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Product Evaluation a Quick Overview Sodium Methohexital SUMMARY

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Product Evaluation a Quick Overview Sodium Methohexital SUMMARY Product Evaluation A quick overview for Formulary status: ‘Formulary’ (ECT) Sodium Methohexital Date: 17.10.13 SUMMARY Propofol and methohexital both appear to be appropriate anaesthetics for patients undergoing ECT. The evidence comparing methohexital with propofol appears to be mixed as some authors have reported little difference in the average number of treatments, change in depression severity or effect on cognitive function. Other studies have shown that owing to its anticonvulsant properties, propofol may be associated with a longer treatment course, higher electrical stimulus and subsequent cognitive impairment. The cost benefit of propofol (£1 per patient dose) needs to be weighed up against the anticipated additional ECT treatment (£620) which may be needed with propofol and which would otherwise cover much of the anaesthetic cost for methohexital. Experience by the staff at the ECT suite at Green Lane supports the use of methohexital based on better patient experience and overall better value due to reduced number of ECT treatments with methohexital. BACKGROUND ECT is a treatment for a small number of severe mental illnesses. It was originally developed in the 1930s and was used widely during the 1950s and 1960s for a variety of conditions. The treatment consists of passing an electrical current through the brain to produce an epileptic fit – hence the name, electro-convulsive. Methohexital is widely used in ECT, is easy to use, has few side effects and has little effect on the seizure threshold. However, the main issue is with supply as there was a nationwide shortage in 2002-03 and again more recently in the Autumn of 2013. What is it? Methohexital is a ultrashort-acting barbiturate which may be considered as a treatment option for the induction of ECT1. Safety Profile. Methohexital has low cardiac toxicity, is rapid acting and is associated with longer seizure duration and a low incidence of post anaesthesia toxicity. However, elevation in systolic and diastolic blood pressure was greater in the methohexital group (than propofol) in one study in older adults over 60 years (propofol n=82; methohexital n=95 ) 2,3. One study 4 has also shown that incidence of nausea and vomiting is lower with propofol. Clinical Efficacy. What do the trials show? Geretsegger C et al showed similar improvement of depressive symptoms and cognitive function in both groups (with the exception of the results from 2 cognition tests which favoured propofol). Some studies have demonstrated that differences in seizure duration are unrelated to seizure-quality 6,7,8 A retrospective study 1 which looked at 1314 treatments over 155 ECT courses demonstrated no improvement in the depression rating scale. However, it did show that the number of required treatments is affected by the position of the electrodes; when right unilateral electrode placement was used, those receiving propofol required more treatment than those Approved by Medicines Optimisation May 2014 Version 2.0 Page 1 receiving methohexital. A higher ECT stimulus for propofol for bilateral electrode placement was also required. Seizure duration was shorter with more requiring re-stimulation for brief seizures. Length of stay and cognitive outcomes were not significantly different between propofol and methohexital patient groups. A study by Walder et al 9 looked at 15 randomised control trials with a total of 706 participants, which compared propofol (349 participants) with methohexital (357 participants). The mean duration of seizures with propofol was significantly shorter than that with methohexital: the weighted mean difference (fixed-effect model) was 8.4 seconds (95% CI: 6.6, 10.0) for motor seizure, and 14.3 seconds (95% CI: 10.8, 17.8) for EEG seizure activity. There was no significant difference in the duration of anaesthesia between propofol and methohexital: the weighted mean difference was 0.25 minutes (95% CI: 0.35, 0.85). Three trials reported on improvement of the underlying disease at the end of an ECT series. One of these reported that a significantly greater number of participants showed improvement with propofol (86%), compared with those receiving methohexital (59%). Fourteen trials reported qualitatively on respiratory adverse events, e.g. hypoventilation; this was shown to occur with both hypnotics. Five trials reported adverse cardiovascular events. Qualitatively, there was on average a smaller increase in blood-pressure with propofol than with methohexital. One report described pain on injection with propofol. What do others say? No submissions noted on SMC or NICE websites. Supplies Methohexital currently available (Oct 2013) from IDIS. Alternative suppliers includes AAH Specials. Propofol from usual wholesaler. What are the alternatives? Etomidate used to be used but it has an unattractive side-effect profile which limits its use. Sodium thiopentone is used by some ECT clinics but owing to its long half-life and cardiotoxicity needs to be used where there are adequate monitoring facilities. Propofol is a short-acting hypnotic agent and is widely used across the country. There is much evidence supporting its use as it is costs effective, associated with a significantly reduced seizure duration (compared to methohexital) and shorter emergence and recovery times (Vaidya). However, owing to its anticonvulsant properties, it requires a 66% higher ECT stimulus dose than if using methohexital, which could also potentially effect cognition How much does it cost? Methohexital: 500mg/mL IDIS: £62 per ampoule AAH Specials: £71.37 per ampoule excl VAT £177.47 powder for injection excl VAT Cost of drug per treatment £35. Propofol: £1 per patient dose Approved by Medicines Optimisation May 2014 Version 2.0 Page 2 Cost effective analysis: Although it may appear that Propofol is far more cost effective than methohexital, the seizure threshold with propofol is raised owing to its anticonvulsive properties, requiring a greater ect stimulus. It also takes longer to establish the seizure threshold (and treat at 1.5 of the threshold) which makes the treatment course longer. As each ECT treatment costs £620, this would cover much of the cost for methohexital. REFERENCES 1. Punit V Vaidya, MD et al A within-subject comparison of propofol and methohexital anesthesia for electroconvulsive therapy, Journal of ECT, Volume 28, Number 1, March 2012 2. Shteinlukht T.P.,Berth U.,Badr R, Propofol and methohexital as anesthetic agents for ECT in older adults, American Journal of Geriatric Psychiatry, March 2009, vol./is. 17/(A92-A93), 1064-7481 (March 2009), 3. Swaim J.C.,Mansour M.,Wydo S.M.,Moore J.L., A retrospective comparison of anesthetic agents in electroconvulsive therapy, Journal of ECT, December 2006, vol./is. 22/4(243-246), 1095-0680;1533-4112 (December 2006) 4. Bailine S.H.,Petrides G.,Doft M.,Lui G, Indications for the use of propofol in electroconvulsive therapy, Journal of ECT, 2003, vol./is. 19/3(129-132), 1095-0680 (2003) 5. Geretsegger C.,Nickel M.,Judendorfer B.,Rochowanski E.,Novak E.,Aichhorn W; Propofol and methohexital as anesthetic agents for electroconvulsive therapy: A randomized, double-blind comparison of electroconvulsive therapy seizure quality, therapeutic efficacy, and cognitive performance; Journal of ECT, December 2007, vol./is. 23/4(239-243), 1095-0680;1533-4112 (December 2007) 6. Geretsegger C.,Rochowanski E.,Kartnig C.,Unterrainer A.F, Propofol and methohexital as anesthetic agents for electroconvulsive therapy (ECT): A comparison of seizure- quality measures and vital signs, Journal of ECT, 1998, vol./is. 14/1(28-35), 1095-0680 (1998) 7. Kirkby K.C.,Beckett W.G.,Matters R.M.,King T.E. Comparison of propofol and methohexitone in anaesthesia for ECT: Effect on seizure duration and outcome, Australian and New Zealand Journal of Psychiatry, 1995, vol./is. 29/2(299-303), 0004- 8674 (1995) 8. Malsch E.,Gratz I.,Mani S.,Backup C.,Levy S.,Allen E, Efficacy of electroconvulsive therapy after propofol and methohexital anesthesia, Convulsive Therapy, 1994, vol./is. 10/3(212-219), 0749-8055 (1994) 9. Walder B, Seeck M, Tramer M R, Propofol versus methohexital for electroconvulsive therapy: a meta-analysis, University of York, Center for reviews and dissemination Journal of Neurosurgical effects. Approved by Medicines Optimisation May 2014 Version 2.0 Page 3 .
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