Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Dose relationship
- Carl S Littlejohns (8 November 2002)
-
Study lack the real control group?
- Abdul Karim Al-Sheikhli (9 November 2002)
-
cardiac arrest and ventricular arrhythmia in antipsychotic treatment
- Detlef Degner, Stefan Bleich,Renate Grohmann,Borwin Bandelow (11 November 2002)
-
Thioridazine - Out of the Dock and Into Primary Care
- Nat MJ Wright, Charlotte N.E. Tompkins (13 December 2002)
|
|
|||
|
Carl S Littlejohns, Consultant Psychiatrist Chester, UK CH2 1BQ
Send response to journal:
|
QTc is regarded as the best indicator for dangerous arrhythmia but is not an exact tool. There appears to be a genetic component to this variable. There is debate as to whether the calculated correction used adequately compensates for heart rate. Individuals may show a diurnal QT variation and seem to vary in how reactive their own QT interval is. A change that appears to be dose related should be investigated during the peak of blood levels as logically a relevant sudden onset arrhythmia leading to death will most likely occur at this point. The authors have probably lessened the power of their study by averaging dose over 30 days instead of looking at peak dosage within shorter time frames. The danger from all of this (undoubtedly important) interest is that other medications may be withdrawn from our use on the basis of incompletely understood effects, inaccurately measured and associated with over-generalised conclusions. The Committee on safety of medicines (CSM) limited the use of thioridazine in late 2000 because of relative QTc changes. http://www.mca.gov.uk/ourwork/monitorsafequalmed/safetymessages/thiolet.pdf My agenda is that the number of lives saved by the restriction on thioridazine is not clinically apparent to me, but the high level of morbidity and misery for patients and families most certainly is. Carl Littlejohns Competing interests: None declared |
|||
|
|
|||
|
Abdul Karim Al-Sheikhli, Loc.Consultant Psychiatrist The Medical Centre,2 Manor Court Avenue,Nuneaton CV11 5HX,UK
Send response to journal:
|
8th,Nov,2002 Dear Editor,I was surprised that Hennessy & colleagues,in their study,Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs:cohort study using adminstrative data(1),include patients on drugs who suffer from glucoma and psoriasis,but did not include a proper control group who are not on any medication,and are not suffering from any illness?,do they agree by that the results will be more informative? References: 1.Hennesy.S,Bilker.W.S,Knauss.J.S,Margolis.R.F,Glasser.D.B,Morrison.M.F,Strom.B.L,Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs:cohort study using administrative data,BMJ;2002:325,1070. Competing interests: None declared |
|||
|
|
|||
|
Detlef Degner, senior doctor University of Göttingen,Department of Psychiatry,D-37075 Göttingen,Germany, Stefan Bleich,Renate Grohmann,Borwin Bandelow
Send response to journal:
|
The problem of cardiac adverse drug reactions (ADR) in antipsychotic drugs has important clinical relevance.The risk of cardio- vascular complications in schizophrenic patients is high (smoking,diabetes,non-compliance in taking their medication etc.). The problems of cardiac arrest-ventricular arrhythmia-sudden death have been investigated and discussed intensively with the introduction of ziprasidone.These risks also have been reported and published in many journals for treatment with sertindole.The paper of Hennessey et al. has some methodological and statistical critical points,f.e.there is no correct control group in this cohort study. The post-marketing independent surveillance project of drug safety in psychiatry in Germany,Austria and Switzerland (AMSP) monitored 122.562 psychiatric in-patients (1993- 2000).In this study we observed different ADR rates of cardiac arrests and arrhythmias in antipychotic drugs.With the introducton of new atypical antipsychotics the relevant risks of cardiac ADR should be investigated and controlled intensively.Different studies and consequent drug safety programs may help to estimate cardiac risk profiles for different antipsychotics. Ref.: Grohmann,R et al. Pharmacopsychiat 32: 21-28 (1999) Competing interests: None declared |
|||
|
|
|||
|
Nat MJ Wright, GP Consultant in Substance Misuse and Homelessness NFA Health Centre for Homeless People, Leeds. LS9 8AA, Charlotte N.E. Tompkins
Send response to journal:
|
Hennessy et al (1) have provided a cohort study with a clinically meaningful outcome of cardiac arrests secondary to ventricular arrhythmia. What a pity that the Committee on Safety of Medicines could not have waited for this type of evidence before sending an urgent cascade fax to UK general practitioners.(2) I have argued through the letters and electronic response pages of this journal that case series studies provided an inadequate evidence base for such a fax.(3) However, Hennessy et al in appropriately describing a good safety profile for thioridazine at moderate doses have not gone far enough. They confirm that the rate ratio for cardiac arrest and ventricular arrest and ventricular arrhythmia is highest for risperidone. They try and excuse this by saying that they were unable to demonstrate a linear dose relationship. However table 3 does not compare like with like. Their lowest average daily dose of risperidone at less than 2.8mg is equivalent to less than 420mg of thioridazine. Such a dose of risperidone is higher than the highest dose compared to for thioridazine. They have inappropriately categorised tests from risperidone and say that the excess mortality from risperidone prescribing could be due to large numbers of frail elderly patients taking small amounts of risperidone. However this is not an appropriate explanation for the data that they have collected. Table 1 gives an excellent collation of the data in ten-year age bands. We would ask why they didn’t go one step further and calculate the adjusted risk ratios for age. They would then find that the rate ratio for risperidone in the elderly is not significantly higher than for the other drugs. An objective conclusion of the findings would be that they have confirmed the results of other studies,(4) namely that all anti-psychotic drugs (including risperidone) have the potential to cause sudden death by cardiac arrest. We recently completed a cross sectional survey of prescribing habits of GPs in Leeds. The three most common drugs prescribed in place of thioridazine were risperidone, haloperidol and chlorpromazine. We will now write to those GPs to draw their attention to the cardiac safety profile of thioridazine, which has been shown to be no worse than that of risperidone. Hennessy et al have produced some excellent data. As a general practice community we should match this with an excellent critical appraisal of that data and so end the witch-hunt against thioridazine! Reference List (1) Hennessy S, Bilker WB, Knauss JS, Margolis DJ, Kimmel SE, Reynolds RF et al. Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data. BMJ 2002; 325(7372):1070. (2) Committee on the Safety of Medicines. Thioridazine: restricted indications and new warnings on cardiotoxicity. 2000. London, CSM. (3) Wright N. Removal of thioridazine from primary care formulary will result in prescribing vacuum. BMJ 2001; 323(7314):695. (4) Kitayama H, Kiuchi K, Nejima J, Katoh T, Takano T, Hayakawa H. Long- term treatment with antipsychotic drugs in conventional doses prolonged QTc dispersion, but did not increase ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease. Eur J Clin Pharmacol 1999; 55(4):259-262. Competing interests: None declared |
|||