Psychostimulants

Methylphenidate and Cognitive Functioning

Methylphenidate is a stimulant whose exact mechanism is unknown (Napolitano et al. 2005). One theory is that methylphenidate acts on the presynaptic nerve to prevent the reabsorption of serotonin and NE, thereby increasing their concentrations within the synaptic cleft. This in turn leads to increased neurotransmission of serotonin and NE (Kim et al. 2006). Methylphenidate has been extensively used as a treatment for attention deficit disorder, as well as narcolepsy (Glenn 1998). A total of six RCTs examined the efficacy of methylphenidate as a treatment for the recovery of cognitive deficits post brain injury.

Table: Effects of Methylphenidate on Cognitive Functioning

Discussion

In an RCT, Whyte et al. (2004) indicated that speed of processing, attentiveness during individual work tasks and caregiver ratings of attention were all significantly improved with methylphenidate treatment. No treatment related improvement was seen in divided or sustained attention, or in susceptibility to distraction. Similarly, Plenger et al. (1996) found methylphenidate significantly improved attention and concentration. 

Speech et al. (1993) conducted a double blind placebo controlled trial evaluating the effects of methylphenidate following closed head injury. In contrast to the results noted by Whyte et al. (2004) and Plenger et al. (1996), methylphenidate did not demonstrate significant differences compared to placebo on measures of attention, information processing speed, or learning. Kim et al. (2006) examined the effects of a single-dose treatment of methylphenidate and, although a trend was found in favour of improved working and visuospatial memory for the treatment group, these results did not reach significance. Recently, Kim et al. (2012) found that reaction time improved significantly while on the methylphenidate.This is in line with Willmott and Ponsford (2009) who found that administering methylphenidate to a group of patients during inpatient rehabilitation, did significantly improve the speed of information processing.

In a recent RCT conducted by Willmott et al. (2013), the authors hypothesized that an individuals’ response to methylphenidate depends on their genotype. More specifically, that individuals possessing the methionine (Met) allele at the catechol-O-methyltransferase (COMT) gene would confer greater response to methylphenidate compared to those with the valine (Val) allele. While both Met/Met and Val/Val carriers performed more poorly in various attentional tasks compared to healthy controls, Met/Met carriers did show greater improvements in strategic control in attention than Val/Val carriers. As well, the authors were able to identify one significant drug and genetic interaction between Met/Met carriers and performance on the Symbol Digit Modalities Test (SDMT). These findings suggest Met/Met carriers may in fact be more responsive to methylphenidate than individuals with the Val genotype. However, further studies are needed to draw firm conclusions.

Conclusions

There is conflicting evidence regarding the effectiveness of the administration of methylphenidate following brain injury for the improvement of cognitive functioning.

There is Level 1a evidence that methylphenidate improves reaction time of working memory.

Based on a single RCT, there is Level 1b evidence that an individual’s response to methylphenidate therapy may be dependent on his/her genotype of the catechol-O-methyltransferase gene.

 

The effectiveness of methylphenidate treatment to improve cognitive impairment following brain injury is unclear.

Methylphenidate is effective in improving reaction time for working memory.

Response to methylphenidate may depend on genotype.

 

Methylphenidate and Fatigue

Of the neurostimulants used in the post-acute care of TBI, methylphenidate is common, assisting with memory, attention, verbal fluency, and improving processing speed. While its use is heavily focused on the improvement of functional and cognitive deficits, methylphenidate has been reported to have unfavourable effects on sleep patterns of individuals with brain injuries. However, little has been written focusing directly on the effects of methylphenidate on the sleep-wake cycles of those with ABI (Al-Adawi et al. 2009).

Table: Effects of Methylphenidate on Sleep Disorders

Discussion

In the study by Al-Adawi et al. (2009) no significant differences were found between those who received methylphenidate and those who did not when looking at the scores of various assessment scales (e.g. activities of daily living, mobility and cognition). More importantly, sleep times between the two groups were not significantly different. Based on this study, methylphenidate does not seem to have adverse effects on the sleep-wake cycle. 

Conclusion

Based on one prospective controlled trial, there is Level 2 evidence that methylphenidate does not have an adverse effect on the sleep-wake cycle of those who have sustained a TBI.

 

Methylphenidate does not have an adverse effect on the sleep-wake cycle of those who have sustained a TBI when given in commonly accepted dosages.

 

Methylphenidate and the Paediatric Population

Methylphenidate, a psychomotor stimulant, is often used in the treatment of attention deficit hyperactivity disorder (ADHD) in children; however, it is also used with children who have sustained a brain injury. It is believed that those with ADHD and those who have sustained a brain injury have similar characteristics including: attention deficits, hyperactivity and impulsivity (Leonard et al. 2004). Methylphenidate has been shown to improve memory and attention in those with ADHD (Kempton et al. 1999).

Table: Effects of Methylphenidate Interventions in Children with ABI

Discussion

Two separate RCTs utilized a series of neurobehavioural tasks of attention, behaviour and concentration to assess children post brain injury. Mahalick et al. (1998) reported significantly improved performance on attention and concentration tasks with methylphenidate treatment, whereas Williams et al. (1998) did not report any significant benefits. As in many paediatric studies, the sample size was small, undermining the quality of the findings. Hornyak et al. (1997) suggest that the introduction of methylphenidate resulted in improved cognitive/behavioural function post TBI. This interpretation however, was based on qualitative data from a retrospective review of 10 charts. To date, no medication has proven to be effective in modifying outcome in the brain injured child. Investigators have studied the role of the psychostimulant methylphenidate and other dopamine enhancing medication including amantadine, pramipexole, bromocriptine, and levodopa.

Conclusion

Based on two small and conflicting RCTs, there is inconclusive evidence whether methylphenidate improves cognitive behavioural function in children post ABI.

 

Evidence regarding the efficacy of methylphenidate to improve cognitive and behavioural function is conflicting in children.