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Research Article                                                                                                                                        Open Access

## The Growing Trend of Prescribing Antipsychotics for Young People in Finland, 2000 to 2010

Kirsi-Maria Haapasalo-Pesu 1* , Max Karukivi 2 , Simo Saarijärvi 3

Psychiatric Care Division, Satakunta Hospital District, Finland

Adolescent Psychiatric Clinic, Pori, Department of Adolescent Psychiatry, University of Turku, Finland Adolescent Psychiatry Clinic VSSP, Department of Adolescent Psychiatry, University of Turku, Finland

*Corresponding author: kirsi-maria.haapasalo-pesu@satshp.fi

## Abstract

Background: According to previous reports from many countries (e.g., the United States, Germany, the United Kingdom), the use of antipsychotic drugs has increased among young people. Antipsychotics have also increasingly been prescribed for non-psychotic disorders.

Objective: The purpose of this study was to estimate the rate at which antipsychotics were prescribed for young people in the age groups of 10 to 14 years, 15 to 19 years, and 20 to 24 years in Finland in the years 2000, 2005, and 2010.

Methods: This was a nationwide register study using data from the databases of Statistics Finland and the Finnish National Prescription Register. Statistics Finland's databases provided background information, including the total number of young people and the Finnish National Prescription Register keeps record of all drug orders reimbursed by the Social Insurance Institution of Finland.

Results: The prescription of antipsychotics grew 6.8-, 4.6-, and 2.6-fold over the study period for these three age groups, respectively. For the youngest age group, use was more common among males than females in all three periods studied. During  the  course  of  the  study  period,  the  use  of  antipsychotics  became  more  common  among  females:  in  2010, antipsychotics were more commonly used among females than males in both the 15- to 19-year-old age group and the 20- to 24-year-old age group. The younger the patient, the higher the probability that the indication for medication was a nonpsychotic disorder.

Conclusions: In Finland, the trends involved in the prescription of antipsychotic medications resemble those seen in many Western  countries.  Therefore,  it  is  important  that  the  safety  and  effectiveness  of  these  pharmaceuticals  be  investigated among young people as well.

Keywords: Antipsychotics, child, adolescent

## Introduction

In many countries (e.g., the United States, Canada, the United Kingdom), since the introduction of the second-generation antipsychotics, antipsychotic medications  have  been  increasingly  prescribed  for adults  as  well  as  children  and  adolescents  (1-4). According to a previous study, there was a nine-fold increase  in  the  prescription  of  antipsychotics  for children  from  the  years  1993  through  1998  to  the years  2005  through  2009  in  the  United  States  (5). The  current  practice  is  to  treat  even  behavioral problems with antipsychotics, and today the majority of antipsychotic medications prescribed for children  and  adolescents  are  for  the  treatment  of disruptive  behavior  (6).  Prepubertal  children  who receive  antipsychotic  medication  are  usually  male and being treated for attention-deficit/hyperactivity disorder  and  conduct  disorders  (3,4).  Among  both youth and adults, the proportion of secondgeneration antipsychotics prescribed for the treatment  of  schizophrenia  has  decreased,  whereas the treatment of anxiety disorders with antipsychotics  has  roughly  doubled  (5).  In  a  large convenience sample of adolescent psychiatric outpatients, 77%  of  those who  were  receiving antipsychotic medication did not have a diagnosis of a psychotic disorder (7).

In  terms  of  effectiveness,  the  differences  among various antipsychotics are relatively small, and they mostly  concern  adverse  effects  (8).  Children  and adolescents seem to have a higher risk than adults of experiencing adverse events, such as extrapyramidal  symptoms,  prolactin  elevation,  sedation, weight  gain,  and  metabolic  effects  (9).  The  typical side effects of second-generation antipsychotics include weight gain, dyslipidemia, and hyperglycemia, all of which increase the risk for cardiovascular disease (10). There is increasing concern about the negative effects of antipsychotics; before treatment with any antipsychotic is begin, a careful risk-benefit assessment should be conducted (8).

The purpose of this study was to assess trends in the  prescription  of  antipsychotic  medications  for young people in Finland during the first decade of the twenty-first century, both overall and separately for  the  genders  as  well  as  separately  for  psychotic and non-psychotic disorders.

## Methods

This was a national register study that made use of information  extracted  from  the  databases  of  two registers: Statistics Finland and the Finnish National Prescription  Register.  Statistics  Finland's  databases served as the source of population statistics, which included the number of young people in the three age groups (i.e., 10 to 14 years, 15 to 19 years, and 20 to  24  years)  in  the  years  2000,  2005,  and  2010. The  age  groups  were  chosen  to  align  with  the practices of the Finnish National Prescription Register,  which  keeps  records  of  all  drug  orders reimbursed  by  the  Social  Insurance  Institution  of Finland. Every individual with at least one reimbursed  prescription  was  considered  to  be  a potential case for this study. 'Higher special reimbursement  for  difficult  psychosis  and  other difficult mental health problems' constituted a category of its own; in practice, this means that all young  people  who  are  entitled  to  'higher  special reimbursement' have psychotic symptoms.

The  drugs  in  the  register  are  coded  using  the Anatomical Therapeutic Chemical classification system; for the antipsychotics, the associated code is N05A (11). The data recorded in the register include patients' ages and genders.

In this study, the prevalence of the prescription of antipsychotics was calculated for the three different age  groups,  for  both  genders  together,  and  for females and males separately and then compared for the years 2000, 2005, and 2010. The actual prevalence was calculated as the proportion of the individuals with reimbursed prescriptions for antipsychotics  in  relation  to  the  total  number  of age-  and  gender-matched  individuals  at  the  given time.  The  use  of  antipsychotics  for  psychosis  was also  analyzed  separately  for  the  same  age  groups and  the  same  years.  The  differences  between  the genders were estimated by comparing the prevalence rates for antipsychotic use in each study year with the use of chi-squared tests. Chi-squared tests were also used to assess the rate of antipsychotic  medication  prescribed  specifically  for psychotic disorders as well as the change in antipsychotic  usage  throughout  the  study  period. The change in the rate  of antipsychotic  usage  was assessed  by  comparing  the  usage  rates  from  2010 with those from 2000. The statistical analyses were carried out with the use of SAS 9.2 software.

## Results

The prevalence of the prescription of antipsychotic medications throughout the study period is presented  in  Table  1.  The  rate  of  antipsychotic usage  increased  many  times  over  from  2000  to 2010, and the differences were statistically significant ( p <  .001). As  shown  in  the  table, depending on the age group, the use of antipsychotics  grew  three-  to  five-fold  in  females and two- to seven-fold in males.

The prevalence of the prescription of antipsychotics  specifically  for  psychotic  disorders was  also  assessed  separately,  and  the  results  are presented in Table 2. These analyses also demonstrated  a  multi-fold  increase  from  2000  to 2010 in the prescription  of  antipsychotics,  and  the changes in the rates were statistically significant ( p < .001)  for  all  age  groups.  The  proportion  of  cases that involved a psychotic disorder being the indication for the prescribed antipsychotic medication increased with age (Figure 1).

## Discussion

According to this study, the prescription of antipsychotics  for  young  people  increased  multiple times  in  Finland  from  2000  to  2010,  and  this  was also the case in other countries, including the United  States  and  Canada  (2-5).  There  was  an increase  in  the  prescription  of  antipsychotics  for psychotic  disorders  as  well  as  for  non-psychotic indications.  In  Canada,  the  use  of  antipsychotic medications  for  the  treatment  of  schizophrenia  in patients who were less than 18 years old remained stable between the years of 1999 and 2008 (2).

In the youngest age group (10 to 14 years old), the use of antipsychotic medication was more common among  males  than  among  females  throughout  the study  period.  This  is  in  accordance  with  previous reports from the United States, Canada, and Germany, which suggests that, in the youngest age group, users of antipsychotic medications are mostly  boys  (3,4,12).  In  2005,  the  prescription  of antipsychotics was more common among 15- to 19year-old females than among males in the same age group. In 2010, the use of antipsychotics was more common among females than among males in those 15  to  19  years  old  and  20  to  24  years  old.  The trends seen in Finnish practice may grow closer to those seen in the United States, where antipsychotic use was significantly greater for female adults than male adults (≥21 years old) between 1993 and 2009 (5).

TABLE 1. The prevalence of the prescription of antipsychotic drugs to Finnish children and adolescents in 2000, 2005, and 2010. The results are presented for three age groups (10 to 14 years old, 15 to 19 years old, and 20 to 24 years old) as well as separately by gender

|                    |                  |         | 2000             |         | 2005             |         | 2010             |   Growth* | Growth*   |
|--------------------|------------------|---------|------------------|---------|------------------|---------|------------------|-----------|-----------|
|                    |                  | N       | Prevalence       | N       | Prevalence       | N       | Prevalence       |           | p †       |
| 10 to 14 years old | Entire age class | 318,634 | 0.10% (n = 323)  | 328,539 | 0.25% (n = 818)  | 296,709 | 0.68% (n = 2024) |       6.8 | <.001     |
|                    | Females          | 155,687 | 0.07% (n = 106)  | 161,212 | 0.11% (n = 179)  | 145,131 | 0.34% (n = 487)  |       4.9 | <.001     |
|                    | Males            | 162,947 | 0.13% (n = 217)  | 167,327 | 0.38% (n = 639)  | 151,578 | 1.01% (n = 1537) |       7.8 | <.001     |
|                    | p ‡              | <.001   |                  | <.001   |                  | <.001   |                  |           |           |
| 15 to 19 years old | Entire age class | 331,778 | 0.33% (n = 1099) | 320,942 | 0.64% (n = 2042) | 332,084 | 1.46% (n = 4835) |       4.6 | <.001     |
|                    | Females          | 162,161 | 0.33% (n = 532)  | 156,824 | 0.83% (n = 1143) | 162,860 | 1.67% (n = 2724) |       5.1 | <.001     |
|                    | Males            | 169,617 | 0.33% (n = 567)  | 164,118 | 0.55% (n = 899)  | 169,224 | 1.25% (n = 2111) |       3.8 | <.001     |
|                    | p ‡              | .76     |                  | <.001   |                  | <.001   |                  |           |           |
| 20 to 24 years old | Entire age class | 327,230 | 0.79% (n = 2597) | 333,936 | 1.16% (n = 3863) | 327,780 | 2.02% (n = 6616) |       2.6 | <.001     |
|                    | Females          | 160,146 | 0.66% (n = 1060) | 163,226 | 1.11% (n = 1809) | 159,963 | 2.23% (n = 3569) |       3.4 | <.001     |
|                    | Males            | 167,084 | 0.92% (n = 1537) | 170,710 | 1.20% (n = 2054) | 167,817 | 1.82% (n = 3047) |       2.0 | <.001     |
|                    | p ‡              | <.001   |                  | .011    |                  | <.001   |                  |           |           |

TABLE 2 . The prevalence of the prescription of antipsychotic drugs for the treatment of psychotic disorders among Finnish children and adolescents in 2000, 2005 and 2010. The results are presented for three age groups: 10 to 14 years old, 15 to 19 years old, and 20 to 24 years old

|                              | 2000    | 2000             | 2005    | 2005             | 2010    | 2010             |   Growth* | Growth*   |
|------------------------------|---------|------------------|---------|------------------|---------|------------------|-----------|-----------|
|                              | N       | Prevalence       | N       | Prevalence       | N       | Prevalence       |           | p †       |
| 10 to 24 years old, in total | 977,642 | 0.21% (n = 2056) | 983,417 | 0.39% (n = 3865) | 956,573 | 0.47% (n = 4482) |       2.2 | <.001     |
| 10 to 14 years old           | 318,634 | 0.015% (n = 48)  | 328,539 | 0.044% (n = 143) | 296,709 | 0.071% (n = 212) |       3.5 | <.001     |
| 15 to 19 years old           | 331,778 | 0.14% (n = 456)  | 320,942 | 0.29% (n = 923)  | 332,084 | 0.35% (n = 1177) |       2.5 | <.001     |
| 20 to 24 years old           | 327,230 | 0.47% (n = 1552) | 333,936 | 0.84% (n = 2799) | 327,780 | 0.94% (n = 3093) |       2.0 | <.001     |

FIGURE 1. The percentage of antipsychotic drugs prescribed for non-psychotic and psychotic conditions among Finnish children and adolescents between the ages of 10 and 24 years in 2000, 2005, and 2010

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In  Finland,  there  are  few  official  indications  for antipsychotic use in children: risperidone is used for conduct  disorders  associated  with  aggressiveness from  the  age  of  5  years;  ziprasidone  is  used  for bipolar disorder from the age of 10 years; aripiprazole  is  used  for  bipolar  disorder  from  the age of 13 years and for schizophrenia from the age of 15 years; and clozapine is used for patients who are more than 15 years old for treatment refractory schizophrenia. However, the off-label use of antipsychotics  is  very  common,  and  children  and adolescents often receive drugs that are not licensed for  use  by  minors  (13).  This  practice  is  an  overall problem in the treatment of children, with 50% to 75%  of the prescription of drugs to children estimated to involve off-label use (17). Antipsychotics are prescribed for children and adolescents for many  indications without  being backed up by scientific data regarding their effectiveness and safety. It is likely that antipsychotics  are  often  used  for  the  treatment  of attention-deficit/hyperactivity disorder and conduct disorders  (15,16).  There  are  also  reports  about  the widened  use  of  atypical  antipsychotics  for  anxiety and depressive disorders (5).

The increase in the prescription of antipsychotics has  taken  place  despite  the  accumulating  evidence of  their  serious  side  effects  (9,10).  Children  and adolescents  are  at  increased  risk  for  antipsychoticrelated  side  effects  as  compared  with  adults  (8). Metabolic  and  endocrine  abnormalities  cause  the most  concern.  In  addition,  there  are  insufficient data  available  regarding  the  long-term  effects  of these pharmaceuticals (16).

For  child  and  adolescent  patients,  treatment  is administered during a time of rapid brain development.  Thus,  it  is  essential  to  evaluate  the possible effects-whether favorable or detrimental-of antipsychotic medications on cognition and other aspects of brain maturation at various ages and with various durations of exposure (16).

## Clinical Significance

The prevalence of the prescription of antipsychotics has increased with the introduction of the secondgeneration  antipsychotics  in  Finland  as  well  as  in several other Western countries. It is important that the safety and effectiveness of these pharmaceuticals be carefully studied for use among children  and  adolescents  and  for  the  treatment  of various disorders.

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