Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Rapid tranquilization should remain a last resort treatment.
- Martina Onajite Esisi (29 October 2007)
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More clarification!
- Raghuthaman Gopal (31 October 2007)
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What do we need from Rapid Tranquillisation
- Premraj Muthuvelu (2 November 2007)
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Rapid tranquilisation with olanzapine versus haloperidol-promethazine: Some queries
- Himanshu Gupta, Om Prakash (5 December 2007)
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Martina Onajite Esisi, Staff grade psychiatrist Leicestershire partnership Nhs trust
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Although a common clinical practice,Rapid tranquillisation is a treatment of last resort, and is not underpined by strong evidence base.( ref.1)This is because patients are too disturbed to consent and therefore participate in clinical trails. As such, the trails by Raveendram and colleagues, and Gisele and collegues are welcome. However, i wondered if a better control group could have been with the use of Haloperidol and Lorazepam, as this is more often recommended and used in clinical practise. Benzodiazepine have been shown to be consistently safer in situations where the diagnosis is uncertain. The greatest concern about acute tranquillization is sudden death, which have been reported in particularly young patients , even with the modest doses of medication.(ref.2)In this respect Benzodiazepines are often preffered and recomended rather than antipsychotics, especially if there is evidence of QT prolongation. The study was in a developing country and one of the aim was to achieve sedation as opposed to calming effect through rapid tranquillization, using limited resources. It is important to note that when sedation is the desired outcome, it becomes even more necessary to keep patients under constant nursing observations(and as such more resources needed), in an attempt to monitor the respiratory rates, pulse rates, blood pressure. The authors did not tell us if these patients have had antipsychotics in the past prior to treatment, as side effects are commoner in patients who are neuroleptic niave. Refrences. 1. The Maudsley prescribing guidlines. 8th edition. David Taylor et al. 2.Use of Drugs in psychiatry. 5th edition. John Cookson et al. Competing interests: None declared |
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Raghuthaman Gopal, Consultant Psychiatrist UK PO10 7JB
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It is very comforting to read this article, which validates the widespread use of intra-muscular haloperidol and promethazine combination in India. Despite its very sound methodology, I like to get clarifications from the authors on certain aspects. In their sample, 53% of their patients are already on antipsychotics and I assume that most of them may be on atypical antipsychotic as this is the recommendation and preferred practice (1,2,3). In this scenario, a new episode of agitation or violent behaviour is a non-responsive symptom to the original antipsychotic. If more of these patients are already on olanzapine means, its non-responsiveness biases against experimental intra-muscular olanzapine. The authors could repeat the analysis excluding patients who are already on olanzapine or on antipsychotic naïve patients. Also, I am interested to know what extra drugs where given for patients who didn’t respond to the experimental drug and their response. The authors mention that one patient developed hypotension within 15 minutes of the injection. In the result section they refer this side effect to halperidol and promethazine combination whereas during the discussion they refer this to Olanzapine group (printed version). 1. National institute of clinical excellence: Full national clinical guideline on core interventions in primary and secondary care, 2003 2. National institute of clinical excellence: The management of bipolar disorder in adults, children and adolescents in primary and secondary care, 2006 3. Essock S, Antipsychotic prescribing practices Schizophrenia bulletin, 28 (1): 1-4, 2002 Competing interests: None declared |
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Premraj Muthuvelu, Specialist Registrar Ty Llywelyn, Llanfairfechan
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Dear Sir, It is clear from the TREC Trials so far that Midazolam used on its own is probably better than the 'Haloperidol and Promethazine' combination.(1) Haloperidol and Promethazine combination is perhaps slighltly better than Olanzapine in terms of noticeable 'clinical improvements' over a period of 2 hours. It however, sends more people to sleep rather than just calm them.(3) While a sleeping patient might be the best solution in a busy, resource stretched, low-middle income country a calm patient is certainly the ideal in a developed country with adequate resources. However, it is still unclear if a potent Benzodiazepine like midazolam on its own would be a better choice than an atypical such as Olanzapine, from the TREC trials, particularly because more patients treated with Olanzapine appear to need more treatment with other agents later on. Intuitively, it does appear that Midazolam on its own should be at least as good if not better than Olanzapine on its own. A trial comparing Midazolam vs Olanzapine and/or Midazolam Vs Olanzapine and a sedative such as promethazine would be interesting. Midazolam has of course, a faster onset of action than Lorazepam and would therefore, be a better choice. We know that a sedative in combination with an antipsychotic is better than an antipsychotic on its own(2). We also have studies showing that a Rapid acting Benzodiazepine is comparable if not better than antipsychotics (4). A benzodiazepine, though not without side effects is probably better all round than an antipsychotic. It has of course to be borne in mind that very often PRN Antipsychotics for rapid tranquillisation is given on top of regular Antipsychotics sending the total dose well above recommended BNF limits.If as it seems, what is really needed is a potent, rapid acting benzodiazepine, a strong case for not using any antipsychotics at all can be made. 1 Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine , for the TREC Collaborative Group,BMJ 2003;327:708-713 2 Gisele Huf, E S F Coutinho, C E Adams TREC Collaborative Group BMJ 2007 335: 869 Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine 3 Nirmal S Raveendran, Prathap Tharyan, Jacob Alexander, Clive Elliot Adams TREC-India II Collaborative Group BMJ 2007 335: 865, Rapid tranquillisation in psychiatric emergency settings in India: pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine 4 Foster, S; Kessel, J; Berman, M. E; Simpson, G. M. Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting. [Journal; Peer Reviewed Journal] International Clinical Psychopharmacology. Vol 12(3) May 1997, 175-179 Competing interests: None declared |
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Himanshu Gupta, Senior Resident of Psychiatry National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore-560029, INDIA, Om Prakash
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We read the article by Raveendran et al. (1) with great interest.The authors have tried to equate the efficacy of olanzapine with the haloperidol-promethazine combination in violent patients. However,some doubts still persist. Firstly, under ideal circumstances drug trials needs a viable placebo or comparator. The study group should have taken lorazepam as comparator arm because they have earlier conducted similar trials with lorazepam (2). Hence,the results of the study would be taken with the caution as the new agent is compared with a drug previously shown to be active,without placebo or comparator unless one agent is superior to other. Moreover for assessing safety profile over another drug,comparator arm is again very useful. Secondly,the authors have not mentioned the details of additional medications and about the status of prior medications during the study period.we feel that these drugs might have influenced the outcome of the study.Thirdly,it appears that haloperidol-promethazine group have more (94%)patients with having moderate to markedly severe illness as compared to (84%)patients in olanzapine group, which might further influence the outcome. It is difficult to understand from the paper that in what way they excluded violent patients having seizure disorder,diabetes and alcoholic liver disease prior to randomization without calming down the patients.It is also not clear that what ethical measures were taken for patients who lost follow-up. Nevertheless,the authors have conducted a well systematized study taking care of the most of the methodological flaws in the area of emergency psychiatry. References 1: Raveendran NS, Tharyan P, Alexander J, Adams CE; TREC-India II Collaborative Group.Rapid tranquillisation in psychiatric emergency settings in India: pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine. BMJ. 2007;335(7625):865. 2: Alexander J, Tharyan P, Adams C, John T, Mol C, Philip J. Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine. Br J Psychiatry. 2004;185:63-9. Competing interests: None declared |
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