Graylands Hospital Drug Bulletin Medications and Electroconvulsive Therapy North Metropolitan Health Service - Mental Health June 201 8 Vol 2 5 No. 1 ISSN 1323 -1251 A review by Sienaert et al concluded that ECT Introduction can be administered safely with Electroconvulsive therapy (ECT) has been anticonvulsants with no reduction in efficacy.6 shown to be highly effective and safe for A trial comparing the efficacy of ECT with or many psychiatric disorders such as major without concurrent sodium valproate therapy depressive disorder, catatonia, psychosis and concluded that continuation of valproate mania.1 It is well documented that certain during ECT does not impair or enhance the medications interact with ECT and can impact efficacy of ECT.7 Similarly, a small clinical trial on the quality of the treatment or cause of 19 patients concluded that therapeutic adverse effects. This bulletin attempts to doses of lamotrigine does not significantly summarise the effect of medications on ECT influence the stimulus dose required or length and vice versa. of ECT-induced seizures.8 Benzodiazepines Medication Optimisation Pre-ECT Benzodiazepines are gamma-aminobutyric Anticonvulsants acid (GABA) receptor modulators which Anticonvulsants, in theory, will reduce the increase seizure threshold, shorten seizure quality of seizures obtained with ECT as they duration and reduce seizure intensity.2 are designed to prevent seizures. However, evidence of anticonvulsants interfering with Multiple studies have shown that the efficacy of ECT is lacking.2 Most guidelines benzodiazepines affect the efficacy of right still advise cessation of anticonvulsants prior unilateral (RUL) ECT but not BT ECT. 2, 4, 9, 10 It to ECT. The Chief Psychiatrist’s Guidelines for has also been shown that withholding the use of Electroconvulsive Therapy in benzodiazepines from the night before ECT Western Australia 2006 recommends night is sufficient to mitigate the cessation of anticonvulsants if possible prior anticonvulsant properties of low dose commencement of ECT.3 benzodiazepines (<6mg lorazepam equivalent).4 No studies looking at the impact A search of the literature produces mixed of z-drugs in ECT could be found, but the half- results on this question. A large retrospective life of zopiclone and zolpidem are quite short study demonstrated that patients on (5 hours and 3 hours respectively) and they anticonvulsants are associated with poorer are likely to have little impact on ECT when response to ECT, with 3.7% of responders they are given the night before. Promethazine receiving anticonvulsants compared to 17.9% is used as the first-line hypnotic at Sir Charles of non-responders.4 On the other hand, Gairdner Hospital Mental Health Unit (SCGH Rakesh et al found a statistically significant MHU) for clients requiring an hypnotic the improvement in patients on full dose night before ECT but zopiclone is routinely anticonvulsants.5 This study randomised administered as a hypnotic if there is patients to three groups, anticonvulsants at inadequate response to promethazine. full dose, half dose or no anticonvulsant and used bitemporal (BT) ECT. Graylands Hospital Drug Bulletin June 2018 Vol 25 No.1 Page 1 Lithium Antidepressants There are older case reports associating An indirect comparison meta-analysis shows concomitant lithium and ECT with excessive no adverse complications with combined cognitive disturbance, prolonged apnoea and antidepressant use and ECT except for a high spontaneous seizure.11 Furthermore, there is rate of memory deterioration four weeks a potential that lithium can enhance and after ECT treatment.21 There are case series prolong the action of suxamethonium.12 More demonstrating the safety of SSRIs in ECT.22, 23 recent evidence show that concomitant lithium is safe to administer with ECT but all Nevertheless, risk of complications with reviews still suggest maintaining lithium concurrent administration of antidepressants therapy at the lower range of the therapeutic and ECT remain. A retrospective review found serum level as there is potential for rare SSRIs prolonged seizure duration compared to complications such as prolonged seizures or, an SNRI or TCA,24 while another study found confusion.11, 13, 14 paroxetine increased the length of seizure during ECT.25 There is one case report of Antipsychotics bupropion causing status epilepticus,26 but a There are multiple trials of concurrent recent retrospective case-control study found administration of antipsychotics with ECT. A bupropion is associated with a shorter seizure meta-analysis of 23 studies assessing the duration. 27 efficacy of antipsychotics and ECT found no Another clinical trial found that concomitant significant adverse effects with concurrent administration of nortriptyline with ECT is treatment.15 A large retrospective study associated with less cognitive adverse effects concluded that adverse effects were not compared to placebo while venlafaxine has influenced significantly by concomitant the potential of worsening cognitive adverse antipsychotic medication.16 Several studies effects compared to nortriptyline and placebo evaluated the safety of ziprasidone or with lower mini-mental state exam (MMSE) aripipazole with ECT and showed minimal and worse recall. 28 There seems to be a adverse effects. 17, 18 Clozapine and higher risk of asystole when the dose of phenothiazines are more likely to prolong venlafaxine exceeds 300mg/day 29 while doses seizure duration 16 and a recent systematic under 225mg appear to be safe when review found 14% of cases reported adverse administered concurrently with ECT.30 events with concurrent clozapine Monoamine oxidase inhibitors appear to be administration and ECT,19 most likely due to safe with ECT.31 clozapine lowering the seizure threshold.19 Other Medications Chi et al investigated the relationship between seizure threshold and psychotropic Cardiovascular medications drugs on ECT and found an association Catecholamine surge during the clonic phase between initial seizure threshold and the total of ECT can lead to tachycardia and 32 chlorpromazine equivalent dose of hypertension. At SCGH MHU, it is routine antipsychotic.20 The authors concluded that practice to give patient’s regular the higher the dose of most groups of antihypertensive and antianginal medication antipsychotics, the higher the initial seizure with a small sip of water before ECT. The only threshold which is contrary to the popular exceptions to the practice are diuretics which belief that all antipsychotics lower the seizure should be withheld, if possible, to reduce risk threshold. The exact mechanism on how of urinary incontinence as a result of the antipsychotic increase seizure threshold is seizure. unclear but the authors hypothesised that dopamine is a proconvulsant and the use of antipsychotics reducing dopamine may result Asthma Medications in a raised seizure threshold.20 If a patient uses routine preventers, they should be administered prior to ECT as there Graylands Hospital Drug Bulletin June 2018 Vol 25 No.1 Page 2 is a small risk of asthma exacerbation post Gastrointestinal Medications ECT.33 Theophylline has been associated with There is a risk of reflux and possible aspiration prolonged seizures and status epilepticus and during ECT, hence routine medications for should be ceased if possible or maintained at dyspepsia and reflux should be administered the lowest effective dose during a course of prior to ECT with a small sip of water.34 34 ECT. Medication Effect on ECT treatment Recommended Action Anticonvulsants Potentially reduce efficacy of ECT If used as mood stabiliser – cease medication if possible. Withhold dose the night before ECT if it cannot be discontinued. If used for epilepsy – continue medication and withhold dose the night before ECT. Benzodiazepines Potentially reduce efficacy of ECT Aim to cease if possible, if benzodiazepine cannot be discontinued, suggest converting to benzodiazepines with shorter half-life such as lorazepam. Consider flumazenil pre-treatment prior to ECT if benzodiazepine cannot be discontinued or converted to alternative benzodiazepines with shorter half-life 36 . Antipsychotics Potential increase in seizure threshold, Continue treatment unless issues are encountered. clozapine and phenothiazines may Generally safe. decrease seizure threshold 20, 34 Lithium Risk of cognitive disturbances, Reduce dose to lower end of therapeutic range prior prolonged apnoea and spontaneous to ECT seizures based on old case reports 11 but more recent evidence demonstrated At SCGH MHU, it is routine practice to halve the safety with concurrent administration regular lithium dose prior to ECT Theoretical interaction with suxamethonium prolonging its action Antidepressants Small risk increasing seizure duration but Continue treatment for all antidepressants except for : minimal clinical impact 21 Venlafaxine/desvenlafaxine – dose reduction to Potential cognitive impairment and <225mg is recommended asystole t with venlafaxine 28 Antihypertensives Risk of hypertension during clonic phase Administer with small sip of water before ECT of ECT if routine dose not given Diuretics Risk of incontinence during seizure Administer post-ECT Asthma Risk of asthma exacerbation post-ECT Administer before ECT with the exception of preventers Theophylline Theophylline Risk of prolonged seizure or status Cease before ECT if possible, or maintain at lowest epilepticus therapeutic dose Gastrointestinal Risk of reflux and potential aspiration Administer