Pharmacological Interventions

6.2.6 Pharmacological Interventions

According to ABIKUS Recommendations (2007)49:

Medication for Management of Memory

Donepezil (5-10 mg/day) is recommended to enhance aspects of memory function for patients with moderate to severe TBI in subacute and chronic periods of recovery (ABIKUS B, adapted from GPT, 1, p. 1482) (G39-p.22)

Methylphenidate in a dose of 0.30 mg/kg bid may be considered as an option to enhance learning and memory in persons who are within a few months of brain injury onset when other strategies are ineffective (ABIKUS B, adapted from GPT, I, p.1483) (G40-p.22)

6.2.6.1 Amantadine

What is the evidence for amantadine in treating memory deficits post ABI?
  1. There is Level 4 evidence that amantadine does not help to improve learning and memory deficits based on the conclusions of a single group intervention study.

Amantadine is anon-competitive N-methyl-D-aspartate receptor antagonist and is currently used as an antiviral agent used as a prophylaxis for influenza A, for the treatment of neurological diseases such as Parkinson’s Disease and in the treatment of neuroleptic side-effects such as dystonia, akinthesia and neuroleptic malignant syndrome 47. It is also thought to work pre- and post-synaptically by increasing the amount of dopamine 5.

One study was identified that investigated the effectiveness of amantadine as a treatment for the remediation of learning and memory deficits.  Kraus et al. 48demonstrated that the administration of amantadine over a 12-week treatment period does not improve measures of memory deficits or attention. 

6.2.6.2 Donezepil

What is the evidence for the use of a cholinesterase inhibitor in treatment of attention disorders following TBI?

1.    There is level 1 evidence, based on a single RCT, that donepezil improves attention and short-term memory.

Zhang et al. (2004)conducted a randomized placebo controlled double-blind cross-over trial of 18 post acute TBI patients which demonstrated that donezpil significantly increased scores on tasks of sustained attention and short-term memory when compared to placebo and that these improved results were sustained after the wash-out period, suggesting a carry over affect of the medication.

Zhang L, Plotkin RC, Want G, Sandel E, Lee S. Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury. Arch Phys Med Rehabil 2004; 85:1050-1055.

  • 18 patients who had sustained a traumatic brain injury and were 2 to 24 months post injury participated in this randomized control cross over study
  • Participants were given either donezpil or placebo for 10 weeks then following a 4 week washout period, they began the second phase of the study.
  • Intragroup comparisons indicate while on the donezpil participants showed significant improvement on the Auditory Immediate Index (AII), the Visual Immediate Index (VII) and the Paced Auditory Serial Addition Test (PASAT).
  • Intergroup comparison results of the AII, VII and the PASAT showed the donepezil group improved significantly compared to the placebo group.

6.2.7 Summary of Learning and Memory Post ABI

Not all patients respond equally to all intervention strategies and no study in the current review indicated whether severity of memory impairment (or memory profile) interacts with a particular external memory aid.  Technology has increased the availability of external aids, although some seem more feasible to use than others (e.g., cell phones or hand-held recorders).  Unfortunately, the studies reviewed did not specify the length of time subjects required to master compensatory strategies nor the nature of the long-term effects, if any. 

Most studies examined only tasks of word list recall and paired-associate learning suggesting that the mnemonic strategies reviewed may not generalize to other types of information(particularly real-world or functional information outside the laboratory).  Errorless learning appears to be one procedure that can be used to enhance learning conditions.  One study highlighted the difference between severity of impairment and ability to benefit from internal strategies.

Frequency of intervention has an impact on learning and retention, although the exact parameters of this are unclear at the present time.  The optimal duration of a program is also open for speculation.  No studies reviewed examined the number of sessions required for memory groups to be effective and only one study evaluated a difference in effectiveness between mild and severely impaired individuals after sessions.

Pharmacologic interventions do not appear to be overly effective in improving learning and memory deficits, with perhaps the exception of anti-cholinergic esterase inhibitors.