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A retrospective study of antipsychotic drug switching in a pediatric population Linton, David; Procyshyn, Ric M; Elbe, Dean; Lee, Lik H N; Barr, Alasdair M Oct 8, 2013

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RESEARCH ARTICLE Open AccessA retrospective study of antipsychotic drugswitching in a pediatric populationDavid Linton1,2, Ric M Procyshyn1,3, Dean Elbe1, Lik Hang N Lee1,2 and Alasdair M Barr1,2*AbstractBackground: Antipsychotic drugs can be used to help treat a wide variety of psychiatric disorders. However,specific antipsychotic drugs for any particular patient may need to be changed for a number of different reasons,including a lack of therapeutic efficacy and / or intolerance to medication side-effects. Drug switching may occurthrough a limited number of established patterns. The nature of these changes is not well characterized in youth,despite their frequent occurrence.Methods: A retrospective analysis of antipsychotic drug switches was conducted on patients who had beenadmitted as inpatients to a tertiary care child and adolescent psychiatric institute. PharmaNet (a large, centraladministrative database) records of all medications prescribed in the 52 weeks prior to admission, and thenbetween admission and discharge, were analyzed for switching patterns. Additional data regarding diagnoses wereobtained from medical chart review.Results: Patients represented a diagnostically heterogeneous population, and almost all antipsychotic drugs wereadministered off-label. In the one year prior to and during admission to the hospital, a total of 31 out of 139patients switched antipsychotic drugs. The frequency of switching increased closer to the time of admission, andthe proportional rate of switching was even higher during hospital stay. The most common switch was fromrisperidone to quetiapine. Our analysis identified three main patterns of drug switching, all occurring with similarfrequency: titrated drug switches, abrupt drug switches and concurrent drug administration.Conclusions: The present study indicates that antipsychotic drug switching in youth may be relatively common,particularly in the year prior to hospitalization. No specific manner of drug switching predominates. This study alsodemonstrates the feasibility of using large administrative databases to characterise switching patterns in youth.Keywords: Adolescent, Antipsychotic, Children, Drug, Polypharmacy, SwitchingBackgroundDue in large part to the advent of the second-generationantipsychotic drugs that are associated with fewer neu-rological side-effects than their predecessors, there hasbeen a widespread recent increase in the utilization ofantipsychotic drugs. This has included the expansion oftheir use to include disorders other than psychosis, forboth on- and off-label indications [1]. One patient po-pulation than has experienced a particularly rapid in-crease in the rate of treatment with second-generationantipsychotic drugs is youth. Rates of antipsychotic druguse among children and adolescents are at historic highs[2,3], and this includes a large proportion of patientstreated for off-label indications [4-6]. Studies of thispopulation have extensively described the patterns andtreatment strategies for antipsychotic drug use in youth:topics range from clinical efficacy [7-9] through to drugassociated side-effects [10-12]. However, almost no re-search has focused on the nature of switching from oneantipsychotic drug to another, which is a common andimportant consideration in the treatment of childrenand adolescents with second-generation antipsychoticdrugs.Switching between antipsychotic drugs may occur fora number of different reasons, in both the youth and* Correspondence: al.barr@ubc.ca1British Columbia Mental Health and Addictions Services Research Institute,938 W 28th Avenue, Vancouver, BC V5Z 4H4, Canada2Department of Anesthesiology, Pharmacology & Therapeutics, University ofBritish Columbia, Vancouver V6T 1Z3, CanadaFull list of author information is available at the end of the article© 2013 Linton et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.Linton et al. BMC Psychiatry 2013, 13:248http://www.biomedcentral.com/1471-244X/13/248adult populations. One of the most frequently citedcauses, regardless of indication, relates to a lack of clin-ical efficacy [13]. A failure of the patient to respond ad-equately, and for the drug to show minimal impact onpsychiatric symptoms, represents a major rationale forantipsychotic drug switching. Similarly, a lack of toler-ance to second-generation antipsychotic drug-associatedside-effects, which typically include cardio-metabolicsequelae [14-18], may result in a change of antipsy-chotic medication [19]. Interestingly, a retrospectivestudy by Nyhius and colleagues [20] of antipsychoticdrug switching in the adult population found that thetwo strongest predictors of switching early duringantipsychotic drug treatment related to a worseningof akathisia and an increase in depression/anxietysymptoms.In adults, not only the drugs which are used duringthe switch itself, but also the manner in which a switchis managed, can strongly increase the risk of developingadditional adverse effects, that may include symptomrelapse [21,22]. Despite these risks, there are often bene-fits conferred by selecting an alternative antipsychoticmedication [23]. Switching antipsychotic medicationshappens frequently in adults, with two U.S. studies pro-viding estimates of between 29.5% [20] and 42% [24] ofpatients treated with antipsychotics switching drugs peryear. Although the risk of rebound or relapse effects hasbeen noted in poorly managed switches [25], we wereunable, in a thorough search of the literature, to identifyprevious studies that had systematically described theprevalence of different techniques of switching anti-psychotic drugs (although see [26]). In addition, there isalso an absence of data describing the frequency and thenature of antipsychotic drug switches in juveniles.In the present study, we therefore evaluated the fre-quency and patterns of antipsychotic drug switching inyouth in the year preceding their admission to a tertiarycare psychiatric institute. Our data consist of prescrip-tions made to inpatients on the psychiatric wards ofa pediatric tertiary care facility in Vancouver, BritishColumbia, as well as all prescriptions made to these pa-tients during the 52-week period prior to their admis-sion. At this tertiary care facility, patients treated withantipsychotic drugs represented a wide range of differentpsychiatric disorders, and as such are a heterogeneouspopulation. Off-label use of antipsychotics in youth iscommon in this population, which includes disordersother than psychosis. In large part , this is because anti-psychotic drugs are used to treat symptoms that arecommon across multiple diagnostic boundaries, such asbehavioral dysregulation [27]. We used a simple andnovel analysis to identify and characterize switches be-tween antipsychotic medications. Due to the nature ofour data, it was also possible to examine when, relativeto the date of admission, switches were performed, andthe prevalence of different switching methods. Addition-ally, we describe the choices of drugs that were used inthis cohort, both in the community and following admis-sion to the hospital.MethodsThe present study represents a retrospective analysis ofdata from all patients, aged 18 years and under, whowere admitted to the psychiatric inpatient program atthe tertiary care BC Children’s Hospital in Vancouver,British Columbia, Canada. Patients were identified basedon admission to one of the psychiatric wards at the B.C.Children’s Hospital between May 1, 2008 and December31, 2009. The Child and Youth Mental Health Programat B.C. Children’s Hospital is a Provincial resource pro-viding mental health assessment and specialized treat-ment for the entire Province. It is also the Province’smain treatment, research and teaching facility for youthmental health. The study protocol was approved by theUniversity of British Columbia Research Ethics Board.The study was conducted in accordance with the princi-ples of Good Clinical Practices and the Declaration ofHelsinki.To investigate psychotropic medication use in the52 weeks prior to hospital admission, data were obtainedfor prescriptions during this period through B.C.PharmaNet, which is a Province-wide network that linksall pharmacies in B.C. to a central set of data systems[28] and can provide medication records as far back as14 months. PharmaNet records contain informationincluding the prescribing physician, name and manu-facturer of the drug, quantity dispensed, dose anddirections for the patient. To investigate medicationsprescribed during hospitalization, which includes the en-tire period between admission and discharge, data wereabstracted from the Department of Pharmacy’s computerdatabase (GE Centricity Pharmacy, v8.2). Data collectedfrom B.C. PharmaNet and the Department of Pharmacyincluded the following list of medications: antipsycho-tics, antidepressants, mood stabilizers, benzodiazepines,anticholinergics, stimulants, and sleep medications. Thismethod did not include “as needed” hora somni medica-tions. A total of 335 patients were identified based ontheir admission date to the B.C. Children’s Hospital; 302of these patients had complete information. These re-cords were used to characterize modifications made toantipsychotic therapy (including starting antipsychotictherapy, discontinuation of antipsychotic therapy andswitching antipsychotic medications), and the drugs,cross-tapering strategies, and doses involved in anti-psychotic switches.“Starts” were defined as a new prescription recordedafter at least 3 weeks with no previous antipsychoticLinton et al. BMC Psychiatry 2013, 13:248 Page 2 of 9http://www.biomedcentral.com/1471-244X/13/248drug prescription. Similarly, “stops” were defined as adiscontinuation of an antipsychotic drug for at least3 weeks, without a new prescription of another anti-psychotic medication. “Switches” were defined as whenone antipsychotic was terminated and a different anti-psychotic was started within at least 3 weeks, or if thetwo antipsychotic prescriptions overlapped with a titrationdown (eventually ending in termination) within 3 weeks.Switches were classified into one of four categories, basedon previously defined approaches: [26,29,30] (i) titratedswitches where at least one drug was tapered, (ii) immedi-ate switches where the first drug was terminated and thesecond drug started abruptly with no overlap or tapering,(iii)“gap” switches, with a gap of less than 3 weeks betweenantipsychotic prescriptions, and (iv) “overlapped” switcheswhere both the initial and the new antipsychotic weregiven concurrently for some period of less than threeweeks ending in a termination of the first antipsychoticwith no titration down. Psychiatric diagnoses representdiagnoses made by physicians at the time of dischargefrom the hospital. All psychiatric diagnoses were obtainedfrom electronic mental health records or physician’s noteswithin the patient’s medical chart.ResultsIn the year prior to hospital admission, there were4818 weeks of antipsychotic prescription which weregiven to a total of 139 patients. Following hospital ad-mission there were 315.4 weeks of prescriptions recor-ded. The mean age of patients was 12.9 ± 3.0 years, andthe population was 63% male. Primary psychiatric diag-nosis at discharge was attention deficit hyperactivity dis-order in 35 patients, anxiety in 35 patients, depressivedisorder in 19 patients, autism in 18 patients, psychosisin 14 patients, bipolar disorder in 12 patients and tic/neurological disorder in 2 patients (Table 1). Antipsy-chotic drug dosing, based on chlorpromazine equiva-lents, differed significantly between diagnoses [F(7,137) =5.86, p < 0.0001)], with dosing notably lower in the twolargest treatment group of ADHD and anxiety patientsthan for patients with depression, bipolar disorder orpsychosis. Antipsychotic polypharmacy (i.e., concurrentadministration of two or more antipsychotic drugs) wasnoted in 35 patients during the study period. Psycho-therapeutic drug combination therapy was relativelycommon. Of the 139 patients receiving antipsychotictreatment, 56 patients were concurrently treated at somepoint with a psychostimulant/ADHD medication, 70 pa-tients with an antidepressant, 33 patients with a moodstabilizer, 11 with a benzodiazepine, and 39 with anyother class of psychotropic drug (such as a sleep medica-tion). By comparison, only two patients were treatedwith a diabetic medication, and 12 were prescribed anantihypertensive agent.Risperidone was the most commonly prescribed anti-psychotic at the time of discharge from the hospital(34% of patients) followed by quetiapine (32% of patients),and olanzapine (9%) (Table 2). The first generation drugschlorpromazine, haloperidol, loxapine, methotrimepra-zine, perphenazine, pimozide, and the second generationdrug ziprasidone accounted for only 7 patients, indicatinginfrequent use of first generation drugs and the low meta-bolic risk second generation antipsychotic ziprasidone.There were no prescriptions of clozapine prior to hospitaladmission, and only one for aripiprazole following ad-mission (aripiprazole was approved in Canada in 2009).Drug dosing, based on chlorpromazine equivalent doses,differed significantly between the antipsychotic drugs[F(5,111) = 8.27, p < 0.0001)]. Amongst the three most com-monly prescribed drugs, doses of risperidone were con-spicuously lower than for olanzapine or quetiapine.Changes to antipsychotic medication were relativelycommon in the year before hospital admission, and thisfrequency increased considerably following admission(Table 3). Of the 139 patients who received antipsychoticprescriptions in the year prior to admission, 25 patientsswitched between antipsychotic medications at somepoint during the year prior to their hospital admission, 1of these patients switched antipsychotic medicationstwice, and 6 different patients switched antipsychoticsfollowing hospital admission for a total of 31 patientsswitching antipsychotics 32 times. Also, 99 unique pa-tients started an antipsychotic prescription a total of 144times, and 63 patients terminated an antipsychotic pre-scription a total of 90 times in the 12 months prior tohospital admission. Following admission, a total of 15patients started antipsychotics 23 times, and 11 patientsstopped antipsychotics 14 times. Many of the switchesrecorded (40.6%, 13 of 32) were in patients changingfrom risperidone to quetiapine. Switches from rispe-ridone to olanzapine, quetiapine to risperidone, andquetiapine to olanzapine each occurred in 4 (12.5%) pa-tients. Of the other switches that were performed, halo-peridol, aripiprazole, and chlorpromazine were involvedin only two switches, and loxapine was involved in asingle switch.The average maintenance doses were also analyzed forthe drugs given before and after all switches. Equivalentdosing of risperidone, olanzapine and quetiapine did notdiffer significantly before or after the switch with the ex-ception of a single patient who was receiving a mainten-ance dose of 1000 mg quetiapine and switched to 10 mgof olanzapine (Table 4). All doses before and after swit-ches were also converted to chlorpromazine equivalentdoses, as previously [31,32]. Chlorpromazine equivalentdoses did not change significantly following the switch.Many of the switches (11 of 32) were clearly titrated,however switches with no sign of titration or a small gapLinton et al. BMC Psychiatry 2013, 13:248 Page 3 of 9http://www.biomedcentral.com/1471-244X/13/248Table 1 Characterization of study population receiving treatment with an antipsychotic medicationDepressive disorder Anxiety Attention-deficithyperactivity disorderPsychosis Bipolar disorder Substance abuse Autism Tics/NeurologicaldisorderSubjects (M/F) 19 (6/13) 35 (27/8) 35 (26/9) 14 (8/6) 12 (6/6) 3 (2/1) 18 (12/6) 2 (2/0)Mean Age (SD) 15.05 (1.92) 11.10 (2.81) 10.45 (2.60) 15.65 (1.25) 13.07 (3.22) 15.76 (0.54) 12.42 (3.17) 10.41 (2.21)Risperidone (% of Dx group) 3 (15.8) 14 (40.0) 17 (48.6) 5 (35.7) 1 (8.3) 0 (0.0) 7 (38.9) 0 (0.0)Mean Dose mg (SD) 0.92 (0.63) 0.89 (0.50) 1.01 (0.50) 2.20 (1.10) 1.00 0 1.54 (1.10) 0Olanzapine (% of Dx group) 5 (26.3) 0 (0.0) 0 (0.0) 5 (35.7) 0 (0.0) 0 (0.0) 3 (16.7) 0 (0.0)Mean Dose mg (SD) 6.00 (1.37) 0 0 15.00 (3.54) 0 0 11.67 (2.89) 0Quetiapine (% of Dx group) 7 (36.8) 11 (31.4) 7 (20.0) 5 (35.7) 8 (66.7) 0 (0.0) 5 (27.8) 1 (50.0)Mean Dose mg (SD) 251.79 (195.31) 138.64 (128.51) 89.29 (34.93) 325.00 (269.26) 276.56 (208.14) 0 160.00 (96.18) 75Ziprasidone (% of Dx group) 0 (0.0) 0 (0.0) 1 (2.9) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)Mean Dose mg (SD) 0 0 40 20 0 0 0 0Aripiprazole (% of Dx group) 0 (0.0) 0 (0.0) 0 (0.0) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)Mean Dose mg (SD) 0 0 0 7.5 0 0 0 0FGAs (% of Dx group) 2 (10.5) 0 (0.0) 0 (0.0) 2 (14.3) 0 (0.0) 0 (0.0) 1 (5.6) 0 (0.0)Mean Dose mg (SD) - - - - - - - -CPZ Equiv mg (SD) 220.60 (217.14) 110.76 (134.21) 73.44 (54.30) 316.07 (253.32) 333.33 (280.50) 0 186.01 (185.73) 100.00# Emergency Visits (SD) 0.58 (0.77) 0.66 (1.37) 0.74 (1.77) 0.79 (1.19) 0.33 (0.78) 1.67 (1.15) 0.78 (2.07) 1.50 (2.12)Switched Pre Hosp (% of Dx group) 7 (36.8) 5 (14.3) 6 (17.1) 1 (7.1) 3 (25.0) 1 (33.3) 2 (11.1) 1 (50.0)Switched Post Hosp (% of Dx group) 0 (0.0) 0 (0.0) 1 (2.9) 4 (28.6) 1 (8.3) 0 (0.0) 0 (0.0) 0 (0.0)139 patients were identified who had been treated with an antipsychotic drug either during hospital admission or in the 52 weeks prior to admission. Table indicates characteristics of groups based on differentpsychiatric diagnosis at time of discharge. FGA = First Generation Antipsychotic; CPZ = Chlorpromazine.Lintonetal.BMCPsychiatry2013,13:248Page4of9http://www.biomedcentral.com/1471-244X/13/248Table 2 Characterization of study population receiving treatment with an antipsychotic medicationRisperidone Olanzapine Quetiapine Ziprasidone Aripiprazole FGAs No medicationSubjects (M/F) 47 (35/12) 13 (6/7) 44 (29/15) 2 (2/0) 1 (0/1) 5 (3/2) 39 (22/17)Mean Age (SD) 11.54 (3.13) 15.16 (2.12) 13.31 (2.97) 14.63 (0.36) 16.77 15.22 (1.16) 11.88 (3.27)Mean Dose mg (SD) 1.18 (0.78) 10.77 (4.83) 196.02 (175.58) 30.00 (14.14) 7.50 - -CPZ Equiv mg (SD) 58.78 (39.09) 215.38 (96.58) 261.36 (234.10) 50.00 (23.57) 100.00 119.29 (111.33) -On-Label Use (% of total on drug) 11 (23.4) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100.0) 0 (0.0) -Off-Label Use (% of total on drug) 36 (76.6) 13 (100.0) 44 (100.0) 2 (100.0) 0 (0.0) 5 (100.0) -Titrated Switch Pre Hosp (% of switches) 1 (3.1) 2 (6.3) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.1) 2 (6.3)Titrated Switch Post Hosp (% of switches) 1 (3.1) 2 (6.3) 2 (6.3) 0 (0.0) 1 (3.1) 0 (0.0) 0 (0.0)Immediate Switch Pre Hosp (% of switches) 0 (0.0) 0 (0.0) 2 (6.3) 0 (0.0) 0 (0.0) 0 (0.0) 2 (6.3)Immediate Switch Post Hosp (% of switches) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)Gap Switch Pre Hosp (% of switches) 0 (0.0) 2 (6.3) 3 (9.4) 0 (0.0) 0 (0.0) 0 (0.0) 3 (9.4)Gap Switch Post Hosp (% of switches) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)Overlapped Switch Pre Hosp (% of switches) 3 (9.4) 1 (3.1) 4 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 2 (6.3)Overlapped Switch Post Hosp (% of switches) 0 (0.0) 0 (0.0) 1 (3.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)139 patients were identified who had been treated with an antipsychotic drug either during hospital admission or in the 52 weeks prior to admission. Table indicates characteristics of groups based on differentantipsychotic drug treatments at time of discharge. FGA = First Generation Antipsychotic; CPZ = Chlorpromazine.Lintonetal.BMCPsychiatry2013,13:248Page5of9http://www.biomedcentral.com/1471-244X/13/248(less than 3 weeks) were also evident (4 of 32 and 7 of32 respectively), and tended to occur with a higher fre-quency closer to admission (Figure 1). There were also anotable proportion of switches where the two drugswere prescribed concurrently for a short period with notapering of either dose (10 of 32 switches).DiscussionIn the present study, we characterized a number of dif-ferent variables related to antipsychotic drug switchingin youth, including frequency of switches, antipsychoticdrugs involved and method of switching prior and dur-ing admission to a tertiary care psychiatric hospital. Thepopulation was heterogeneous in terms of diagnoses,with 63% of all patients having a diagnosis of an anxietydisorder, autism or ADHD at the time of discharge. Dos-ing in patients treated with risperidone at time of dis-charge was significantly lower than in patients treatedwith the alternate second generation antipsychotic drugsolanzapine or quetiapine. This likely reflects the moreselective use of risperidone for disruptive behavior and/or anxiety than the other antipsychotics which are pre-ferred for treating the symptoms of psychosis or bipolardisorder.The frequency of switching in children and adoles-cents in this cohort was similar to reported frequenciesin adults. The rate of 0.31 switches per year of therapyin the community is very close to the rate of 29.5% thatwas found by Nyhuis et al. [20] in a prospective adultcohort (n = 648), although somewhat lower than the rateof 42% reported by Covell et al. [24] in a chart review of400 adults with schizophrenia. Whether this differencewith the latter study may be due to the age of the currentpopulation or use of antipsychotics for disorders primarilyother than psychosis remains unknown. Following ad-mission to the B.C. Children’s Hospital, modifications toantipsychotic therapy were made more frequently. This isperhaps not unexpected, as any patient experiencing anexacerbation of their symptoms may tend to be admittedand switch antipsychotics due to a lack of efficacy. How-ever, it is unclear whether the increased switch frequencyfollowing admission may also result from differences inprescribing practices between hospital and communityphysicians, including general practitioners [6].It is notable that a large proportion of the switches(13, 40.6%) were made from risperidone to quetiapine. Alimitation of the current study is that we were not ableto ascertain the physician’s reasons for switching anti-psychotic drugs. Thus, we do not know whether theseswitches were related to a lack of efficacy or an intoler-ance to drug side-effects. For example, risperidone hasbeen associated with equal if not greater efficacy in con-trolling psychosis in youth [33]. While metabolic side-effects are generally similar between the two drugs [34],risperidone has been associated with higher rates ofextrapyramidal symptoms, akathisia and elevated prolac-tin levels than quetiapine [35,36]. A large proportion ofswitches from risperidone to quetiapine would thereforebe consistent with a lack of drug tolerance in patients,but prospective studies are needed to confirm such hy-potheses. The similar levels of dosing before and afterantipsychotic switches suggest that the new drug startedfollowing a switch did not tend to be effective at lowerdoses than the drug that was being discontinued. Con-versely, the lack of a significant increase in dosing fol-lowing the switch suggests a level of consistency in dosein terms of chlorpromazine equivalent doses on the partof physicians.When analyzing the patterns of switching, it was clearthat no one particular type of drug switch strategy waspredominant. Titrated switches accounted for approxi-mately one third of all switches, while “abrupt” switchesTable 3 Numbers of patient-weeks as well as the number of starts, stops, and switches were comparedNumberof weeksNumberof switchesSwitchesper yearNumberof startsStartsper yearNumberof stopsStopsper yearBefore Admission 4321 26 0.313 144 1.733 90 1.083After Admission 247.7 6 1.260 23 4.828 14 2.939Starts were defined as any new antipsychotic prescription following a period of at least 3 weeks with no antipsychotic prescriptions; similarly stops were definedas the discontinuation of antipsychotic prescription for at least three weeks. Switches were defined as a new antipsychotic medication started within three weeks(before or after) the termination or beginning of titrating down to termination of another antipsychotic prescription. Frequencies were compared using aChi-squared test, and all changes were significant.Table 4 Average, minimum, and maximum maintenance doses for antipsychoticsPrior to switch Following switchDrug Average Minimum Maximum Drug Average Minimum MaximumRisperidone (n = 19) 1.24 0.25 2.5 Risperidone (n = 5) 1.2 0.5 4.0Olanzapine (n = 3) 10 5 15 Olanzapine (n = 9) 9.17 5 15Quetiapine (n = 8) 168.75 25 1000 Quetiapine (n = 13) 95.8 37.5 150Both prior to switching, and following a switch between antipsychotic medications. The doses (mg) are largely similar before and after a switch ofantipsychotic medication.Linton et al. BMC Psychiatry 2013, 13:248 Page 6 of 9http://www.biomedcentral.com/1471-244X/13/248accounted for another third, and the final third wasevident as concurrent administration of full doses of twodrugs for a period followed by abrupt termination of theinitial drug. We found no evidence for other types ofswitches, including the “plateau cross-taper switch”[29,30] (i.e. gradual start of new antipsychotic, followedby treatment with full dose of both drugs, followed bytapering of the original antipsychotic). However, giventhe modest number of total switches out of a total of4818 weeks of antipsychotic drug prescription, it is likelythat additional strategies for switching antipsychoticdrugs would have been evident with a larger sample size.It has been suggested that specific switching strategiesmay be best suited to certain antipsychotic drug combi-nations. For example, Buckley and Correll suggested thatthe plateau cross-titration switch may be preferable for aswitch to a drug with a long half-life, such as aripipra-zole [29]. We did not find strong evidence for specificpatterns of drug switches with specific antipsychoticdrug combinations, but again this may reflect the needto reproduce these findings in a considerably largerdataset. However, we did note a greater proportion of ti-trated switches following admission to hospital com-pared to prior to admission. This may reflect the highlevel of expertise and knowledge about antipsychoticdrug use and drug titration at the tertiary care facilitycompared to community settings.By examining the data on switching longitudinally inthe year prior to admission to the hospital, we were ableto determine that the frequency of all switches–parti-cularly those without any kind of titration–was clearlyhigher approaching hospital admission. This finding isopen to interpretation. It seems most likely that this re-flects a worsening of symptoms which remain refractoryto drug treatment, ultimately leading to hospitalization,with switches occurring as an attempt to improve clini-cal efficacy. While inopportune antipsychotic drug swit-ching can cause adverse effects [25], it would be unlikelyfor these effects to result in hospitalization.ConclusionsIn summary, to our knowledge the present findingsdescribe for the first time the frequencies of differentpatterns of antipsychotic drug switching techniques usedin youth with a heterogeneous diagnostic background.Three distinct patterns of switches occurred with similarfrequency. Less common switching patterns may also bepresent in the larger population, as well as switches as-sociated with specific antipsychotic drug combinations.However, observation of these may require the use ofType of Switch0123456-48 -44 -40 -36 -32 -28 -24 -20 -16 -12 -8 -4 0 4 8 12Week (Relative to Admission)# of SwitchesImmediateGapOverlap – no Titration TitratedFigure 1 Distribution and type of switch between antipsychotics made in 52-weeks prior to hospital admission. Titrated switches weredefined as any switch involving either a gradual reduction in dose of the old antipsychotic or a gradual increase in the new antipsychotic within3 weeks of starting the second drug. Immediate switches were made with no overlap between the two drugs, and no titration. Gap switchesinvolved the termination of one medication with a period of less than three weeks where there were no records of antipsychotic prescriptionsprior to starting a different antipsychotic. Overlapped switches involved the two drugs being prescribed concurrently for a period of less thanthree week with no reduction of dose in the initial antipsychotic, nor a gradual increase in dose in the second drug.Linton et al. BMC Psychiatry 2013, 13:248 Page 7 of 9http://www.biomedcentral.com/1471-244X/13/248larger sample sizes from major administrative databases.Nevertheless, the present study has indicated the feasi-bility of studying such switches retrospectively usingnon-chart based procedures, which may be useful forunderstanding how switching occurs at a larger scale. Ef-fective antipsychotic drug switching remains an import-ant concern, and suboptimal switching may contributeto both patient discomfort and lack of drug adherence.A better understanding of how most antipsychotic drugsswitches happen may be one of the first steps to ad-dressing this amenable issue.Competing interestsDr Procyshyn is a paid consultant and is on the speaker’s bureau forAstraZeneca, Bristol-Myers Squibb, Janssen, Otsuka, Pfizer, and Sunovion.Dr Barr has received grants from Bristol-Myers Squibb and advisory fees fromRoche. Dr Elbe, Mr Linton and Mr Lee declare no relevant competing interests.Authors’ contributionsDL and LHNL acquired and transcribed the data, and developed andanalyzed the database. DE and AMB analyzed and interpreted the data. RMP,DL and AMB wrote the manuscript. All authors approved the final version ofthe manuscript.AcknowledgementsThis research was supported by CIHR Grant #230198 to Drs Procyshynand Barr.Author details1British Columbia Mental Health and Addictions Services Research Institute,938 W 28th Avenue, Vancouver, BC V5Z 4H4, Canada. 2Department ofAnesthesiology, Pharmacology & Therapeutics, University of British Columbia,Vancouver V6T 1Z3, Canada. 3Department of Psychiatry, University of BritishColumbia, Vancouver V6T 1Z3, Canada.Received: 5 December 2012 Accepted: 3 October 2013Published: 8 October 2013References1. Procyshyn RM, Honer WG, Wu TK, Ko RW, McIsaac SA, Young AH, JohnsonJL, Barr AM: Persistent antipsychotic polypharmacy and excessive dosingin the community psychiatric treatment setting: a review of medicationprofiles in 435 Canadian outpatients. J Clin Psychiatry 2010, 71(5):566–573.2. 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Cohen D, Bonnot O, Bodeau N, Consoli A, Laurent C: Adverse effects ofsecond-generation antipsychotics in children and adolescents: aBayesian meta-analysis. J Clin Psychopharmacol 2012, 32(3):309–316.35. Pringsheim T, Lam D, Ching H, Patten S: Metabolic and neurologicalcomplications of second-generation antipsychotic use in children: asystematic review and meta-analysis of randomized controlled trials.Drug Saf 2011, 34(8):651–668.36. Potkin SG, Gharabawi GM, Greenspan AJ, Mahmoud R, Kosik-Gonzalez C,Rupnow MF, Bossie CA, Davidson M, Burtea V, Zhu Y, et al: A double-blindcomparison of risperidone, quetiapine and placebo in patients withschizophrenia experiencing an acute exacerbation requiringhospitalization. Schizophr Res 2006, 85(1–3):254–265.doi:10.1186/1471-244X-13-248Cite this article as: Linton et al.: A retrospective study of antipsychoticdrug switching in a pediatric population. BMC Psychiatry 2013 13:248.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitLinton et al. BMC Psychiatry 2013, 13:248 Page 9 of 9http://www.biomedcentral.com/1471-244X/13/248


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