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European Archives of Psychiatry and Clinical Neuroscience

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Open Access 01-02-2021 | Affective Disorder | Original Paper

Concomitant lorazepam use and antidepressive efficacy of repetitive transcranial magnetic stimulation in a naturalistic setting

Authors: M. Deppe, M. Abdelnaim, T. Hebel, P. M. Kreuzer, T. B. Poeppl, B. Langguth, M. Schecklmann

Published in: European Archives of Psychiatry and Clinical Neuroscience | Issue 1/2021

Abstract

Background/objectives:

Repetitive transcranial magnetic stimulation (rTMS) has been established as an effective therapeutic intervention for the treatment of depression. Preliminary data suggest that the efficacy of rTMS is reduced in patients taking benzodiazepines (BZD). Here, we use real-world data from a large sample to investigate the influence of lorazepam on the effectiveness of rTMS.

Methods

From a retrospective cohort of clinically depressed patients that were treated with rTMS, we compared 176 patients not taking any BZD with 73 patients taking lorazepam with respect to changes in the Hamilton Depression Rating Scale (HRDS).

Results

Both groups improved during rTMS according to HRDS scores, but the amelioration of symptoms was significantly less pronounced in patients taking lorazepam (18% vs. 38% responders in the non-lorazepam group). We could not see any association of intake regimen of lorazepam with response in rTMS.

Conclusion

Our observational study suggests that intake of lorazepam impedes the response to rTMS. The impact of lorazepam and other BZD on rTMS should receive more attention and be further investigated in prospective, hypothesis-based treatment studies to determine causal relationships between medication treatments and outcome. This could lead to specific recommendations for pharmacological treatment for depressed patients undergoing rTMS.

Belmaker RH, Agam G (2008) Major depressive disorder. New Eng J Med 358(1):55–68. https://doi.org/10.1056/NEJMra073096CrossRefPubMed

Nemeroff CB (2007) The burden of severe depression: a review of diagnostic challenges and treatment alternatives. J Psychiatry Res 41(3–4):189–206. https://doi.org/10.1016/j.jpsychires.2006.05.008CrossRef

Lépine J-P, Briley M (2011) The increasing burden of depression. Neuropsychiatr Dis Treat 7(Suppl 1):3–7. https://doi.org/10.2147/NDT.S19617CrossRefPubMedPubMedCentral

Deutsche Gesellschaft für Psychiatrie, Psychotherapie und Nervenheilkunde, Ärztliches Zentrum für Qualität in der Medizin (ÄZQ) (2015) S3-Leitlinie/Nationale VersorgungsLeitlinie Unipolare Depression–Langfassung, 2. Auflage. Deutsche Gesellschaft für Psychiatrie, Psychotherapie und Nervenheilkunde (DGPPN); Bundesärztekammer (BÄK); Kassenärztliche Bundesvereinigung (KBV); Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF)

Kessler RC, Berglund P, Demler O et al (2003) The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 289(23):3095–3105. https://doi.org/10.1001/jama.289.23.3095CrossRefPubMed

Pehrson AL, Sanchez C (2015) Altered γ-aminobutyric acid neurotransmission in major depressive disorder: a critical review of the supporting evidence and the influence of serotonergic antidepressants. Drug Des Devel Ther 9:603–624. https://doi.org/10.2147/DDDT.S62912CrossRefPubMedPubMedCentral

Reininghaus U, Böhnke JR, Chavez-Baldini U et al (2019) Transdiagnostic dimensions of psychosis in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). World Psychiatry 18(1):67–76. https://doi.org/10.1002/wps.20607CrossRefPubMedPubMedCentral

Duman RS, Aghajanian GK, Sanacora G et al (2016) Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med 22(3):238–249. https://doi.org/10.1038/nm.4050CrossRefPubMedPubMedCentral

Daly EJ, Singh JB, Fedgchin M et al (2018) Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry 75(2):139–148. https://doi.org/10.1001/jamapsychiatry.2017.3739CrossRefPubMed

10.

Swainson J, Thomas RK, Archer S et al (2019) Esketamine for treatment resistant depression. Expert Rev Neurother 19(10):899–911. https://doi.org/10.1080/14737175.2019.1640604CrossRefPubMed

11.

Schatzberg AF, Rush AJ, Arnow BA et al (2005) Chronic depression: medication (nefazodone) or psychotherapy (CBASP) is effective when the other is not. Arch Gen Psychiatry 62(5):513–520. https://doi.org/10.1001/archpsyc.62.5.513CrossRefPubMed

12.

McIntyre RS, Filteau M-J, Martin L et al (2014) Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord 156:1–7. https://doi.org/10.1016/j.jad.2013.10.043CrossRefPubMed

13.

George MS, Nahas Z, Li X et al (2002) Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS). Semin Clin neuropsychiatry 7(4):293–304CrossRef

14.

George MS, Lisanby SH, Avery D et al (2010) Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry 67(5):507–516. https://doi.org/10.1001/archgenpsychiatry.2010.46CrossRefPubMed

15.

Levkovitz Y, Isserles M, Padberg F et al (2015) Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial. World Psychiatry 14(1):64–73. https://doi.org/10.1002/wps.20199CrossRefPubMedPubMedCentral

16.

O'Reardon JP, Solvason HB, Janicak PG et al (2007) Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry 62(11):1208–1216. https://doi.org/10.1016/j.biopsych.2007.01.018CrossRefPubMed

17.

Lefaucheur J-P, Aleman A, Baeken C et al (2020) Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014–2018). Clin Neurophysiol 131(2):474–528. https://doi.org/10.1016/j.clinph.2019.11.002CrossRef

18.

Gaynes BN, Lloyd SW, Lux L et al (2014) Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis. J Clin Psychiatry 75(5):477–489. https://doi.org/10.4088/JCP.13r08815(quiz 489)CrossRefPubMed

19.

Baeken C, Brem A-K, Arns M et al (2019) Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions. Curr Opin Psychiatry 32(5):409–415. https://doi.org/10.1097/YCO.0000000000000533CrossRefPubMedPubMedCentral

20.

Rasmussen KG (2011) Some considerations in choosing electroconvulsive therapy versus transcranial magnetic stimulation for depression. J ECT 27(1):51–54. https://doi.org/10.1097/YCT.0b013e3181da84c6CrossRefPubMed

21.

Rossi S, Hallett M, Rossini PM et al (2009) Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 120(12):2008–2039. https://doi.org/10.1016/j.clinph.2009.08.016CrossRefPubMedPubMedCentral

22.

Janicak PG, O'Reardon JP, Sampson SM et al (2008) Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment. J Clin Psychiatry 69(2):222–232. https://doi.org/10.4088/jcp.v69n0208CrossRefPubMed

23.

Abdelnaim MA, Langguth B, Deppe M et al (2019) Anti-suicidal efficacy of repetitive transcranial magnetic stimulation in depressive patients: a retrospective analysis of a large sample. Front Psychiatry 10:929. https://doi.org/10.3389/fpsyt.2019.00929CrossRefPubMed

24.

Mutz J, Vipulananthan V, Carter B et al (2019) Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis. BMJ (Clinical research ed) 364:1079. https://doi.org/10.1136/bmj.l1079CrossRef

25.

Olfson M, King M, Schoenbaum M (2015) Benzodiazepine use in the United States. JAMA psychiatry 72(2):136–142. https://doi.org/10.1001/jamapsychiatry.2014.1763CrossRefPubMed

26.

Romach M, Busto U, Somer G et al (1995) Clinical aspects of chronic use of alprazolam and lorazepam. Am J Psychiatry 152(8):1161–1167. https://doi.org/10.1176/ajp.152.8.1161CrossRefPubMed

27.

Rowntree R, Sweeney J, Crumlish N et al (2018) How do we compare with best practice? A completed audit of benzodiazepine and z-hypnotic prescribing. Ir J psychol Med 35(4):321–324. https://doi.org/10.1017/ipm.2016.24CrossRefPubMed

28.

Hessmann P, Jan Z, Neubauer S et al (2018) Continuity of treatment with benzodiazepines in dementia patients: an analysis of German health insurance claims data. Int Clin Psychopharmacol 33(5):282–289. https://doi.org/10.1097/YIC.0000000000000230CrossRefPubMed

29.

Hunter AM, Minzenberg MJ, Cook IA et al (2019) Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of major depressive disorder. Brain Behav 9(5):e01275. https://doi.org/10.1002/brb3.1275CrossRefPubMedPubMedCentral

30.

Blumberger DM, Vila-Rodriguez F, Thorpe KE et al (2018) Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. The Lancet 391(10131):1683–1692. https://doi.org/10.1016/S0140-6736(18)30295-2CrossRef

31.

Kaster TS, Downar J, Vila-Rodriguez F et al (2019) Trajectories of response to dorsolateral prefrontal rTMS in major depression: a three-D study. Am J Psychiatry 176(5):367–375. https://doi.org/10.1176/appi.ajp.2018.18091096CrossRefPubMed

32.

Kaster TS, Downar J, Vila-Rodriguez F et al (2020) Caution when continuing benzodiazepines during rTMS: response to hunter and leuchter. Am J Psychiatry 177(2):172–173. https://doi.org/10.1176/appi.ajp.2019.19060603rCrossRefPubMed

33.

Caulfield KA, Stern AP (2019) Therapeutic high-frequency repetitive transcranial magnetic stimulation concurrently improves mood and anxiety in patients using benzodiazepines. Neuromodulation. https://doi.org/10.1111/ner.13024CrossRefPubMed

34.

Prasser J, Schecklmann M, Poeppl TB et al (2015) Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. World J Biol Psychiatry 16(1):57–65. https://doi.org/10.3109/15622975.2014.964768CrossRefPubMed

35.

Kreuzer PM, Schecklmann M, Lehner A et al (2015) The ACDC pilot trial: targeting the anterior cingulate by double cone coil rTMS for the treatment of depression. Brain Stimul 8(2):240–246. https://doi.org/10.1016/j.brs.2014.11.014CrossRefPubMed

36.

Frank E, Eichhammer P, Burger J et al (2011) Transcranial magnetic stimulation for the treatment of depression: feasibility and results under naturalistic conditions: a retrospective analysis. Eur Arch Psychiatry Clin Neurosci 261(4):261–266. https://doi.org/10.1007/s00406-010-0137-7CrossRefPubMed

37.

Cohen J (2013) Statistical power analysis for the behavioral sciences, 2nd edn. Taylor and Francis, HobokenCrossRef

38.

Kaiser RH, Andrews-Hanna JR, Wager TD et al (2015) Large-scale network dysfunction in major depressive disorder: a meta-analysis of resting-state functional connectivity. JAMA Psychiatry 72(6):603–611. https://doi.org/10.1001/jamapsychiatry.2015.0071CrossRefPubMedPubMedCentral

39.

Williams LM (2016) Precision psychiatry: a neural circuit taxonomy for depression and anxiety. Lancet Psychiatry 3(5):472–480. https://doi.org/10.1016/S2215-0366(15)00579-9CrossRefPubMedPubMedCentral

40.

Drysdale AT, Grosenick L, Downar J et al (2017) Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nat Med 23(1):28–38. https://doi.org/10.1038/nm.4246CrossRefPubMed

41.

Gold BI, Bowers MB, Roth RH et al (1980) GABA levels in CSF of patients with psychiatric disorders. Am J Psychiatry 137(3):362–364. https://doi.org/10.1176/ajp.137.3.362CrossRefPubMed

42.

Sanacora G, Mason GF, Rothman DL et al (1999) Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry 56(11):1043–1047. https://doi.org/10.1001/archpsyc.56.11.1043CrossRefPubMed

43.

Waagepetersen HS, Sonnewald U, Schousboe A (1999) The GABA paradox: multiple roles as metabolite, neurotransmitter, and neurodifferentiative agent. J Neurochem 73(4):1335–1342. https://doi.org/10.1046/j.1471-4159.1999.0731335.xCrossRefPubMed

44.

Hasler G, van der Veen JW, Tumonis T et al (2007) Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 64(2):193–200. https://doi.org/10.1001/archpsyc.64.2.193CrossRefPubMed

45.

Kugaya A, Sanacora G, Verhoeff NPLG et al (2003) Cerebral benzodiazepine receptors in depressed patients measured with [123i]iomazenil SPECT. Biol Psychiatry 54(8):792–799. https://doi.org/10.1016/S0006-3223(02)01788-2CrossRefPubMed

46.

Price RB, Shungu DC, Mao X et al (2009) Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder. Biol Psychiatry 65(9):792–800. https://doi.org/10.1016/j.biopsych.2008.10.025CrossRefPubMedPubMedCentral

47.

Sanacora G, Gueorguieva R, Epperson CN et al (2004) Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry 61(7):705–713. https://doi.org/10.1001/archpsyc.61.7.705CrossRefPubMed

48.

Sanacora G, Mason GF, Rothman DL et al (2003) Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry 160(3):577–579. https://doi.org/10.1176/appi.ajp.160.3.577CrossRefPubMed

49.

Sanacora G, Mason GF, Rothman DL et al (2002) Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. Am J Psychiatry 159(4):663–665. https://doi.org/10.1176/appi.ajp.159.4.663CrossRefPubMed

50.

Dubin MJ, Mao X, Banerjee S et al (2016) Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy. J Psychiatry Neurosci 41(3):E37–45CrossRef

51.

Hasler G, Neumeister A, van der Veen JW et al (2005) Normal prefrontal gamma-aminobutyric acid levels in remitted depressed subjects determined by proton magnetic resonance spectroscopy. Biol Psychiatry 58(12):969–973. https://doi.org/10.1016/j.biopsych.2005.05.017CrossRefPubMed

52.

Philip NS, Barredo J, Aiken E et al (2018) Neuroimaging mechanisms of therapeutic transcranial magnetic stimulation for major depressive disorder. Biol psychiatry Cogn Neurosci Neuroimaging 3(3):211–222. https://doi.org/10.1016/j.bpsc.2017.10.007CrossRefPubMed

53.

Hadas I, Sun Y, Lioumis P et al (2019) Association of repetitive transcranial magnetic stimulation treatment with subgenual cingulate hyperactivity in patients with major depressive disorder: a secondary analysis of a randomized clinical trial. JAMA Netw Open 2(6):e195578. https://doi.org/10.1001/jamanetworkopen.2019.5578CrossRefPubMedPubMedCentral

54.

Baeken C, de Raedt R (2011) Neurobiological mechanisms of repetitive transcranial magnetic stimulation on the underlying neurocircuitry in unipolar depression. Dialogues Clin Neurosci 13(1):139–145CrossRef

55.

Darmani G, Ziemann U (2019) Pharmacophysiology of TMS-evoked EEG potentials: a mini-review. Brain Stimul 12(3):829–831. https://doi.org/10.1016/j.brs.2019.02.021CrossRefPubMed

56.

Olsen RW (2018) GABAA receptor: Positive and negative allosteric modulators. Neuropharmacology 136(Pt A):10–22. https://doi.org/10.1016/j.neuropharm.2018.01.036CrossRefPubMedPubMedCentral

57.

Chen S, Huang X, Zeng XJ et al (1999) Benzodiazepine-mediated regulation of α1, α2, β1–3 and γ2 GABAA receptor subunit proteins in the rat brain hippocampus and cortex. Neuroscience 93(1):33–44. https://doi.org/10.1016/S0306-4522(99)00118-9CrossRefPubMed

58.

Galpern WR, Miller LG, Greenblatt DJ et al (1990) Differential effects of chronic lorazepam and alprazolam on benzodiazepine binding and GABAA-receptor function. Br J Pharmacol 101(4):839–842. https://doi.org/10.1111/j.1476-5381.1990.tb14167.xCrossRefPubMedPubMedCentral

59.

Gouzer G, Specht CG, Allain L et al (2014) Benzodiazepine-dependent stabilization of GABA(A) receptors at synapses. Mol Cell Neurosci 63:101–113. https://doi.org/10.1016/j.mcn.2014.10.004CrossRefPubMed

60.

Impagnatiello F, Pesold C, Longone P et al (1996) Modifications of gamma-aminobutyric acidA receptor subunit expression in rat neocortex during tolerance to diazepam. Mol Pharmacol 49(5):822–831PubMed

61.

Pesold C, Caruncho HJ, Impagnatiello F et al (1997) Tolerance to diazepam and changes in GABA(A) receptor subunit expression in rat neocortical areas. Neuroscience 79(2):477–487. https://doi.org/10.1016/s0306-4522(96)00609-4CrossRefPubMed

62.

Uusi-Oukari M, Korpi ER (2010) Regulation of GABA(A) receptor subunit expression by pharmacological agents. Pharmacol Rev 62(1):97–135. https://doi.org/10.1124/pr.109.002063CrossRefPubMed

63.

Ziemann U, Hallett M, Cohen LG (1998) Mechanisms of deafferentation-induced plasticity in human motor cortex. J Neurosci 18(17):7000–7007. https://doi.org/10.1523/JNEUROSCI.18-17-07000.1998CrossRefPubMedPubMedCentral

64.

Ziemann U, Muellbacher W, Hallett M et al (2001) Modulation of practice-dependent plasticity in human motor cortex. Brain 124(Pt 6):1171–1181. https://doi.org/10.1093/brain/124.6.1171CrossRefPubMed

65.

Ferrarelli F, Massimini M, Sarasso S et al (2010) Breakdown in cortical effective connectivity during midazolam-induced loss of consciousness. Proc Natl Acad Sci USA 107(6):2681–2686. https://doi.org/10.1073/pnas.0913008107CrossRefPubMed

66.

Sarasso S, Boly M, Napolitani M et al (2015) Consciousness and complexity during unresponsiveness induced by propofol, xenon, and ketamine. Curr Biol 25(23):3099–3105. https://doi.org/10.1016/j.cub.2015.10.014CrossRefPubMed

67.

Premoli I, Castellanos N, Rivolta D et al (2014) TMS-EEG signatures of GABAergic neurotransmission in the human cortex. J Neurosci 34(16):5603–5612. https://doi.org/10.1523/JNEUROSCI.5089-13.2014CrossRefPubMedPubMedCentral

68.

Fitzgerald PB, Daskalakis ZJ, Hoy KE (2020) Benzodiazepine use and response to repetitive transcranial magnetic stimulation in major depressive disorder. Brain Stimul 13(3):694–695. https://doi.org/10.1016/j.brs.2020.02.022CrossRefPubMed

69.

Hunter AM, Leuchter AF (2020) Benzodiazepine Use and rTMS Outcome. Am J Psychiatry 177(2):172. https://doi.org/10.1176/appi.ajp.2019.19060603CrossRefPubMed

70.

Gunderson JG, Elliott GR (1985) The interface between borderline personality disorder and affective disorder. Am J Psychiatry 142(3):277–288. https://doi.org/10.1176/ajp.142.3.277CrossRefPubMed

Title: Concomitant lorazepam use and antidepressive efficacy of repetitive transcranial magnetic stimulation in a naturalistic setting
Authors: M. Deppe
M. Abdelnaim
T. Hebel
P. M. Kreuzer
T. B. Poeppl
B. Langguth
M. Schecklmann
Publication date: 01-02-2021
Publisher: Springer Berlin Heidelberg
Keywords: Affective Disorder
Repetitive Transcranial Magnetic Stimulation
Affective Disorder
Lorazepam
Benzodiazepine
Z-Drugs
Published in: European Archives of Psychiatry and Clinical Neuroscience / Issue 1/2021
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-020-01160-9

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Concomitant lorazepam use and antidepressive efficacy of repetitive transcranial magnetic stimulation in a naturalistic setting

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