments for depression and thus rTMS was adopted. During the TMS treatment, disease progression was assessed using the standard Quick Inventory of Depressive Symptomatology (QIDS) (Rush et al., 2003) and blood pressure was monitored prior to each rTMS session using an automated blood pressure cuff. The QIDS score at his first TMS visit was 24 [Figure 1]. He underwent a course of 39 high-frequency left dorsolateral prefrontal cortex rTMS treatments, followed by another series of 11 rTMS treatments in 2020 after the coronavirus disease 2019 lockdown and a series of 25 more rTMS treatments in 2021. rTMS was administered 5 days per week until treatment 24, 2 days per week until treatment 31, once a week until treatment 37, every 2 weeks until treatment 43, and once per month until treatment 45 (the last treatment of his first round of rTMS). His second round of TMS began with 5 days per week for 12 treatments, then once a week until treatment 26, then once every 2 weeks until treatment 29, and the last treatment was done 1 month later. The parameters used for a single rTMS treatment were 5 seconds of 10 Hz trains, with an inter-train interval of 1 minute.
Figure 1: Quick Inventory of Depressive Symptomatology scores at each repetitive transcranial magnetic stimulation session throughout patient’s treatment in 2020 and 2021.
Note:* indicates the point at which dextroamphetamine-amphetamine extended-release was completely discontinued. # indicates the point at which liothyronine was started due to patient’s low thyroxine levels.


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After the first 20 treatments delivered 5 days per week, the QIDS score decreased to 2. After continuing rTMS at an interval tapered to once a week and tapering dextroamphetamine-amphetamine extended-release 30 mg to 10 mg gradually, the QIDS score increased slightly to 7 and then dropped to 0 [Figure 1]. While we noticed a slight recurrence of symptoms after the medication was discontinued, it was not clinically relevant enough to warrant a change in the treatment plan. Therefore, the first course of rTMS was safe as an alternative to adjunctive medication and achieved remission of his depression in 2020.

However, the patient reported being more depressed with a QIDS score of 19 at his first visit in 2021 [Figure 1], 12 days after his last treatment in 2020. In February 2021, blood tests indicated that the patient had marginally decreased free thyroxine (0.64 ng/d; normal range 0.7-1.7 ng/d), while the other thyroid indices were all within normal limits (e.g., thyroid stimulating hormone was 1.69 mIU/L (normal range: 0.45-5.33 mIU/L). Consequently, he was administered liothyronine 25 μg/d, to augment the efficacy of antidepressant treatments. At the 1-week follow-up visit, the patient stated that he felt “better than ever” with the continuation of duloxetine, clonazepam, the addition of liothyronine, and a 2nd shorter series of rTMS treatments. For the first time, he claimed to “have more energy and the desire to do new things”. His QIDS score reduced from 20 to 10 within a week [Figure 1]. The patient felt “greater energy and decreased depression” in addition to success in his work as a catering cook. He stated that “his world felt brighter than it did in a very long time.” His QIDS score was 7 at his most recent rTMS session [Figure 1]. This indicates a return to remission after a brief relapse. Two months later, however, he discontinued liothyronine on his own. He still felt very well in 2022 and denied depressive symptoms. He has tapered and discontinued clonazepam without any difficulty.

Throughout the treatments in 2021, we noted a gradual and consistent drop in systolic and diastolic blood pressures measured at each rTMS visit. The average blood pressure for the patient’s first three rTMS treatments in 2021 was measured to be 155/97 mmHg whereas his three most recent visits average 136/85 mmHg. The blood pressure was reduced and stayed low with the discontinuation of dextroamphetamine-amphetamine extended release while continuing rTMS with the duloxetine and clonazepam being continued at the same dosages throughout the entire treatment [Figure 2]. The decline in blood pressure seemed to serve as possible physiological verification of the improvement in depression and anxiety symptoms. The case report was approved by the Ethics Committee of Wayne State University and the patient provided written informed consent for the study.
Figure 2: Blood pressure readings at each repetitive transcranial magnetic stimulation session throughout patient’s treatment in 2020 and 2021.
Note: Average blood pressure of first three sessions was 155/97 mmHg and average of last three sessions was 136/85 mmHg.


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  Discussion Top


The addition of rTMS had a positive effect on our patient’s emotional and physiological well-being. The patient reported reaching “levels of energy” that had not been previously noted when he had relied solely on medication for treatment. rTMS gradually substituted the adjunctive psychostimulant. This is similar to the results of a study by Mantovani et al. (2012) which investigated persistence of TMS benefits in patients who either continued adjunctive antidepressants with rTMS treatment or discontinued all oral medications. While a third of their sample population was lost to follow-up, their study demonstrated that rTMS benefits persisted regardless of whether a medication was continued or not (Mantovani et al., 2012). It seems that a promising new avenue for the continuous treatment of chronic depression may be continuous intermittent administration of rTMS with progressive discontinuation or reduction of antidepressant medication. This may be available, especially in patients who report severe side effects from medications.

The presence of thyroid dysfunction with major depressive disorder has been well documented for years. Several studies reported the successful use of thyroid supplementation of either liothyronine or supraphysiological thyroxine in augmentation of antidepressant treatment or in addressing possible subclinical hypothyroidism comorbid with major depressive disorder (Dwyer et al., 2020; Bauer and Whybrow, 2021). Our patient’s continuous improvement after discontinuing liothyronine while continuing rTMS suggested that thyroid dysfunction was not an underlying factor in his major depressive disorder.

Since our study also seemed to demonstrate a decreasing trend in blood pressure as rTMS treatment progressed, we explored the literature to see if there was any major effect of rTMS in depression treatment on cardiovascular health. In a systematic review of cases of rTMS depression treatment that detected various physiological measures such as blood pressure, glucose levels, and cortisol levels, Sampaio et al. (2012) found that in general rTMS seemed to lower high blood pressure and glucose levels, although one study demonstrated blood pressure to increase after an rTMS session. While they focused on the acute effects of a single rTMS session and our case study was more longitudinal in nature, both suggesting that the potential rTMS can have on cardiovascular health (Sampaio et al., 2012). This would be an important benefit for depressed patients as depression is a significant risk factor for cardiovascular death.

Long-term administration of rTMS may have unexpected benefits, including possible reduction or discontinuation of medication while continuing administration of antidepressants and possible improvement of some abnormal physiological measures, such as increased blood pressure.

Author contributions:

Medication regimen management: RB; rTMS sessions management: NM; data collection at patient’s r TMS sessions: AV, CB; data analysis: BS, DA; manuscript draft: AV, NM. All authors read and approved the final version of the manuscript.

Conflicts of interest:

No conflicts of interest exist.

Open access statement:

This is an open access journal, and articles are distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.



 
  References Top

1.
Bauer M, Whybrow PC (2021) Role of thyroid hormone therapy in depressive disorders. J Endocrinol Invest 44:2341-2347.  Back to cited text no. 1
    
2.
Dwyer JB, Aftab A, Radhakrishnan R, Widge A, Rodriguez CI, Carpenter LL, Nemeroff CB, McDonald WM, Kalin NH; APA Council of Research Task Force on Novel Biomarkers and Treatments (2020) Hormonal treatments for major depressive disorder: state of the art. Am J Psychiatry 177:686-705.   Back to cited text no. 2
    
3.
Hunter AM, Minzenberg MJ, Cook IA, Krantz DE, Levitt JG, Rotstein NM, Chawla SA, Leuchter AF (2019) Concomitant medication use and clinical outcome of repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder. Brain Behav 9:e01275.   Back to cited text no. 3
    
4.
Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipović SR, Grefkes C, Hasan A, Hummel FC, Jääskeläinen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, et al. (2020) Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol 131:474-528.   Back to cited text no. 4
    
5.
Mantovani A, Pavlicova M, Avery D, Nahas Z, McDonald WM, Wajdik CD, Holtzheimer PE, 3rd, George MS, Sackeim HA, Lisanby SH (2012) Long-term efficacy of repeated daily prefrontal transcranial magnetic stimulation (TMS) in treatment-resistant depression. Depress Anxiety 29:883-890.   Back to cited text no. 5
    
6.
Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, Markowitz JC, Ninan PT, Kornstein S, Manber R, Thase ME, Kocsis JH, Keller MB (2003) The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 54:573-583.   Back to cited text no. 6
    
7.
Sampaio LA, Fraguas R, Lotufo PA, Benseñor IM, Brunoni AR (2012) A systematic review of non-invasive brain stimulation therapies and cardiovascular risk: implications for the treatment of major depressive disorder. Front Psychiatry 3:87.   Back to cited text no. 7
    
8.
Wilson S, Croarkin PE, Aaronson ST, Carpenter LL, Cochran M, Stultz DJ, Kozel FA (2022) Systematic review of preservation TMS that includes continuation, maintenance, relapse-prevention, and rescue TMS. J Affect Disord 296:79-88.  Back to cited text no. 8
    


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