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Benzodiazepine and cyclopyrrolone reduction in general practice — does this lead to concomitant change in the use of antipsychotics?
Journal of Affective Disorders 126 (2010) 293–298 Contents lists available at Journal of Affective Disorders Benzodiazepine and cyclopyrrolone reduction in general practice — Doesthis lead to concomitant change in the use of antipsychotics?A study based on a Danish population Viggo Rask Kragh Jørgensen Medicine Team, Central Denmark Region, Lægårdvej 12, 7500 Holstebro, Denmark Introduction: In the period 2004–2006, 15 doctors in the Danish municipality of Lemvig Received 11 February 2010 introduced a more restrictive approach to the prescription of benzodiazepines and Received in revised form 6 March 2010 cyclopyrrolones. A prescription could be renewed only following personal consultation, and Accepted 7 March 2010Available online 22 April 2010 prescriptions were issued for only a single month's usage. The intervention reduced theprescription of benzodiazepine anxiolytics by 50%, cyclopyrrolones by 57% and benzodiazepinehypnotics by 55% over a 1½ year period. There is a paucity of knowledge about whether such an intervention reduces drug consumption in general or merely shifts consumption to other drugs. Here especially antipsychotics (AP) are in the spotlight.
Materials and methods: The current article describes the prescription of antipsychotics before and after the intervention. Consumption was followed via the Danish Medicines Agency's website Ordiprax, where the quantity of pharmacy-sold prescription drugs by individual medical practices can be monitored.
Results: The overall increase in the prescription of antipsychotics during the interventiondescribed here was not more than 3.1% of the reduction in prescriptions of benzodiazepine andcyclopyrrolone measured in deﬁned daily doses (DDD).
Conclusion: The intervention against benzodiazepine and cyclopyrrolone did not result in anuncontrollable increase in the prescription of antipsychotic drugs. It cannot be excluded thatthe intervention impacted individual prescriptions. For future interventions of a similar nature,it is recommended that GPs are trained in the use of antipsychotics.
2010 Elsevier B.V. All rights reserved.
Benzodiazepines were introduced in 1960 as a successor Their hypnotic effect disappears to the barbiturates, chloral hydrate and meprobamate after a few months, while their anxiolytic effect has almost Speciﬁc advantages include their disappeared after a few months ( low toxicity and broad therapeutic application. It is now ). Accordingly, patients are consuming recognized that there are signiﬁcant problems associated medicines which have no positive effect in long-term with the use of benzodiazepines and cyclopyrrolones. They may give rise to strong dependence with a pronounced In Denmark 8.2% of the population were users of tolerance development benzodiazepines and cyclopyrrolones in 2008 ). The problem is not only Danish, and the number ofusers in, for example, Ireland and Spain is 25% and 18% of thepopulation respectively. In Norway the corresponding ﬁgureis 6.5% of the adult population ). In ⁎ Ærøvej 1b, 7680 Thyborøn, Denmark. Tel.: +45 97 832300 (Work), +45 Denmark it is estimated that around 2% of the population is 97 832493 (Private); fax: + 45 97 832057.
dependent on these substances ( 0165-0327/$ – see front matter 2010 Elsevier B.V. All rights reserved.
V.R.K. Jørgensen / Journal of Affective Disorders 126 (2010) 293–298 1. Materials and methods corresponding ﬁgure for Switzerland is 1.6% ).
Data were obtained from 15 general practitioners, The rules for the prescription of benzodiazepines and covering 12 medical practices in the Danish municipality of cyclopyrrolones are almost identical in, for example, England, Lemvig. Doctors had a patient base of approximately 20,830 Norway and Denmark patients, of which approximately 1000 patients participated Benzodiazepines and cyclopyrrolones should only be pre- in the intervention All practices scribed for a few weeks, after which a re-evaluation must take participated in the intervention against the overuse of place. These rules of good clinical practice were ﬁrst benzodiazepines and cyclopyrrolones. The two primary advocated in 1988 in a Bulletin of the Royal College of practices initiated the intervention in 2004 and the remaining Psychiatrists (However, no 10 practices followed after the second quarter of 2005. The methods for implementation where indicated, and the practices' results are calculated as the average quarterly scientiﬁc basis for the effectiveness of these rules was prescription in the years preceding the intervention, followed by prescription six quarters later.
In 2003, doctors at two medical practices in the Danish The data compiled here are grouped according to their village of Thyborøn chose to address the issues Anatomical Therapeutic Chemical (ATC) codes The groups give a complete overview of antipsychotics registered collaboration with the Medicine Unit of Ringkjøbing County in Denmark, and are included for the sake of completeness, and the County Medical Health Ofﬁcer, a few simple rules without considering their direct relevance and usefulness as were introduced in the two practices for the prescription of substitutes for benzodiazepines and cyclopyrrolones.
benzodiazepines and cyclopyrrolones, including: The internet site was used for evaluation ), since data were easily available and covers the desired material.
the discontinuation of telephone prescriptions The Ordiprax data base comprises data reported by prescription only following personal consultation pharmacists to the Danish Medicines Agency Pharmaceutical prescription for a maximum of 1 month's consumption Statistics Register for the sale of prescription drugs toindividuals, registered as number of deﬁned daily doses The intervention led to the patient and the doctor re- evaluating on a monthly basis whether current prescription The average of the prescribed volume of antipsychotics levels were appropriate and therefore should continue, or in the four quarters preceding the intervention, is termed whether a reduction should be initiated.
pre-intervention ("Before"). In practices 1 and 2, "Before" In a 3 1/4 year period from 2004, the two practices achieved data covers the year 2003, and for the other practices the a signiﬁcant reduction in the prescription of benzodiazepine period from the second quarter of 2004 to ﬁrst quarter of anxiolytics by 85%, of cyclopyrrolones by 91% and of benzodi- 2005. The average of the prescribed volume of antipsycho- azepine hypnotics by 83% . The remain- tics six quarters after the initiation of the intervention is ing doctors in the municipality were inspired, and subsequently termed post-intervention ("After"). In practices 1 and 2 this introduced similar rules in their practices. One and a half covers the second quarter of 2005, and the third quarter of years after the joint implementation of the rules, prescrip- 2006 for the other practices. The total prescribed volume as tions of benzodiazepine anxiolytics were reduced by 50%, well as the prescribed volume of all of the subgroups was cyclopyrrolones by 57% and benzodiazepine-hypnotics by 55% (). The overall reduction of benzo- In order to facilitate comparison with data from the rest of diazepines and cyclopyrrolones was 2395 DDD / 1000 patients the country, gender and age-standardized data were chosen and no speciﬁc information on antipsychotics was given to Among colleagues it was argued that consumption was patients, or to the staff of the participating physicians, and no probably just transferred to antipsychotics instead. This unusual prescription initiatives in this area were implemented.
objection is academically relevant, as it is known that other The annual average increase in the prescription of interventions of a similar nature have lead to a shift in the antipsychotics for the county was calculated on the basis of consumption of other drugs (). The use quarterly ﬁgures from 2003 to 2006. County prescription of antipsychotics for anxiety disorders are generally consid- levels are illustrated through the use of a bar chart with error ered to be scientiﬁcally poorly elucidated ( bars indicating the least signiﬁcant difference (LSD), p = 0.05 ). In Denmark antipsychotics have occasionally been calculated using analysis of variance (ANOVA) followed by used for the treatment of anxiety disorders.
the Student–Newman–Keuls post-ANOVA test.
This article seeks to illuminate the issue of whether an intervention as described above leads to an actual reduction in benzodiazepine and cyclopyrrolone consumption ormerely shifts consumption to other drugs, and the article 2.1. County results focuses on changes in the prescription of antipsychoticsfollowing a systematic review of the group. The article also The county prescription of antipsychotics increased by aims to strengthen the basis for decision-makers in health 3.7% per year on average during the period 2003–6. The systems who work with addictive medication, as well as increase was statistically signiﬁcant (see ). At the being an inspiration to fellow practitioners.
national level, the increase during the period 2005–6 was 2%.
V.R.K. Jørgensen / Journal of Affective Disorders 126 (2010) 293–298 Each practice had differences in the prescription of The classiﬁcation of antipsychotics after the Anatomical Therapeutic Chemical antipsychotics ranging from 194 to 2474 DDD/1000 patients Classiﬁcation System (ATC)-codes.
per quarter at initiation of the intervention. Six quarters after the initiation the differences ranged from 178 to 2669 DDD/ 1000 patients per quarter. There were also considerable differences in the percentage change in prescriptions, theseranged from a decline of 32% to an increase of 70%. Practice 33 was assigned to the area's only psychiatric institution Phenothiazines with aliphatic side chains The changes in prescriptions within the individual sub- groups are shown in During the initiative the groups N05AF and N05AX showed marked changes. The other groups had only minor variations in prescriptions.
Phenothiazines with piperazine structure In the group N05AF prescription decreased by 37%, equivalent to 1151 DDD throughout the municipality, corresponding to 55 DDD per 1000 patients. This group ﬁrst generation antipsychotics. At the national Phenothiazines with piperidine structure level, prescription in this group is also declining.
Group N05AX consists of second generation antipsycho- tics and shows a numerical increase of 2105 DDD throughout the municipality, representing an increase of 167%. The corresponding result is 101 DDD/ 1000 patients per quarter.
At the national level, a marked increase in prescription also took place within this group.
N05AEIndole derivatives A Danish study from 2003 reveals that 12% of patients Thioxanthen derivatives undergoing a reduction in their prescriptions of benzodiaz- epine were prescribed an alternative nerve medicine, including a signi ﬁcant proportion of antipsychotics ( The overall municipal increase in the prescription of antipsychotics during the intervention was 12.4%, represent- ing an annual increase of 8.2%. The corresponding numerical N05AHDiazepins and oxazepines increase was 76 DDD/1000 patients per quarter. This is considerably larger than the statistically signiﬁcant increase at the county level of 3.7% per year during the intervention period. However this amount corresponds to less than one patient having been treated with 1 DDD/1000 patients per Neuroleptica for tardive dyskinesia quarter. This should also be compared to the fact that the overall reduction in the prescription of benzodiazepines and cyclopyrrolones was 2395 DDD/1000 patients per quarter ). Thus, the increase in prescription of antipsychotics was merely 3.1% of the reduction in prescrip- tions of benzodiazepines and cyclopyrrolones measured in This increase in the prescription of antipsychotics is Other antipsychotics mainly ascribed to the N05AX group, comprising Risperidone (risperdal, ridal) and Aripiprazole (abilify). Both are secondgeneration antipsychotics and are generally regarded to be atleast as effective as ﬁrst generation antipsychotics, and are 2.2. Municipality results much better tolerated with fewer side effects. This group isincreasingly prescribed by local psychiatrists. The N05AF In Lemvig municipality the average prescription of group comprising Flupentixol (ﬂuanxol, depixol, emergil) antipsychotics in 2003 was 65% of county prescription levels Chlorprothixene (truxal, taractan) and Zuclopenthixol (cisor- at initiation of the intervention.
dinol, clopixol, acuphase) are ﬁrst generation antipsychotics, The overall increase in the prescription of antipsychotics and their use is decreasing. This is consistent with the general during the intervention was 12.4%, which represents an national trend ), which is to replace the annual increase of 8.2%. The numerical increase was 76 DDD/ older ﬁrst generation antipsychotics with more modern, 1000 patients per quarter, representing an annual increase of second generation antipsychotics having fewer side effects.
51 DDD/1000 patients per quarter.
The prescription of Flupentixol is declining in spite of the fact
V.R.K. Jørgensen / Journal of Affective Disorders 126 (2010) 293–298 Fig. 1. The total volume of prescribed antipsychotics in Ringkøbing County. The columns indicate average daily deﬁned doses (DDD) per quarter per thousandregistered patients for the year indicated. Errors bars indicate least signiﬁcant difference (p = 0.05) calculated using Analysis of Variance followed by the Student–Newman–Keuls post-ANOVA test.
that is has, to some extent, been prescribed for anxiety increase in prescription of antipsychotics noted in the disorders. The N05AF group is mostly prescribed by psychia- municipality during the intervention may be attributed to trists, and general practices are usually responsible for patients with psychiatric diseases for whom, upon reduction prescription renewals. For the remaining groups of antipsy- of their prescriptions of benzodiazepine and cyclopyrrolone, chotics, changes in prescription volumes are so small that it is discovered that they could be more appropriately treated they are judged to be irrelevant to this study as prescriptions for a few patients could inﬂuence the results.
In accordance with the present study, the consumption of In Lemvig municipality the prescription of antipsychotics antidepressants during the intervention showed no signiﬁ- is substantially under the county average. Part of the cant increase ).
explanation may be that there is only one major psychiatric This study does not address the quality of treatment with institution in the area. There may therefore be a departure antipsychotics. It is also not possible to infer from the results from the municipality by users of antipsychotics to regions whether an under- or over-treatment took place. In addition, having multiple psychiatric facilities. Part of the slight the study provides no information about changes in prescrip- Fig. 2. Change in the prescription of antipsychotics for individual practices over a 1½ year period. On the x-axis, practices are identiﬁed by a double-digit code, with"Total" Indicating the total average change. (A) Changes in the daily deﬁned doses (DDD) per quarter per thousand registered patients. The ﬁrst column indicatesthe average prescription rate in the four quarters prior to the intervention ("Before"), while the second column indicates the prescription rate in the sixth quarterfollowing the start of the intervention ("After"). (B) The percent change in prescriptions of antipsychotics for individual practices.
V.R.K. Jørgensen / Journal of Affective Disorders 126 (2010) 293–298 Fig. 3. Change in the total prescription of antipsychotics issued by twelve Danish practices, during six quarters following the start of the intervention. The ﬁrstcolumn ("Total") indicates the total change in prescriptions. On the x-axis antipsychotic groups are identiﬁed as deﬁned in tions to individual users or about changes in the numbers of users. This study answers only the question of whether thetotal prescribed amount of antipsychotics increased as a Thanks are extended to practitioners in Lemvig for their result of the restrictive attitude towards the prescription of cooperation, as well as their willingness to be the ﬁrst to benzodiazepines and cyclopyrrolones.
implement the new rules in a larger region.
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