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Polypharmacy among children and adolescents with psychiatric disorders in a mental referral hospital in Botswana

BMC PsychiatryBMC series – open, inclusive and trusted201717:174

https://doi.org/10.1186/s12888-017-1347-6

Received: 15 September 2016

Accepted: 3 May 2017

Published: 10 May 2017

Abstract

Background

There is a dearth of data on polypharmacy in child and adolescent mental health in Africa, especially Botswana where children and adults are treated in the same facility by general adult psychiatrists. This study was therefore designed to assess the prevalence and the risk factors of psychiatric polypharmacy among children and adolescents treated at Sbrana Psychiatric Hospital, Lobatse, Botswana.

Methods

Data involving socio-demographics, diagnosis (using ICD-10 classification) and pharmacological treatment were retrieved from the records of 120 children and adolescents aged below 18 years, between 1 January 2012 and 31 July 2016, who presented with psychiatric disorders. They were analysed with univariate and multivariate models.

Results

The prevalence of psychiatric polypharmacy was 29.2%. Psychiatric co-morbidity (OR = 3.374, 95% CI: 1.177–9.9673) and psychotropic side effects (OR = 5.782, 95% CI: 1.636–20.430) were significantly associated with polypharmacy after regression analysis.

Conclusion

Psychiatric co-morbidity and psychotropic side effects were significant risk factors for polypharmacy in Botswana.

Keywords

Polypharmacy Children and adolescents Psychiatric disorders

Background

Psychopharmacological treatment in the child and adolescents with psychiatric disorder is increasingly becoming a matter of concern both in the western worlds and developing countries [1, 2]. Of greater concern is the rate of off-label use of psychotropic medication and polypharmacy especially in the developing countries [2] where the practice of specialized care is still very rudimentary. Some patients might present with more than one psychiatric diagnosis or resistance to monotherapy, necessitating the use of multiple psychotropic medications or other non-evidenced based methods of care [35]. Other instances are the use of another medication to treat the adverse reaction of an effective agent or adjunctive use of medications (adjunctive polypharmacy) and augmentation (augmentation polypharmacy) [3, 4, 6, 7]. In psychiatry, polypharmacy has been defined by the National Association of State Mental Health Program Directors (NASMHPD) as the use of two or more psychiatric medications in the same patient [6, 7]. NASMHPD described other types of polypharmacy: “Same-class polypharmacy”, where agents from the same class are used for the same symptoms, e.g., use of two types of Phenothiazines in a case of psychosis; “Multi-class polypharmacy”, use of more than one agents from different classes for the same disorder, e.g., carbamazepine and olanzapine for mania; and “Total polypharmacy” which is described as ‘total drug load’ including non-psychotropic medications e.g., ibuprofen for co-morbid aches [4, 6, 7].

There is a high prevalence of psychiatric polypharmacy in child and adolescents ranging from 2.9–27% worldwide [8, 9]. Another study from India, with a smaller sample size among inpatients reported a rate of 52% [10]. While there is little evidence to support this practice, there are growing concerns on the adverse effect of combining two or more medications [3, 4]. It compounds regimens complexity leading to non-compliance to treatment and increases the effects of drug interaction. Some medications affect liver enzymes, hence the bio-availability and therapeutic effect of drugs. For example, carbamazepine which is an enzyme inducer may reduce the effectiveness of some antipsychotics [3, 4]. Moreover, the fact that children often need longer duration of treatment exposes them to more adverse effects of polypharmacy or drug interaction [2, 3, 9].

To the best of our knowledge, there is a dearth of data on polypharmacy in child and adolescent mental health in Africa, especially Botswana where children and adults are treated in the same facility by general adult psychiatrists. This study was designed to assess the prevalence and the risk factors of psychiatric polypharmacy among children and adolescents treated at our referral hospital between 1 January 2012 and 31 July December 2016. This we believe will add more weight to the on-going advocacy on the need for specialized care for children and adolescents in Botswana.

Methods

After obtaining institutional ethics approval, we reviewed the records of children and adolescents aged below 18 years between 1 January 2012 and 31 July 2016 who presented with psychiatric disorders. The study was conducted in Sbrana Psychiatric Hospital (SPH) Lobatse, located in the south western district of Botswana. It is the only tertiary mental institution in the country with facilities to cater for all general adult as well as paediatric psychiatric patients, and it accepts all types of mental disorders, ranging from minor to severe conditions. Data were retrieved from the patients’ medical records comprising socio-demographics, diagnosis and treatments (including follow-up notes) using a form designed by the authors. The diagnosis was extracted from the most prominent and consistent group of symptoms using ICD-10 classification and as indicated by the members of the multidisciplinary care teams. Only subjects who had pharmacotherapy alone or both pharmacotherapy and psychotherapy were studied. Polypharmacy was only considered when two or more psychotropic medications (i.e., antipsychotics, antidepressants, anticholinergics, stimulants, mood stabilizers, etc.) were used at the same treatment period (i.e., same class, adjunctive, multi-class and augmentation polypharmacy), not total polypharmacy. We excluded cases where switching of psychiatric medications were established from documentation, either in the same episode or different episodes. We also excluded patients who received only psychotherapy such as counselling, psycho-education and cognitive behavioral therapy. Out of a total of 238 patients treated during the study period; 118 who had only psychotherapy were excluded. The disorders were grouped into externalizing conditions (conduct disorder and hyperkinetic disorder), internalizing (anxiety disorder and mood disorders) and others (epilepsy, enuresis, somatoform disorder, psychosis, conversion disorder, etc). We used age 10 years as cut-off between the younger child and older child for our analysis.

Data Analysis was done using the Statistical Package for Social Sciences (SPSS for windows 16.0, SPSS Inc., Chicago, IL, USA). Frequency tables were employed for descriptive statistics such as socio-demographics and clinical variables. Cross-tabulations were done to show the relationships between relevant socio-demographics (such as age group, birth order), clinical variable and polypharmacy. Chi-square test was used to determine associations between the categorical variables. Predictor variables (i.e., independent factors) for identified dependent variables which is polypharmacy was further investigated using binary logistic regression analysis. The level of statistical significance for all tests was set at p < 0.05.

Results

Only 120 subjects met the inclusion criteria. The mean age (sd) of the subjects was 11.9 (4.4) years (67.5% males, 32.5% females). Forty-six (38.3%) were 10 years and below (Table 1).
Table 1

Socio-demographic characteristics of children and adolescents with psychiatric disorders in Sbrana Psychiatric Hospital Lobatse, Botswana, January 2012 to July 2016

Variable

N (%)

Age (years, M = 11.94, SD = 4.4)

 

Age group

120 (100)

 ≤ 10

46 (38.3)

 >10 years

74 (61.7)

Gender

120 (100)

 Male

81 (67.5)

 Female

39 (32.5)

Birth ordera

115 (100)

 First child

41 (35.7)

 Others

74 (64.3)

aN not equal to 120 due to missing data

The disorder grouped as others comprising epilepsy, enuresis, somatoform disorder, psychosis, conversion disorder, etc. had the highest proportion 70 (58.3%), followed by externalizing disorders 43 (35.8%) and internalizing disorders 7 (5.8%). Sixty-nine (57%) patients had co-morbid psychiatric disorders while 35 (29.2%) had 2 or more psychotropic medications (polypharmacy) (Table 2).
Table 2

Detailed clinical variables in children and adolescents with psychiatric disorders in Sbrana Psychiatric Hospital Lobatse, Botswana, January 2012 to July 2016

Variables

N (%)

Disorders

120 (100)

 Externalizing disorders

43 (35.8)

 Internalizing disorders

7 (5.8)

 Other disorders

70 (58.3)

Past psychiatric history

120 (100)

 Absent

24 (20)

 Present

96 (80)

Past medical history

120 (100)

 Absent

109 (90.8)

 Present

11 (9.2)

Psychiatric co-morbidity

120 (100)

 Absent

51 (42.5)

 Present

69 (57.5)

Physical/medical comorbidity

120 (100)

 Absent

106 (83.3)

 Present

14 (11.7)

Mode of care

120 (100)

 In-patient

31 (25.8)

 Out-patient

89 (74.2)

Prescribing pattern

120 (100)

 Monotherapy

85 (70.8)

 Poly-therapy

35 (29.2)

The factors with significant association with polypharmacy were age group (χ2 = 5.319, p = 0.021), psychiatrist care (χ 2  = 5.772, p = 0.016), psychiatric co-morbidity (χ2 = 7.802, p = 0.005) and psychotropic side effect (χ 2  = 6.640, p = 0.010) using Chi-square test (Table 3). The logistic regression analyses indicated that the significant risk factors of polypharmacy were psychiatric co-morbidity (odds ratio [OR] 3.374, 95% confidence interval [CI] 1.177–9.673, p = 0.024) and psychotropic side effects (OR 5.782, 95% CI: 1.636–20.430, p = 0.006) (Table 4), after adjusting for all factors that were significant as well as birth order and diagnosis, which slightly fell short of being significant, with p values of 0.063 and 0.068 respectively, on Chi-square test.
Table 3

Association between clinical variables and polypharmacy in children and adolescents with psychiatric disorders in Botswana, January 2012 to July 2016

Risk factors

Mono –pharmacy

N (%)

Polypharmacy N (%)

df

χ2

p

Age group

 ≤10

27 (58.7)

19 (41.3)

1

5.319

0.021

 >10

58 (78.4)

16 (21.6)

   

Gender

 Female

29 (74.4)

10 (25.6)

1

0.348

0.555

 Male

56 (69.1)

25 (30.9)

   

Birth order

 First born

16(39.0)

25(61.0)

1

3.322

0.068

 Others

17(23.0)

57(77.0)

   

Past psychiatric history

 Absent

14 (58.3)

10 (41.7)

1

2.269

0.132

 Present

71 (74.0)

25 (26.0)

   

Medical history

 Absent

78 (71.6)

31 (28.4)

1

0.307

0.582

 Present

7 (63.6)

4 (36.4)

   

Psychiatrist care

 Not given

64 (66.0)

33 (34.0)

1

5.772

0.016

 Given

21 (91.3)

2 (8.7)

   

Psychiatric co-morbidity

 Absent

43 (84.3)

8 (15.7)

1

7.802

0.005

 Present

42 (60.9)

27 (39.1)

   

Physical co-morbidity

 Absent

77 (72.6)

29 (27.4)

1

1.438

0.230

 Present

8 (57.1)

6 (42.9)

   

Diagnosis

 Externalizing disorders

26 (60.5)

17 (39.5)

2

5.524

0.063

 Internalizing disorders

7 (100)

-

   

 Others

52 (74.3)

18 (25.7)

   

Psychotropic side effect

 Absent

75 (75.8)

24 (24.2)

1

6.640

0.010

 Present

10 (47.6)

11 (52.4)

   

Mode of care

 In-patient

22 (71.0)

9 (29.0)

1

0.000

0.985

 Out-patient

63 (70.8)

26 (29.2)

   

Type of intervention

 Only Pharmacological

30 (68.2)

14 (31.8)

1

0.28

0.866

 Both Psychological and pharmacological

46 (69.7)

20 (30.3)

   

Significant p-value in italics, χ2 = Chi-square, df degree of freedom, p = P value

Table 4

Factors associated with polypharmacy

Risk factors

Wald

df

p-value

OR

95% CI

Lower

Upper

Age groupa

.850

1

.356

1.786

.521

6.124

Diagnosisb

.001

1

.974

1.021

.291

3.587

Psychiatrist carec

1.557

1

.212

.347

.066

1.829

Birth orderd

3.503

1

.061

.376

.135

1.047

Psychiatric comorbiditye

5.122

1

.024

3.374

1.177

9.673

Psychotropic side effectf

7.424

1

.006

5.782

1.636

20.430

Significant test of association in italics, OR  odds ratio, CI  confidence interval, df  degree of freedom

a> 10 years

bInternalizing disorders

cPsychiatrist care given

dOthers

eAbsent

fAbsent

Discussion

The prevalence of polypharmacy (29.2%) in this study is slightly outside the range of 2.9–27% reported in a systematic review by Toteja et al. [11]. It is about two-fold the rate reported in a US study (13.8%) among paediatric patients at discharge from hospitalization, this is not surprising as our series covered in-patient and outpatient services [11]. It is much less than the 52.4% reported in an Indian study and 51% by Dean et al. in Australia about a decade ago [10, 12]. However, our rate of 41.3% in the younger child compared to 21% in the older was in direct opposition to the trend; lower rates were reported in the younger child than adolescents [11]. We cannot explain this difference given that the general adult psychiatrists employed at our centre treat mainly adults with mental health conditions and lack the expertise for complete treatment plan in children and adolescents, which prioritizes developmental and psychosocial interventions over psychotropic medications [13, 14]. Our results do indicate that polypharmacy is a common practice in our centre as in other parts of the world [1, 2, 15].

The mean age of our sample 11.9 (4.4) years and a preponderance of male children (67.5%) was comparable to the mean of Toteja et al.’s systematic review of 15 studies that involved 58,041 subjects [11]. We differed in the most commonly reported diagnoses: ours were those grouped under “others” such as epilepsy, enuresis, somatoform disorder, psychosis, conversion disorders, etc., while they reported more externalizing mental conditions hyperkinetic disorder and conduct disorder. Whereas mood disorders (internalizing conditions) accounted for the mostly treated mental illnesses with polypharmacy in the Indian study earlier mentioned [10]. Our finding of 5.8% with internalizing disorders is too small a sample to derive meaningful conclusions. The pattern of presentation of psychiatric cases to our treatment centre restricts us to these groupings for convenience. These differences however highlight the complexity of child and adolescent mental disorders involved in polypharmacy all over the world.

An initial analysis did not find significant association with gender and diagnosis in keeping with previous studies [10, 11]. Our data showed that age group, psychiatrist care, psychiatric co-morbidity and psychotropic side effects influenced the rate of polypharmacy in our series. These variables including diagnosis were further analyzed with the logistic regression. Our results indicated that psychiatric co-morbidity and psychotropic side effects were significantly associated with the presence of polypharmacy as their odds ratio were high contrary to the findings of Russell et al. [10]. However, other studies agreed with our findings that co-morbidity and more complex presentation (diagnosis that are not clear-cut) significantly correlate with the risk of polypharmacy [12, 15, 16]. The pressure to quickly resolve patients’ symptoms which make non-pharmacological options less attractive and favour an increase in polypharmacy with attendant psychotropic side effects have been reported by other investigators [17, 18].

Being a retrospective study, we could not explore if other risk factors were involved in polypharmacy in our centre. Another limitation of this study is the small number of subjects, which imposes restriction on the external validity of our results. We admit that while cases where switching of psychiatric medications were clear-cut from documentation were excluded; given the retrospective design, few cases could have been missed. There were some missing data: birth order as a variable was omitted for some patients which could have impacted our result. A prospective, long-term study would address these concerns. Despite these constraints, we believe this study has highlighted the practice of polypharmacy in paediatric psychiatric patients in Botswana and the need for specialized care of this population.

Conclusions

In conclusion, the prevalence of psychiatric polypharmacy was 29.2% among children and adolescents with psychiatric disorders in Botswana; co-morbidity and psychotropic side effects were significantly associated with the presence of polypharmacy.

Abbreviations

ICD 10: 

International Classification of Diseases

version 10

SPH: 

Sbrana Psychiatric Hospital

Declarations

Acknowledgement

Thanks to the management of SPH for granting us permission to access patients’ records.

Funding

There is no external source of funding.

Availability of data and materials

Supporting data (dataset) and materials are available at: https://doi.org/10.13140/RG.2.2.22775.21929.

Authors’ contributions

AO conceptualised and designed the study. AO and AR carried out the data analysis and interpretation. AO and AR drafted and approved the final version of the manuscript.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Ethics approval and consent to participate

Ethical approval was obtained from the University of Botswana Ethical Committee. Permission to access patients’ records was also sought from the Ministry of Health and the Management of SPH.

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Authors’ Affiliations

(1)
Department of Psychiatry, University of Botswana
(2)
Department of Anesthesia and Critical Care, University of Botswana

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Copyright

© The Author(s). 2017