Pharmacoepidemiology of Tourette and Chronic Tic Disorders in Sweden 2005

Abstract

Background:

Monitoring “real world” dispensation patterns over time is important to build the evidence base for safe and efficient use of psychotropic drugs. In this study, we aimed to comprehensively examine the patterns of psychotropic drug dispensations in patients with Tourette and chronic tic disorders (TD/CTD) in Sweden between 2005 and 2013.

Methods:

A cohort of 6979 TD/CTD patients was identified through the Swedish National Patient Register. Their drug dispensation patterns, collected in the Swedish Prescribed Drug Register, were examined between July 1, 2005 and December 31, 2013. Frequencies of drug dispensations were further stratified by gender and comorbidities. Additionally, differences in the patterns of dispensation in children and adolescents versus adults in the last year of the follow-up were examined, as well as the time trends of the dispensations over the 8-year study period.

Results:

A total of 5299 (75.9%) TD/CTD patients were dispensed at least one drug during the study period. The most frequently dispensed medications were attention-deficit/hyperactivity disorder (ADHD) drugs (53.8%), antidepressants (50.7%), hypnotics/sedatives (41.7%), and antipsychotics (41.5%). Most of the medicated patients (72.1%) were dispensed more than one drug during the study period. Patterns of dispensation varied according to patient's gender, associated comorbidities, and age group. Dispensation of quetiapine and aripiprazole, antiadrenergics, ADHD drugs, antiepileptics, and hypnotics/sedatives and anxiolytics (particularly the nonbenzodiazepine types) significantly increased over time, whereas dispensation of antidepressants, typical antipsychotics, and benzodiazepine-based anxiolytics significantly decreased over the study period.

Conclusions:

Long-term monitoring of these drug dispensation patterns and the study of both their beneficial and adverse effects is warranted.

Introduction

Tourette disorder (TD) and chronic tic disorders (CTD) are childhood-onset neurodevelopmental disorders characterized by multiple motor and at least one vocal tic in TD, and multiple motor tics or vocal tics in CTD, persisting for more than 1 year. TD/CTD affect up to 0.5%–1% of the population (Scahill et al. 2014; Scharf et al. 2015). A majority of patients (80%–90%) have comorbid conditions, including attention-deficit/hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and pervasive developmental disorders (PDD), which are often more impairing than the tics themselves (Robertson 2015).

Treatment strategies for TD/CTD may differ depending on the impairment associated with the tics and the presence of comorbid conditions (Debes et al. 2010). Mild cases with low levels of impairment may benefit from a “wait and see” strategy, psychoeducation, and reassurance (Murphy et al. 2013). However, in cases with more severe levels of impairment, an active intervention should be considered (Roessner et al. 2011). Evidence-based interventions for the treatment of TD/CTD include both behavior therapy and pharmacological treatment (Hollis et al. 2016).

Drug trials in TD/CTD are scarce, based on small sample sizes, have generally short-term follow-up periods (Farag et al. 2015), and rarely account for the presence of comorbidities (Whittington et al. 2016). Consequently, current clinical guidelines for TD/CTD are mainly based on expert consensus rather than on rigorous controlled treatment studies (Müller-Vahl and Roessner 2011; Roessner et al. 2011; Verdellen et al. 2011; Pringsheim et al. 2012; Steeves et al. 2012; Murphy et al. 2013). This leads to a lack of consistency across different treatment guidelines, especially regarding pharmacological treatments. For example, while the European clinical guidelines (Roessner et al. 2011) recommend risperidone as first-line treatment, followed by clonidine and aripiprazole, the Canadian guidelines (Pringsheim et al. 2012) recommend clonidine and guanfacine as first treatment options, and the German guidelines (Rothenberger et al. 2007) recommend sulpiride and tiapride. The Food and Drug Administration (FDA) in the United States (US) has to date only approved haloperidol (Shapiro et al. 1989), pimozide (Shapiro and Shapiro 1984), and aripiprazole (Sallee et al. 2017) for the treatment of tic disorders. In Sweden, clinicians are encouraged to follow the recommendations by the European guidelines (Roessner et al. 2011), but only haloperidol is approved for the treatment of tic disorders (Andrén 2017).

In an attempt to understand the prescription practices for CTDs in the “real world,” a handful of studies have previously evaluated use of psychotropic medication in children and adolescents with TD/CTD. In a Danish clinical cohort of 314 children and adolescents with TD, 60.5% had received pharmacological treatment, mainly methylphenidate (61%) and risperidone (29.5%). Additionally, clonidine, pimozide, and serotonin reuptake inhibitors (SRIs) were prescribed in about 20% of the children (Debes et al. 2009). Farag et al. (2015) examined the prescribing patterns of 400 TD patients seen over a 10-year period in a specialized clinic in the United Kingdom. The most frequently used drugs were aripiprazole (64%), clonidine (40%), risperidone (30%), sulpiride (29%), and haloperidol (20%).

Bachmann et al. (2015) studied the psychopharmacological prescriptions of 7058 children and adolescents with tic disorders for the years 2006 and 2011 in the largest German health insurance fund. Of these, 1499 (21%) had at least one prescription of psychotropic medication in 2011, although this percentage was age related and increased from 4.9% in individuals 0–4 years of age to 36.6% in15–19 years of age. The highest frequency of prescription was found in TD (52% in 2006 and 53% in 2011). ADHD drugs (methylphenidate and atomoxetine) were the most prescribed medications, followed by antipsychotics. In 2011, prescriptions of atypical antipsychotics were higher and prescriptions of typical antipsychotics were lower than in 2006.

Olfson et al. (2011) examined the use of medication in tic disorders over the course of 1 year in privately and publicly insured youth from the U.S. population. The results showed that the privately insured group of patients was mainly treated with antiadrenergic agents (36%), followed by antidepressants (35%), antipsychotics (33%), and psychostimulants (32%), whereas in the publicly insured group, antipsychotics were the most commonly prescribed medication (54%). However, most of these previous studies employed retrospective data from medical charts, had short follow-up times, or focused on specific populations (e.g., only children and adolescents).

This Swedish population-based study aimed to prospectively investigate the patterns of psychotropic drug dispensations in children and adults with TD/CTD during a period of 8 years. As a secondary aim, we also examined the influence of gender, comorbidities, age group, and time trends in the dispensation patterns of this group. Monitoring of such “real-world” dispensation practices over time is vitally important to build the evidence base for safe and efficient use of psychotropic drugs.

Methods

The study was approved by the Regional Ethics Review Board in Stockholm (2013/862-31/5). The requirement for informed consent was waived because the study was register based and the included individuals were not identifiable at any time.

Swedish national registers

Using the unique national identification numbers assigned to Swedish citizens as key and recoded for anonymity (Ludvigsson et al. 2009), we linked several Swedish population-based registers. The Total Population Register contains demographic information on individuals registered as Swedish inhabitants. The National Patient Register (NPR) comprises information on all inpatient care (from 1969) and outpatient specialist services (from 2001) in Sweden. Diagnoses in the NPR are based on the International Classification of Diseases (ICD), eighth (ICD-8; 1969–1986), ninth (ICD-9; 1987–1996), and tenth (ICD-10; 1997–2013) revisions. The Prescribed Drug Register (PDR) was introduced in July 2005 and includes a record for all medications dispensed in Sweden (registered using Anatomical Therapeutic Chemical [ATC] codes) and the corresponding dosage. The PDR has full coverage of the Swedish population. The Cause of Death Register and the Migration Register were used to exclude those individuals who were not alive or had emigrated from Sweden during the study period.

Patient cohort

Patients with a diagnosis of TD or CTD (ICD-8 code 306.2; ICD-9 code 307C; ICD-10 codes F95.0 [transient tic disorder], F95.1 [chronic motor or vocal tic disorder], F95.2 [TD], F95.8 [other tic disorders], or F95.9 [unspecified tic disorder]) between January 1, 1969 and December 31, 2013 were identified from the NPR. A previously validated algorithm, described in detail in Rück et al. (2015) was used. This approach results in nearly perfect interrater reliability and highly valid diagnoses.

Identified individuals with a diagnosis of TD/CTD who were living in Sweden during the period July 1, 2005 and December 31, 2013 were included in the study. Lifetime comorbid diagnoses of ADHD, OCD, PDD, depressive, anxiety, conduct, and nonorganic sleep disorders were identified. We excluded patients who had a lifetime diagnosis of any of the following comorbid conditions that may confound the usual patterns of prescription in TD/CTD: organic mental disorders, epilepsy, schizophrenia spectrum disorders, or bipolar disorder. ICD codes of the included and excluded comorbidities are shown in Supplementary Table S1 (Supplementary Data are available online at www.liebertpub.com/cap).

Drug dispensation outcomes

Drugs affecting the central nervous system were identified from the PDR according to the ATC classification system (codes N01-07) and included ADHD drugs, antidepressants, antipsychotics, anxiolytics, hypnotics/sedatives, antiadrenergic agents, antiepileptics, anesthetics, analgesics, antiparkinson drugs, and other nervous system drugs (ATC codes are listed in Supplementary Table S2).

Statistical analyses

Analyses were primarily descriptive (i.e., counts of different classes of drugs according to their ATC codes during the study period). Frequencies of drug dispensations were further stratified by gender and comorbidities. Examining the role of comorbid disorders in the dispensation patterns was particularly relevant since the PDR does not specify the indication of the drugs dispensed. Additionally, the dispensation patterns in children and adolescents (<18 years) versus adults (≥18 years) in the last year of the follow-up (2013) were examined. Individuals turning 18 in 2013 were left out to allow for mutually exclusive age groups. Results were expressed as odds ratios (ORs) and 95% confidence intervals (CI).

Annual trends of the dispensation patterns were examined for each year from 2006 to 2013. Data from 2005 were not analyzed, as PDR covers only 6 months in 2005. The relative change (RC) is reported in percentages, with positive values corresponding to over time increases and negative values corresponding to decreases. Cochran–Armitage tests for trend were used to assess whether there was a trend in annual prevalence or proportions of each class of medication across time, with two-sided p-value <0.05 supporting the trend hypothesis.

Results

Study cohort

A total of 7889 TD/CTD cases were identified in the period from January 1, 1969 to December 31, 2013, of which 910 were excluded due to the comorbidities listed above. Of the final 6979 included patients, 77.3% (n = 5397) were male. A large majority (n = 5702; 81.7%) had at least one lifetime comorbid diagnosis (Supplementary Table S3).

Drug dispensation patterns in TD/CTD

The majority of TD/CTD patients (n = 5299; 75.9%) were dispensed at least one drug during the study period (July 1, 2005 to December 31, 2013). Medicated (n = 5299) and unmedicated (n = 1680) individuals had a similar gender distribution (77.34% vs. 77.32% of men, respectively; Chi-square = 0.0001, p = 0.9905). Compared with unmedicated individuals, medicated individuals were older (64.89% vs. 46.16% of patients older than 18 at the end of the follow-up, respectively; Chi-square = 173.56, p < 0.0001) and had a higher percentage of any psychiatric comorbidity (81.68% vs. 30.18%, respectively; Chi-square = 1589.43, p < 0.0001).

Among the 5299 medicated TD/CTD cases, the most frequently dispensed medications were ADHD drugs (53.8%), antidepressants (50.7%), hypnotics/sedatives (41.7%), and antipsychotics (41.5%). Other commonly dispensed drugs were anxiolytics (36.5%), analgesics (33.3%), antiepileptics (13.5%), other nervous system drugs (5.2%), anesthetics (5.1%), antiparkinson drugs (3.6%), and antiadrenergic agents (3.4%; Table 1).

Table 1.

Most Frequent Dispensations in Individuals with Tourette/Chronic Tic Disorders During the Study Period (July 1, 2005 to December 31, 2013)

	n	Proportion of the total of TD/CTD patients (n = 6979) % ^a	Proportion of the medicated TD/CTD patients (n = 5299) % ^a
ADHD drugs	2851	40.9	53.8
Methylphenidate	2559	36.7	48.3
Atomoxetine	1450	20.8	27.4
Antidepressants	2685	38.5	50.7
SRIs	2392	34.3	45.1
SNRIs	486	7.0	9.2
Other antidepressants	885	12.7	16.7
Antipsychotics	2197	31.5	41.5
Typical antipsychotics	591	8.5	11.2
Haloperidol	250	3.6	4.7
Pimozide	86	1.2	1.6
Tiapride	4	0.1	0.1
Atypical antipsychotics	2009	28.8	37.9
Risperidone	1394	20.0	26.3
Aripiprazole	714	10.2	13.5
Olanzapine	375	5.4	7.1
Quetiapine	337	4.8	6.4
Ziprasidone	81	1.2	1.5
Anxiolytics	1934	27.7	36.5
Benzodiazepine-based anxiolytics	934	13.4	17.6
Nonbenzodiazepine-based anxiolytics	1447	20.8	27.3
Hypnotics/sedatives	2212	31.7	41.7
Benzodiazepine-based hypnotics	1019	14.6	19.2
Nonbenzodiazepine-based hypnotics	1784	25.6	33.7
Antiadrenergic agents	182	2.6	3.4
Clonidine	171	2.5	3.2
Guanfacine	13	0.19	0.2
Antiepileptics	715	10.2	13.5
Anesthetics	269	3.9	5.1
Analgesics	1764	25.3	33.3
Antiparkinson drugs	189	2.7	3.6
Other nervous system drugs	274	3.9	5.2

The sum of percentages exceeds 100% because most patients were on more than one class of drugs during the study period.

SNRI, serotonin–norepinephrine reuptake inhibitors; SRI, serotonin reuptake inhibitors; TD, Tourette disorder; CTD, chronic tic disorder.

Gender

The same proportion of males and females (75.9%) were dispensed medications during the study period (4098 of 5397 males, 1201 of 1582 females). However, the dispensation patterns were different according to the gender. ADHD were more likely to be dispensed to males, compared with females (OR = 0.52). Conversely, females were more likely than males to be dispensed analgesics (OR = 1.93), all groups of antidepressants (OR = 1.74), anxiolytics (OR = 1.72), benzodiazepine-based hypnotics (OR = 1.77), antiepileptics (OR = 1.54), anesthetics (OR = 1.53), and antiparkinson drugs (OR = 1.54). Additionally, females were also more likely to be dispensed certain antipsychotics, such as typical antipsychotics (OR = 1.45), quetiapine (OR = 1.33), and aripiprazole (OR = 1.28; Table 2).

Table 2.

Drug Dispensations in Medicated Individuals with Tourette/Chronic Tic Disorders (n = 5299) During the Study Period (July 1, 2005 to December 31, 2013), by Gender

		n	%	OR (95% CI)^a
ADHD drugs	Males	2354	57.4	0.52 (0.46–0.60)
ADHD drugs	Females	497	41.4	0.52 (0.46–0.60)
Methylphenidate	Males	2113	51.6	0.56 (0.49–0.63)
Methylphenidate	Females	446	37.1	0.56 (0.49–0.63)
Atomoxetine	Males	1214	29.6	0.58 (0.50–0.68)
Atomoxetine	Females	236	19.7	0.58 (0.50–0.68)
Antidepressants	Males	1950	47.6	1.74 (1.52–1.98)
Antidepressants	Females	735	61.2	1.74 (1.52–1.98)
SRIs^b	Males	1731	42.2	1.67 (1.47–1.91)
SRIs^b	Females	661	55.0	1.67 (1.47–1.91)
SNRIs^c	Males	327	8.0	1.76 (1.44–2.15)
SNRIs^c	Females	159	13.2	1.76 (1.44–2.15)
Other antidepressants^d	Males	625	15.3	1.54 (1.31–1.81)
Other antidepressants^d	Females	260	21.6	1.54 (1.31–1.81)
Antipsychotics	Males	1676	40.9	1.11 (0.97–1.26)
Antipsychotics	Females	521	43.4	1.11 (0.97–1.26)
Typical antipsychotics	Males	420	10.2	1.45 (1.20–1.76)
Typical antipsychotics	Females	171	14.2	1.45 (1.20–1.76)
Haloperidol	Males	186	4.5	1.18 (0.88–1.59)
Haloperidol	Females	64	5.3	1.18 (0.88–1.59)
Pimozide	Males	59	1.4	1.57 (0.99–2.49)
Pimozide	Females	27	2.2	1.57 (0.99–2.49)
Atypical antipsychotics	Males	1550	37.8	1.02 (0.89–1.16)
Atypical antipsychotics	Females	459	38.2	1.02 (0.89–1.16)
Tiapride	Males	4	0.1	—
Tiapride	Females	0	0.0	—
Risperidone	Males	1098	26.8	0.89 (0.77–1.04)
Risperidone	Females	296	24.6	0.89 (0.77–1.04)
Aripiprazole	Males	524	12.8	1.28 (1.07–1.54)
Aripiprazole	Females	190	15.8	1.28 (1.07–1.54)
Olanzapine	Males	283	6.9	1.12 (0.88–1.43)
Olanzapine	Females	92	7.7	1.12 (0.88–1.43)
Quetiapine	Males	244	6.0	1.33 (1.04–1.70)
Quetiapine	Females	93	7.7	1.33 (1.04–1.70)
Ziprasidone	Males	56	1.4	1.53 (0.95–2.47)
Ziprasidone	Females	25	2.1	1.53 (0.95–2.47)
Anxiolytics	Males	1375	33.6	1.72 (1.51–1.97)
Anxiolytics	Females	559	46.5	1.72 (1.51–1.97)
Benzodiazepine-based anxiolytics	Males	619	15.1	2.00 (1.71–2.33)
Benzodiazepine-based anxiolytics	Females	315	26.2	2.00 (1.71–2.33)
Nonbenzodiazepine-based anxiolytics	Males	1045	25.5	1.47 (1.28–1.69)
Nonbenzodiazepine-based anxiolytics	Females	402	33.5	1.47 (1.28–1.69)
Hypnotics/sedatives	Males	1659	40.5	1.26 (1.10–1.43)
Hypnotics/sedatives	Females	553	46.0	1.26 (1.10–1.43)
Benzodiazepine-based hypnotics	Males	699	17.1	1.77 (1.52–2.06)
Benzodiazepine-based hypnotics	Females	320	26.6	1.77 (1.52–2.06)
Nonbenzodiazepine-based hypnotics	Males	1372	33.5	1.04 (0.91–1.19)
Nonbenzodiazepine-based hypnotics	Females	412	34,3	1.04 (0.91–1.19)
Antiadrenergic agents	Males	149	3.6	0.75 (0.51–1.10)
Antiadrenergic agents	Females	33	2.7	0.75 (0.51–1.10)
Clonidine	Males	139	3.4	0.78 (0.53–1.15)
Clonidine	Females	32	2.7	0.78 (0.53–1.15)
Guanfacine	Males	12	0.3	0.28 (0.04–2.18)
Guanfacine	Females	1	0.1	0.28 (0.04–2.18)
Antiepileptics	Males	502	12.2	1.54 (1.30–1.84)
Antiepileptics	Females	213	17.7	1.54 (1.30–1.84)
Anesthetics	Males	187	4.6	1.53 (1.17–2.00)
Anesthetics	Females	82	6.8	1.53 (1.17–2.00)
Analgesics	Males	1223	29.8	1.93 (1.69–2.20)
Analgesics	Females	541	45.0	1.93 (1.69–2.20)
Antiparkinson drugs	Males	131	3.2	1.54 (1.12–2.11)
Antiparkinson drugs	Females	58	4.8	1.54 (1.12–2.11)
Other central nervous system drugs	Males	217	5.3	0.89 (0.66–1.20)
Other central nervous system drugs	Females	57	4.7	0.89 (0.66–1.20)

Significant ORs are highlighted in bold.

Males are the reference category.

Selective serotonin reuptake inhibitors (SSRIs) and clomipramine.

Venlafaxine and duloxetine.

Antidepressants other than SRIs or SRNIs.

CI, confidence interval; OR, odds ratio; SNRI, serotonin–norepinephrine reuptake inhibitors; SRI, serotonin reuptake inhibitors.

Comorbidities

The dispensation patterns for each group of comorbidities in the medicated individuals with TD/CTD are detailed in Supplementary Table S4.

As expected, individuals diagnosed with ADHD and/or PDD were more likely to be dispensed ADHD drugs, compared with those TD/CTD cases without these comorbidities (OR adjusted for sex [ORa] = 62.26 and ORa = 1.63, respectively).

Patients with comorbid anxiety disorders, depressive disorders, and OCD were more likely to get any type of antidepressants (ORa = 7.58, ORa = 11.24, and ORa = 6.74, respectively), anxiolytics (ORa = 5.31, ORa = 3.86, and ORa = 1.98, respectively), and atypical antipsychotics (ORa = 1.92, ORa = 1.83, and ORa = 2.11, respectively). These patients were also more likely to receive both nonbenzodiazepine and benzodiazepine-based anxiolytics and hypnotics/sedatives and antiepileptics.

TD/CTD patients with conduct disorders and nonorganic sleep disorders were more likely to receive ADHD drugs (ORa = 4.14 and ORa = 1.87, respectively), anxiolytics (ORa = 1.22 and ORa = 1.75, respectively), and hypnotics (ORa = 1.52 and ORa = 6.38, respectively), particularly the nonbenzodiazepine-based group.

Age group

During the year 2013, ADHD drugs (including methylphenidate and atomoxetine), antiadrenergic agents (including clonidine), and nonbenzodiazepine-based hypnotics were more likely to be dispensed to children and adolescents with TD/CTD, compared with the adults in the same cohort (OR = 0.13, OR = 0.16, and OR = 0.45, respectively; Table 3). On the other hand, antidepressants, antipsychotics (both typical and atypical), anxiolytics, benzodiazepine-based hypnotics, antiepileptics, analgesics, antiparkinson drugs, and other central nervous system drugs were more likely to be dispensed in adults, compared with the pediatric group (Table 3). There were no differences in the dispensation of the broader group of hypnotics/sedatives, anesthetics, and some specific atypical antipsychotics, namely aripiprazole and olanzapine.

Table 3.

Dispensed Medications in Individuals with Tourette/Chronic Tic Disorders During the Year 2013, by Age Group (Children and Adolescents vs. Adults)

	All n = 3667		Children and adolescents (<18 years) n = 1524 ^a		Adults (≥18 years) n = 2143 ^a
N	%	N	%	N	%	OR (95% CI) ^b
ADHD drugs	1778	48.5	1157	75.9	621	29.0	0.13 (0.11–0.15)
Methylphenidate	1444	39.4	939	61.6	505	23.6	0.19 (0.17–0.22)
Atomoxetine	554	15.1	435	28.5	119	5.6	0.15 (0.12–0.18)
Antidepressants	1573	42.9	364	23.9	1209	56.4	4.13 (3.57–4.77)
SRIs	1234	33.7	349	22.9	885	41.3	2.37 (2.04–2.74)
SNRIs	185	5.0	1	0.1	184	8.6	—
Other antidepressants	368	10.0	29	1.9	339	15.8	9.68 (6.59–14.23)
Antipsychotics	1101	30.0	346	22.7	755	35.2	1.85 (1.60–2.15)
Typical antipsychotics	220	6.0	11	0.7	209	9.8	14.86 (8.08–27.36)
Haloperidol	85	2.3	2	0.1	83	3.9	30.66 (7.53–124.85)
Pimozide	34	0.9	2	0.1	32	1.5	11.54 (2.76–48.21)
Atypical antipsychotics	978	26.7	341	22.4	637	29.7	1.47 (1.26–1.71)
Tiapride	3	0.1	0	0.0	3	0.1	—
Risperidone	466	12.7	209	13.7	257	12.0	0.86 (0.71–1.04)
Aripiprazole	344	9.4	146	9.6	198	9.2	0.96 (0.77–1.20)
Olanzapine	138	3.8	10	0.7	128	6.0	9.62 (5.04–18.37)
Quetiapine	133	3.6	16	1.0	117	5.5	5.44 (3.21–9.22)
Ziprasidone	19	0.5	3	0.2	16	0.7	3.81 (1.11–13.11)
Anxiolytics	748	20.4	149	9.8	599	28.0	3.58 (2.95–4.34)
Benzodiazepine-based anxiolytics	388	10.6	13	0.9	375	17.5	24.65 (14.12–43.02)
Nonbenzodiazepine-based anxiolytics	426	11.6	140	9.2	286	13.3	1.52 (1.23–1.89)
Hypnotics/sedatives	1121	30.6	452	29.7	669	31.2	1.08 (0.93–1.24)
Benzodiazepine-based hypnotics	471	12.8	5	0.3	466	21.7	84.36 (34.86–204.12)
Nonbenzodiazepine-based hypnotics	787	21.5	449	29.5	338	15.8	0.45 (0.38–0.53)
Antiadrenergic agents	69	1.9	56	3.7	13	0.6	0.16 (0.09–0.29)
Clonidine	58	1.6	45	3.0	13	0.6	0.20 (0.11–0.37)
Guanfacine	12	0.3	12	0.8	0	0.0	—
Antiepileptics	329	9.0	34	2.2	295	13.8	7.00 (4.87–10.04)
Anesthetics	41	1.1	18	1.2	23	1.1	0.91 (0.49–1.69)
Analgesics	566	15.4	66	4.3	500	23.3	6.72 (5.15–8.77)
Antiparkinson drugs	76	2.1	2	0.1	74	3.5	27.22 (6.67–111.05)
Other central nervous system drugs	75	2.0	4	0.3	71	3.3	13.02 (4.75–35.73)

Significant ORs are highlighted in bold.

Individuals who were younger than 18 during 2013 were classified as children and adolescents, whereas those who were 18 or older during 2013 were classified as adults. Individuals turning 18 during 2013 were excluded from these analyses.

Adjusted for gender. Children and adolescents is the reference category.

CI, confidence interval; OR, odds ratio; SNRI, serotonin–norepinephrine reuptake inhibitors; SRI, serotonin reuptake inhibitors.

Polypharmacy

The majority of TD/CTD patients that were on medication were dispensed more than one drug during the study period (n = 3822, 72.1%; Fig. 1). Among those that were dispensed only one medication, ADHD drugs were the most dispensed (41.6%), followed by analgesics (20.4%), antidepressants (13.1%), antipsychotics (11.9%), and other drugs (12.9%). The group of other drugs included anxiolytics, hypnotics/sedatives, anesthetics, antiadrenergic agents, antiepileptics, and other central nervous system drugs, and all of them were dispensed to less than 5% of the medicated individuals. Among those patients that were dispensed multiple drugs, the most common combination was the dispensation of ADHD drugs and hypnotics/sedatives (19.5% of the medicated patients), followed by ADHD drugs and antipsychotics (11.8% of the medicated patients).

FIG. 1.

Percentage of medicated individuals with Tourette/chronic tic disorders that were dispensed one, two, three, or four or more groups of drugs during the 8-year study period (July 1, 2005 to December 31, 2013). For those that were on only one group of drugs, the medication is specified.

Time trends

Dispensation of some atypical antipsychotics significantly increased over time (RC for quetiapine = 227.8%; RC for aripiprazole = 167.2%). A significant increase was also noticeable for antiadrenergics (RC = 81.3%); ADHD drugs (RC = 51.1%); hypnotics/sedatives and anxiolytics, particularly the nonbenzodiazepine-based types (RC = 70.5% and RC = 29.3%, respectively); antiepileptics (RC = 26.5%); and antidepressants other than SRIs or serotonin–norepinephrine reuptake inhibitors (SNRIs) (RC = 12.9%). Conversely, dispensation of antidepressants, particularly SRIs and SNRIs, antipsychotics, particularly typical, but also some atypical such as ziprasidone or risperidone, benzodiazepine-based anxiolytics, anesthetics, and other central nervous system drugs decreased over the study period (Table 4).

Table 4.

Time Trends of Dispensed Medications in Individuals with Tourette/Chronic Tic Disorders During the Study Period (2006–2013)

Year	2006		2007		2008		2009		2010		2011		2012		2013
N of individuals that were dispensed medication during that year	2206		2472		2710		2975		3236		3456		3666		3757
	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	%	Relative change	p for lineality
ADHD drugs	715	32.4	909	36.8	1098	40.5	1308	44.0	1493	46.1	1684	48.7	1787	48.7	1840	49.0	51.1	<0.0001
Methylphenidate	600	27.2	736	29.8	839	31.0	1023	34.4	1182	36.5	1330	38.5	1410	38.5	1496	39.8	46.4	<0.0001
Atomoxetine	150	6.8	248	10.0	381	14.1	439	14.8	498	15.4	560	16.2	607	16.6	570	15.2	123.1	<0.0001
Antidepressant	1035	46.9	1121	45.3	1202	44.4	1292	43.4	1410	43.6	1492	43.2	1538	42.0	1606	42.7	−8.9	<0.0001
SRIs	854	38.7	927	37.5	979	36.1	1027	34.5	1142	35.3	1185	34.3	1241	33.9	1264	33.6	−13.1	<0.0001
SNRIs	122	5.5	137	5.5	158	5.8	179	6.0	175	5.4	176	5.1	169	4.6	186	5.0	−10.5	0.019
Other antidepressants	194	8.8	200	8.1	218	8.0	253	8.5	298	9.2	342	9.9	335	9.1	373	9.9	12.9	0.003
Antipsychotics	770	34.9	828	33.5	900	33.2	918	30.9	990	30.6	1043	30.2	1084	29.6	1122	29.9	−14.4	<0.0001
Typical antipsychotics	232	10.5	241	9.7	244	9.0	232	7.8	223	6.9	220	6.4	224	6.1	222	5.9	−43.8	<0.0001
Haloperidol	87	3.9	98	4.0	102	3.8	82	2.8	77	2.4	85	2.5	87	2.4	86	2.3	−42.0	<0.0001
Pimozide	55	2.5	51	2.1	46	1.7	45	1.5	43	1.3	41	1.2	40	1.1	35	0.9	−62.6	<0.0001
Atypical antipsychotics	616	27.9	659	26.7	730	26.9	773	26.0	857	26.5	905	26.2	957	26.1	998	26.6	−4.9	0.252
Tiapride	0	0.0	4	0.2	4	0.1	4	0.1	3	0.1	3	0.1	3	0.1	3	0.1	–	0.752
Risperidone	454	20.6	460	18.6	476	17.6	432	14.5	461	14.2	477	13.8	495	13.5	478	12.7	−38.2	<0.0001
Aripiprazole	78	3.5	104	4.2	152	5.6	225	7.6	270	8.3	303	8.8	333	9.1	355	9.4	167.2	<0.0001
Olanzapine	83	3.8	91	3.7	96	3.5	102	3.4	115	3.6	119	3.4	130	3.5	138	3.7	−2.4	0.829
Quetiapine	24	1.1	40	1.6	64	2.4	83	2.8	102	3.2	102	3.0	117	3.2	134	3.6	227.8	<0.0001
Ziprasidone	24	1.1	26	1.1	27	1.0	27	0.9	32	1.0	19	0.5	19	0.5	19	0.5	−53.5	0.0001
Anxiolytics	415	18.8	490	19.8	521	19.2	576	19.4	668	20.6	687	19.9	735	20.0	758	20.2	7.2	0.167
Benzodiazepine-based anxiolytics	267	12.1	275	11.1	298	11.0	312	10.5	374	11.6	370	10.7	363	9.9	389	10.4	−14.5	0.017
Nonbenzodiazepine-based anxiolytics	198	9.0	264	10.7	273	10.1	325	10.9	354	10.9	388	11.2	441	12.0	436	11.6	29.3	0.0002
Hypnotics/sedatives	501	22.7	553	22.4	661	24.4	756	25.4	873	27.0	1011	29.3	1063	29.0	1150	30.6	34.8	<0.0001
Benzodiazepine-based hypnotics	298	13.5	314	12.7	338	12.5	356	12.0	393	12.1	435	12.6	440	12.0	475	12.6	−6.4	0.364
Nonbenzodiazepine-based hypnotics	281	12.7	315	12.7	401	14.8	506	17.0	599	18.5	707	20.5	761	20.8	816	21.7	70.5	<0.0001
Antiadrenergic	23	1.0	37	1.5	43	1.6	46	1.5	58	1.8	66	1.9	60	1.6	71	1.9	81.3	0.017
Clonidine	23	1.0	37	1.5	43	1.6	46	1.5	58	1.8	66	1.9	60	1.6	59	1.6	50.6	0.116
Guanfacine	0	0.0	0	0.0	0	0.0	0	0.0	0	0.0	0	0.0	0	0.0	13	0.3	–	<0.0001
Antiepileptics	155	7.0	189	7.6	237	8.7	270	9.1	312	9.6	328	9.5	306	8.3	334	8.9	26.5	0.017
Anesthetics	49	2.2	38	1.5	29	1.1	30	1.0	46	1.4	37	1.1	39	1.1	42	1.1	−49.7	0.001
Analgesics	353	16.0	379	15.3	389	14.4	443	14.9	491	15.2	525	15.2	554	15.1	574	15.3	−4.5	0.844
Antiparkinson drugs	51	2.3	58	2.3	63	2.3	59	2.0	63	1.9	70	2.0	71	1.9	76	2.0	−12.5	0.167
Other central nervous system drugs	61	2.8	74	3.0	77	2.8	77	2.6	87	2.7	96	2.8	93	2.5	75	2.0	−27.8	0.028

Significant relative changes are highlighted in bold.

Discussion

This pharmacoepidemiological study provides a picture of the “real world” dispensation patterns in children and adults with TD/CTD at the Swedish national level during an 8-year study period. Out of a sample of almost 7000 TD/CTD patients, three quarters were dispensed at least one drug during the study period. Importantly, most of the medicated patients (72.1%) were dispensed more than one drug during the study period.

Consistent with typical specialist clinic-based samples and previous pharmacoepidemiological studies (Debes et al. 2009; Olfson et al. 2011; Bachmann et al. 2015; Farag et al. 2015), a large majority of patients had at least one lifetime comorbidity (81.7%), ADHD being the most common (46.7% of TD/CTD patients). In line with this, the most commonly dispensed medications were ADHD drugs. The second most dispensed drugs were antidepressants–also unsurprising given the rates of comorbidity with anxiety disorders, depressive disorders, and OCD. Antipsychotics (mainly atypical) and antiadrenergic drugs, which are the main evidenced-based pharmacological treatments for tic disorders, were dispensed to 41.5% (37.9% for atypical, 11.2% for typical) and 3.4% of the medicated patients, respectively.

These percentages are similar to those found in two previous European pharmacoepidemiological studies (Debes et al. 2009; Bachmann et al. 2015), including the high dispensation of ADHD drugs and the low dispensation of antiadrenergics. Conversely, Farag et al. (2015) found clonidine to be the second most prescribed medication (60%) in their 2015 study in the United Kingdom, and Olfson et al. (2011) found antiadrenergics to be the first prescribed treatment for TD among privately insured patients (36%) and the second among publically insured patients (42%) in the United States. Recent studies (Murphy et al. 2013; Whittington et al. 2016) recommend antiadrenergics as first-line medication for tics in TD, especially in younger populations. The balance between clinical benefits and adverse effects favors antiadrenergic drugs over atypical antipsychotics, which are considered as a second option due to the risk of metabolic effects and tardive dyskinesia (Pena et al. 2011).

The reasons for the low dispensation rates of antiadrenergics in our sample could be related to the lack of consensus between guidelines (i.e., Canadian and U.S. guidelines recommend antiadrenergics, whereas European guidelines recommend antipsychotics as first-line treatments for tics), the off-label use of these drugs in TD/CTD patients without ADHD (i.e., guanfacine and clonidine are only indicated for patients diagnosed with ADHD), and differences across countries in the approval of these drugs (i.e., guanfacine was only approved for the treatment of ADHD in Sweden in 2016; Huss et al. 2016). Additionally, a handful of studies have not supported the efficacy of antiadrenergics in tic disorders (Murphy et al. 2017) or have shown efficacy only in TD/CTD individuals with comorbid ADHD (Weisman et al. 2013), which may also contribute to the heterogeneous pattern of prescription of these drugs across countries and studies and probably the lack of approval by the FDA for TD/CTD.

Our results showed that females, compared with males, were more likely to be dispensed drugs from any group, except for ADHD drugs, which were more dispensed among males, in line with the gender distribution of the disorder. The reasons for this are unclear, but it may be that the diagnostic threshold for diagnosing tic disorders in girls is particularly high, resulting in an overrepresentation of severe or complex female patients in our cohort.

As expected, ADHD drugs were more likely to be dispensed to patients with comorbid ADHD, conduct disorders, and sleep disorders, conditions which tend to co-occur. Methylphenidate, the most dispensed drug in our cohort (48.3% of the medicated patients) has shown to be efficacious and safe to treat ADHD, also when appearing with conduct disorders (Sinzig et al. 2007), with or without TD/CTD (Cohen et al. 2015; Ganos et al. 2017). A large percentage of TD/CTD patients also received antidepressants, anxiolytics, and hypnotics/sedatives, particularly females and those with comorbid anxiety, depression, sleep disorders, and OCD. These findings are consistent with pharmacoepidemiological studies of other psychiatric disorders, such as OCD. For example, Isomura et al. (2016) found that OCD patients with psychiatric comorbidities had between three- and five-fold increased odds of dispensation of other classes of drugs in addition to the evidence-based treatments for OCD (SRIs).

Regarding the time trends, we found that the dispensation of some atypical antipsychotics (quetiapine and aripiprazole) increased over time, in line with other studies (Bachmann et al. 2015; Halfdanarson et al. 2017). In turn, typical and some atypical antipsychotics (ziprasidone and risperidone) decreased over time, probably due to their worse profile and tolerability compared with the newer atypical antipsychotics. In line with the anti-benzodiazepine campaigns developed in Scandinavian countries aiming at decreasing the overprescription of these drugs due to their potential risk of chronic use (Clay et al. 2013), we found a decrease in prescriptions of benzodiazepine-based drugs and an increase in nonbenzodiazepine-based hypnotics/sedatives and anxiolytics. Dispensation of ADHD drugs also increased by over 50% over time. Contrary to the study by Bachmann et al. (2015), dispensation of antidepressants decreased over the study period.

Most patients (72.1%) were dispensed more than one drug during the study period and up to one third of the cohort received four or more groups of drugs. This pattern, consistent with previous research (Farag et al. 2015), may reflect the high complexity in the management of tic disorders, partly due to the high rates of comorbidity, given that combination and augmentation strategies are often required according to which primary symptom is being treated (Robertson 2000). Additionally, TD/CTD patients appear refractory to many treatments and idiosyncratic responses are frequently found (Farag et al. 2015). Nevertheless, the results may also reflect the lack of uniform prescription practices and highlights the need for more evidence-based treatment-controlled studies. Finally, the high rates of dispensed drugs in patients with TD/CTD may be associated with the limited availability of behavioral therapy in clinical settings (Whittington et al. 2016; Ganos et al. 2017).

The strengths of this study include the use of the world's largest population-based cohort of patients with TD/CTD of all ages, the full population coverage of all drug dispensations, and the relatively long follow-up study period, which allowed us to examine time trends at a national level. Additionally, the diagnostic validity and reliability of the TD/CTD diagnoses in the Swedish national registers is high (Rück et al. 2015).

However, this study is not without limitations. The main limitation is that the Swedish PDR does not contain information regarding the indication of each dispensation, meaning that it is not known whether the dispensed drugs have been prescribed for the treatment of tics or for a comorbid condition. To minimize this problem, we excluded patients with lifetime diagnosis of organic mental disorders, schizophrenia spectrum disorders, bipolar disorder, or epilepsy, conditions that may mask the usual patterns of prescription in TD/CTD.

Additionally, our definition of polypharmacy did not allow to establish with certainty whether the drugs dispensed during the 8-year study period were taken concurrently or sequentially. Another possible limitation is that our cohort does not represent the totality of all TD/CTD patients in Sweden. This is because many sufferers may not seek help, the incomplete coverage of the register until 2001, and those patients diagnosed by general practitioners and other nonspecialists are not included. Thus, while the patients included in our cohort resemble other patients recruited from specialist tic disorder clinics around the world, it is possible that our results do not generalize to less complex patient samples. Our analyses are based on dispensation data and, thus, we cannot be certain that prescriptions that were collected were actually used. Finally, Swedish registers do not contain information of nonpharmacological treatments.

Conclusions

Over three-quarters of patients with TD/CTD in Swedish specialist settings, received at least one type of medication during the study period and, of those, over 70% received multiple classes of drugs over a period of 8 years. A range of clinical variables, notably psychiatric comorbidity, influence what classes of drugs are dispensed to this patient group, in line with the widely held view that comorbidities are often more problematic for the patients than the tics themselves.

Clinical Significance

Long-term monitoring of the drug dispensation patterns in patients with TD/CTD is warranted as is the systematic study of both their potentially beneficial and adverse effects.

Footnotes

Acknowledgments

This research is funded by grants from the Stockholm County Council. Dr. Marta Carulla-Roig was funded by the Alicia Koplowitz Foundation.

Disclosures

Prof. Mataix-Cols and Dr. Fernández de la Cruz receive royalties for contributing articles to UpToDate, Wolters Kluwer Health. Prof. Hellner has served as a speaker for Shire and has received a grant from the research foundation of Svenska Spel (the state owned gambling company in Sweden). Prof. Larsson has served as a speaker for Eli-Lilly and Shire and has received research grants from Shire. The other authors report no financial relationships with commercial interests.

References

Andrén

: Tourette's syndrome and other tic disorders [Tourettes syndrom och andra ticssyndrom], in Psykiatristöd Stockholms Läns Landsting. Available at: www1.psykiatristod.se/Psykiatristod/Psykiatriprogram/OCD-och-relaterade-syndrom/Tourettes-syndrom-och-andra-ticssyndrom (last accessed April, 9, 2018 ), 2017.

Bachmann

, Roessner

, Glaeske

, and Hoffmann

: Trends in psychopharmacologic treatment of tic disorders in children and adolescents in Germany. Eur Child Adolesc Psychiatry, 24:199–207, 2015.

Clay

, Falissard

, Moore

, and Toumi

: Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and Z-drugs consumption in nine European countries. Eur J Clin Pharmacol, 69:1–10, 2013.

Cohen

, Mulqueen

, Ferracioli-Oda

, Stuckelman

, Coughlin

, Leckman

, and Bloch

. Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials. J Am Acad Child Adolesc Psychiatry, 54:728–736, 2015.

Debes

, Hjalgrim

, and Skov

The presence of comorbidity in Tourette syndrome increases the need for pharmacological treatment. J Child Neurol, 24:1504–1512, 2009.

Debes

, Hjalgrim

, and Skov

The presence of attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder worsen psychosocial and educational problems in Tourette syndrome. J Child Neurol, 25:171–181, 2010.

Farag

, Stern

, Simmons

, and Robertson

MM.

Serial pharmacological prescribing practices for tic management in Tourette syndrome. Hum Psychopharmacol, 30:435–441, 2015.

Ganos

, Martino

, and Pringsheim

. Tics in the Pediatric

Population

: Pragmatic Management. Mov Disord Clin Pract, 4:160–172, 2017.

Halfdanarson

, Zoega

, Aagaard

, Bernardo

, Brandt

, Fuste

, Furu

, Garuoliene

, Hoffmann

, Huybrechts

, Kalverdijk

, Kawakami

, Kieler

, Kinoshita

, Litchfield

, Lopez

, Machado-Alba

, Machado-Duque

, Mahesri

, Nishtala

, Pearson

, Reutfors

, Saastamoinen

, Sato

, Schuiling-Veninga

CCM

, Shyu

, Skurtveit

, Verdoux

, Wang

, Yahni

, and Bachmann

. International trends in antipsychotic use: A study in 16 countries, 2005–2014. Eur Neuropsychopharmacol, 27:1064–1076, 2017.

10.

Hollis

, Pennant

, Cuenca

, Glazebrook

, Kendall

, Whittington

, Stockton

, Larsson

, Bunton

, Dobson

, Groom

, Hedderly

, Heyman

, Jackson

, Murphy

, Rickards

, Robertson

, and Stern

. Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with

Tourette syndrome

: A systematic review and qualitative analysis. Health Technol Assess, 20:1–450, vii-viii, 2016.

11.

Huss

, Chen

, and Ludolph

. Guanfacine extended release: A new pharmacological treatment option in Europe. Clin Drug Investig, 36:1–25, 2016.

12.

Isomura

, Nordsletten

, Ruck

, Ljung

, Ivarsson

, Larsson

, and Mataix-Cols

. Pharmacoepidemiology of obsessive-compulsive disorder: A Swedish nationwide cohort study. Eur Neuropsychopharmacol, 26:693–704, 2016.

13.

Ludvigsson

, Otterblad-Olausson

, Pettersson

, and Ekbom

. The

Swedish personal identity number

: Possibilities and pitfalls in healthcare and medical research. Eur J Epidemiol, 24:659–667, 2009.

14.

Müller-Vahl

, and Roessner

. Treatment of tics in patients with

Tourette syndrome

: Recommendations according to the European Society for the Study of Tourette Syndrome. Mov Disord, 26:2447; author reply 2448, 2011.

15.

Murphy

, Lewin

, Storch

, and Stock

Practice parameter for the assessment and treatment of children and adolescents with tic disorders. J Am Acad Child Adolesc Psychiatry, 52:1341–1359, 2013.

16.

Murphy

, Fernandez

, Coffey

, Rahman

, Gavaletz

, Hanks

, Tillberg

, Gomez

, Sukhodolsky

, Katsovich

, and Scahill

Extended-release guanfacine does not show a large effect on tic severity in children with chronic tic disorders. J Child Adolesc Psychopharmacol, 27:762–770, 2017.

17.

Olfson

, Crystal

, Gerhard

, Huang

, Walkup

, Scahill

, and Walkup

JT.

Patterns and correlates of tic disorder diagnoses in privately and publicly insured youth. J Am Acad Child Adolesc Psychiatry, 50:119–131, 2011.

18.

Pena

, Yaltho

, and Jankovic

Tardive dyskinesia and other movement disorders secondary to aripiprazole. Mov Disord, 26:147–152, 2011.

19.

Pringsheim

, Doja

, Gorman

, McKinlay

, Day

, Billinghurst

, Carroll

, Dion

, Luscombe

, Steeves

, and Sandor

. Canadian guidelines for the evidence-based treatment of tic disorders: Pharmacotherapy. Can J Psychiatry, 57:133–143, 2012.

20.

Rothenberger

, Banaschewski

, and Roessner

. Tic Disorders. In: German Society for Child and Adolescent Psychiatry (eds.). Guidelines for the diagnosis and treatment of mental disorders in infancy, childhood and adolescence [In German]. Cologne: Deutscher Ärzteverlag, 2007.

21.

Robertson

MM.

Tourette syndrome, associated conditions and the complexities of treatment. Brain, 123 (Pt 3):425–462, 2000.

22.

Robertson

. A personal 35 year perspective on Gilles de la Tourette syndrome: Prevalence, phenomenology, comorbidities, and coexistent psychopathologies. Lancet Psychiatry, 2:68–87, 2015.

23.

Roessner

, Plessen

, Rothenberger

, Ludolph

, Rizzo

, Skov

, Strand

, Stern

, Termine

, Hoekstra

, and Group

. European clinical guidelines for Tourette syndrome and other tic disorders. Part

: Pharmacological treatment. Eur Child Adolesc Psychiatry, 20:173–196, 2011.

24.

Rück

, Larsson

, Lind

, Perez-Vigil

, Isomura

, Sariaslan

, Lichtenstein

, and Mataix-Cols

Validity and reliability of chronic tic disorder and obsessive-compulsive disorder diagnoses in the Swedish National Patient Register. BMJ Open, 5:e007520, 2015.

25.

Sallee

, Kohegyi

, Zhao

, McQuade

, Cox

, Sanchez

, van Beek

, Nyilas

, Carson

, and Kurlan

Randomized, double-blind, placebo-controlled trial demonstrates the efficacy and safety of oral aripiprazole for the treatment of Tourette's disorder in children and adolescents. J Child Adolesc Psychopharmacol, 27:771–781, 2017.

26.

Scahill

, Specht

, and Page

The prevalence of tic disorders and clinical characteristics in children. J Obsessive Compuls Relat Disord, 3:394–400, 2014.

27.

Scharf

, Miller

, Gauvin

, Alabiso

, Mathews

, and Ben-Shlomo

. Population prevalence of

Tourette syndrome

: A systematic review and meta-analysis. Mov Disord, 30:221–228, 2015.

28.

Shapiro

, and Shapiro

Controlled study of pimozide vs. placebo in Tourette's syndrome. J Am Acad Child Adolesc Psychiatry, 23:161–173, 1984.

29.

Shapiro

, Shapiro

, Fulop

, Hubbard

, Mandeli

, Nordlie

, and Phillips

RA.

Controlled study of haloperidol, pimozide and placebo for the treatment of Gilles de la Tourette's syndrome. Arch Gen Psychiatry, 46:722–730, 1989.

30.

Sinzig

, Dopfner

, Lehmkuhl

, Uebel

, Schmeck

, Poustka

, Gerber

, Gunter

, Knolker

, Gehrke

, Hassler

, Resch

, Brunger

, Ose

, and Fischer

Long-acting methylphenidate has an effect on aggressive behavior in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 17:421–432, 2007.

31.

Steeves

, McKinlay

, Gorman

, Billinghurst

, Day

, Carroll

, Dion

, Doja

, Luscombe

, Sandor

, and Pringsheim

. Canadian guidelines for the evidence-based treatment of tic disorders: Behavioural therapy, deep brain stimulation, and transcranial magnetic stimulation. Can J Psychiatry, 57:144–151, 2012.

32.

Verdellen

, van de Griendt

, Hartmann

, and Murphy

. European clinical guidelines for Tourette syndrome and other tic disorders. Part

III

: Behavioural and psychosocial interventions. Eur Child Adolesc Psychiatry, 20:197–207, 2011.

33.

Weisman

, Qureshi

, Leckman

, Scahill

, and Bloch

. Systematic review: pharmacological treatment of tic disorders-efficacy of antipsychotic and alpha-2-adrenergic agonist agents. Neurosci Biovehav Rev, 37:1162–1171, 2013.

34.

Whittington

, Pennant

, Kendall

, Glazebrook

, Trayner

, Groom

, Hedderly

, Heyman

, Jackson

, Murphy

, Rickards

, Robertson

, Stern

, and Hollis

. Practitioner

Review

: Treatments for Tourette syndrome in children and young people—a systematic review. J Child Psychol Psychiatry, 57:988–1004, 2016.

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Pharmacoepidemiology of Tourette and Chronic Tic Disorders in Sweden 2005–2013

Abstract

Background:

Methods:

Results:

Conclusions:

Introduction

Methods

Swedish national registers

Patient cohort

Drug dispensation outcomes

Statistical analyses

Results

Study cohort

Drug dispensation patterns in TD/CTD

Gender

Comorbidities

Age group

Polypharmacy

Time trends

Discussion

Conclusions

Clinical Significance

Footnotes

Acknowledgments

Disclosures

References

Supplementary Material