Introduction Depression is a serious common disease characterized by mood disorders, with an approximate prevalence of 15%- 25%. In the past, depression was considered a short-term issue, but today it is a disease with a high recurrence rate in many patients. The probability of the second occurrence of major depression after the first one is about 50%, and this probability increases from 80% to about 90% in the next episodes (1). Major depressive disorder (MDD) occurs during the periods of depression with no recorded history of mixed or hypomanic episodes (2). This disorder can lead to severe functional disorder, disability, and relapse and sometimes can cause a chronic disorder, with a 15% risk of suicide (3). The prevalence of suicidal attempts and self-harm in this disorder is relatively high, reaching 47% in patients who refer to emergency departments of hospitals. Interestingly, this number increased from 0.8 to 1.5 per 1000 people in 2012 in the United States. Suicidal ideation in MDD patients is an emergency and serious clinical condition that must be carefully considered and immediately treated (4, 5). The importance of this issue has been reflected in a recent study conducted on the effect of ketamine (KET) on suicidal ideation in patients with MDD. In this study, 74 cases of patients had a very short-term decision- making ability. Moreover, recognizing and treating the risk factors were found to be the key factors in preventing suicide (6). Because most of the patients were young and elderly (but in their active years of life), the rate of mortality was high (7). Over the past five decades, the drugs and medicines developed to cure depression required a long time to be effective (minimum of 2 to 4 weeks) and for most of the patients, it was not possible to tolerate the symptom of these drugs. Considering the ineffectiveness of the treatment with those drugs, further The Effect of Intravenous Ketamine on Suicidal Ideation in Depressed Patients: A Randomized Clinical Trial Farah Moayedi 1 ID , Ali Massoudifar 2 ID , Sholeh Namazi 2 ID , Hossein Mirzaei Zadeh 3 , Seyed Hamzeh Seddigh 2* ID , Saeed Hosseini Teshnizi 4 ID 1 Tobacco and Health Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran 2 Department of Psychiatry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran 3 Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran 4 Department of Community Medicine, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran © 2023 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Major depressive disorder (MDD) generally occurs together with depression in patients with no history of manic, mixed, or hypomanic episodes. The suicidal ideation in MDD patients is very common and can potentially be considered an emergency circumstance in many cases. Among the developed drugs and medicines, ketamine (KET) is a potential option to treat patients with MDD. This study aims at investigating the effect of KET on the treatment of suicidal ideation and the reduction of the intensity of symptoms in patients suffering from MDD. Materials and Methods: This randomized double-blind clinical trial was performed on 30 patients who suffered from MDD and had suicidal ideation at Ibn Sina Hospital, Bandar Abbas, Iran, during 2016-2017. The patients were divided into two groups: the KET group which received 0.5 mg/kg of intravenous (IV) KET diluted in 500 mL of normal saline over 30 minutes and the control group which received 500 mL of normal saline without KET over 30 minutes. Results: According to the statistical analysis, 24 hours after the intervention, suicidal ideation score reached 2.53 and 20.6 in the KET and control groups, respectively. In fact, KET caused a significant reduction in the score of the suicidal ideation (SSI) (SSI < 4) in comparison with the control group (P < 0.001). Conclusion: It was observed that KET can play a key role in the treatment of depression disorders, especially severe and life-threatening forms that require immediate intervention, such as the use of electroconvulsive therapy. Keywords: Depressive disorder, Ketamine, Suicidal ideation, Injection, Double-blind study *Correspondence to Seyed Hamzeh Seddigh, Email: dr.seddigh@gmail. com Received: July 22, 2022, Accepted: November 5, 2022, ePublished: December, 7 2022 Disease and Diagnosis Original Article 10.34172/ddj.2023.437 Dis Diagn. 2023; 12(3):106-111 doi