PICO GG haldol et alcool

SEVRAGE ALCOOLIQUE ET ANTIPSYCHOTIQUES
Question : Devrait-on éviter les antipsychotiques chez les patients en sevrage
alcoolique qui sont agités ou en délirium tremens ?
AUTEURE : Geneviève Gagnon (MAI 2009)
P
I
C
O
: patients en sevrage alcoolique
: antipsychotiques
: benzodiazepines
: contrôle des symptômes, convulsions
Contexte
La question du pico m’est venue alors qu’un patron optait, dans le cas d’un patient en
sevrage alcoolique aux prises avec des hallucinations (délirium ? hallucinose ?), pour
l’haloperidol plutôt que les benzodiazépines. J’ai voulu vérifier s’il était acceptable
d’opter pour un médicament de cette classe, sachant qu’avec ceux-ci, qu’il existe un
risque de réduire le seuil convulsif chez des patients déjà à risque de convulsions.
Recherche
Dans Cochrane, avec alcohol, alcohol withdrawal, delirium tremens, alcoholism...
Je poursuis dans d’autres banques de données avec les mêmes termes de recherche.
Résultats
Cochrane
1.
Ntais C, Pakos E, Kyzas P, Ioannidis JPA. Benzodiazepines for alcohol
withdrawal. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.:
CD005063.
Fifty-seven trials, with a total of 4,051 people were included. Despite the
considerable number of randomized controlled trials, there was a very large variety
of outcomes and of different rating scales and relatively limited quantitative synthesis
of data was feasible. Benzodiazepines offered a large benefit against alcohol
withdrawal seizures compared to placebo (relative risk [RR] 0.16; 95% confidence
interval [CI] 0.04 to 0.69; p = 0.01). Benzodiazepines had similar success rates as
other drugs (RR 1.00; 95% CI 0.83 to 1.21) or anticonvulsants in particular (RR 0.88;
95% CI 0.60 to 1.30) and offered a significant benefit for seizure control against nonanticonvulsants (RR 0.23; 95% CI 0.07 to 0.75; p = 0.02), but not against
anticonvulsants (RR 1.99; 95% CI 0.46 to 8.65). Changes in Clinical Institute
Withdrawal Assessment for Alcohol (CIWA-Ar) scores at the end of treatment were
similar with benzodiazepines versus other drugs, although some small studies
showed isolated significant differences for other, less commonly, used scales. Data
on other comparisons were very limited, thus making quantitative synthesis for
various outcomes not very informative.
Sevrage alcoolique et antipsychotique
Page 2
Sur les 57 études, les suivantes ont inclus un antipsychotique :
Borg 1986 : convulsions 0.11 [ 0.01, 1.90 ]
Golbert 1967 succès thérapeutique 0.59 [ 0.25, 1.37 ], « any succes » (inclue les
anti-convulsivants ) 0.59 [ 0.25, 1.37 ], delirium 1.04 [ 0.52, 2.09 ], mortalité (inclue
les anti-convulsivants) : 0.58 [ 0.03, 11.40 ]
Kaim 1972 : Rien de significatif quand aux convulsions, au délirium, à la mortalité, à
l’abandon du traitement suite à des effets secondaires.
Lepola 1984 : Rien de significatif quand à l’efficacité globale du traitement et aux
effets secondaires.
Lucht 2003
Overall 1973
Palestine 1976 (haloperidol)
Pena-Ramos 1977
Pena-Ramos 1977
Globalement, études très hétérogènes, qui montrent que les benzo sont préférables
quand un patient convulse, mais les données ne sont pas assez solide pour
permettre de conclure qu’elles sont préférables à un autre traitement pour le contrôle
des autres symprômes.
Dare
Mayo-Smith M F. Pharmacological management of alcohol withdrawal: a metaanalysis and evidence-based practice guideline. JAMA.1997;278(2):144-151.
OBJECTIVE: To provide an evidence-based
pharmacological management of alcohol withdrawal.
practice
guideline
on
the
DATA SOURCES: English-language articles published before July 1, 1995, identified
through MEDLINE search on "substance withdrawal--ethyl alcohol" and review of
references from identified articles.
STUDY SELECTION: Articles with original data on human subjects.
DATA ABSTRACTION: Structured review to determine study design, sample size,
interventions used, and outcomes of withdrawal severity, delirium, seizures,
completion of withdrawal, entry into rehabilitation, adverse effects, and costs. Data
from prospective controlled trials with methodologically sound end points
corresponding to the Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition, were abstracted by 2 independent reviewers and underwent meta-analysis.
Sevrage alcoolique et antipsychotique
Page 3
DATA SYNTHESIS: Benzodiazepines reduce withdrawal severity, reduce incidence
of delirium (-4.9 cases per 100 patients; 95% confidence interval, -9.0 to -0.7; P=.04),
and reduce seizures (-7.7 seizures per 100 patients; 95% confidence interval, -12.0
to -3.5; P=.003). Individualizing therapy with withdrawal scales results in
administration of significantly less medication and shorter treatment (P<.001). betaBlockers, clonidine, and carbamazepine ameliorate withdrawal severity, but evidence
is inadequate to determine their effect on delirium and seizures. Phenothiazines
ameliorate withdrawal but are less effective than benzodiazepines in reducing
delirium (P=.002) or seizures (P<.001).
CONCLUSIONS: Benzodiazepines are suitable agents for alcohol withdrawal, with
choice among different agents guided by duration of action, rapidity of onset, and
cost. Dosage should be individualized, based on withdrawal severity measured by
withdrawal scales, comorbid illness, and history of withdrawal seizures. betaBlockers, clonidine, carbamazepine, and neuroleptics may be used as adjunctive
therapy but are not recommended as monotherapy.
Résultats :
Risk difference with benzodiazepine versus placebo for delirium: -4.9 cases of
delirium per 100 patients (95% CI: -9.0, -0.7, P=0.04).
Risk difference with benzodiazepine versus placebo for seizures: -7.7 cases of
seizures per 100 patients (95% CI: -12.0, -3.5, P<0.001).
Risk difference with long-acting as opposed to short-acting benzodiazepines for
seizure: -6.7 cases of seizure per 100 patients (95% CI: -13.0, 0.0, P=0.07).
Risk difference with phenothiazine versus placebo for delirium: 0.0 cases of delirium
per 100 patients (95% CI: -5.8, +6.6, P=0.92).
Risk difference with phenothiazine versus cross-tolerant medication for delirium: +6.6
cases of delirium per 100 patients (95% CI: 2.4, 10.8, P=0.002).
Risk difference with phenothiazine versus placebo for seizure: +4.6 cases of seizure
per 100 patients (95% CI: -2.6, +11.9, P=0.19).
Risk difference with phenothiazine versus cross-tolerant medication for seizure:
+11.4 cases of seizure per 100 patients (95% CI: 6.2, 16.6, P<0.001).
Beta-blockers, clonidine and carbamazepine ameliorate withdrawal severity, but
evidence is inadequate to determine their effect on delirium and seizures.
Individualising therapy with withdrawal scales results in the administration of
significantly less medication and shorter treatment.
On ne parle pas du résultat de la comparaison de l’haloperidol avec un placebo ou
une benzo, quoiqu’on mentionne cet agent dans l’abstract.
Sevrage alcoolique et antipsychotique
Page 4
2.
Franck J. Pharmacotherapy for alcohol withdrawal syndrome. (dans
Treating Alcohol and Drug Abuse.) Wiley-VCH Veriag GmbH and Co KGaA,
2003:189-246.
« The aim of this chapter is to present an overview of published clinical drug trials on
withdrawal treatment for the respective groups of agents. Furthermore, recent metaanalyses in the area are summarized to compare the effectiveness of different
agents in alleviating the symptoms of alcohol withdrawal and reducing the risk of
withdrawal seizures and delirium. »
« Eighty-two randomized controlled trials were found on drug treatment of alcohol
withdrawal in clinical patient groups, i.e., patients who presented for care in
hospitals or other health care facilities. The corresponding number of studies of
delirium tremens was 13. Two of the studies fell within both of these categories and
are therefore presented twice. Conclusions are presented for three meta-analyses of
pharmacotherapy in alcohol withdrawal published since 1983. No meta-analyses
addressing the treatment of delirium tremens were found. »
« Strong evidence from placebo controlled studies shows that benzodiazepines,
betareceptor antagonists, calcium antagonists, carbamazepine, and clonidine reduce
unspecific withdrawal symptoms more effectively than placebo does. Only the
benzodiazepine group has a documented effect as a preventive treatment against
withdrawal seizures or delirium tremens. Hence, evidence is lacking to support the
recommendation of other drugs as monotherapy in alcohol withdrawal. The studies
of nitrous oxide treatment are difficult to interpret because of several methodological
problems, but nitrous oxide appears to reduce unspecific withdrawal symptoms.
There is insufficient evidence to show that nitrous oxide could prevent the origin of
seizures or delirium. Few randomized controlled clinical trials have investigated
pharmacological treatment in fully developed delirium tremens. Published studies
have consistently small patient databases. The state of knowledge is insufficient. On
the basis of proven clinical experience, most textbooks recommend benzodiazepines
and chlormethiazole as first-line agents for treating delirium tremens.
Chlormethiazole has more potentially serious side effects than benzodiazepines,
mainly respiratory depression and increased airway secretion.»
Donc peu d’études avec des antipsychotiques et des données insuffisantes pour se
prononcer en faveur d’un tel traitement dans les cas de sevrages alcooliques.
1. Williams D, McBride A J. The drug treatment of alcohol withdrawal
symptoms: a systematic review. Alcohol and Alcoholism.1998;33(2):103-115
Brièvement : « The quality of methodological design was often poor. Further
research using better methods is required to allow comparison of different drugs in
the treatment of alcohol withdrawal symptoms. On the evidence available, a longacting benzodiazepine should be the drug of first choice. »
Sevrage alcoolique et antipsychotique
Page 5
BestBets
1.
Should benzodiazepines always be first choice in Alcohol Withdrawal ?
In [Adult patients with withdrawal symptoms] is[Chlordiazepoxide better than
chlormethiazole] at [treating withdrawal symptoms]?
Donc, la question est de savoir si les benzo constituent la meilleure option
thérapeutique.
On a cherché dans Medline, avec plusieurs termes de recherche, mais pas de mots
s’approchant d’un semblant d’antipsychotique. On a surtout cherché avec
« chlormethiazole » et « chlordiapoxezide »
On conclut que « Benzodiazepines or Chlormethiazole can be given but there is
more evidence availble to support administering a benzodiazepine. »
Donc on ne répond pas vraiment à ma question ici.
Trip Database
1. Mayo-Smith MF, Beecher LH, Fischer TL, Gorelick DA, Guillaume JL, Hill A, Jara
G, Kasser C, Melbourne J. Management of alcohol withdrawal delirium. An
evidence-based practice guideline. Arch Intern Med 2004 Jul 12;164(13):140512.
« NEUROLEPTIC AGENTS
No placebo-controlled trials of neuroleptic agents in AWD were identified. The trials
reviewed earlier demonstrated that neuroleptic drug therapy is inferior to
sedativehypnotic drug use in reducing mortality and duration. Nevertheless,
neuroleptic agents, especially haloperidol, are commonly used with sedativehypnotic drugs to calm patients with AWD. However, neuroleptic agents have the
potential to cause a variety of serious adverse effects, particularly when used in very
high doses, which may be required to control severe agitation. Chlorpromazine,
promazine, and other low-potency typical antipsychotic agents have been reported to
have the greatest effect on lowering seizure threshold. Chlorpromazine and
thioridazine are the most common offenders for causing hypotension, and
thioridazine may also prolong the QTc interval, increasing risk for torsade de pointes
and sudden death. All neuroleptic agents are thought to have the potential for
causing neuroleptic malignant syndrome, and cases have been reported in patients
with AWD who have received neuroleptic drugs. No studies were identified
describing the use of newer “atypical” antipsychotic agents, such as risperidone,
olanzapine, and quetiapine, for AWD. These agents are at least as efficacious as
typical antipsychotic agents for other indications and have a preferable adverse
effect profile. »
Sevrage alcoolique et antipsychotique
Page 6
2.
Delirium Tremens: Treatment & Medication dans E-medecine
On ne parle pas de l’haloperidol, on note qu’une benzo demeure le meilleur choix et
qu’il faut éviter les phénothiazines.
PubMed
1.
[No authors listed]. Alcohol withdrawal syndrome: how to predict, prevent,
diagnose and treat it. Prescrire Int. 2007 Feb;16(87):24-31.
« An oral benzodiazepine is the best-assessed treatment for a single episode of
generalised seizures or hallucinations during alcohol withdrawal. (15) In randomised
comparative trials benzodiazepines were more effective than neuroleptics in
preventing delirium-related mortality. »
2.
McKeon A, Frye MA, Delanty M. The alcohol withdrawal syndrome. J
Neurol Neurosurg Psychiatry. 2008 Aug;79(8):854-62. Epub 2007 Nov 6.
« A practice guideline fromthe American Society of Addiction Medicine has advised
against the use of neuroleptic agents as the sole pharmacological agents in the
setting of delirium tremens, as they are associated with a longer duration of delirium,
higher complication rate and, ultimately, a higher mortality.8 However, neuroleptic
agents have a role as a selected adjunct to benzodiazepines when agitation, thought
disorder or perceptual disturbances are not sufficiently controlled by
benzodiazepines. Although haloperidol is well established in this setting,
chlorpromazine is contraindicated as it is epileptogenic »
Conclusion et commentaire
Le traitement de base d’un sevrage alcoolique symptomatique se fonde sur le concept
de « cross-tolerance » entre les benzo et l’alcool, et les études qui existent sur ce sujet
appuient leur utilisation, tant pour les symptômes autonomiques que pour le délirium et
l’hallucinose. Il y a peu de données sur l’utilisation de neuroleptiques dans les sevrages
alcooliques, il semble néanmoins sécuritaire d’administrer de petites doses de ceux-ci, à
l’exclusion de la classes des phénothiazines, en traitement d’appoint lorsque le patient
présente une grande agitation.