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COGNITIVE SLOWING
A universal feature of the acute stage of TBI. In the 1960s and 1970s doctors used to administer amphetamines to speed up the working of the brain by increasing the supply of dopamine (a neurotransmitter which boosts alertness and focuses attention). However, this had mixed results, with negative effects including insomnia, weight loss and addiction. We are living at a time when drugs developed to help one population of neurologically impaired people may be tried out to help another. Anti-cholinesterase inhibitors like Donzepril (Aricept) have helped some people with Alzheimer's Disease to improve their orientation, attention and short term memory by boosting supplies of acetylcholine in their brains. Older anti-depressant medications such as Wellbutrin and newer versions like Effexor are sometimes prescribed to "jump start" the frontal lobes and speed up cognitive processes. Wellbutrin increases dopamine, while Effexor increases supplies of serotonin and norepinephrine. These medications are helpful to some TBI patients, but their efficacy may be outweighed by side effects. Each patient is different.

Levodopa and Amantadine (Symmetrel), which boost supplies of dopamine in the brain, have been used with some success to increase arousal, alertness and attention in Parkinson's patients. They have been tried in a very few published cases with severe TBI patients to achieve the same result. Concerns over side effects (including stomach upset, drops in blood pressure, tardive dyskinesias and psychological disturbances have restricted clinical experimentation with these agents. Some investigators have tried Bromocriptine (an agonist of dopamine receptors which has a much longer duration of action in the brain than L-Dopa) but achieved only limited success in improving executive function, speech and verbal memory.

Modafinil, a waking medication, has been used effectively with narcoleptic patients. It promotes wakefulness by activating neurons in the tuberomammilary nucleus (TMN) and perifornical area of the hypothalamus (PFx). J. Neuroscience 11/15/00 20(22):8620-8628. Neurons in the PFx secrete a neuropeptide called hypocretin which activates the locus coeruleus in the brainstem, the main source of the excitatory neurotransmitter norepinephrine. Modafinal may be a good candidate for clinical trials with TBI patients. There is clearly a need for formal, double-blind placebo-controlled studies on these and other medications, to see which ones are safe and effective for improvement in cognitive processing speed in the TBI population. An important area for advocacy is to get the US Government to fund these kinds of medication studies specifically for TBI.