Cost-Effectiveness of Treatment Options for ADHD: A Systematic Literature Review

Research Article

Austin J Psychiatry Behav Sci. 2016; 3(1): 1048.

Cost-Effectiveness of Treatment Options for ADHD: A Systematic Literature Review

Klora M¹*, Zeidler J¹ and Greiner W²

¹Center for Health Economics Research Hannover (CHERH), Leibniz University Hannover, Germany

²Faculty of Health Sciences, University of Bielefeld, Germany

*Corresponding author: Mike Klora, Center for Health Economics Research Hannover (CHERH), Leibniz University Hannover, Otto-Brenner-Str. 1, Hannover, 30159, Germany

Received: January 12, 2016; Accepted: March 09, 2016; Published: March 11, 2016


Backround: Interest in cost-effective Attention Deficit Hyperactivity Disorder (ADHD) treatment is rising, and the reduction of costs is important due to increasing health care expenditures. Treatment strategies for ADHD patients consist of medication, behavioral treatment, and combined treatment and have to be compared regarding cost-effectiveness to enable reliable decisions on appropriate treatment.

Objective: The objective is to present evidence on cost-effectiveness of ADHD treatment strategies and to discuss the potential for economic optimization from an international perspective.

Methods: A literature review was conducted within the German Institute of Medical Documentation and Information (DIMDI) literature database and presented according to the PRISMA scheme. Inclusion criteria consist of costeffectiveness and the potential for cost reduction by treatment.

Results: While there is evidence for the cost-effectiveness of pharmacotherapies, there is less information regarding the cost-effectiveness of other treatment options, such as behavioral treatment. Medication is cost-effective according to the international threshold values. Atomoxetine, dextroamphetamine and guanfacine represent an alternative or supplement treatment to methylphenidate depending on patient characteristics.

Discussion: There is only small evidence for the cost-effectiveness of multimodal treatment for ADHD patients worldwide. Cost factors such as comorbidities, hospitalization and compliance have to be considered in addition for the choice of therapy.

Conclusion: The cost-effectiveness of ADHD medications is well documented, whereas studies on the behavioral measures and multimodal therapy are lacking. There is an urgent need for evaluation, especially, because the multimodal therapy is defined as an important element treatment by experts and guidelines.

Keywords: Attention Deficit Hyperactivity Disorder (ADHD); Atomoxetine; Behavioral treatment; Cost-effectiveness; Methylphenidate


ADHD: Attention Deficit Hyperactivity Disorder; DALY: Disability-Adjusted Life Years; DIMDI: German Institute of Medical Documentation and Information; DSM: Diagnostic and Statistical Manual of Mental Disorders; GIR: Guanfacine Immediate-Release; GRX: Guanfacine Extended-Release; ICD: International Classification of Diseases; ICER: Incremental Cost-Effectiveness Ratio; MTA: Multimodal Treatment Study of Children with ADHD; MEPS: Medical Expenditure Panel Survey; N: Number; OROS: Long-Acting Osmotic Release Oral System; PICOS: Participants-Interventions- Comparisons-Outcomes-Study; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; QALY: Quality-Adjusted Life Year


Relevance of ADHD

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most commonly diagnosed mental disorders in children and adolescents. The prevalence is approximately 3 to 5% worldwide [1,2]. The rate of persistence into adulthood varies from 30 to 80% across countries, illustrating that ADHD persists in the elderly population [3,4]. A bibliometric study demonstrates the increase in international publications and productivity in the field of ADHD research from 1980 to 2005 [5]. However, there has been no evidence to suggest an increase in the number of children with ADHD, although such hypotheses have been made due to the rising prescriptions of ADHD medications (e.g. methylphenidate) [6]. Despite the majority of the ADHD disease burden occurring in childhood, its overall prevalence warrants the attention of decision makers regarding early intervention, treatment [7], cost reduction potential, and increased therapeutic efficacy.

The symptoms of ADHD are mainly characterized by a deficit in attention, lack of persistence in activities, impulsivity, and hyperactivity. Attention deficit hyperactivity disorder is found as code F90.x in the International Classification of Diseases, 10th Revision (ICD-10), and 314.x in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) [8,9]. The diagnosis is more common in males [10], and medication, behavioral treatment, and combined therapy are the main treatment options. Typical first and second line medications are methylphenidate and atomoxetine in most parts of the world. The annual treatment costs associated with atomoxetine are higher than those for methylphenidate [7,11–13]. Other treatment strategies are conceivable, for example in countries where the restriction of resources renders cheaper treatments to be viable alternatives. Furthermore, comorbidities influence treatment strategy, thereby contributing to a higher severity of illness and higher treatment costs [14]. Typical comorbidities include social behavioral disorders, oppositional disorder, mood disorders (i.e., bipolar disorder and depression), anxiety disorders, tic disorders, learning disabilities, and enuresis. The proportion of comorbidities differs by age [15,16].

In 2000, the costs associated with ADHD in the USA were 30.1 billion € and encompassed treatment costs, other healthcare costs, and work loss costs [17]. A more recent systematic literature review provides increased overall national annual incremental costs associated with ADHD, which ranged from 108 to 201 billion € in 2010 [18]. Total direct costs in Germany for the age group below 15 years were 287 million € in 2006. This amount includes costs associated with inpatient treatment, outpatient treatment, medication, and other treatment costs [19]. However, economic burden estimates differ depending on which costs are included and which age groups are considered, as well as from which country this information is recruited.

There are many studies focusing on the economic burden of ADHD, and several reviews can be identified [20,21]. Cost projection studies by Schlander et al., (2007) pointed out rising medication costs, which have been the main impetus for considering the costeffectiveness of medication strategies [22–25]. In summary, existing reviews provide information regarding total costs associated with ADHD or compare the cost-effectiveness of medication strategies but only little evidence for potential reduction in treatment costs of all other forms of treatment (including behavioral treatment)is published until now. Additionally, there are methodological reviews regarding aspects of “assessing the efficacy of treatments for ADHD” as well as reviews regarding the “international guidelines on ADHD” [26,27]. The literature has provided information regarding the mean and total cost associated with ADHD first- and second-line treatments by country. However, limitations in these medication studies exist. For example, only short-term effects were considered and no evidence on the long-term effects e.g. compared to behavioral options, which may be more effective in the long-term, is published. Furthermore, most studies consist of indirect treatment comparisons, such as no treatment and no medications.

Therefore, the objective and rationale of this review is to provide a systematic overview of the potential strategies to reduce treatment costs for ADHD and their cost-effectiveness as well as to provide a speculative view on this topic for cost reduction, if monetary values are missing.

The following questions were addressed according to the Participants-Interventions-Comparisons-Outcomes-Study (PICOS) design scheme. The participants were international ADHD patients. Our main questions were, which therapy is the most cost-effective and how is cost reduction potential affected by ADHD characteristics and behavior (e.g., comorbidities, and persistent or non-persistent patients). The considered interventions were medication strategies, behavioral therapy, and innovative treatments, such as diet or sports. Our main questions regarding comparisons were which the most cost-effective therapy is and for which treatment strategies do studies about cost-effectiveness exist? For outcomes we observed cost-effectiveness across treatments, while the study design consisted of surveys and economic modelling. The different methods of each study design had to be recognized as well.

Materials and Methods

We conducted a literature review in German and English within the German Institute of Medical Documentation and Information (DIMDI) literature database, which is a commonly used and comprehensive database with international focus (search date: 08.01.2015). No time limit was imposed on the search period. The DIMDI literature database consists of MEDLINE, BIOSIS Previews, EMBASE Alert, EMBASE, GMS, GMS Meetings, and Sci Search. Study characteristics were cost, disease, and treatment focused. The English and German combined literature search terms were [? Cost? or ?Kost? or Ressourcen? or resource? or Krankheitskosten?] [ADHD or ADHS or Attention deficit hyperactivity disorder or Aufmerksamkeitsdefizit-/Hyperaktivitatss?] [Treatment? or Behandlung?]. During the initial inspection, we searched for duplicates. Afterwards, the title of every identified publication was scanned for relevance regarding cost-effectiveness and the potential for cost reduction by treatment before scanning for the same aspects in the abstracts. This was done because only evidence-based monetary value can be used in clinical practice to reduce treatment costs. Without a monetary value, only a speculative view remains as to whether there was any reduction in treatment cost potential. If the publication was available, papers included by the relevance of the abstract were scanned for relevance regarding the content of the publication as a whole. The paper was included in the study sample (Table 1) if clear evidence was shown by an issued monetary value for treatment cost reduction compared to the standard treatment or no treatment. Only original studies were included. The rationale for this was that the contents of posters or abstracts do not include full analyses or may consist of preliminary results. Reviews were excluded because the original paper had already been covered by our literature review or were added manually. Currencies that were not denominated in Euros were converted at the exchange rate of the evaluation year. The methods of this literature review are defined according to the PRISMA scheme.


Evidence of Cost-Effectiveness in ADHD Treatment

The database search revealed 582 studies (1063 studies before the duplicates were excluded). After manual search and afterwards scanning for relevance of title and abstract, 151 studies remained.19studies were not available as full publication, and 115 were excluded (see the Flow Chart for exclusion reasons). Finally, 17 publications were identified to show clear evidence for reduction of treatment costs (Table 1 and 2). These studies consisted predominantly of surveys and health economic modelling. The primary reason for exclusion was a lack of focus on costs and reduction of treatment costs compared to standard treatment (e.g., no information on costeffectiveness) (Figure 1). However, these studies were considered in the discussion, for example, if a new efficient treatment approach was investigated and a reduction in treatment costs could be assumed.