Background Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT). Early research suggested that isoflurane anesthesia may be an effective alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isoflurane's antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition. Method Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20) or isoflurane (n = 8) over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24) and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency) were assessed at Pretreatment, Post all treatments and 4-week Follow-up. Results Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane) patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement. Conclusions Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial.
References
[1]
Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, et al. (2006) Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 354: 1231–1242.
[2]
UK ECT Review Group (2003) Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 361: 799–808.
[3]
Prudic J, Haskett RF, Mulsant B, Malone KM, Pettinati HM, et al. (1996) Resistance to antidepressant medications and short-term clinical response to ECT. Am J Psychiatry 153: 985–992.
[4]
Prudic J, Olfson M, Marcus SC, Fuller RB, Sackeim HA (2004) Effectiveness of electroconvulsive therapy in community settings. Biol Psychiatry 55: 301–312.
[5]
Khalid N, Atkins M, Tredget J, Giles M, Champney-Smith K, et al. (2008) The effectiveness of electroconvulsive therapy in treatment-resistant depression: a naturalistic study. J ECT 24: 141–145.
[6]
Semkovska M, McLoughlin DM (2010) Objective cognitive performance associated with electroconvulsive therapy for depression: a systematic review and meta-analysis. Biol Psychiatry 68: 568–577.
[7]
Dunne RA, McLoughlin DM (2012) Systematic review and meta-analysis of bifrontal electroconvulsive therapy versus bilateral and unilateral electroconvulsive therapy in depression. World J Biol Psychiatry 13: 248–258.
[8]
Payne NA, Prudic J (2009) Electroconvulsive therapy: Part I. A perspective on the evolution and current practice of ECT. J Psychiatr Pract 15: 346–368.
[9]
Langer G, Neumark J, Koinig G, Graf M, Schonbeck G (1985) Rapid psychotherapeutic effects of anesthesia with isoflurane (ES narcotherapy) in treatment-refractory depressed patients. Neuropsychobiology 14: 118–120.
[10]
Langer G, Karazman R, Neumark J, Saletu B, Schonbeck G, et al. (1995) Isoflurane narcotherapy in depressive patients refractory to conventional antidepressant drug treatment. A double-blind comparison with electroconvulsive treatment. Neuropsychobiology 31: 182–194.
[11]
Engelhardt W, Carl G, Hartung E (1993) Intra-individual open comparison of burst-suppression-isoflurane-anaesthesia versus electroconvulsive therapy in the treatment of severe depression. Eur J Anaesthesiol 10: 113–118.
[12]
Carl C, Engelhardt W, Teichmann G, Fuchs G (1988) Open comparative study with treatment-refractory depressed patients: electroconvulsive therapy–anesthetic therapy with isoflurane (preliminary report). Pharmacopsychiatry 21: 432–433.
[13]
Greenberg LB, Gage J, Vitkun S, Fink M (1987) Isoflurane anesthesia therapy: a replacement for ECT in depressive disorders? Convuls Ther 3: 269–277.
[14]
Garcia-Toro M, Segura C, Gonzalez A, Perello J, Valdivia J, et al. (2001) Inefficacy of burst-suppression anesthesia in medication-resistant major depression: a controlled trial. J ECT 17: 284–288.
[15]
Tadler SC, Light AR, Hughen R (2009) Isoflurane demonstrates antidepressant-like activity in a mouse model of depression . Anesthesia and Analgesia 108: 212.
[16]
Wang L BP, Elmer GI, Mayo CL, Gould TD, Shepard PD (2012) Isoflurane impedes the development of a depression-like phenotype in rats. Society for Neuroscience Annual Meeting Planner 665.06/X17
[17]
Fraser LM, O'Carroll RE, Ebmeier KP (2008) The effect of electroconvulsive therapy on autobiographical memory: a systematic review. J ECT 24: 10–17.
[18]
Semkovska M, Noone M, Carton M, McLoughlin DM (2012) Measuring consistency of autobiographical memory recall in depression. Psychiatry Res 197: 41–48.
[19]
Norman MA, Moore DJ, Taylor M, Franklin D Jr, Cysique L, et al. (2011) Demographically corrected norms for African Americans and Caucasians on the Hopkins Verbal Learning Test-Revised, Brief Visuospatial Memory Test-Revised, Stroop Color and Word Test, and Wisconsin Card Sorting Test 64-Card Version. J Clin Exp Neuropsychol 33: 793–804.
[20]
Theisen ME, Rapport LJ, Axelrod BN, Brines DB (1998) Effects of practice in repeated administrations of the Wechsler Memory Scale Revised in normal adults. Assessment 5: 85–92.
[21]
Wroolie TE, Williams KE, Keller J, Zappert LN, Shelton SD, et al. (2006) Mood and neuropsychological changes in women with midlife depression treated with escitalopram. J Clin Psychopharmacol 26: 361–366.
[22]
Longman RS, Saklofske DH, Fung TS (2007) WAIS-III percentile scores by education and sex for U.S. and Canadian populations. Assessment 14: 426–432.
Tombaugh TN, Kozak J, Rees L (1999) Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming. Arch Clin Neuropsychol 14: 167–177.
[25]
Delis DC, Kaplan E, Kramer JH (2001) Delis Kaplan D-KEFS Executive Function System: Examiners Manual. The Psychological Corporation, San Antonio, TX.
[26]
Attix DK, Story TJ, Chelune GJ, Ball JD, Stutts ML, et al. (2009) The prediction of change: normative neuropsychological trajectories. Clin Neuropsychol 23: 21–38.
[27]
Allan CL, Herrmann LL, Ebmeier KP (2011) Transcranial magnetic stimulation in the management of mood disorders. Neuropsychobiology 64: 163–169.
[28]
Loo CK, Alonzo A, Martin D, Mitchell PB, Galvez V, et al. (2012) Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. Br J Psychiatry 200: 52–59.
[29]
Kirov G, Ebmeier KP, Scott AI, Atkins M, Khalid N, et al. (2008) Quick recovery of orientation after magnetic seizure therapy for major depressive disorder. Br J Psychiatry 193: 152–155.
[30]
Perrin JS, Merz S, Bennett DM, Currie J, Steele DJ, et al. (2012) Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder. Proc Natl Acad Sci U S A 109: 5464–5468.
[31]
Iacob E, Light KC, Tadler SC, Weeks HR, Hughen RW, et al. (2012) Stress and immune gene expression dysregulation in patients with refractory depression. Brain Behav Immun In Review.
