Blog

Serotonin syndrome after electroconvulsive therapy for refractory depression

  • Post author:
  • Reading time:21 mins read

Related Resources

Note: Claims that ECT is safe and effective are common in electroconvulsive therapy study introductions. These are assertions without a scientific basis. See Electroconvulsive Therapy for Depression: A Review of the Quality of ECT versus Sham ECT Trials and Meta-Analyses and Thymatron System IV Manual page 7, section 1

Case Report

Serotonin syndrome after electroconvulsive therapy for refractory depression

Full article: Serotonin syndrome after electroconvulsive therapy for refractory depression (tandfonline.com)

Abstract

Abstract

Serotonin syndrome is a toxicological entity with potential morbidity and mortality if unrecognized and untreated. Toxicity can occur after dose or increase or initiation of additional serotonergic medication, but can also be idiopathic. We report a case in which serotonin syndrome occurred after electroconvulsive therapy in the absence of escalation of medical therapy, and theorize a pathophysiologic mechanism based on basic science of blood–brain barrier integrity change after ECT.

Introduction

An estimated 16.2 million adults in the United States experience major depression and about 50% receive medical therapy [1Bose J, Hedden SL, Lipari RN, Park-Lee E. Key substance use and mental health indicators in the United States: results from the 2015 National Survey on Drug Use and Health (HHS Publication No. 2017). [Google Scholar]].

Most antidepressant medications act by increasing serotonin (5-HT) signaling, either via enhancing serotonin secretion, preventing re-uptake of synaptic serotonin, or hindering breakdown of the neurotransmitter.

This hyperserotonergic state places patients at risk of developing serotonin syndrome, a condition comprised of altered mental status, tremor, clonus, hyperreflexia, seizures, and autonomic instability. A detailed discussion of its pathophysiology, diagnosis, and management exists elsewhere [2Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112–1120. [Crossref], [Web of Science ®], [Google Scholar]].

Patients with medication resistant major depressive disorder, often with debilitating psychotic features, may be candidates for ECT once they fail a reasonable trial of antidepressants, and combination therapies.

Under general anesthesia, patients receive a cerebral electric stimulus above seizure threshold. Electroconvulsive therapy produces temporary retrograde and anterograde amnesia, but serotonin syndrome is not a known adverse event of ECT.

The body of scientific literature describes three cases that feature strong temporal association between ECT and onset of serotonin syndrome [35 Okamoto N, Sakamoto K, Yamada M. Transient serotonin syndrome by concurrent use of electroconvulsive therapy and selective serotonin reuptake inhibitor: a case report and review of the literature.

Case Rep Psychiatry. 2012;215214:1–3. DOI: 10.1155/2012/215214 [Crossref], [Google Scholar]

Cheng Y-C, Liang C-M, Liu H-C. Serotonin syndrome after electroconvulsive therapy in a patient on trazodone, bupropion, and quetiapine: a case report.

Clin Neuropharmacol. 2015;38(3):112–113. [Crossref], [Web of Science ®], [Google Scholar]Deuschle M, Bohringer A, Meyer-Lindenberg A, Sartorius A. Electroconvulsive therapy induces transient sensitivity for a serotonin syndrome: a case report.

Pharmacopsychiatry. 2017;50(1):41–42. [Crossref], [Web of Science ®], [Google Scholar]].

Case

A 56-year-old woman with pertinent past medical history of depression, excessive fatigue, and hypothyroidism whose medication regimen included lamotrigine 400 mg daily, levothyroxine 125 mcg daily, mirtazapine 15 mg at bedtime, and venlafaxine 450 mg daily underwent ECT due to poorly controlled symptoms.

She remained on these medications for the past 2 years with last dosage adjustment 4 months prior to her presentation. She had not previously experienced psychotic features with her depression.

On day 0, the patient received ECT under general anesthesia including labetalol 20 mg IV, glycopyrrolate 0.2 mg IV, rocuronium 2.5 mg IV, succinylcholine chloride 100 mg IV, and methohexital 100 mg IV.

After awaking, the patient began feeling restless and had insomnia. Her symptoms worsened the on day 1 and she developed subjective akathisia, but did not seek care.

She was again unable to sleep, and her son found her sitting on her couch with confusion and restlessness on day 2.

He brought her to the ECT suite for her appointment, but the medical staff referred her to the emergency department (ED) for medical clearance to facilitate psychiatric evaluation.

Upon arrival in the ED, she was tachycardic (126 bpm, sinus), hypertensive (160/87 mmHg), mildly tachypneic (20 rpm), and euthermic (37.2 °C). The physical exam revealed mydriasis, psychomotor agitation with restlessness but no aggression, and verbal perseverance.

She was oriented to person and place only, mildly diaphoretic, and able to follow basic commands. The initial medical provider did not document clonus, tremor, hyperreflexia, or nystagmus as present or absent.

Cerebral computed tomography was grossly normal, and laboratory evaluation showed normal serum electrolyte concentrations with mildly depressed bicarbonate (22 mEq/L), normal complete blood count, normal thyroid stimulating hormone (2.90 mIU/L), normal lactate (1.0 mEq/L), and negative urine drug immunoassay. An electrocardiogram featured sinus tachycardia at 119 bpm with the following electrical intervals: PR 136 ms, QRS 105 ms, and QT/QTc 340 ms/478 ms.

The initial medical provider suspected worsening depression with psychotic features or delirium from sleep deprivation.

A psychiatry consultant recommended trazodone 50 mg by mouth at bedtime in addition to her home dose of mirtazapine to help the patient re-establish a circadian rhythm. The patient remained in the ED overnight.

The following day, the medical team noted the patient was diaphoretic with worsening confusion, and noted spontaneous rhythmic movements in her lower extremities. The treating physician consulted a medical toxicologist.

On evaluation by the medical toxicologist, the physical exam revealed diaphoresis and mydriasis (6 mm) without nystagmus or ocular clonus. She was hyperreflexic in all extremities, had non-extinguishable ankle clonus and patellar clonus, as well as positive Hoffman’s reflex.

The patient satisfied Hunter Serotonin Toxicity Criteria [6Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96(9):635–642. [Crossref], [Web of Science ®], [Google Scholar].

She received lorazepam 2 mg IV and the medical provider discontinued all serotonergic drugs. The patient required two additional lorazepam 1 mg IV doses over the subsequent 5 h.

The patient’s symptoms resolved over the subsequent day, and she transitioned from the intensive care unit to the medical floor where she awaited placement to an inpatient psychiatric unit for further treatment of her depression.

Her psychiatric provider discontinued lamotrigine and venlafaxine, but continued mirtazapine. The patient underwent repeat ECT 1 week after initial presentation without further complications.

References

  • Bose J, Hedden SL, Lipari RN, Park-Lee E. Key substance use and mental health indicators in the United States: results from the 2015 National Survey on Drug Use and Health (HHS Publication No. 2017). [Google Scholar]
  • Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112–1120. [Crossref], [Web of Science ®], [Google Scholar]
  • Okamoto N, Sakamoto K, Yamada M. Transient serotonin syndrome by concurrent use of electroconvulsive therapy and selective serotonin reuptake inhibitor: a case report and review of the literature. Case Rep Psychiatry. 2012;215214:1–3. DOI: 10.1155/2012/215214 [Crossref], [Google Scholar]
  • Cheng Y-C, Liang C-M, Liu H-C. Serotonin syndrome after electroconvulsive therapy in a patient on trazodone, bupropion, and quetiapine: a case report. Clin Neuropharmacol. 2015;38(3):112–113. [Crossref], [Web of Science ®], [Google Scholar]
  • Deuschle M, Bohringer A, Meyer-Lindenberg A, Sartorius A. Electroconvulsive therapy induces transient sensitivity for a serotonin syndrome: a case report. Pharmacopsychiatry. 2017;50(1):41–42. [Crossref], [Web of Science ®], [Google Scholar]
  • Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96(9):635–642. [Crossref], [Web of Science ®], [Google Scholar]
  • Adan-Manes J, Novalbos J, Lopez-Rodriguez R, Ayuso-Mateos JL, Abad-Santos F. Lithium and venlafaxine interaction: a case of serotonin syndrome. J Clin Pharm Ther. 2006;31(4):397–400. [Crossref], [Web of Science ®], [Google Scholar]
  • Shyr MH, Tsai TH, Yang CH, Chen HM, Ng HF, Tan PP. Propofol anesthesia increases dopamine and serotonin activities at the somatosensory cortex in rats: a microdialysis study. Anesth Analg. 1997;84(6):1344–1348. [Crossref], [Web of Science ®], [Google Scholar]
  • Fosse R, Read J. Electroconvulsive treatment: hypotheses about mechanisms of action. Front Psychiatry. 2013;4:94. [Crossref], [Google Scholar]
  • Markianos M, Hatzimanolis J, Lykouras L. Serotonergic and dopaminergic neuroendocrine responses of male depressive patients before and after a therapeutic ECT course. Eur Arch Psychiatry Clin Neurosci. 2002;252(4):172–176. [Crossref], [Web of Science ®], [Google Scholar]
  • Shapira B, Newman ME, Gelfin Y, Lerer B. Blunted temperature and cortisol responses to ipsapirone in major depression: lack of enhancement by electroconvulsive therapy. Psychoneuroendocrinology. 2000;25(5):421–438. [Crossref], [Web of Science ®], [Google Scholar]
  • Zimmermann R, Schmitt H, Rotter A, Sperling W, Kornhuber J, Lewczuk P. Transient increase of plasma concentrations of amyloid beta peptides after electroconvulsive therapy. Brain Stimul. 2012;5(1):25–29. [Crossref], [Web of Science ®], [Google Scholar]
  • Awasthi PK, Shanker K, Gulati A, Dhawan KN, Bhargava KP. Increased permeability of blood brain barrier after electro-convulsive shocks (ECS). Pharmacol Res Commun. 1982;14(10):983–992. [Crossref], [Google Scholar]
  • Mander AJ, Whitfield A, Kean DM, Smith MA, Douglas RH, Kendell RE. Cerebral and brain stem changes after ECT revealed by nuclear magnetic resonance imaging. Br J Psychiatry. 1987;151:69–71. [Crossref], [Web of Science ®], [Google Scholar]