Open access peer-reviewed chapter

Ketamine Anesthesia in Electroconvulsive Therapy

Written By

Maiko Satomoto

Submitted: 08 October 2021 Reviewed: 23 October 2021 Published: 18 November 2021

DOI: 10.5772/intechopen.101365

From the Edited Volume

Ketamine Revisited - New Insights into NMDA Inhibitors

Edited by Nieves Saiz-Sapena and Manuel Granell-Gil

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Abstract

Electroconvulsive therapy (ECT) is highly effective both Major Depressive Disorder (MDD) and Bipolar Disorder (BD). Ketamine, an antagonist of the N-Methyl-D-aspartate receptor, has been described to have antidepressant properties. There is a hypothesis that ECT performed with anesthesia using ketamine is more effective than conventional ECT. Also, although ECT is the gold standard for BD and MDD, there are questions about which is more effective, ketamine treatment or ECT, and whether ketamine is more effective when used in combination with ECT. In this chapter, we review the current literature on the effectiveness of ECT and ketamine. Furthermore, we discuss whether ketamine can be an alternative treatment to ECT for patients with TRD.

Keywords

  • ketamine
  • electroconvulsive therapy
  • depression
  • side effect
  • cognitive impairment

1. Introduction

Major Depressive Disorder (MDD) and Bipolar Disorder (BD) are very popular psychiatric disorders that affect 10–15% of people in their lifetime. If symptoms do not improve during episodes of depression with at least two types of antidepressants, this condition is referred to as Treatment-Resistant Depression (TRD), which is observed in 12–20% of patients with depression [1]. The gold standard treatment for TRD is Electroconvulsive Therapy (ECT) [2]. ECT is a safe and effective treatment for TRD. Data shows that the efficacy rate is 79%, and the remission rate is 75% when ECT is used for patients with MDD [3]. Various oral treatments have been introduced since the 1990s. Tricyclic and tetracyclic antidepressants had emerged by the 1990s, and second-generation antidepressants such as selective serotonin reuptake inhibitors (SSRI) and serotonin-noradrenaline reuptake inhibitors (SNRI) were introduced at the end of the 1990s. Although the cause of depression is not clear, the monoamine hypothesis attributes depression to a decrease in neurotransmitters such as serotonin and noradrenaline, which are monoamines, and the action mechanism of the antidepressants is often explained based on the monoamine hypothesis. SSRI and SNRI have fewer side effects, such as dry mouth and dysuria, compared with tricyclic antidepressants, and internationally, they are recognized as the standard treatment. However, the availability of many antidepressants does not necessarily mean that the drug therapy for depression is adequate. STAR*D [4], a large-scale clinical trial investigating the efficacy of switching to the next stage of treatment in patients with depression showing inadequate response to antidepressant medication, found that about half of the total population responded to the initial SSRI treatment, with one-third achieving remission; the response and remission rates decreased with each switch to a different treatment.

Remission has been pointed out to be related to social functioning and prognosis, which is emphasized [5] as a therapeutic goal of depression treatment. According to the results of STAR*D [4], the cumulative remission rate is approximately 67% when medication is switched thrice. This finding suggests that a certain number of patients do not show an adequate response even after treatment with multiple antidepressants, and the limited efficacy of standard treatments is a clinical problem.

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2. What is ECT?

Electroconvulsive therapy (ECT) is a treatment method in which generalized seizure activity is induced in the brain through electrical stimulation, producing neurobiological effects to improve clinical symptoms. The history of ECT can be traced back to 1938 when Cerletti U and Bini L of Italy developed a method to induce seizures by passing an electric current through the brain from the scalp on the head, which was the beginning of ECT. Since then, ECT has spread rapidly. Earlier in ECT, an electric current was passed without pretreatment, such as intravenous anesthesia, causing generalized tonic-clonic seizures, feeling of extreme fear experienced by patients, and side effects such as bone fractures or dislocations due to seizures were the problems posed by the treatment. For this reason, ECT was developed, in the 1950s, to pass an electric current without causing seizures of skeletal muscles by keeping patients on mechanical ventilation and administering a combination of anesthetics and muscle relaxants under the supervision of an anesthesiologist.

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3. Indications for ECT

ECT is said to have no absolute contraindications. Relative contraindications include (1) intracranial lesions, (2) increased intracranial pressure, (3) recent myocardial infarction, (4) recent cerebral infarction, (5) unstable aneurysm or vascular malformation, (6) pheochromocytoma, and (7) patients with poor physical condition (physical status of 4 or 5 as per the American Society of Anesthesiologists, i.e., with severe threatening systemic disease or moribund). Although medical history interview (allergies, asthma, and history of surgery), blood biochemical tests, electrocardiogram, chest and abdominal X-rays, head CT, and electroencephalogram are performed and recorded before ECT, an echocardiogram, head MRI, and MRA should also be conducted. The cognitive function should also be evaluated in advance, as postictal delirium and transient cognitive impairment may occur, which are described later. ECT is indicated for psychiatric disorders such as depression, schizophrenia, and mania, and has also been shown to be effective in treating Parkinson’s disease, malignant syndromes, and chronic pain. The effectiveness of ECT differs depending on the subtype of schizophrenia. At the same time, the treatment is effective for catatonic and acute onset paranoia cases, and there is little effect in hebephrenic and chronic cases. The primary use of ECT should be considered in the following situations: (1) severe symptoms, such as the high risk of suicide attempt or extreme agitation; (2) general deterioration of the patient’s condition due to psychiatric symptoms, such as refusing food or catatonic condition; (3) high risk of other forms of treatment, such as in the case of elderly patients or pregnant women; (4) history of ECT treatment with a favorable response; and (5) preference of the patient. The secondary use of ECT may be considered when the patient is resistant to drug therapy or the patient’s tolerability to drug therapy is poor. The indication for ECT is determined based on a combination of diagnosis, symptom type, severity, treatment history, consideration of the expected risks and benefits of ECT with other treatments, and patient’s preference.

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4. Side effects of ECT

The most common side effects of ECT are postictal delirium and transient cognitive impairment. However, the stimulation dose can be adjusted according to the seizure threshold of each patient by using pulse wave therapy devices, which has significantly reduced seizures compared with conventional treatments. Although the parasympathetic nervous system is dominant immediately after an electric current is passed during ECT, the sympathetic nervous system subsequently becomes dominant. Therefore, bradycardia and sinus arrest may temporarily occur early on. Thereafter, tachycardia and elevated blood pressure are observed, and ventricular arrhythmias may also occur. Although tachycardia and elevated blood pressure are transient, patients with a history of hypertension or ischemic heart disease should be intravenously administered antihypertensive drugs. Even with using muscle relaxants in ECT, the masseter muscle contracts when an electric current passes and can damage the teeth and oral cavity. Although dentures are removed to prevent this, and a bite block is used, dental treatment may be required before ECT if the teeth shake significantly. Other side effects include headache, myalgia, nausea, and prolonged convulsions. Manic episodes may also occur in bipolar depression.

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5. Procedure of ECT

ECT is performed in the operating theater under respiratory and circulatory management by an anesthesiologist. In addition to stimulation electrodes and Electroencephalogram (EEG) electrodes (two channels on the left and right) attached to the forehead, Electrocardiogram (ECG) electrodes and Electromyography (EMG) electrodes (on the dorsum of one foot) are attached, the vital signs of the patient are checked, and intravenous anesthesia is administered. When the patient falls asleep, the blood flow to the lower leg with the EMG electrodes is restricted by applying a pressure equal to or more than the systolic blood pressure using the manchette of a sphygmomanometer and a muscle relaxant is administered intravenously. After muscle relaxation is confirmed, a bite block is inserted in the patient’s mouth. After passing an electric current, tonic-clonic seizures are observed only in the lower leg with restricted blood flow. The bag-valve-mask ventilation is used when the patient falls asleep until it is confirmed that the patient has resumed spontaneous breathing. The vital signs are rechecked after the patient is fully awake and taken out from the operating theater. Even after returning to the ward, a monitor is attached to the patient for around 1 hour to check the vital signs. This procedure is performed 2–3 times a week, for a total of 8–12 times.

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6. Drugs commonly used in ECT

Short-acting intravenous anesthetics are used. Propofol and thiopental are commonly used. The higher the dose of the anesthetic drug, the less likely that seizures will occur; hence, the minimum dose of the intravenous anesthetic drug that puts the patient to sleep is administered. The muscle relaxant used is succinylcholine, which is a depolarizing muscle relaxant. Although non-depolarizing muscle relaxants may also be used to reduce myalgia and increased intragastric pressure, their long duration of action may lead to problems such as the need for a muscle relaxant antagonist [6] after ECT and residual muscle relaxation. Anesthesiologists are also aware that hyperventilation can lead to seizures.

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7. Information on ketamine

Although ketamine is an old N-methyl-D-aspartate (NMDA) receptor antagonist, in recent years, the use of subanesthetic doses of ketamine as a therapeutic agent has been reported to have antidepressant effects. Some reports indicate remission rates exceeding 80% with the use of low doses of ketamine [7, 8, 9, 10]. There have also been reports that the response to seizures was good when used as an adjunct to ECT, so we did a comprehensive study of the reports. Ketamine may be used independently or as an adjunct, in addition to propofol or thiopental.

We have cited reference Jankauskas et al., [11], which includes a summary up to 2017. Most studies show that when ketamine is used independently or in combination with non-barbiturates such as propofol at doses of 0.8 mg/kg or more during ECT, there is a faster improvement in symptoms and a significant improvement in depressive symptoms compared with the control group where ketamine is not used [12, 13, 14, 15, 16]. Seizures during ECT are longer in the intravenous anesthesia group with ketamine or ketamine alone than the intravenous anesthesia group without ketamine [14, 17, 18]. Ketamine was observed to significantly improve cognitive function in the original cases of cognitive decline [14]. Some results show a faster recovery in the ketamine group even if there is no change in the outcome [14, 19].

On the other hand, even if ketamine prolongs the duration of seizures, according to some reports, ketamine is not better than other anesthetics in reducing depressive symptoms or improving cognition [16, 20, 21, 22, 23]. The effect of ketamine on the duration of seizures during ECT has been evaluated differently in each study, and the ECT protocols vary from institution to institution making efficacy assessment difficult [11]. The additional problem is that the assessment items (seizure duration, early stage of rapport, or cognitive improvement) do not match.

Since propofol suppresses the disadvantages of ketamine such as agitation, cardiotoxicity, nausea, and psychotomimetic effects, the combination of propofol and ketamine is good as propofol suppresses the disadvantages of ketamine without compromising its efficacy [13, 17]. Ketamine also reduces hypotension, a side effect of propofol, another reason for considering the combination as good [17]. Many reports indicate that the benefits of ketamine are not effective when used in combination with barbiturates due to the anti-seizure action of barbiturates and did not show a reduction effect for depression [12, 16, 20, 24].

Safety concerns with ECT include high rates of hypertension, prolonged QTc interval, transient arrhythmias, confusion or fear, and hallucinations that may occur upon awakening from the anesthetic [12, 13, 17, 20, 25, 26, 27]. The incidence of hallucinations has a positive correlation with the increase in ketamine dose, especially in the dose range of 0.8–2.0 mg/kg [13, 17, 20, 25, 26, 27]. Caution should be exercised when using ketamine in patients with cardiovascular diseases, as the drug increases blood pressure. Caution should also be exercised when using ketamine in patients with a history of psychomimetic episodes, as there is a possibility of psychotogenesis.

Concomitant use of propofol may be considered to mitigate some of these adverse effects [13]. However, the complexity and cost of the medication will increase. Most of the adverse effects such as agitation, cardiotoxicity, nausea, and psychotomimetic effects are temporary [12, 16]. Therefore, an analysis of individual risks and benefits needs to be considered.

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8. Role of ketamine in ECT in recent years

Although studies of varying scales and assessment have continued, some studies have found the addition of ketamine to ECT to be effective [28, 29], and some have found the addition as not effective [30]. We will introduce one such study. A multi-site randomized, placebo-controlled, double-blind trial, “Ketamine-ECT study” was planned at the University of Newcastle in the United Kingdom to investigate whether the adjunctive use of ketamine can attenuate the cognitive impairment caused by ECT [31]. ECT continues to be the gold standard for severe and treatment-resistant depression. However, a significant limitation contributing to the declining use of ECT is its association with cognitive impairment, especially in anterograde and retrograde memory and functional impairment.

On the other hand, preliminary data suggest that ketamine, used either as the sole anesthetic drug or in addition to other anesthetics, may reduce or prevent cognitive impairment after ECT. A hypothesis has been postulated that ketamine protects from excess excitatory neurotransmitter stimulation during ECT through glutamate receptor antagonism. The primary aim of the “ketamine-ECT study” was to investigate whether the adjunctive use of ketamine can attenuate the cognitive impairment caused by ECT. The secondary aim was to examine if ketamine increases the speed of clinical improvement with ECT. The summary of the study is that moderately to severely depressed patients who had been prescribed ECT were randomly grouped on a 1:1 basis to receive either adjunctive ketamine or saline in addition to standard anesthesia for ECT. A 0.5 mg/kg dose of ketamine was administered as a bolus instead of continuous administration. The primary neuropsychological outcome is anterograde verbal memory (Hopkins Verbal Learning Test-Revised delayed recall task) after four ECT treatments. Secondary cognitive outcomes include verbal fluency, autobiographical memory, visuospatial memory, and digitization span. Efficacy was assessed using evaluation by observer and report of subjects on the depressive symptoms by patients.

This randomized trial validated the hypothesis that low doses of ketamine administered with a course of ECT treatment would improve outcomes in depression. We did not find significant evidence for cognitive and efficacy outcomes by administering a dose of 0.5 mg/kg ketamine as an adjunct in patients treated with ECT for depression.

However, the number of subjects was less than the number of patients recruited, which implies that the small to medium benefits and medium to extensive harms of ketamine cannot be ruled out. Therefore, it is not always possible to conclude based on only these results. It is also debated that evaluation in this field is complicated, especially the evaluation of cognitive function after ECT. For example, although patients recover most of the cognitive decline after ECT within a few days to a few weeks after the completion of treatment, it is challenging to accurately measure the recovery of retrograde autobiographical memory, which is the primary concern for patients. Although this paper has been discussed extensively, the study did not indicate that ketamine improved the outcome of depression. However, since treatment-resistant depression still exists and some papers have shown that ketamine is effective, we believe it is worth continuing research by evaluating various subgroups or using an optimal psychological index to determine the efficacy.

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9. Future of ketamine in ECT

As introduced in Section 8, there are more than 130 papers on the adjunctive use of ketamine with ECT; however, only a few are definitive. Although well-conceived studies with sufficient resources are needed, they are not conducted, and the availability of funding is also not likely. Many papers have recognized the efficacy of ketamine with small-scale studies. ECT is an effective treatment method in clinical practice since patients showing resistance to treatment with only oral medication are high at 33%. Memory impairment caused by ECT is a significant problem faced by patients. The condition of patients with depression before ECT treatment varies widely; hence, it is necessary to divide them into subgroups. If there is a possibility that ECT can improve cognitive impairment, we consider that further studies are needed to evaluate the effects of ketamine by dividing patients into more specific subgroups.

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10. Ketamine as an alternative to ECT

As described in Section 8, the decline in cognitive function after the ECT procedure causes significant distress to patients [32]. Unfortunately, additional ECT is sometimes required due to the frequent recurrence of TRD. The recurrence rate of TRD within 6 months of ECT is reported to be between 39% (with continued medication) and 84% (without continued medication) [33]. If patients become aware of their cognitive impairment even once, ECT treatment becomes unbearably painful for them [33]. There is a pressing need to develop a treatment with the same effectiveness as ECT but with fewer side effects and recurrences. Ketamine, an NMDA receptor antagonist, has repeatedly shown an immediate and strong antidepressant effect in patients with MDD [34, 35]. Ketamine demonstrates a positive effect even in patients with severe TRD [36]. Whether ketamine can be an alternative treatment to ECT for patients with TRD is discussed in this section. There are six papers at present [37]. While randomized control trials [38, 39, 40] are discussed in three papers, the other three cover open-label trials [41, 42, 43]. The results suggest that ketamine therapy develops antidepressant effects more quickly than ECT, but perhaps the effect is not sustained compared with ECT. Unlike ECT, cognitive impairment was found to be less with ketamine therapy. The sample size of the studies was limited, followed different treatment protocols, and long-term follow-up was lacking in most trials. The occurrence of assignment bias is high as the trials were not randomized, and performing ECT and ketamine therapy in double-blind trials is difficult. The results of the current studies do not provide convincing evidence to indicate that ketamine therapy is an equally effective alternative to ECT for patients with TRD. If ketamine is used in high doses for chronic cases because of its advantages over ECT during treatment at the initial stage, it may cause memory impairment [44]. Long-term maintenance therapy with ketamine may make patients prone to ketamine-related addiction. This risk should be considered when comparing ketamine therapy to ECT. The reported acute side effects of ketamine therapy are dizziness, headache, blurred vision, body numbness, depersonalization, vertigo, double vision, and nausea. The reasons for discontinuing ketamine were dissociative symptoms, hypertension, and unpleasant experience. The impact of acute and chronic adverse events attributable to ketamine therapy needs to be compared with the common side effects of ECT treatment, such as cognitive impairment, myalgia, arthralgia, headache, and risks associated with general anesthesia. Studies with larger sample sizes and longer follow-up duration are needed.

11. Conclusions

ECT is still the gold standard for severe and treatment-resistant depression patients, but cognitive dysfunction after ECT is the problem. Although the antidepressant effect of ketamine has been attracting attention in recent years, it cannot be said that ketamine is an effective treatment alternative to ECT at this stage. Many studies have shown that adding small amounts of ketamine during ECT is effective with small-scale studies. Although well-conceived studies with sufficient resources are needed, they are not conducted.

Acknowledgments

This work was supported by Grants-in-Aid for Scientific Research (KAKENHI) Grants No. 19 K18308.

Conflict of interest

The author declares no conflict of interest.

References

  1. 1. Mrazek DA, Hornberger JC, Altar CA, Degtiar I. A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013. Psychiatric Services. 2014;65:977-987. DOI: 10.1176/appi.ps.201300059
  2. 2. UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: A systematic review and meta-analysis. Lancet. 2003;361:799-808. DOI: 10.1016/S0140-6736(03)12705-5
  3. 3. Tang YL, Jiang W, Ren YP, Ma X, Cotes RO, McDonald WM. Electroconvulsive therapy in China: Clinical practice and research on efficacy. The Journal of ECT. 2012;28:206-212. DOI: 10.1097/YCT.0b013e31825957b1
  4. 4. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. American Journal of Psychiatry. 2006;163:1905-1917. DOI: 10.1176/ajp.2006.163.11.1905
  5. 5. Rush AJ, Kraemer HC, Sackeim HA, Fava M, Trivedi MH, Frank E, et al. Report by the ACNP Task Force on response and remission in major depressive disorder. Neuropsychopharmacology. 2006;31:1841-1853. DOI: 10.1038/sj.npp.1301131
  6. 6. Kadoi Y, Nishida A, Saito S. Recovery time after sugammadex reversal of rocuronium-induced muscle relaxation for electroconvulsive therapy is independent of cardiac output in both young and elderly patients. The Journal of ECT. 2013;29:33-36. DOI: 10.1097/YCT.0b013e31826cf348
  7. 7. aan het Rot M, Collins KA, Murrough JW, Perez AM, Reich DL, Charney DS, et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biological Psychiatry. 2010;67:139-145. DOI: 10.1016/j.biopsych.2009.08.038
  8. 8. Rasmussen KG, Lineberry TW, Galardy CW, Kung S, Lapid MI, Palmer BA, et al. Serial infusions of low-dose ketamine for major depression. Journal of Psychopharmacology. 2013;27:444-450. DOI: 10.1177/0269881113478283
  9. 9. Shiroma PR, Johns B, Kuskowski M, Wels J, Thuras P, Albott CS, et al. Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression. Journal of Affective Disorders. 2014;155:123-129. DOI: 10.1016/j.jad.2013.10.036
  10. 10. Naughton M, Clarke G, O'Leary OF, Cryan JF, Dinan TG. A review of ketamine in affective disorders: Current evidence of clinical efficacy, limitations of use and pre-clinical evidence on proposed mechanisms of action. Journal of Affective Disorders. 2014;156:24-35. DOI: 10.1016/j.jad.2013.11.014
  11. 11. Jankauskas V, Necyk C, Chue J, Chue P. A review of ketamine's role in ECT and non-ECT settings. Neuropsychiatric Disease and Treatment. 2018;14:1437-1450. DOI: 10.2147/NDT.S157233
  12. 12. Jarventausta K, Chrapek W, Kampman O, Tuohimaa K, Björkqvist M, Häkkinen H, et al. Effects of S-ketamine as an anesthetic adjuvant to propofol on treatment response to electroconvulsive therapy in treatment-resistant depression: A randomized pilot study. The Journal of ECT. 2013;29:158-161. DOI: 10.1097/YCT.0b013e318283b7e9
  13. 13. Wang X, Chen Y, Zhou X, Liu F, Zhang T, Zhang C. Effects of propofol and ketamine as combined anesthesia for electroconvulsive therapy in patients with depressive disorder. The Journal of ECT. 2012;28:128-132
  14. 14. Yoosefi A, Sepehri AS, Kargar M, Akhondzadeh S, Sadeghi M, Rafei A, et al. Comparing effects of ketamine and thiopental administration during electroconvulsive therapy in patients with major depressive disorder: A randomized, double-blind study. The Journal of ECT. 2014;30:15-21. DOI: 10.1097/YCT.0b013e31824d1d02
  15. 15. Rybakowski JK, Bodnar A, Krzywotulski M, Chlopocka-Wozniak M, Michalak M, Rosada-Kurasinska J, et al. Ketamine anesthesia, efficacy of electroconvulsive therapy, and cognitive functions in treatment-resistant depression. The Journal of ECT. 2016;32(3):164-168. DOI: 10.1097/YCT.0000000000000317
  16. 16. Zhong X, He H, Zhang C, Wang Z, Jiang M, Li Q , et al. Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression. Journal of Affective Disorders. 2016;201:124-130. DOI: 10.1016/j.jad.2016.05.011
  17. 17. Yalcin S, Aydogan H, Selek S, Kucuk A, Yuce HH, Karababa F, et al. Ketofol in electroconvulsive therapy anesthesia: Two stones for one bird. Journal of Anesthesia. 2012;26:562-567. DOI: 10.1007/s00540-012-1378-6
  18. 18. Erdil F, Begec Z, Kayhan GE, Yologlu S, Ersoy MO, Durmus M. Effects of sevoflurane or ketamine on the QTc interval during electroconvulsive therapy. Journal of Anesthesia. 2015;29:180-185. DOI: 10.1007/s00540-014-1899-2
  19. 19. Salehi B, Mohammadbeigi A, Kamali AR, Taheri-Nejad MR, Moshiri I. Impact comparison of ketamine and sodium thiopental on anesthesia during electroconvulsive therapy in major depression patients with drug-resistant; a double-blind randomized clinical trial. Annals of Cardiac Anaesthesia. 2015;18:486-490. DOI: 10.4103/0971-9784.166444
  20. 20. Kuscu OO, Karacaer F, Biricik E, Gulec E, Tamam L, Gunes Y. Effect of ketamine, thiopental and ketamine-thiopental combination during electroconvulsive therapy for depression. Turkish Journal of Anaesthesiology and Reanimation. 2015;43:313-317. DOI: 10.5152/TJAR.2015.92668
  21. 21. Fernie G, Currie J, Perrin JS, Stewart CA, Anderson V, Bennett DM, et al. Ketamine as the anaesthetic for electroconvulsive therapy: The KANECT randomised controlled trial. The British Journal of Psychiatry. 2017;210:422-428. DOI: 10.1192/bjp.bp.116.189134
  22. 22. Rasmussen KG, Kung S, Lapid MI, Oesterle TS, Geske JR, Nuttall GA, et al. A randomized comparison of ketamine versus methohexital anesthesia in electroconvulsive therapy. Psychiatry Research. 2014;215:362-365. DOI: 10.1016/j.psychres.2013.12.027
  23. 23. Loo CK, Katalinic N, Garfield JB, Sainsbury K, Hadzi-Pavlovic D, Mac-Pherson R. Neuropsychological and mood effects of ketamine in electroconvulsive therapy: A randomised controlled trial. Journal of Affective Disorders. 2012;142:233-240. DOI: 10.1016/j.jad.2012.04.032
  24. 24. Abdallah CG, Fasula M, Kelmendi B, Sanacora G, Ostroff R. Rapid antidepressant effect of ketamine in the electroconvulsive therapy setting. The Journal of ECT. 2012;28:157-161. DOI: 10.1097/YCT.0b013e31824f8296
  25. 25. Erdil F, Ozgul U, Colak C, Cumurcu B, Durmus M. Effect of the addition of ketamine to sevoflurane anesthesia on seizure duration in electroconvulsive therapy. The Journal of ECT. 2015;31:182-185. DOI: 10.1097/YCT.0000000000000225
  26. 26. Lenze EJ, Farber NB, Kharasch E, Schweiger J, Yingling M, Olney J, et al. Ninety-six hour ketamine infusion with co-administered clonidine for treatment-resistant depression: A pilot randomised controlled trial. The World Journal of Biological Psychiatry. 2016;17:230-238. DOI: 10.3109/15622975.2016.1142607
  27. 27. Ibrahim L, Diazgranados N, Franco-Chaves J, Schweiger J, Yingling M, Olney J, et al. Course of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: Results from a 4-week, double-blind, placebo-controlled study. Neuropsychopharmacology. 2012;37:1526-1533. DOI: 10.1038/npp.2011.338
  28. 28. Altinay M, Karne H, Anand A. Administration of sub-anesthetic dose of ketamine and electroconvulsive treatment on alternate week days in patients with treatment resistant depression: A double blind placebo controlled trial. Psychopharmacology Bulletin. 2019;49:8-16
  29. 29. Zhang M, Rosenheck R, Lin X, Li Q , Zhou Y, Xiao Y, et al. A randomized clinical trial of adjunctive ketamine anesthesia in electro-convulsive therapy for depression. Journal of Affective Disorders. 2018;227:372-378. DOI: 10.1016/j.jad.2017.11.034
  30. 30. Gamble JJ, Bi H, Bowen R, Weisgerber G, Sanjanwala R, Prasad R, et al. Ketamine-based anesthesia improves electroconvulsive therapy outcomes: A randomized-controlled study. Canadian Journal of Anesthesia. 2018;65:636-646. DOI: 10.1007/s12630-018-1088-0
  31. 31. Anderson IM, Blamire A, Branton T, Clark R, Downey D, Dunn G, et al. Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (ketamine-ECT): A multicentre, double-blind, randomised, parallel-group, superiority trial. The Lancet Psychiatry. 2017;4:365-377. DOI: 10.1016/S2215-0366(17)30077-9
  32. 32. Verwijk E, Obbels J, Spaans HP, Sienaert P. Doctor, will I get my memory back? Electroconvulsive therapy and cognitive side-effects in daily practice. Tijdschrift Voor Psychiatrie. 2017;59:632-637
  33. 33. Sackeim HA, Haskett RF, Mulsant BH, Thase ME, Mann JJ, Pettinati HM, et al. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: A randomized controlled trial. JAMA. 2001;285:1299-1307. DOI: 10.1001/jama.285.10.1299
  34. 34. Han Y, Chen J, Zou D, Zheng P, Li Q , Wang H, et al. Efficacy of ketamine in the rapid treatment of major depressive disorder: A meta-analysis of randomized, double-blind, placebo-controlled studies. Neuropsychiatric Disease and Treatment. 2016;12:2859-2867. DOI: 10.2147/NDT.S117146
  35. 35. Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, et al. Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: A meta-analysis of efficacy, safety and time trajectories. Psychological Medicine. 2016;46:1459-1472. DOI: 10.1017/S0033291716000064
  36. 36. Ruberto VL, Jha MK, Murrough JW. Pharmacological treatments for patients with treatment-resistant depression. Pharmaceuticals (Basel). 2020;13:116. DOI: 10.3390/ph13060116
  37. 37. Veraart JKE, Smith-Apeldoorn SY, Spaans HP, Kamphuis J, Schoevers RA. Is ketamine an appropriate alternative to ECT for patients with treatment resistant depression? A systematic review. Journal of Affective Disorders. 2021;281:82-89. DOI: 10.1016/j.jad.2020.11.123
  38. 38. Ghasemi M, Kazemi MH, Yoosefi A, Ghasemi A, Paragomi P, Amini H, et al. Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder. Psychiatry Research. 2014;215:355-361. DOI: 10.1016/j.psychres.2013.12.008
  39. 39. Kheirabadi G, Vafaie M, Kheirabadi D, Mirlouhi Z, Hajiannasab R. Comparative effect of intravenous ketamine and electroconvulsive therapy in major depression: A randomized controlled trial. Advanced Biomedical Research. 2019;8:25. DOI: 10.4103/abr.abr_166_18
  40. 40. Sharma RK, Kulkarni G, Kumar CN, Arumugham SS, Sudhir V, Mehta UM, et al. Antidepressant effects of ketamine and ECT: A pilot comparison. Journal of Affective Disorders. 2020;276:260-266. DOI: 10.1016/j.jad.2020.07.066
  41. 41. Allen AP, Naughton M, Dowling J, Walsh A, Ismail F, Shorten G, et al. Serum BDNF as a peripheral biomarker of treatment-resistant depression and the rapid antidepressant response: A comparison of ketamine and ECT. Journal of Affective Disorders. 2015;186:306-311. DOI: 10.1016/j.jad.2015.06.033
  42. 42. Basso L, Bönke L, Aust S, Gärtner M, Heuser-Collier I, Otte C, et al. Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients. Journal of Psychiatric Research. 2020;123:1-8. DOI: 10.1016/j.jpsychires.2020.01.002
  43. 43. Loureiro JRA, Leaver A, Vasavada M, Sahib AK, Kubicki A, Joshi S, et al. Modulation of amygdala reactivity following rapidly acting interventions for major depression. Human Brain Mapping. 2020;41(7):1699-1710. DOI: 10.1002/hbm.24895
  44. 44. Morgan CJ, Dodds CM, Furby H, Pepper F, Fam J, Freeman TP, et al. Long-term heavy ketamine use is associated with spatial memory impairment and altered hippocampal activation. Frontiers in Psychiatry. 2014;5:149. DOI: 10.3389/fpsyt.2014.00149

Written By

Maiko Satomoto

Submitted: 08 October 2021 Reviewed: 23 October 2021 Published: 18 November 2021