CLINICAL CASE DISCUSSIONSIs Ketamine the Future Clozapine for Depression? A Case Series and Literature Review on Maintenance Ketamine in Treatment-resistant Depression With Suicidal BehaviorCHAN, LAI FONG MD, MMedPsych, MSc; EU, CHOON LENG MD; SOH, SHEAN YIH MBBS; MANIAM, THAMBU MBBS, MPM; SHAHIDII KADIR, ZURI MBBS; CHONG, BENEDICT TAK WAI MD; LOO, JIANN LIN MD, DrPsych; SHARIP, SHALISAH PhD; WONG, VINCENT CHOONG WAI MBBS, MMedPsych; LOO, TSUI HUEI MBBS, MMedPsych; NG, YIN PING MB BCh BAO, DrPsych, MScHR; KAHN, DAVID A. MD Author Information CHAN, EU, SOH, KADIR, CHONG, SHARIP: Universiti Kebangsaan Malaysia Medical Centre (UKMMC), National University of Malaysia Medical Centre, Cheras, Malaysia T. MANIAM: UKMMC, National University of Malaysia Medical Centre, Cheras, and Mind Faculty, Solaris Mont Kiara, Malaysia J.L. LOO: UKMMC, National University of Malaysia Medical Centre, Cheras, and Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia WONG: Brain Mind Specialist Clinic, Petaling Jaya, Selangor, Malaysia T.H. LOO: Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia NG: RCSI and UCD Malaysia Campus, Penang, Malaysia KAHN: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY Supported by the Fundamental Research Grant Scheme by the Malaysian Ministry of Higher Education (FRGS/2/2014/SKK09/UKM/02/1) and the University Research Fund by the National University of Malaysia (GUP-2015-043) granted to L.F.C. (primary investigator). L.F.C. and M.T. have received conference sponsorship/honoraria for lectures/research fee from the following firms: Otsuka, Mansa Pharma, GlaxoSmithKline, Lundbeck, Astra Zeneca, Eli Lilly, Ortho-McNeil Janssen, Menarini, and Johnson & Johnson. Y.P.N. has received conference sponsorship/honoraria for lectures from the following firms: Menarini, Johnson & Johnson, Eli Lilly, Astra Zeneca, Lundbeck, Mansa, and Servier. T.H.L. has received conference sponsorship/honoraria for lectures/research fee from the following firms: Menarini, Pfizer, Johnson & Johnson, Sanofi, Lundbeck, Abbott, Servier, Astra Zeneca, Otsuka Pharmaceutical Co. Ltd, Sumitomo Dainippon Pharma, and is a subinvestigator in the Esketamine Trial (ESKETINTRD3004; Phase 3 JNJ-54135419) sponsored by Johnson & Johnson. V.C.W.W. has received conference sponsorship/honoraria for lectures/research fee from the following firms: Lundbeck and Pfizer. L.F.C. is the primary investigator and J.L.L. is subinvestigator in the Esketamine Trial 54135419SUI3001 sponsored by Johnson & Johnson. The remaining authors declare no conflicts of interest.Chan et al: DOI: 10.1097/PRA.0000000000000316Kahn: DOI: 10.1097/PRA.0000000000000317 Please send correspondence to: Lai Fong Chan, MD, MMedPsych, MSc, Associate Professor and Consultant Psychiatrist, Pusat Perubatan Universiti Kebangsaan Malaysia, Psychiatry, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur Federal Territory 56000, Malaysia (e-mail: [email protected]). Journal of Psychiatric Practice: July 2018 - Volume 24 - Issue 4 - p 279-291 doi: 10.1097/PRA.0000000000000316 Buy Metrics Abstract Ketamine has shown effectiveness as a rapid-acting antidepressant with antisuicidal effects in terms of reduction of suicidal ideation in the short term. However, the evidence for long-term maintenance ketamine therapy for treatment-resistant depression (TRD) and suicidal behavior is limited. This case series (N=13) highlights the role of adjunctive serial maintenance ketamine infusions in restoring functionality in treatment-resistant unipolar and bipolar (mixed) depression with significant suicide risk and multiple comorbidities, including alcohol dependence. Two cases of TRD achieved functional remission with long-term maintenance ketamine treatment. The first case illustrates the potential synergistic interaction between ketamine and lamotrigine to achieve a sustained antidepressant response in the patient for 7 months. The second case may possibly be the longest reported case of maintenance ketamine therapy, with treatment continuing for 5 years to date. Ketamine treatment showed acute effectiveness in another 7 cases, especially in terms of reduction of suicidal ideation, albeit without significant long-term antidepressant effect. Factors that may contribute to lack of effectiveness of serial ketamine include inadequate mood stabilization in TRD in bipolar spectrum diagnoses, concomitant benzodiazepine use, complex comorbidities, and adverse effects such as significant hypertension and severe dissociation. Future systematic controlled studies are warranted to establish the efficacy and safety profile of long-term ketamine as maintenance therapy for TRD with suicidal behavior. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.