Medication management during electroconvulsant therapy

Figures & data

Table 1 Medications during the ECT procedure

Anesthetic induction agents	Methohexital
	Thiopental
	Propofol
	Etomidate
	Ketamine
Neuromuscular blocking agents	Succinylcholine (suxamethonium)
	Rocuronium
	Atracurium
	Mivacurium
Antihypertensives	β-blockers (atenolol, esmolol, and labetalol)
	Calcium channel blockers (nifedipine and nicardipine)
Anticholinergic agents	Glycopyrrolate
	Atropine
Narcotics	Fentanyl
	Remifentanyl
	Alfentanyl

Abbreviation: ECT, electroconvulsive therapy.

Table 2 Drug interactions reported in patients undergoing ECT

Class	Evidence	Possible undesired effect	Management strategies
Anticonvulsants/mood stabilizers
Lithium^Citation6,Citation29^–^Citation31	• Combination has a significant risk of delirium, prolonged seizures, toxic lithium levels, and prolonged neuromuscular blockade • Combination not an absolute contraindication. In certain emergencies where the benefits clearly outweigh the risks, combined therapy could be considered • Case reports in elderly patients indicate that only 24 hours of holding lithium therapy might result in a lithium level sufficient to contribute to delirium after ECT	• Delirium, postictal confusion (the elderly may be at increased risk) • Prolonged seizure duration • Increased lithium levels • Prolonged action of neuromuscular blocking agents (eg, succinylcholine) • Potential serotonin syndrome	• Avoid combination if possible • If lithium cannot be discontinued, give at a dose to maintain a blood level in the lowest therapeutic range and/or hold day before ECT • If patient is already taking lithium without clear benefit, stop lithium before ECT. A washout period is unnecessary unless high blood level is present • If lithium has provided clear benefit, lithium can be continued during index ECT, with close monitoring for unwanted adverse effects at the lowest possible therapeutic level • Alternatively, substitute lithium for another mood stabilizer (eg, atypical antipsychotic) to provide protection against mania while ECT is being given for depression • Nondepolarizing neuromuscular blockers should be administered in incremental and reduced doses and titrated to the degree of block required
VPA^Citation14,Citation32^–^Citation34	• Case reports of difficulty in eliciting seizures with patients on VPA • Possible drug–drug interaction competing for protein binding, which can elevate VPA levels • Decrease in the propofol dose required to induce anesthesia during ECT in the presence of VPA	• Seizure inhibition or difficulty in eliciting adequate seizures during ECT • Theoretically, the anticonvulsant activity of VPA may interact with the efficacy of ECT	• Dose reduction or withholding doses (eg, the morning of, or the evening or morning prior to the ECT procedure) • Changing the anesthetic regimen (addition of remifentanyl to a lower dose of methohexital, or etomidate instead of methohexital), to produce adequate seizures
CBZ^Citation14,Citation32,Citation33	• Case reports show mixed results. Some indicate no negative effect of CBZ on ECT, and others report difficulty in eliciting seizures • CBZ–ECT group compared to control group had a shorter duration of seizures and a higher stimulus dose when unilateral treatments were used • Development of moderately severe postictal confusion has also been reported • CBZ may prolong the action of succinylcholine (few clinical implications) • Long-term CBZ demonstrated resistance to nondepolarizing neuromuscular blockers (except mivacurium)	• Seizure inhibition • Accelerated recovery and need for increased doses to achieve complete neuromuscular block (induce a mild upregulation of neuromuscular acetylcholine)	• Dose reduction or withholding doses (eg, the morning of, or the evening or morning prior to the ECT procedure) • Neuromuscular blockade: if suxamethonium is contraindicated, mivacurium seems to be the preferred neuromuscular blocker in patients receiving CBZ therapy
LTG^Citation14,Citation32,Citation34,Citation35	• Case reports/series show minimal or no influence on seizures and/or seizure duration • Interaction with halothane; reducing effect of LTG on glutamate release, either at the receptor or via effects at the inactivated sodium channel • ECT attenuates the inhibitory dose-dependent effects of LTG on synaptic transmission at a low frequency. Clinical significance remains unknown	• Theoretically, seizure inhibition	• None have been recommended
Others: gabapentin^Citation14,Citation32,Citation34 and topiramate^Citation36	• No complications were found in two case reports using gabapentin • No interactions have as yet been reported between gabapentin or topiramate and the anesthetics used for ECT • The use of topiramate for post-ECT headaches did not result in adverse ECT outcomes	• Theoretically, seizure inhibition	• None have been recommended
Antidepressants
MAOI^Citation4,Citation14,Citation37^–^Citation39	• No evidence of an interaction between ECT and MAOI use • A prospective study looked at the risks associated with the combination of MAOIs and ECT, no differences between the study and control groups were reported • Ketamine should be avoided as it causes sympathetic stimulation. Propofol and etomidate can be used safely with MAOIs	• Theoretically, risk of hypertensive crisis if combined with indirect acting sympathomimetics	• Usual recommendation for the combination of MAOI with other medications should be provided to avoid hypertensive crises • If the MAOI has not been effective, a cautious approach when discontinuing the MAOI before ECT is recommended. There is no need for a washout period before starting ECT • If the medication has been helpful, the MAOI can be continued. Alternatively, patients could be switched to a reversible MAOI (eg, moclobemide) as it carries a decreased risk
TCA^Citation4,Citation6,Citation14,Citation39,Citation40	• Retrospective review of the literature found that the use of TCAs in combination with ECT was associated with better outcomes and shorter total seizure time than with ECT alone • No differences were found in the measures of confusion and cardiac adverse effects, and there was even a trend toward fewer adverse effects in the groups receiving the ECT and TCA combination	• Theoretically, reduced seizure threshold and an increased risk of cardiotoxicity • Chronic therapy with TCAs depletes cardiac catecholamines, potentiating the cardiac depressant effects of anesthetic agents	• The TCA dose should be decreased if possible to minimize the likelihood of an exaggerated hypertensive response during ECT • Abrupt withdrawal of TCAs should be avoided because of the risk of mainly cholinergic symptoms • Best avoid TCA use in the elderly and in those with cardiac conditions
Others^Citation1,Citation4,Citation14,Citation39^–^Citation45	• Minimal effect on ECT-related seizure duration has been reported with SSRIs, SNRIs, or trazodone • Possibility of increased risk of asystole with venlafaxine (SNRI) at doses >300 mg/d • Status epilepticus has been reported with concomitant use of bupropion during ECT • Serotonin syndrome has been reported with paroxetine and fluoxetine	• Theoretically, reduced seizure threshold with SSRIs and SNRIs • Seizure length may increase when ECT is administered during bupropion treatment • Pharmacokinetic interactions with some SSRIs and anesthetic agents	• Some clinicians recommend bupropion discontinuation or dose reduction prior to ECT • If SSRIs are discontinued, clinicians should be aware that withdrawal may cause symptoms similar to the side effects of ECT (eg, headache, myalgia, nausea, and fatigue) • It is necessary to pay attention to the rare side effect of serotonin syndrome by ECT in combination with SSRIs
Anxiolytics
BZD^Citation6,Citation14,Citation39	• The impact of BZDs on seizure adequacy may be low if the BZD has been routinely used • Can produce additive sedative effects during the anesthetic induction phase	• Increased seizure threshold, decreased seizure duration, and decreased potential efficacy of ECT • Possibly increased cognitive side effects when given with ECT	• If possible, stop BZD before ECT. Many BZDs are long acting and may need to be discontinued some days before ECT • If the BZD cannot be discontinued, the use of higher stimulus or using flumazenil just before ECT to temporarily reverse effects of the BZD has been suggested • The dose of thiopental or propofol used for induction of anesthesia should be titrated to the desired effect
Antipsychotics
FGA^Citation1,Citation14,Citation39,Citation46	• The combination of FGAs, particularly phenothiazines (eg, chlorpromazine) and ECT has been reported to cause prolonged seizures	• Theoretically, FGAs reduce seizure threshold	• None have been recommended • Their antiadrenergic and anticholinergic effects are unpredictable, and caution in the use of drugs with similar effects during anesthesia should be exercised
SGA^Citation14,Citation39,Citation46	• Some data suggest beneficial and additive efficacy when in combination, particularly with clozapine	• Clozapine is known to decrease the seizure threshold in a dose-dependent manner (usually at doses >600 mg/d)	• None have been recommended • For patients on clozapine, a dose reduction prior to ECT may be considered
CNS stimulants
Methylphenidate^Citation14	• Methylphenidate was shown to reduce sedation and improve respiratory function in patients recovering from halothane anesthesia	• Theoretically, there is an increased risk for potentiating seizure activity, thereby leading to prolonged seizures or a risk for status epilepticus • Methylphenidate can also produce dysrhythmias and elevate blood pressure during anesthesia	• None have been recommended
Miscellaneous
Cholinesterase inhibitors^Citation4,Citation47,Citation48	• No evidence of adverse incidents involving concurrent use with ECT • Successful use of donepezil in treating cognitive deficits associated with maintenance ECT has been reported	• Theoretically, synergistic effects with neuromuscular blocking agents. This combination also has the potential to induce significant bradycardia, cardiac arrhythmias, and asystole	• Caution has been recommended particularly with neuromuscular blocking agents
Lidocaine^Citation1,Citation7,Citation17,Citation49,Citation50	• Ineffective in ameliorating the robust sympathetic response associated with ECT • Pretreatment with lidocaine is associated with decreased seizure duration and a higher likelihood of patients requiring multiple applications of electric current during a single ECT session to achieve a therapeutic seizure	• Seizure inhibition • Potentially useful for reducing tachycardia in high-risk patients and reducing the severity of propofol injection pain	• Recommended to be used only in life threatening situations to control heart rate, when β-blockers are not available or are contraindicated
Theophylline^Citation4,Citation6,Citation14	• Reports of status epilepticus after ECT • High levels of theophylline during ECT associated with status epilepticus	• Can increase seizure duration and increase risk of status epilepticus	• If possible, discontinue theophylline by tapering the dose. Continue with a regimen of bronchodilators and inhaled glucocorticoids • Alternatively, decrease dose to the lowest therapeutic drug level and monitor levels closely • Provide standard treatment during an asthma exacerbation (inhaled β-agonists and, if necessary, glucocorticoids, before proceeding with ECT)
Antigastric agents (eg, antacids and proton pump inhibitors)^Citation6,Citation51	• No evidence of adverse incidents involving concurrent use with ECT		• Continue as patients with GERD may have worsened symptoms undergoing ECT due to vagal stimulation
Diabetic agents (eg, oral hypoglycemic and insulin)^Citation7,Citation51	• Individual ECT treatments raise blood glucose levels in patients with diabetes to the same degree as in patients without diabetes	• Can cause hypoglycemia	• Measure blood glucose levels before and after ECT treatment. Give half the usual amount of long-acting insulin in the morning of the procedure • Withhold oral agents until patient can eat. Provide short-acting insulin to treat elevations in blood glucose level
Warfarin^Citation51^–^Citation53	• A retrospective case review found that over one-third of the patients INRs during ECT were subtherapeutic • However, ECT appears to be safe in patients who require long-term anticoagulation	• The potential for methohexital to increase the metabolism of warfarin, decrease the INR, and possibly affect warfarin’s efficacy exists	• Continue anticoagulation to maintain an INR of up to 3.5, unless there is an increased risk of intracranial hemorrhage (eg, intracranial mass or aneurysm)

Herbals^Citation54	Mechanism of action and potential effect on ECT	Management strategies
Gingko biloba	• GABA agonist: potentiates CNS depressant effects of barbiturates and BZDs and may increase ECT seizure threshold • Inhibit platelet activating factor: increase risk of cerebral hemorrhage • May contain convulsive agent: lower ECT seizure threshold • Cerebral arterial vasodilation: increased intracranial pressure • Induce CYP3A4: increase metabolism of barbiturates and BZDs	• For all herbal medicines: assess its potential impact on the procedure, weigh benefits, and risk • Similar considerations when assessing conventional pharmacotherapy
Ginseng	• CNS depressant: potentiates CNS depressant effects of barbiturates and BZDs and may increase ECT seizure threshold • CNS stimulant: may increase anesthetic requirement and decrease ECT seizure threshold • Facilitates acetylcholine release: parasympathetically mediated bradycardia
St Johns Wort	• GABA agonist: potentiates CNS depressant effects of barbiturates and BZDs and may increase ECT seizure threshold • Reduces cholinesterase levels: potentiates neuromuscular blockade effect (eg, succinylcholine) • Inhibits MAO and COMT: hypertension or cardiovascular collapse
Valerian	• CNS depressant, GABA agonist, inhibits GABA uptake and metabolism: potentiates CNS effects of barbiturates and BZDs and may increase ECT seizure threshold
Kava kava	• CNS depressant, GABA agonist: potentiates CNS effects of barbiturates and BZDs and may increase ECT seizure threshold

Abbreviations: BZD, benzodiazepine; CBZ, carbamazepine; ECT, electroconvulsive therapy; FGA, first-generation antipsychotics; LTG, lamotrigine; MAOI, monoamine oxidase inhibitor; SGA, second-generation antipsychotics; SNRIs, serotonin norepinephrine reuptake inhibitors; SSRIs, serotonin reuptake inhibitors; TCA, tricyclic antidepressant; VPA, valporic acid; CNS, Central Nervous System; GERD, Gastroesophageal Reflux Disease; INR, International Normalization Ratio; COMT, Catecholl-O-Amine Transferase; GABA, Gamma Amino-Butiric Acid.

TaylorSElectroconvulsive therapy: a review of history, patient selection, technique and medication managementSouth Med J2007100549449817534086

 PubMed Web of Science ®Google Scholar

DolencTJRasmussenKGThe safety of electroconvulsive therapy and lithium in combination: a case series and review of the literatureJ ECT20052116517016127306

 PubMed Web of Science ®Google Scholar

SartoriusAWolfJHennFALithium and ECT-concurrent use still demands attention: three case reportsWorld J Biol Psychiatry20056212112416156485

 PubMed Web of Science ®Google Scholar

NaguibMKoornRInteractions between psychotropics, anaesthetics and electroconvulsive therapy: implications for drug choice and patient managementCNS Drugs200216422924711945107

 PubMed Web of Science ®Google Scholar

SienaertPPeuskensJAnticonvulsants during electroconvulsive therapy: review and recommendationsJ ECT20072312012317548985

 PubMed Web of Science ®Google Scholar

BundyBDHewerWAndresFJGassPSartoriusAInfluence of anesthetic drugs and concurrent psychiatric medication on seizure adequacy during electroconvulsive therapyJ Clin Psychiatry201071677577720051218

 PubMed Web of Science ®Google Scholar

Hızlı SayarGEryılmazGŞemieoğluSÖztenEGöğcegöz GülIInfluence of valproate on the required dose of propofol for anesthesia during electroconvulsive therapy of bipolar affective disorder patientsNeuropsychiatr Dis Treat20141043343824623978

 PubMed Web of Science ®Google Scholar

SienaertPRoelensYDemunterHVansteelandtKPeuskensJVan HeeringenCConcurrent use of lamotrigine and electroconvulsive therapyJ ECT201127214815220562637

 PubMed Web of Science ®Google Scholar

YeLKarlapatiSKLippmannSTopiramate for post-electroconvulsive therapy headachesJ ECT2013293e4923965610

 PubMed Web of Science ®Google Scholar

GreenbergRMKellnerCHElectroconvulsive therapy: a selected reviewAm J Geriatr Psychiatry20051326828115845752

 PubMed Web of Science ®Google Scholar

DolencTJHablSSBarnesRDRasmussenKGElectroconvulsive therapy in patients taking monoamine oxidase inhibitorsJ ECT20042025826115591861

 PubMed Web of Science ®Google Scholar

PeckTWongANormanEAnaesthetic implications of psychoactive drugsContin Educ Anaesth Crit Care Pain2010106177181

 Google Scholar

DursunSMPatelJKDrybalaTShinkwinRDrybalaGReveleyMAEffects of antidepressant treatments on first-ECT seizure duration in depressionProg Neuropsychopharmacol Biol Psychiatry200125243744311294487

 PubMed Web of Science ®Google Scholar

American Psychiatric AssociationThe Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging. A Task Force Report of the American Psychiatric Association2nd edWashington, DCAmerican Psychiatric Publishing2001

 Google Scholar

KlysnerRBendsenBBHansenMSTransient serotonin toxicity evoked by combination of electroconvulsive therapy and fluoxetineCase Rep Psychiatry2014201416250224982810

 PubMedGoogle Scholar

NothdurfterCEserDSchüleCThe influence of concomitant neuroleptic medication on safety, tolerability and clinical effectiveness of electroconvulsive therapyWorld J Biol Psychiatry20067316217016861142

 PubMed Web of Science ®Google Scholar

BomanBConcurrent use of ECT and cholinesterase inhibitor medicationsAust N Z J Psychiatry200236681612406126

 PubMed Web of Science ®Google Scholar

RaoNPPalaniyappanPChandurJVenkatasubramanianGGangadharBNSuccessful use of donepezil in treatment of cognitive impairment caused by maintenance electroconvulsive therapy: a case reportJ ECT200925321621819190508

 PubMed Web of Science ®Google Scholar

PandyaMPozueloLMaloneDElectroconvulsive therapy: what the internist needs to knowCleve Clin J Med200774967968517879522

 PubMed Web of Science ®Google Scholar

GordonKWoloschukDMMWalusANPatients’ physical response to thiopental and alternative anesthetic agents in the setting of electroconvulsive therapyCan J Hosp Pharm201467644745225548403

 PubMedGoogle Scholar

ZahoorMUMasroorRAliMWUse of lignocaine or nitroglycerine for blunting of hemodynamic stress response during electroconvulsive therapyEgypt J Anaesth20143012730

 Google Scholar

WajimaZYoshikawaTOguraAShigaTInoueTOgawaRThe effects of intravenous lignocaine on haemodynamics and seizure duration during electroconvulsive therapyAnaesth Intensive Care200230674274612500511

 PubMed Web of Science ®Google Scholar

TessASmetanaGWMedical consultation for electroconvulsive therapyAuerbachADParkLUpToDateWaltham, MAUpToDate2015Accessed December 15, 2015

 Google Scholar

BleichSDegnerDScheschonkaAElectroconvulsive therapy and anticoagulationCan J Psychiatry2000458710696500

 PubMed Web of Science ®Google Scholar

PatraKKCoffeyCEImplications of herbal alternative medicine for electroconvulsive therapyJ ECT20042018619415343004

 PubMed Web of Science ®Google Scholar