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• W3138996951 abstract "Vagus Nerves Stimulation (VNS) can treat both treatment-refractory epilepsy [[1]Dibue-Adjei M. Brigo F. Yamamoto T. Vonck K. Trinka E. Vagus nerve stimulation in refractory and super-refractory status epilepticus - a systematic review.Brain Stimul. 2019; 12: 1101-1110Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar,[2]Wheless J.W. Gienapp A.J. Ryvlin P. Vagus nerve stimulation (VNS) therapy update.Epilepsy Behav. 2018; 88S: 2-10Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar] and treatment resistant major depressive episodes (MDE) [[3]Aaronson S.T. Conway C.R. Vagus nerve stimulation: changing the paradigm for chronic severe depression?.Psychiatr Clin North Am. 2018; 41: 409-418Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar,[4]Aaronson S.T. Sears P. Ruvuna F. Bunker M. Conway C.R. Dougherty D.D. et al.A 5-year observational study of patients with treatment-resistant depression treated with vagus nerve stimulation or treatment as usual: comparison of response, remission, and suicidality.Am J Psychiatry. 2017; 174: 640-648Crossref PubMed Scopus (137) Google Scholar]. However, VNS can induce or exacerbate psychotic symptoms in epileptic patients [5Blumer D. Davies K. Alexander A. Morgan S. Major psychiatric disorders subsequent to treating epilepsy by vagus nerve stimulation.Epilepsy Behav. 2001; 2: 466-472Abstract Full Text PDF PubMed Scopus (37) Google Scholar, 6De Herdt V. Boon P. Vonck K. Goossens L. Nieuwenhuis L. Paemeleire K. et al.Are psychotic symptoms related to vagus nerve stimulation in epilepsy patients?.Acta Neurol Belg. 2003; 103: 170-175PubMed Google Scholar, 7Gatzonis S.D. Stamboulis E. Siafakas A. Angelopoulos E. Georgaculias N. Sigounas E. et al.Acute psychosis and EEG normalisation after vagus nerve stimulation.J Neurol Neurosurg Psychiatry. 2000; 69: 278-279Crossref PubMed Scopus (38) Google Scholar], and exclusion of psychotic depression from VNS studies in MDE is routine in investigational trials [[8]Rush A.J. Marangell L.B. Sackeim H.A. George M.S. Brannan S.K. Davis S.M. et al.Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial.Biol Psychiatry. 2005; 58: 347-354Abstract Full Text Full Text PDF PubMed Scopus (410) Google Scholar]. Thus, there is some concern and no data available about the risk/benefit ratio of adjunctive VNS in psychotic depression. We report here a case showing both efficacy and safety of adjunctive VNS for the treatment of resistant depression with psychotic features. The patient provided written informed consent for anonymized publication of his data. A middle aged married man and father of three children, with a high educational level and a job history as an engineer, experienced five previous MDE, with five hospitalizations in psychiatry and two severe suicide attempts (drug overdoses) within the past 13 years. During these previous MDE, he had psychotic features which remitted after treatment combination of antidepressant and antipsychotic drugs. His current MDE began 32 months ago. It was severe (HDRS-17 score: 28), inducing a 32-month work leave. He had mood congruent auditory and intrapsychic hallucinations with suicidal injunctions that appeared after the beginning of his MDE. His BPRS-5 score for psychotic depression (score range: 0–20) [[9]Ostergaard S.D. Pedersen C.H. Uggerby P. Munk-Jorgensen P. Rothschild A.J. Larsen J.I. et al.Clinical and psychometric validation of the psychotic depression assessment scale.J Affect Disord. 2015; 173: 261-268Crossref PubMed Scopus (20) Google Scholar] was 12. This MDE was resistant to six sequences of antidepressant drugs (adequate doses and durations of SSRI, SNRI, tricyclics, MAOI) and ECT, co-prescribed with several antipsychotics (risperidone, loxapine, cyamemazine). Because of insufficient response to a combination of phenelzine (60mg/d) and cyamemazine (200mg/d), adjunctive VNS (Demipulse™ Model 103, Cyberonics, Inc. Houston, Texas) was proposed and, after informed consent and successful surgery, adjunctive treatment with VNS was turned on. The VNS stimulation parameters were titrated during a 4-month period, up to an output of 1.75 mA, a signal frequency of 20 Hz, a signal on time of 30 s, a signal off time of 3 min, and a pulse width of 130 μs. MDE symptoms improved progressively: a partial improvement of sadness was first observed after two weeks of VNS, followed by improvements of insomnia after three months, then anhedonia, psychomotor retardation and psychotic features after four months and finally suicidal ideations after 4.5 months. Sadness, depressed mood and psychotic symptoms disappeared after 4.5 months of VNS (HDRS score: 14, BPRS-5 score: 3). Thus, as expected with VNS treatment, the significant therapeutic response did not appear before four months of VNS. Of note, there were medication changes during this period: At time of implantation, the patient received phenelzine 45mg/d and cyamemazine 200mg/d. Four months later, he received phenelzine 30mg/d at stable dosage since one month and amisulpride 200mg/d at stable dosage since two months. Interestingly, adjunctive VNS was not only effective and well tolerated in the acute phase of treatment, but also in the continuation/maintenance phase (six months: HDRS score: 4, BPRS-5 score: 0; eight months: HDRS score: 9, BPRS-5 score: 1). Except for expected mild pain and coughing during titration, adjunctive VNS was well tolerated and induced no psychotic symptoms. This case report shows the efficacy and safety of adjunctive VNS for the treatment of a treatment resistant MDE with psychotic features, VNS being added to a combination of antidepressant and antipsychotic drugs. We evidenced a complete relief of depressive and psychotic symptoms in the acute and maintenance/continuation treatment phases. Two points argue for the fact that the clinical response may be due to VNS. First, the timing of clinical response (several months) is compatible with VNS efficacy. Second, the antidepressant dosage was decreased and the antipsychotic dosage was stable during the same period. However, since it is difficult to draw firm conclusions from a single case, further studies including patients with psychotic depression are necessary. Indeed, available studies of VNS in patients with treatment resistant MDE (two randomized controlled trials, four observational studies) excluded MDE patients with psychotic features [[3]Aaronson S.T. Conway C.R. Vagus nerve stimulation: changing the paradigm for chronic severe depression?.Psychiatr Clin North Am. 2018; 41: 409-418Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar]. Concerns over psychotic symptoms induction in epileptic patients by VNS have been previously reported (one case report in Gatzonis et al., 2000; four patients out of 81 in Blumer et al., 2001; four patients out of 70 in De Herdt et al., 2003). Since psychotic symptoms appear after epileptic seizure control in patients treated with VNS, it seems that psychotic symptoms are not induced by the direct effect of VNS, but by the decrease of seizures, a mechanism, also observed with anti-epileptic drugs, known as “forced normalization”. Since “forced normalization” cannot be involved in depressed patients without epilepsy, it can explain the efficacy and tolerability of VNS in depressed patients. To conclude, this case report suggests that adjunctive VNS is a therapeutic option that requires additional studies in patients with treatment-resistant depression with psychotic features. RC, AAT, EC: data acquisition, drafting, revising, editing, final approval. CF, NA: data acquisition, revising, editing, final approval. BB, MG, SM, PD: revising, editing, final approval. RC, AAT, BB, MG, SM, PD, CF, WC, NA and EC have no conflict of interest to disclose." @default.
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• W3138996951 title "Efficacy and safety of adjunctive vagus nerve stimulation in the treatment of resistant depression with psychotic features: A case report" @default.
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