EDITORIALS
Use of Electroconvulsive Therapy in Bipolar Depression Mauricio Tohen, M.D., Dr.P.H., M.B.A., and Christopher C. Abbott, M.D., M.S.
Clinical experience and evidence-based research have provided support for the efficacy of electroconvulsive therapy (ECT) for unipolar depressive episodes (1), but the relative efficacy of ECT in treatment-resistant bipolar depression remains understudied. Bipolar depression, which dominates the longitudinal course of bipolar disorder, is associated with psychosocial and cognitive impairment and with significant total health care costs (2). Although the prevalence of treatmentresistant bipolar depression appears to be relatively high, few randomized controlled trials have been conducted for this condition. Unlike unipolar depression, bipolar depression has only four pharmacological treatments approved by the Food and Drug Administration (FDA): a combination of olanzapine and fluoxetine (3), quetiapine (4, 5), and, most recently, lurasidone monotherapy or lurasidone in combination with lithium or valproate (6, 7). Antidepressant agents that are effective in unipolar depression do not appear to provide similar benefits in bipolar depression (8). In this issue of the Journal, Schoeyen and colleagues (9) address an important scientific and clinical question: does a treatment with proven efficacy in treatment-resistant unipolar depression have the same effect in treatment-resistant bipolar depression? Bipolar depression is undoubtedly one of the psychiatric conditions with the most unmet medical need. The authors conducted a 6-week randomized controlled trial (N573) comparing ECT and an algorithm-based pharmacological treatment in patients with treatment-resistant bipolar depression in seven sites across Norway. This study appears to be the first randomized controlled trial comparing the efficacy of ECT and algorithm-based pharmacotherapy in treatment-resistant bipolar depression. Patients assigned to ECT received three sessions per week for up to 6 weeks using right unilateral placement of stimulus electrodes and brief pulse stimulation. The ECT group had adequate seizure duration and number of treatments. As cited by the authors, larger studies have supported comparable efficacy of right unilateral and bitemporal electrode placements in depressive episodes (10). The results show that ECT was significantly more effective than pharmacological treatment. The mean score on the Montgomery-Åsberg Depression Rating Scale (MADRS) was 6.6 points lower in the ECT group than in the group receiving algorithm-based pharmacological treatment. More than twice as many ECT patients had a significant response (73.9% versus 35.0%, p50.01), but the remission rate did not show significance and was quite Am J Psychiatry 172:1, January 2015
modest for both groups (34.8% versus 30.0%, p50.74). The low remission rate occurred in spite of a nonstringent remission definition, a MADRS score of 12 or less, rather than the more conservative criterion of 8 or less, as recommended by the International Society for Bipolar Disorders task force (11). An important question is whether the recruited patients truly represent a treatment-resistant group. The investigators defined treatment resistance as lack of response to two lifetime trials of antidepressants, lithium, lamotrigine, quetiapine, or olanzapine. For unipolar depression, more stringent definitions of treatment resistance have been utilized (12). FDA-approved treatments have also defined treatment resistance as lack of response to two or more treatments in the current episode (13). Furthermore, the pharmacological treatment algorithm used by the authors, although state of the art in 2007, would currently not be considered standard, as newer treatments for bipolar depression, includ- Bipolar depression is ing the combination of undoubtedly one of the olanzapine and fluoxe- psychiatric conditions with tine (3) or lurasidone in the most unmet medical monotherapy (6) or com- need. bination (7), were apparently not included as first-line treatments. The latter was understandably excluded because the data had not been published when the present trial was conducted. Another limitation is that patients with a rapid cycling course, who are frequently treatment resistant, were excluded. The generalizability of the findings is also limited because patients with comorbid substance abuse, which are the majority in U.S. clinical settings, were excluded. It appears that all patients initially received lamotrigine, valproate, or lithium (14). These medications have shown limited efficacy in the treatment of bipolar depression (2). Many patients later received either quetiapine or the combination of olanzapine and fluoxetine, but these were not firstline treatments. A challenge with the interpretation of the data is that the duration of each pharmacological treatment is not provided. As the study was not blinded, bias could have been introduced, especially because the treatment procedures differed considerably (15). It is not clear that having independent investigators rating audiotaped interviews prevented bias. In spite of the above limitations, this report adds major value to the evidence-based data on the use of ECT as a treatment option for bipolar depression. As stated by the authors, the ajp.psychiatryonline.org
3
EDITORIALS
low remission rate with either treatment highlights the importance of developing better approaches to treatmentresistant bipolar depression. Another major area of unmet medical need is of course maintenance treatment. The role of ECT in maintenance treatment still needs to be determined. With some possible exceptions, all patients who recover from an episode of bipolar depression will need maintenance treatment. Clinical randomized trials have provided evidence that continuation of the same treatment given during acute phases of the illness may be associated with the best outcome for maintenance treatment (16). However, there are few data on the efficacy of ECT in maintenance treatment, and such data are desperately needed. The acute phase of this investigation is presented in this issue, but the entire study protocol has been described previously (14). The longitudinal aspect of this investigation will include 21 weeks of follow-up in both treatment arms, permitting further information regarding characteristics of sustained response versus relapse. Identified by Lisanby as the “most pressing issue in the field” (17), relapse rates after ECT are as high as 50% despite optimal continuation therapies (17, 18). The majority of patients that relapse do so within 6 to 9 weeks of completing an ECT series (18, 19). The treatmentresistant patients in this study who experienced syndromal response, defined as having persistent depressive symptoms after meeting response criteria, may have higher relapse rates at follow-up than the patients who achieved remission of their symptoms following the index ECT series. The field looks forward to the findings of the 21-week follow up results. Although debated, ECT use in the United States may be declining (20). Further investigations and rigorous clinical trials will solidify and expedite the use of ECT in treatmentresistant bipolar disorders. Patients need better treatment. We applaud the authors for their study, as it provides additional evidence of the value of ECT in the treatment of bipolar depression. AUTHOR AND ARTICLE INFORMATION From the Department of Psychiatry and Behavioral Sciences, Health Sciences Center, University of New Mexico, Albuquerque. Address correspondence to Dr. Tohen ([email protected]). Dr. Tohen was a full-time employee at Lilly from 1997 to 2008; he has received honoraria from or consulted for Abbott, AstraZeneca, BristolMyers Squibb, GlaxoSmithKline, Lilly, Johnson & Johnson, Otsuka, Merck, Sunovion, Forest, Roche, Elan, Alkermes, Lundbeck, Teva, Pamlab, Wyeth, and Wiley Publishing; his spouse was a full-time employee at Lilly from 1998 to 2013. Dr. Abbott reports no financial relationships with commercial interests. Accepted October 2014. Am J Psychiatry 2015; 172:3–5; doi: 10.1176/appi.ajp.2014.14101215
REFERENCES 1. UK ECT Review Group: Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and metaanalysis. Lancet 2003; 361:799–808 2. Baldessarini RJ, Vieta E, Calabrese JR, Tohen M, Bowden CL: Bipolar depression: overview and commentary. Harv Rev Psychiatry 2010; 18:143–157 4
ajp.psychiatryonline.org
3. Tohen M, Vieta E, Calabrese J, Ketter TA, Sachs G, Bowden C, Mitchell PB, Centorrino F, Risser R, Baker RW, Evans AR, Beymer K, Dube S, Tollefson GD, Breier A: Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 2003; 60:1079–1088 4. Calabrese JR, Keck PE Jr, Macfadden W, Minkwitz M, Ketter TA, Weisler RH, Cutler AJ, McCoy R, Wilson E, Mullen J: A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 2005; 162:1351–1360 5. Thase ME, Macfadden W, Weisler RH, Chang W, Paulsson B, Khan A, Calabrese JR, Group BIS; BOLDER II Study Group: Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol 2006; 26:600–609 6. Loebel A, Cucchiaro J, Silva R, Kroger H, Hsu J, Sarma K, Sachs G: Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry 2014; 171:160–168 7. Loebel A, Cucchiaro J, Silva R, Kroger H, Sarma K, Xu J, Calabrese JR: Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry 2014; 171:169–177 8. Pacchiarotti I, Bond DJ, Baldessarini RJ, Nolen WA, Grunze H, Licht RW, Post RM, Berk M, Goodwin GM, Sachs GS, Tondo L, Findling RL, Youngstrom EA, Tohen M, Undurraga J, GonzálezPinto A, Goldberg JF, Yildiz A, Altshuler LL, Calabrese JR, Mitchell PB, Thase ME, Koukopoulos A, Colom F, Frye MA, Malhi GS, Fountoulakis KN, Vázquez G, Perlis RH, Ketter TA, Cassidy F, Akiskal H, Azorin JM, Valentí M, Mazzei DH, Lafer B, Kato T, Mazzarini L, Martínez-Aran A, Parker G, Souery D, Ozerdem A, McElroy SL, Girardi P, Bauer M, Yatham LN, Zarate CA, Nierenberg AA, Birmaher B, Kanba S, El-Mallakh RS, Serretti A, Rihmer Z, Young AH, Kotzalidis GD, MacQueen GM, Bowden CL, Ghaemi SN, Lopez-Jaramillo C, Rybakowski J, Ha K, Perugi G, Kasper S, Amsterdam JD, Hirschfeld RM, Kapczinski F, Vieta E: The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry 2013; 170: 1249–1262 9. Schoeyen HK, Kessler U, Andreassen OA, Auestad BH, Bergsholm P, Malt UF, Morken G, Oedegaard KJ, Vaaler A: Treatment-resistant bipolar depression: a randomized controlled trial of electroconvulsive therapy versus algorithm-based pharmacological treatment. Am J Psychiatry 2015; 172:41–51 10. Kellner CH, Knapp R, Husain MM, Rasmussen K, Sampson S, Cullum M, McClintock SM, Tobias KG, Martino C, Mueller M, Bailine SH, Fink M, Petrides G: Bifrontal, bitemporal and right unilateral electrode placement in ECT: randomised trial. Br J Psychiatry 2010; 196:226–234 11. Tohen M, Frank E, Bowden CL, Colom F, Ghaemi SN, Yatham LN, Malhi GS, Calabrese JR, Nolen WA, Vieta E, Kapczinski F, Goodwin GM, Suppes T, Sachs GS, Chengappa KR, Grunze H, Mitchell PB, Kanba S, Berk M: The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders. Bipolar Disord 2009; 11:453–473 12. Fava M: Diagnosis and definition of treatment-resistant depression. Biol Psychiatry 2003; 53:649–659 13. McIntyre RS, Filteau MJ, Martin L, Patry S, Carvalho A, Cha DS, Barakat M, Miguelez M: Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord 2014; 156:1–7 14. Kessler U, Vaaler AE, Schøyen H, Oedegaard KJ, Bergsholm P, Andreassen OA, Malt UF, Morken G: The study protocol of the Norwegian randomized controlled trial of electroconvulsive therapy in treatment resistant depression in bipolar disorder. BMC Psychiatry 2010; 10:16 15. Tohen M: Bias and other methodological issues in follow-up (cohort) studies, in Research Designs and Methods in Psychiatry. Am J Psychiatry 172:1, January 2015
EDITORIALS
Edited by Fava M, Rosenbaum G. Amsterdam, Elsevier, 1992, pp 119–125 16. Baldessarini RJ, Tohen M, Tondo L: Maintenance treatment in bipolar disorder. Arch Gen Psychiatry 2000; 57:490–492 17. Lisanby SH: Electroconvulsive therapy for depression. N Engl J Med 2007; 357:1939–1945 18. Kellner CH, Knapp RG, Petrides G, Rummans TA, Husain MM, Rasmussen K, Mueller M, Bernstein HJ, O’Connor K, Smith G, Biggs M, Bailine SH, Malur C, Yim E, McClintock S, Sampson S, Fink M: Continuation electroconvulsive therapy vs pharmacotherapy
Am J Psychiatry 172:1, January 2015
for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry 2006; 63:1337–1344 19. Jelovac A, Kolshus E, McLoughlin DM: Relapse following successful electroconvulsive therapy for major depression: a metaanalysis. Neuropsychopharmacology 2013; 38:2467–2474 20. Case BG, Bertollo DN, Laska EM, Price LH, Siegel CE, Olfson M, Marcus SC: Declining use of electroconvulsive therapy in United States general hospitals. Biol Psychiatry 2013; 73:119– 126
ajp.psychiatryonline.org
5
Use of Electroconvulsive Therapy in Bipolar Depression Mauricio Tohen, M.D., Dr.P.H., M.B.A., and Christopher C. Abbott, M.D., M.S.
Clinical experience and evidence-based research have provided support for the efficacy of electroconvulsive therapy (ECT) for unipolar depressive episodes (1), but the relative efficacy of ECT in treatment-resistant bipolar depression remains understudied. Bipolar depression, which dominates the longitudinal course of bipolar disorder, is associated with psychosocial and cognitive impairment and with significant total health care costs (2). Although the prevalence of treatmentresistant bipolar depression appears to be relatively high, few randomized controlled trials have been conducted for this condition. Unlike unipolar depression, bipolar depression has only four pharmacological treatments approved by the Food and Drug Administration (FDA): a combination of olanzapine and fluoxetine (3), quetiapine (4, 5), and, most recently, lurasidone monotherapy or lurasidone in combination with lithium or valproate (6, 7). Antidepressant agents that are effective in unipolar depression do not appear to provide similar benefits in bipolar depression (8). In this issue of the Journal, Schoeyen and colleagues (9) address an important scientific and clinical question: does a treatment with proven efficacy in treatment-resistant unipolar depression have the same effect in treatment-resistant bipolar depression? Bipolar depression is undoubtedly one of the psychiatric conditions with the most unmet medical need. The authors conducted a 6-week randomized controlled trial (N573) comparing ECT and an algorithm-based pharmacological treatment in patients with treatment-resistant bipolar depression in seven sites across Norway. This study appears to be the first randomized controlled trial comparing the efficacy of ECT and algorithm-based pharmacotherapy in treatment-resistant bipolar depression. Patients assigned to ECT received three sessions per week for up to 6 weeks using right unilateral placement of stimulus electrodes and brief pulse stimulation. The ECT group had adequate seizure duration and number of treatments. As cited by the authors, larger studies have supported comparable efficacy of right unilateral and bitemporal electrode placements in depressive episodes (10). The results show that ECT was significantly more effective than pharmacological treatment. The mean score on the Montgomery-Åsberg Depression Rating Scale (MADRS) was 6.6 points lower in the ECT group than in the group receiving algorithm-based pharmacological treatment. More than twice as many ECT patients had a significant response (73.9% versus 35.0%, p50.01), but the remission rate did not show significance and was quite Am J Psychiatry 172:1, January 2015
modest for both groups (34.8% versus 30.0%, p50.74). The low remission rate occurred in spite of a nonstringent remission definition, a MADRS score of 12 or less, rather than the more conservative criterion of 8 or less, as recommended by the International Society for Bipolar Disorders task force (11). An important question is whether the recruited patients truly represent a treatment-resistant group. The investigators defined treatment resistance as lack of response to two lifetime trials of antidepressants, lithium, lamotrigine, quetiapine, or olanzapine. For unipolar depression, more stringent definitions of treatment resistance have been utilized (12). FDA-approved treatments have also defined treatment resistance as lack of response to two or more treatments in the current episode (13). Furthermore, the pharmacological treatment algorithm used by the authors, although state of the art in 2007, would currently not be considered standard, as newer treatments for bipolar depression, includ- Bipolar depression is ing the combination of undoubtedly one of the olanzapine and fluoxe- psychiatric conditions with tine (3) or lurasidone in the most unmet medical monotherapy (6) or com- need. bination (7), were apparently not included as first-line treatments. The latter was understandably excluded because the data had not been published when the present trial was conducted. Another limitation is that patients with a rapid cycling course, who are frequently treatment resistant, were excluded. The generalizability of the findings is also limited because patients with comorbid substance abuse, which are the majority in U.S. clinical settings, were excluded. It appears that all patients initially received lamotrigine, valproate, or lithium (14). These medications have shown limited efficacy in the treatment of bipolar depression (2). Many patients later received either quetiapine or the combination of olanzapine and fluoxetine, but these were not firstline treatments. A challenge with the interpretation of the data is that the duration of each pharmacological treatment is not provided. As the study was not blinded, bias could have been introduced, especially because the treatment procedures differed considerably (15). It is not clear that having independent investigators rating audiotaped interviews prevented bias. In spite of the above limitations, this report adds major value to the evidence-based data on the use of ECT as a treatment option for bipolar depression. As stated by the authors, the ajp.psychiatryonline.org
3
EDITORIALS
low remission rate with either treatment highlights the importance of developing better approaches to treatmentresistant bipolar depression. Another major area of unmet medical need is of course maintenance treatment. The role of ECT in maintenance treatment still needs to be determined. With some possible exceptions, all patients who recover from an episode of bipolar depression will need maintenance treatment. Clinical randomized trials have provided evidence that continuation of the same treatment given during acute phases of the illness may be associated with the best outcome for maintenance treatment (16). However, there are few data on the efficacy of ECT in maintenance treatment, and such data are desperately needed. The acute phase of this investigation is presented in this issue, but the entire study protocol has been described previously (14). The longitudinal aspect of this investigation will include 21 weeks of follow-up in both treatment arms, permitting further information regarding characteristics of sustained response versus relapse. Identified by Lisanby as the “most pressing issue in the field” (17), relapse rates after ECT are as high as 50% despite optimal continuation therapies (17, 18). The majority of patients that relapse do so within 6 to 9 weeks of completing an ECT series (18, 19). The treatmentresistant patients in this study who experienced syndromal response, defined as having persistent depressive symptoms after meeting response criteria, may have higher relapse rates at follow-up than the patients who achieved remission of their symptoms following the index ECT series. The field looks forward to the findings of the 21-week follow up results. Although debated, ECT use in the United States may be declining (20). Further investigations and rigorous clinical trials will solidify and expedite the use of ECT in treatmentresistant bipolar disorders. Patients need better treatment. We applaud the authors for their study, as it provides additional evidence of the value of ECT in the treatment of bipolar depression. AUTHOR AND ARTICLE INFORMATION From the Department of Psychiatry and Behavioral Sciences, Health Sciences Center, University of New Mexico, Albuquerque. Address correspondence to Dr. Tohen ([email protected]). Dr. Tohen was a full-time employee at Lilly from 1997 to 2008; he has received honoraria from or consulted for Abbott, AstraZeneca, BristolMyers Squibb, GlaxoSmithKline, Lilly, Johnson & Johnson, Otsuka, Merck, Sunovion, Forest, Roche, Elan, Alkermes, Lundbeck, Teva, Pamlab, Wyeth, and Wiley Publishing; his spouse was a full-time employee at Lilly from 1998 to 2013. Dr. Abbott reports no financial relationships with commercial interests. Accepted October 2014. Am J Psychiatry 2015; 172:3–5; doi: 10.1176/appi.ajp.2014.14101215
REFERENCES 1. UK ECT Review Group: Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and metaanalysis. Lancet 2003; 361:799–808 2. Baldessarini RJ, Vieta E, Calabrese JR, Tohen M, Bowden CL: Bipolar depression: overview and commentary. Harv Rev Psychiatry 2010; 18:143–157 4
ajp.psychiatryonline.org
3. Tohen M, Vieta E, Calabrese J, Ketter TA, Sachs G, Bowden C, Mitchell PB, Centorrino F, Risser R, Baker RW, Evans AR, Beymer K, Dube S, Tollefson GD, Breier A: Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 2003; 60:1079–1088 4. Calabrese JR, Keck PE Jr, Macfadden W, Minkwitz M, Ketter TA, Weisler RH, Cutler AJ, McCoy R, Wilson E, Mullen J: A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 2005; 162:1351–1360 5. Thase ME, Macfadden W, Weisler RH, Chang W, Paulsson B, Khan A, Calabrese JR, Group BIS; BOLDER II Study Group: Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol 2006; 26:600–609 6. Loebel A, Cucchiaro J, Silva R, Kroger H, Hsu J, Sarma K, Sachs G: Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry 2014; 171:160–168 7. Loebel A, Cucchiaro J, Silva R, Kroger H, Sarma K, Xu J, Calabrese JR: Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry 2014; 171:169–177 8. Pacchiarotti I, Bond DJ, Baldessarini RJ, Nolen WA, Grunze H, Licht RW, Post RM, Berk M, Goodwin GM, Sachs GS, Tondo L, Findling RL, Youngstrom EA, Tohen M, Undurraga J, GonzálezPinto A, Goldberg JF, Yildiz A, Altshuler LL, Calabrese JR, Mitchell PB, Thase ME, Koukopoulos A, Colom F, Frye MA, Malhi GS, Fountoulakis KN, Vázquez G, Perlis RH, Ketter TA, Cassidy F, Akiskal H, Azorin JM, Valentí M, Mazzei DH, Lafer B, Kato T, Mazzarini L, Martínez-Aran A, Parker G, Souery D, Ozerdem A, McElroy SL, Girardi P, Bauer M, Yatham LN, Zarate CA, Nierenberg AA, Birmaher B, Kanba S, El-Mallakh RS, Serretti A, Rihmer Z, Young AH, Kotzalidis GD, MacQueen GM, Bowden CL, Ghaemi SN, Lopez-Jaramillo C, Rybakowski J, Ha K, Perugi G, Kasper S, Amsterdam JD, Hirschfeld RM, Kapczinski F, Vieta E: The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry 2013; 170: 1249–1262 9. Schoeyen HK, Kessler U, Andreassen OA, Auestad BH, Bergsholm P, Malt UF, Morken G, Oedegaard KJ, Vaaler A: Treatment-resistant bipolar depression: a randomized controlled trial of electroconvulsive therapy versus algorithm-based pharmacological treatment. Am J Psychiatry 2015; 172:41–51 10. Kellner CH, Knapp R, Husain MM, Rasmussen K, Sampson S, Cullum M, McClintock SM, Tobias KG, Martino C, Mueller M, Bailine SH, Fink M, Petrides G: Bifrontal, bitemporal and right unilateral electrode placement in ECT: randomised trial. Br J Psychiatry 2010; 196:226–234 11. Tohen M, Frank E, Bowden CL, Colom F, Ghaemi SN, Yatham LN, Malhi GS, Calabrese JR, Nolen WA, Vieta E, Kapczinski F, Goodwin GM, Suppes T, Sachs GS, Chengappa KR, Grunze H, Mitchell PB, Kanba S, Berk M: The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders. Bipolar Disord 2009; 11:453–473 12. Fava M: Diagnosis and definition of treatment-resistant depression. Biol Psychiatry 2003; 53:649–659 13. McIntyre RS, Filteau MJ, Martin L, Patry S, Carvalho A, Cha DS, Barakat M, Miguelez M: Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord 2014; 156:1–7 14. Kessler U, Vaaler AE, Schøyen H, Oedegaard KJ, Bergsholm P, Andreassen OA, Malt UF, Morken G: The study protocol of the Norwegian randomized controlled trial of electroconvulsive therapy in treatment resistant depression in bipolar disorder. BMC Psychiatry 2010; 10:16 15. Tohen M: Bias and other methodological issues in follow-up (cohort) studies, in Research Designs and Methods in Psychiatry. Am J Psychiatry 172:1, January 2015
EDITORIALS
Edited by Fava M, Rosenbaum G. Amsterdam, Elsevier, 1992, pp 119–125 16. Baldessarini RJ, Tohen M, Tondo L: Maintenance treatment in bipolar disorder. Arch Gen Psychiatry 2000; 57:490–492 17. Lisanby SH: Electroconvulsive therapy for depression. N Engl J Med 2007; 357:1939–1945 18. Kellner CH, Knapp RG, Petrides G, Rummans TA, Husain MM, Rasmussen K, Mueller M, Bernstein HJ, O’Connor K, Smith G, Biggs M, Bailine SH, Malur C, Yim E, McClintock S, Sampson S, Fink M: Continuation electroconvulsive therapy vs pharmacotherapy
Am J Psychiatry 172:1, January 2015
for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry 2006; 63:1337–1344 19. Jelovac A, Kolshus E, McLoughlin DM: Relapse following successful electroconvulsive therapy for major depression: a metaanalysis. Neuropsychopharmacology 2013; 38:2467–2474 20. Case BG, Bertollo DN, Laska EM, Price LH, Siegel CE, Olfson M, Marcus SC: Declining use of electroconvulsive therapy in United States general hospitals. Biol Psychiatry 2013; 73:119– 126
ajp.psychiatryonline.org
5
