Design and Rationale of the PACt-MD Randomized Clinical Trial: Prevention of Alzheimer’s dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression
Restricted accessResearch articleFirst published online July 21, 2020
Design and Rationale of the PACt-MD Randomized Clinical Trial: Prevention of Alzheimer’s dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression
By the time Alzheimer’s disease and related disorders (ADRD) are diagnosed, efficacy of treatments is limited. Preventive interventions are urgently needed.
Objective:
To design a randomized controlled trial to assess a novel intervention that aims to prevent ADRD in high-risk groups.
Methods:
We report on the rationale and describe the design of a multisite randomized controlled trial that aims to prevent ADRD in older persons with: (1) mild cognitive impairment (MCI); (2) remitted major depressive disorder (MDD) without MCI; or (3) remitted MDD with MCI.
Results:
PACt-MD (Prevention of Alzheimer’s dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression) is a trial that randomized 375 older participants with MCI, MDD, or MCI + MDD to cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) or sham-CR + sham-tDCS for 5 days/week for 8 weeks followed by boosters for 5 days/week once every 6 months until participants progress to MCI or ADRD, or the end of the study. Between boosters, participants are asked to train on CR daily. At baseline, end of 8 weeks, and yearly from baseline, participants undergo clinical, cognitive, and functional assessments. The primary aims are to compare the efficacy of CR + tDCS versus sham + sham in preventing: 1) long-term cognitive decline; and 2) incidence of ADRD or MCI. The secondary aim is to assess for cognitive improvement after the 8-week course. We will also explore the moderating and mediating effects of several biomarkers collected from the participants.
Conclusion:
PACt-MD is unique in combining brain stimulation and a psychosocial intervention to prevent ADRD. PACt-MD is also a platform for studying multi-domain biomarkers that will advance our understanding of the relationships among MCI, MDD, and ADRD.
SchneiderLS (2010) The potential and limits for clinical trials for early Alzheimer’s disease and some recommendations. J Nutr Health Aging14, 295–298.
2.
SchneiderLS (2012) Recruitment methods for united states Alzheimer disease prevention trials. J Nutr Health Aging16, 331–335.
ChangYL, JacobsonMW, Fennema-NotestineC, HaglerDJ, JenningsRG, DaleAM, McEvoyLK, Alzheimer’s Disease Neuroimaging Initiative (2010) Level of executive function influences verbal memory in amnestic mild cognitive impairment and predicts prefrontal and posterior cingulate thickness. Cereb Cortex20, 1305–1313.
6.
GomarJJ, Bobes-BascaranMT, Conejero-GoldbergC, DaviesP, GoldbergTE, Alzheimer’s Disease Neuroimaging Initiative (2011) Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer’s Disease Neuroimaging Initiative. Arch Gen Psychiatry68, 961–969.
7.
PetersenRC, LopezO, ArmstrongMJ, GetchiusTSD, GanguliM, GlossD, GronsethGS, MarsonD, PringsheimT, DayGS, SagerM, StevensJ, Rae-GrantA, Amer AcadN (2018) Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology90, 126–135.
8.
AlexopoulosGS, MeyersBS, YoungRC, MattisS, KakumaT (1993) The course of geriatric depression with reversible dementia - A controlled-study. Am J Psychiatry150, 1693–1699.
9.
ReynoldsCF, ButtersMA, LopezO, PollockBG, DewMA, MulsantBH, LenzeEJ, HolmM, RogersJC, MazumdarS, HouckPR, BegleyA, AndersonS, KarpJF, MillerMD, WhyteEM, StackJ, GildengersA, SzantoK, BensasiS, KauferDI, KambohMI, DeKoskyST (2011) Maintenance treatment of depression in old age: A randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy. Arch Gen Psychiatry68, 51–60.
10.
DaviglusML, BellCC, BerrettiniW, BowenPE, ConnollyES, CoxNJ, Dunbar-JacobJM, GranieriEC, HuntG, McGarryK, PatelD, PotoskyAL, Sanders-BushE, SilberbergD, TrevisanM (2010) National Institutes of Health State-of-the-Science Conference Statement: Preventing Alzheimer disease and cognitive decline.. Ann Intern Med153, 176U172.
11.
BarnesDE, YaffeK (2011) The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol10, 819–828.
VinogradovS, FisherM, de Villers-SidaniE (2012) Cognitive training for impaired neural systems in neuropsychiatric illness. Neuropsychopharmacology37, 43–76.
14.
BrunoniAR, NitscheMA, BologniniN, BiksonM, WagnerT, MerabetL, EdwardsDJ, Valero-CabreA, RotenbergA, Pascual-LeoneA, FerrucciR, PrioriA, BoggioPS, FregniF (2012) Clinical research with transcranial direct current stimulation (tDCS): Challenges and future directions. Brain Stimul5, 175–195.
15.
KronbergG, RahmanA, SharmaM, BiksonM, ParraLC (2020) Direct current stimulation boosts Hebbian plasticity in vitro. Brain Stimul13, 287–301.
16.
LieblichSM, CastleDJ, PantelisC, HopwoodM, YoungAH, EverallIP (2015) High heterogeneity and low reliability in the diagnosis of major depression will impair the development of new drugs. Bjpsych Open1, E5–E7.
17.
MontgomerySA, AsbergM (1979) New depression scale designed to be sensitive to change. Br J Psychiatry134, 382–389.
18.
FolsteinMF, FolsteinSE, McHughPR (1975) Mini-Mental State - Practical method for grading cognitive state of patients for clinician. J Psychiatr Res12, 189–198.
19.
NasreddineZS, PhillipsNA, BedirianV, CharbonneauS, WhiteheadV, CollinI, CummingsJL, ChertkowH (2005) The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment. J Am Geriatr Soc53, 695–699.
20.
FreedmanM, LeachL, TartagliaMC, StokesKA, GoldbergY, SpringR, NourhaghighiN, GeeT, StrotherSC, AlhajMO, BorrieM, DarveshS, FernandezA, FischerCE, FogartyJ, GreenbergBD, GyenesM, HerrmannN, KerenR, KirsteinJ, KumarS, LamB, LenaS, McAndrewsMP, NaglieG, PartridgeR, RajjiTK, ReichmannW, WolfMU, VerhoeffN, WasermanJL, BlackSE, Tang-WaiDF (2018) The Toronto Cognitive Assessment (TorCA): Normative data and validation to detect amnestic mild cognitive impairment. Alzheimers Res Ther10, 65.
21.
WoodsAJ, AntalA, BiksonM, BoggioPS, BrunoniAR, CelnikP, CohenLG, FregniF, HerrmannCS, KappenmanES, KnotkovaH, LiebetanzD, MiniussiC, MirandaPC, PaulusW, PrioriA, ReatoD, StaggC, WenderothN, NitscheMA (2016) A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin Neurophysiol127, 1031–1048.
22.
GandigaPC, HummelFC, CohenLG (2006) Transcranial DC stimulation (OCS): A tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol117, 845–850.
23.
BrunoniAR, AmaderaJ, BerbelB, VolzMS, RizzerioBG, FregniF (2011) A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int J Neuropsychopharmacol14, 1133–1145.
24.
FirstMB (2002) Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition, Biometrics Research, State Psychiatric Institute., New York.
25.
BhallaRK, ButtersMA, MulsantBH, BegleyAE, ZmudaMD, SchoderbekB, PollockBG, ReynoldsCF, BeckerJT (2006) Persistence of neuropsychologic deficits in the remitted state of late-life depression. Am J Geriatr Psychiatry14, 419–427.
26.
ButtersMA, BeckerJL, NebesRD, ZmudaMD, MulsantBH, PollockBG, ReynoldsCF (2000) Changes in cognitive functioning following treatment of late-life depression. Am J Psychiatry157, 1949–1954.
27.
ButtersMA, WhyteEM, NebesRD, BegleyAE, DewMA, MulsantBH, ZmudaMD, BhallaR, MeltzerCC, PollockBG, ReynoldsCF, BeckerJT (2004) The nature and determinants of neuropsychological functioning in late-life depression. Arch Gen Psychiatry61, 587–595.
28.
WilkinsonGS, RobertsonGJ (2006) Wide Range Achievement Test - Fourth Edition, Psychological Assessment Resources, Lutz, FL.
29.
AlbertMS, DeKoskyST, DicksonD, DuboisB, FeldmanHH, FoxNC, GamstA, HoltzmanDM, JagustWJ, PetersenRC, SnyderPJ, CarrilloMC, ThiesB, PhelpsCH (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement7, 270–279.
30.
HouckPR, MazuradarS, Koru-SengulT, TangG, MulsantBH, PollockBG, ReynoldsCF (2004) Estimating treatment effects from longitudinal clinical trial data with missing values: Comparative analyses using different methods. Psychiatry Res129, 209–215.
31.
MazumdarS, TangG, HouckPR, DewMA, BegleyAE, ScottJ, MulsantBH, ReynoldsCF (2007) Statistical analysis of longitudinal psychiatric data with dropouts. J Psychiatr Res41, 1032–1041.
32.
GaynorJJ, FeuerEJ, TanCC, WuDH, LittleCR, StrausDJ, ClarksonBD, BrennanMF (1993) On the use of cause-specific failure and conditional failure probablities - Examples from clinical oncology data. J Am Stat Assoc88, 400–409.
33.
GrambschPM, TherneauTM (1994) Proportional hazards tests and diagnostics based on weighted residuals. Biometrika81, 515–526.
34.
AzueroA (2016) A note on the magnitude of hazard ratios. Cancer122, 1298–1299.
35.
BookheimerS, BurggrenA (2009) APOE-4 genotype and neurophysiological vulnerability to Alzheimer’s and cognitive aging. Annu Rev Clin Psychol5, 343–362.
36.
GigiA, BabaiR, PenkerA, HendlerT, KorczynAD (2010) Prefrontal compensatory mechanism may enable normal semantic memory performance in mild cognitive impairment (MCI). J Neuroimaging20, 163–168.
37.
van VeluwSJ, SawyerEK, CloverL, CousijnH, De JagerC, EsiriMM, ChanceSA (2012) Prefrontal cortex cytoarchitecture in normal aging and Alzheimer’s disease: A relationship with IQ. Brain Struct Funct217, 797–808.
38.
GradyC (2012) The cognitive neuroscience of ageing. Nat Rev Neurosci13, 491–505.
39.
VoytekB, DavisM, YagoE, BarceloF, VogelEK, KnightRT (2010) Dynamic neuroplasticity after human prefrontal cortex damage. Neuron68, 401–408.
40.
NebesRD, PollockBG, HouckPR, ButtersMA, MulsantBH, ZmudaMD, ReynoldsCF (2003) Persistence of cognitive impairment in geriatric patients following antidepressant treatment: A randomized, double-blind clinical trial with nortriptyline and paroxetine. J Psychiatr Res37, 99–108.
41.
KoenigAM, DeLozierIJ, ZmudaMD, MarronMM, BegleyAE, AndersonSJ, ReynoldsCF, ArnoldSE, BeckerJT, ButtersMA (2015) Neuropsychological functioning in the acute and remitted states of late-life depression. J Alzheimers Dis45, 175–185.
42.
AreanPA, RaueP, MackinRS, KanellopoulosD, McCullochC, AlexopoulosGS (2010) Problem-solving therapy and supportive therapy in older adults with major depression and executive dysfunction. Am J Psychiatry167, 1391–1398.
43.
ElgamalS, McKinnonMC, RamakrishnanK, JoffeRT, MacqueenG (2007) Successful computer-assisted cognitive remediation therapy in patients with unipolar depression: A proof of principle study. Psychol Med37, 1229–1238.
44.
NaismithSL, Redoblado-HodgeMA, LewisSJG, ScottEM, HickieIB (2010) Cognitive training in affective disorders improves memory: A preliminary study using the NEAR approach. J Affect Disord121, 258–262.
45.
BowieCR, GuptaM, HolshausenK, JokicR, BestM, MilevR (2013) Cognitive remediation for treatment resistant depression: Effects on cognition and functioning and the role of online homework. J Nerv Ment Dis201, 680–685.
46.
WykesT, HuddyV, CellardC, McGurkSR, CzoborP (2011) A meta-analysis of cognitive remediation for schizophrenia: Methodology and effect sizes. Am J Psychiatry168, 472–485.
47.
DeckersbachT, NierenbergAA, KesslerR, LundHG, AmetranoRM, SachsG, RauchSL, DoughertyD (2010) Cognitive rehabilitation for bipolar disorder: An open trial for employed patients with residual depressive symptoms. CNS Neurosci Ther16, 298–307.
48.
MeuselLA, McKinnonM, HallG, MacQueenGM (2009) Evidence for sustained improvement in memory deficits following computer-assisted cognitive remediation in patients with a mood disorder. Biol Psychiatry65, 234S.
49.
RuppCI, KemmlerG, KurzM, HinterhuberH, FleischhackerWW (2012) Cognitive remediation therapy during treatment for alcohol dependence. J Stud Alcohol Drugs73, 625–634.
50.
FerrucciR, MameliF, GuidiI, Mrakic-SpostaS, VergariM, MarcegliaS, CogiamanianF, BarbieriS, ScarpiniE, PrioriA (2008) Transcranial direct current stimulation improves recognition memory in Alzheimer disease. Neurology71, 493–498.
51.
BoggioPS, KhouryLP, MartinsDCS, MartinsO, de MacedoEC, FregniF (2009) Temporal cortex direct current stimulation enhances performance on a visual recognition memory task in Alzheimer disease. J Neurol Neurosurg Psychiatry80, 444–447.
52.
BoggioPS, FerrucciR, MameliF, MartinsD, MartinsO, VergariM, TadiniL, ScarpiniE, FregniF, PrioriA (2012) Prolonged visual memory enhancement after direct current stimulation in Alzheimer’s disease. Brain Stimul5, 223–230.
53.
BlumbergerDM, TranLC, FitzgeraldPB, HoyK, DaskalakisJZ (2012) A randomized double-blind sham-controlled study of transcranial direct current stimulation for treatment-resistant major depression. Front Psychiatry3, 74.
54.
BrunoniAR, ValiengoL, BaccaroA, ZanaoTA, de OliveiraJF, GoulartA, BoggioPS, LotufoPA, BensenorIM, FregniF (2013) The sertraline vs. electrical current therapy for treating depression clinical study: Results from a factorial, randomized, controlled trial. JAMA Psychiatry70, 383–391.
55.
OliveiraJF, ZanaoTA, ValiengoL, LotufoPA, BensenorIM, FregniF, BrunoniAR (2013) Acute working memory improvement after tDCS in antidepressant-free patients with major depressive disorder. Neurosci Lett537, 60–64.
56.
WolkensteinL, PlewniaC (2013) Amelioration of cognitive control in depression by transcranial direct current stimulation. Biol Psychiatry73, 646–651.
57.
MaybergHS (2003) Modulating dysfunctional limbic-cortical circuits in depression: Towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull65, 193–207.
58.
PhillipsML, DrevetsWC, RauchSL, LaneR (2003) Neurobiology of emotion perception II: Implications for major psychiatric disorders. Biol Psychiatry54, 515–528.
59.
GrimmS, BeckJ, SchuepbachD, HellD, BoesigerP, BermpohlF, NiehausL, BoekerH, NorthoffG (2008) Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: An fMRI study in severe major depressive disorder. Biol Psychiatry63, 369–376.
60.
KoenigsM, GrafmanJ (2009) The functional neuroanatomy of depression: Distinct roles for ventromedial and dorsolateral prefrontal cortex. Behav Brain Res201, 239–243.
61.
HerrmannMJ, EhlisAC, FallgatterAJ (2004) Bilaterally reduced frontal activation during a verbal fluency task in depressed patients as measured by near-infrared spectroscopy. J Neuropsychiatry Clin Neurosci16, 170–175.
62.
KlumppH, DeldinP (2010) Review of brain functioning in depression for semantic processing and verbal fluency. Int J Psychophysiol75, 77–85.
63.
DmochowskiJP, DattaA, BiksonM, SuYZ, ParraLC (2011) Optimized multi-electrode stimulation increases focality and intensity at target. J Neural Eng8, 046011.
64.
DattaA, BansalV, DiazJ, PatelJ, ReatoD, BiksonM (2009) Gyri-precise head model of transcranial direct current stimulation: Improved spatial focality using a ring electrode versus conventional rectangular pad. Brain Stimul2, 201–207.
65.
PanicoF, SaglianoL, GrossiD, TrojanoL (2018) Bi-cephalic parietal and cerebellar direct current stimulation interferes with early error correction in prism adaptation: Toward a complex view of the neural mechanisms underlying visuomotor control. Cortex109, 226–233.
RiggsA, PatelV, PaneriB, PortenoyRK, BiksonM, KnotkovaH (2018) At-home transcranial direct current stimulation (tDCS) with telehealth support for symptom control in chronically-ill patients with multiple symptoms. Front Behav Neurosci12, 1–10.
71.
ImJJ, JeongH, BiksonM, WoodsAJ, UnalG, OhJK, NaS, ParkJS, KnotkovaH, SongIU, ChungYA (2019) Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer’s disease. Brain Stimul12, 1222–1228.
72.
RohanJG, MiklasevichMK, McInturfSM, BechmannNA, MooreRJ, Hatcher-SolisC, JankordR (2020) Polarity and subfield specific effects of transcranial direct current stimulation on hippocampal plasticity. Neurobiol Learn Mem167, 107126.
73.
KronbergG, BridiM, AbelT, BiksonM, ParraLC (2017) Direct current stimulation modulates LTP and LTD: Activity dependence and dendritic effects. Brain Stimul10, 51–58.
74.
JacksonMP, RahmanA, LafonB, KronbergG, LingD, ParraLC, BiksonM (2016) Animal models of transcranial direct current stimulation: Methods and mechanisms. Clin Neurophysiol127, 3425–3454.
75.
RanieriF, PoddaMV, RiccardiE, FrisulloG, DileoneM, ProficeP, PilatoF, Di LazzaroV, GrassiC (2012) Modulation of LTP at rat hippocampal CA3-CA1 synapses by direct current stimulation. J Neurophysiol107, 1868–1880.
76.
FritschB, ReisJ, MartinowichK, SchambraHM, JiYY, CohenLG, LuB (2010) Direct current stimulation promotes BDNF-dependent synaptic plasticity: Potential implications for motor learning. Neuron66, 198–204.
77.
FregniF, BoggioPS, NitscheM, BermpohlF, AntalA, FeredoesE, MarcolinMA, RigonattiSP, SilvaMTA, PaulusW, Pascual-LeoneA (2005) Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Exp Brain Res166, 23–30.
78.
AndrewsSC, HoyKE, EnticottPG, DaskalakisZJ, FitzgeraldPB (2011) Improving working memory: The effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex. Brain Stimul4, 84–89.
79.
DockeryCA, Hueckel-WengR, BirbaumerN, PlewniaC (2009) Enhancement of planning ability by transcranial direct current stimulation. J Neurosci29, 7271–7277.
80.
NitscheMA, PaulusW (2001) Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology57, 1899–1901.
81.
PellicciariMC, BrignaniD, MiniussiC (2013) Excitability modulation of the motor system induced by transcranial direct current stimulation: A multimodal approach. Neuroimage83, 569–580.
82.
AlonzoA, BrassilJ, TaylorJL, MartinD, LooCK (2012) Daily transcranial direct current stimulation (tDCS) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation. Brain Stimul5, 208–213.
83.
BrunoniAR, MoffaAH, FregniF, PalmU, PadbergF, BlumbergerDM, DaskalakisZJ, BennabiD, HaffenE, AlonzoA, LooCK (2016) Transcranial direct current stimulation for acute major depressive episodes: Meta-analysis of individual patient data. Br J Psychiatry208, 522–531.
84.
BlumbergerDM, MulsantBH, FitzgeraldPB, RajjiTK, RavindranAV, YoungLT, LevinsonAJ, DaskalakisZJ (2012) A randomized double-blind sham-controlled comparison of unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant major depression. World J Biol Psychiatry13, 423–435.
85.
NitscheMA, LiebetanzD, LangN, AntalA, TergauF, PaulusW (2003) Safety criteria for transcranial direct current stimulation (tDCS) in humans. Clin Neurophysiol114, 2220–2222.
86.
LangN, NitscheMA, PaulusW, RothwellJC, LemonRN (2004) Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability. Exp Brain Res156, 439–443.
87.
FregniF, BoggioPS, ValleAC, RochaRR, DuarteJ, FerreiraMJL, WagnerT, FecteauS, RigonattiSP, RibertoM, FreedmanSD, Pascual-LeoneA (2006) A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients. Stroke37, 2115–2122.
88.
PoreiszC, BorosK, AntalA, PaulusW (2007) Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull72, 208–214.
89.
BarrMS, FarzanF, RajjiTK, VoineskosAN, BlumbergerDM, ArenovichT, FitzgeraldPB, DaskalakisZJ (2013) Can repetitive magnetic stimulation improve cognition in schizophrenia? Pilot data from a randomized controlled trial. Biol Psychiatry73, 510–517.
90.
SunYM, GiacobbeP, TangCW, BarrMS, RajjiT, KennedySH, FitzgeraldPB, LozanoAM, WongW, DaskalakisZJ (2015) Deep brain stimulation modulates gamma oscillations and theta-gamma coupling in treatment resistant depression. Brain Stimul8, 1033–1042.
91.
GoughN, BrkanL, SubramaniamP, ChiuccarielloL, De PetrilloA, MulsantBH, BowieCR, RajjiTK (2020) Feasibility of remotely supervised transcranial direct current stimulation and cognitive remediation: A systematic review. PLoS One15, e0223029.
92.
CharvetLE, KasschauM, DattaA, KnotkovaH, StevensMC, AlonzoA, LooC, KrullKR, BiksonM (2015) Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: Guidelines for technology and protocols. Front Syst Neurosci9, 26.
93.
SackeimHA, HaskettRF, MulsantBH, ThaseME, MannJJ, PettinatiHM, GreenbergRM, CroweRR, CooperTB, PrudicJ (2001) Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: A randomized controlled trial. JAMA285, 1299–1307.
94.
PrudicJ, HaskettRF, McCallWV, IsenbergK, CooperT, RosenquistPB, MulsantBH, SackeimHA (2013) Pharmacological strategies in the prevention of relapse after electroconvulsive therapy. J ECT29, 3–12.
95.
BrownED, LeeH, ScottD, CummingsGG (2014) Efficacy of continuation/maintenance electroconvulsive therapy for the prevention of recurrence of a major depressive episode in adults with unipolar depression a systematic review. J ECT30, 195–202.
96.
EliasA, PhutaneVH, ClarkeS, PrudicJ (2018) Electroconvulsive therapy in the continuation and maintenance treatment of depression: Systematic review and meta-analyses. Aust N Z J Psychiatry52, 415–424.
97.
DunnerDL, AaronsonST, SackeimHA, JanicakPG, CarpenterLL, BoyadjisT, BrockDG, Bonneh-BarkayD, CookIA, LanochaK, SolvasonHB, DemitrackMA (2014) A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: Durability of benefit over a 1-year follow-up period. J Clin Psychiatry75, 1394–1401.
