Skip to main content
×
×
Home

Information:

  • Access
  • Open access
  • Cited by 5
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    McGirr, Alexander and Berlim, Marcelo T. 2018. Clinical Usefulness of Therapeutic Neuromodulation for Major Depression. Psychiatric Clinics of North America,

    Dandekar, M P Fenoy, A J Carvalho, A F Soares, J C and Quevedo, J 2018. Deep brain stimulation for treatment-resistant depression: an integrative review of preclinical and clinical findings and translational implications. Molecular Psychiatry, Vol. 23, Issue. 5, p. 1094.

    Norman, Richard Lawrence 2016. Homeostatic Conductance and Parasympathetic Basis Alteration: Two Alternative Approaches to Deep Brain Stimulation in Parkinson’s, Obsessive Compulsive Disorder and Depression. World Journal of Neuroscience, Vol. 06, Issue. 01, p. 52.

    Livingston, Robin Anandan, Sharadamani and Moukaddam, Nidal 2016. Electroconvulsive Therapy, Transcranial Magnetic Stimulation, and Deep Brain Stimulation in Treatment-Resistant Depression. Psychiatric Annals, Vol. 46, Issue. 4, p. 240.

    Bauer, Michael Severus, Emanuel Köhler, Stephan Whybrow, Peter C. Angst, Jules and Möller, Hans-Jürgen 2015. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders. Part 2: Maintenance Treatment of Major Depressive Disorder-Update 2015. The World Journal of Biological Psychiatry, Vol. 16, Issue. 2, p. 76.

    ×

Actions:

      • Send article to Kindle

        To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

        Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

        Find out more about the Kindle Personal Document Service.

        Exploratory meta-analysis on deep brain stimulation in treatment-resistant depression
        Available formats
        ×
        Send article to Dropbox

        To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

        Exploratory meta-analysis on deep brain stimulation in treatment-resistant depression
        Available formats
        ×
        Send article to Google Drive

        To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

        Exploratory meta-analysis on deep brain stimulation in treatment-resistant depression
        Available formats
        ×
Export citation

Abstract

Objective

Deep brain stimulation is currently an experimental treatment for major depressive disorder. Information is lacking, however, on how sham responding may affect efficacy. This article applies exploratory meta-analysis to address that topic.

Methods

Data on benefits of deep brain electrical stimulation come from a recent review. Stimulated brain regions included subgenual cingulate, capsular interna, nucleus accumbens, and medial forebrain bundle. Expert opinion plus random number software was used to generate hypothetical values for sham responding.

Results

An effect size of 1.71 (95% CI: 1.47–1.96) was obtained for deep brain stimulation versus sham treatment in patients suffering from long-term treatment-resistant depression.

Conclusion

Preliminary findings on deep brain electrical stimulation suggest that the procedure may be 71% more effective than sham treatment. Expressing these findings as patients-needed-to-treat, deep brain electrical stimulation is required by 2.9 patients with long-term treatment-resistant depression in order for one of them to benefit.

Significant outcomes

  • This exploratory meta-analysis showed a statistically significant effect in favour of deep brain stimulation in treatment-resistant major depressive disorder.

  • In terms of patients-needed-to-treat, the results show that one out of three patients with long-term treatment-resistant depression can be expected to benefit from deep brain electrical stimulation.

Limitation

  • Estimates of sham responding to deep brain stimulation are derived by expert opinion rather than by properly controlled clinical trials.

Introduction

Direct electrical stimulation in the brain continues to attract much attention for relief of treatment-resistant depression (1,2). There is, however, still great uncertainty concerning efficacy, due in part to lack of information on sham responding to the intensive selection and surgical procedures (3). In the absence of such information, we cannot establish the likelihood of success of the intervention. There are, however, ways of estimating the likelihood of sham responding in certain situations (4). Here, expert opinion is applied to gain an understanding of the potential role of sham responding in the efficacy of deep brain stimulation in patients suffering from long-term treatment-resistant depression.

Materials and methods

Information on the likelihood of sham responding in patients with long-term treatment-resistant depression was solicited from three eminent colleagues (Helen Mayberg, Donald A. Malone Jr., and Thomas E. Schlaepfer) with extended experience using deep brain stimulation for psychiatric disorders (57). The information that they supplied along with the present authors’ understanding of treatment-resistant depression (8) placed the likelihood of sham responding in the range 10–25%. Using random number software (http://www.random.org/integers/), nine values were generated and were applied consecutively to the data provided by a recent review on deep brain stimulation in long-term treatment-resistant depression (Table 1) (2).

Table 1 Summary of data used for an exploratory meta-analysis on benefit of deep brain electrical stimulation in patients with long-term treatment-resistant depression

The information in the first three columns is summarised from a very recent review (2). The estimates of sham response were obtained by expert opinion plus random number software (http://www.random.org/integers/) (see ‘Materials and methods’ section).

Results

Effect sizes were too heterogeneous to uphold a fixed effects model (Q=36.2, df=7, p<0.01) (9). Therefore, a random effects model was used, and it provided an estimate of effect size of 1.71 (95% CI: 1.47–1.96; Z=13.6, df=7, p<0.01) for deep brain stimulation versus sham treatment in patients with long-term treatment-resistant depression. In the present context, an effect size of 1.71 means that deep brain stimulation was 71% more likely than sham treatment to be of benefit for patients with long-term treatment-resistant depression.

Discussion

The present exploratory finding can be expressed in terms of patients-needed-to-treat (10). Assuming a sham response rate of 20% to the intensive selection and surgical procedures required by deep brain stimulation, then we can expect 2 out of 10 patients to report some benefit even in the absence of electrical stimulation. The estimate of effect size derived by the present exploratory meta-analysis indicates that, in addition to sham responding, another 1.4 patients (i.e. sham response×0.71) can be expected to benefit from electrical stimulation. Thus, for every 2.9 patients (10/3.4) with long-term treatment-resistant depression receiving deep brain electrical stimulation, one can be expected to benefit. Whether this level for patients-needed-to-treat is viewed as large or small is, of course, a matter of opinion.

A shortcoming of the present analysis relates to the current lack of empirical evidence on the level of sham responding to deep brain non-stimulation in patients with long-term treatment-resistant depression. Information on that topic can be expected to come eventually from properly controlled, large-scale clinical trials that either disprove or confirm the present findings. One reviewer of this article noted that two presentations at recent conferences concerned as yet unpublished accounts on clinical trials on deep brain stimulation that were discontinued owing to no difference between active versus sham treatment in depressed subjects. Be that as it may, at least 10 additional clinical trials on deep brain stimulation in depressed subjects are currently underway, according to records available at clinicaltrials.gov. Perhaps the outcome of those studies, once published, can provide further insight concerning the ultimate value of sham versus active deep brain stimulation in treatment-resistant depression.

Acknowledgements

The author thanks Chief Physicist Søren B. Hansen for helpful comments. Helen Mayberg, Donald A. Malone Jr., and Thomas E. Schlaepfer have been informed about the content of this article. The author declares no conflict of interest. This work was done during the author’s employment at Aarhus University.

References

1.Berlim, MT, Mcgirr, A, Van Den Eynde, F, Fleck, MP, Giacobbe, P. Effectiveness and acceptability of deep brain stimulation (DBS) of the subgenual cingulate cortex for treatment-resistant depression: a systematic review and exploratory meta-analysis. J Affect Disord 2014;159:3138.
2.Schlaepfer, TE, Bewernick, BH, Kayser, S, Hurlemann, R, Coenen, VA. Deep brain stimulation of the human reward system for major depression-rationale, outcomes and outlook. Neuropsychopharmacology 2014;39:13031314.
3.Blumberger, DM, Mulsant, BH, Daskalakis, ZJ. What is the role of brain stimulation therapies in the treatment of depression? Curr Psychiatry Rep 2013;15:368378.
4.Merkl, A, Schneider, GH, Schonecker, Tet al. Antidepressant effects after short-term and chronic stimulation of the subgenual cingulate gyrus in treatment-resistant depression. Exp Neurol 2013;249:160168.
5.Mayberg, HS, Lozano, AM, Voon, Vet al. Deep brain stimulation for treatment-resistant depression. Neuron 2005;45:651660.
6.Malone, DA Jr. Use of deep brain stimulation in treatment-resistant depression. Cleve Clin J Med 2010;77(Suppl. 3):S77S80.
7.Schlaepfer, TE, Cohen, MX, Frick, Cet al. Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology 2008;33:368377.
8.Smith, DF, Stork, BS, Wegener, Get al. [11C]Mirtazapine binding in depressed antidepressant nonresponders studied by PET neuroimaging. Psychopharmacology (Berl) 2009;206:133140.
9.Lipsey, MW, Wilson, DB. Practical meta-analysis. Thousand Oaks, CA: Sage Publications Inc., 2001.
10.Connolly, KR, Thase, ME. If at first you don’t succeed: a review of the evidence for antidepressant augmentation, combination and switching strategies. Drugs 2011;71:4364.
11.Kennedy, SH, Giacobbe, P, Rizvi, SJet al. Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years. Am J Psychiatry 2011;168:502510.
12.Puigdemont, D, Perez-Egea, R, Portella, MJet al. Deep brain stimulation of the subcallosal cingulate gyrus: further evidence in treatment-resistant major depression. Int J Neuropsychopharmacol 2012;15:121133.
13.Holtzheimer, PE, Kelley, ME, Gross, REet al. Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression. Arch Gen Psychiatry 2012;69:150158.
14.Lozano, AM, Giacobbe, P, Hamani, Cet al. A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression. J Neurosurg 2012;116:315322.
15.Dougherty, DD, Carpenter, LL, Bhati, MTet al. A randomized sham-controlled trial of DBS of the VC/VS for treatment-resistant depression. 67th Annual Scientific Convention, Society of Biological Psychiatry, Philadelphia, PA. 2012.
16.Bewernick, BH, Kayser, S, Sturm, V, Schlaepfer, TE. Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy. Neuropsychopharmacology 2012;37:19751985.
17.Schlaepfer, TE, Bewernick, BH, Kayser, S, Madler, B, Coenen, VA. Rapid effects of deep brain stimulation for treatment-resistant major depression. Biol Psychiatry 2013;73:12041212.