Why Personalized Medicine (Precision Medicine) and Neuromodulation in ADHD and Depression?


Recently the landscape in psychiatry is undergoing a dramatic change. Some recent large-scale studies investigating the effects of conventional treatments for ADHD and depression in practice have demonstrated on the group-level limited efficacy of antidepressant medication and cognitive behavioral therapy in depression (STAR*D: Rush et al., 2006), an overestimation of the effects of cognitive-behavioural therapy for depression as a result of publication bias (Cuijpers, Smit, Bohlmeijer, Hollon, & Andersson, 2010) and limited long-term effects of stimulant medication, multicomponent behavior therapy and multimodal treatment in ADHD (NIMH-MTA trial: Molina et al., 2009). Furthermore, several large pharmaceutical companies have announced to ‘…pull the plug on drug discovery in some areas of neuroscience….’ (Miller, 2010) including GlaxoSmithKline (GSK) and AstraZeneca. Below figure 1 further demonstrates this trend. In this figure the number of scientific publications per year are plotted covering 'drug-treatments' in psychiatry for Depression and ADHD. Note the declining trends that further emphasize this development. This can be considered a worrying development, since there is still much to improve in treatments for depression and ADHD. Therefore, a move beyond data regarding the average effectiveness of treatment, to identify the best treatment for any individual (Simon & Perlis, 2010) or personalized medicine is crucial. In personalized medicine it is the goal to prescribe the right treatment, for the right person at the right time as opposed to the current ‘trial-and-error’ approach, by using biomarkers of endophenotypes.


Trends for drug treatments: stimulants and antidepressants across years

Figure 1: This figure demonstrates the number of scientific publications over the years, covering 'drug-treatments' in Depression (left) and ADHD (right). This figure further confirms the trend that the pharmaceutical industry has suspended most of its R&D budgets in CNS drugs (data from Scopus). 


In addition to this develoment we also witness a shift from a ‘systemic treatment approach’ (i.e. systemically applying medication to the whole body) to a more ‘focal treatment approach’ also subsumed under the term ‘Neuromodulation’. In this development there are currently many new treatments developed and applied such as deep-brain stimulation in depression (Hamani et al., 2011); Parkinson: (Zahodne et al., 2009), intracranial stimulation of primary and secondary auditory cortex in tinnitus (De Ridder et al., 2006); rTMS in depression (Schutter 2010; Schutter 2009a), fMRI neurofeedback in pain (deCharms et al., 2005), neurofeedback in ADHD (Arns, de Ridder, Strehl, Breteler & Coenen, 2009), Vagus Nerve Stimulation (VNS) in depression (Daban, Martinez-Aran, Cruz & Vieta, 2008) etc. See figure 2 below, where - in contrast to 'drug-treatments' - the number of scientific publications demonstrates a strong growth over the years for neuromodulation techniques such as rTMS and Neurofeedback.



Trend for neuromodulation treatments such as rTMS and neurofeedback across years

Figure 2: This figure demonstrates the number of scientific publications over the years, covering neuromodulation techniques such as rTMS (left) and Neurofeedback (right). In contrast to figure 1, this figure demonstrates a marked exponential increase in literature covering rTMS (often applied in the treatment of depression) and Neurofeedback (often applied in the treatment of ADHD). Data based on Scopus.


Along with the development of these new techniques it is interesting to note that the application of some of these neuromodulation approaches do not solely rely on a DSM-IV diagnosis, but lean more towards identifying dysfunctional brain networks and application of treatment to specifically modulate those networks. For example, deep brain stimulation studies specifically aim to modulate the subcallosal cingulate gyrus (Hamani et al., 2011), fMRI neurofeedback patients learn to specifically regulate activity in the rostral anterior cingulate (deCharms et al., 2005) and for neurofeedback treatment in ADHD, the protocol can be personalized to specific deviating EEG patterns (Arns et al. 2012).

As pointed out above, a focus on biomarkers and endophenotypes which can predict treatment outcome will become crucial to improving treatments for ADHD and depression. The development of personalized medicine is hence a very important development in psychiatry. Our main aim is to investigate if there are reliable predictors for response and non-response to various treatments in ADHD and depression, with a focus on predictors for non-response. In the following sections we will summarize the main findings from our research and the literature and discuss the implications of these findings for the future of personalized medicine / precision medicine. 


Below also find an illustration of 'Why Personalized Medicine' with a wink ;-)