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LETTER TO THE EDITOR
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Intravenous ketamine in refractory depression


 Department of Psychiatry, Dr. D. Y. Patil Medical College, Hospital and Research Center, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India

Date of Submission09-Jul-2021
Date of Decision11-Jul-2021
Date of Acceptance12-Jul-2021

Correspondence Address:
Suprakash Chaudhury,
Department of Psychiatry, Dr. D. Y. Patil Medical College, Hospital and Research Center, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjdrdypu.mjdrdypu_549_21



How to cite this URL:
Gandhi S, Chaudhari B, Chaudhury S. Intravenous ketamine in refractory depression. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2022 Dec 1]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=336824



Dear Sir,

Major depressive disorder (MDD) is often associated with partial recovery, frequent relapses, and lasting psychosocial and functional impairment. At least 20% of all depressed patients do not respond adequately to several antidepressant drugs.[1] Glutamate is postulated to play a role in mood modulation. Ketamine, a nonnoncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, in early trials was rapidly effective in both MDD and treatment-resistant depression.

A 37-year-old married male, singer by profession, presented to the psychiatry OPD with chief complaints of persistent low mood, decreased interest in day-to-day activities and pleasurable activities, reduced libido, and disturbed sleep and appetite. All his complaints started 3 years back without any stressor and gradually worsened over a time. He had consulted various psychiatrists but had minimal improvement. When he presented to our psychiatry OPD, he had been sequentially treated with paroxetine, amitryptiline, venlafaxine in adequate doses. He was also tried with the combination of antidepressants along with adjuvant lithium and atypical antipsychotics but showed very minimal improvement in depressive symptoms. He was not willing for electroconvulsive therapy. Hence, finally, it was decided to treat him with ketamine infusion therapy. He was given six cycles of intravenous 0.5 mg/kg ketamine on alternate days. He showed significant clinical improvement and did not suffer from any adverse effects due to ketamine. After the sixth infusion, the mean reduction in MADRS scores was 85%. He continued to maintain improvement in his condition on follow-up after a month.

Currently, available antidepressants acting on monoaminergic system have delayed onset of action and limitations in clinical efficacy. In the last few decades, glutamate has been scrutinized as a target of antidepressant therapy. There have been some case reports open-label studies, and randomized double-blind controlled studies which reported the efficacy of ketamine, a noncompetitive antagonist of the NMDA receptors, in treatment-resistant depression.[2],[3],[4],[5] These studies have demonstrated good response and remission rates, good effect on depressive cognition as well as suicidal cognition, and rapid onset of action with ketamine infusion therapy.

Ketamine for the treatment of depression is usually administered in the dose of 0.5 mg/kg, but some patients may respond to doses as low as 0.1 mg/kg, and others may require up to 0.75 mg/kg. The duration of ketamine infusion therapy is conventionally 40 min. While the drug is administered most commonly by the intravenous route, the safety and efficacy of oral, sublingual, intranasal, and intramuscular, routes have been established.[6] The psychotomimetic and dissociative symptoms may complicate the clinical outcome of ketamine infusion therapy.[7] However, other side effects such as dizziness, dry mouth, poor coordination, poor concentration, and hemodynamic changes after ketamine infusion can be the cause of concern.[8] Although the patient presented here showed significant clinical improvement and no adverse effects the ketamine infusion therapy still has a long way to go before its acceptance as treatment modality for the depressive disorder because of the lack long-term efficacy and side effects.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Petersen T, Gordon JA, Kant A, Fava M, Rosenbaum JF, Nierenberg AA. Treatment resistant depression and axis I co-morbidity. Psychol Med 2001;31:1223-9.  Back to cited text no. 1
    
2.
Segmiller F, Rüther T, Linhardt A, Padberg F, Berger M, Pogarell O, et al. Repeated S-ketamine infusions in therapy resistant depression: A case series. J Clin Pharmacol 2013;53:996-8.  Back to cited text no. 2
    
3.
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. J Affect Disord 2014;155:123-9.  Back to cited text no. 3
    
4.
Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, Collins KA, et al. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry 2013;74:250-6.  Back to cited text no. 4
    
5.
Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: A two-site randomized controlled trial. Am J Psychiatry 2013;170:1134-42.  Back to cited text no. 5
    
6.
Andrade C. Ketamine for depression, 4: In what dose, at what rate, by what route, for how long, and at what frequency? J Clin Psychiatry 2017;78:e852-7.  Back to cited text no. 6
    
7.
Katalinic N, Lai R, Somogyi A, Mitchell PB, Glue P, Loo CK. Ketamine as a new treatment for depression: A review of its efficacy and adverse effects. Aust N Z J Psychiatry 2013;47:710-27.  Back to cited text no. 7
    
8.
Andrade C. Ketamine for depression, 1: Clinical summary of issues related to efficacy, adverse effects, and mechanism of action. J Clin Psychiatry 2017;78:e415-9.  Back to cited text no. 8
    




 

 
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