Awakenings and awareness recovery in disorders of consciousness is there a role for drugs?

Disorders of consciousness (DOC) include coma, vegetative state (VS) and
minimally conscious state (MCS). Coma is a condition of unarousability with
a complete absence of wakefulness and awareness, whereas VS is characterized
by a lack of awareness despite a preserved wakefulness. Patients in coma
are unconscious because they lack both wakefulness and awareness. Patients
in a VS are unconscious because, although they are wakeful, they lack
awareness. Patients in a MCS show minimal but definite behavioural evidence
of self and environmental awareness.
Coma results from diffuse bilateral hemispheric lesions or selective damage
to the ascending reticular system (which is functionally connected to the
cerebral cortex by intralaminar thalamic nuclei). VS is a syndrome that is
considered to be the result of a disconnection of different cortical networks
rather than a dysfunction of a single area or a global reduction in cortical
metabolism. As revealed by functional imaging studies, clinical recovery is
often associated with a functional restoration of cortico-thalamo-cortical
connections. Depending on the amount of network restored, patients may
regain full consciousness or remain in a MCS. Molecular and neural mediators
may indirectly contribute to the above restoration processes owing to
their role in the phenomenon of neural synaptic plasticity. Therefore, there is
growing interest in the possible effects of drugs that act at the level of the CNS
in promoting emergence from DOC.
Sporadic cases of dramatic recovery from DOC after the administration of
various pharmacological agents, such as baclofen, zolpidem and amantadine,
have been recently supported by intriguing scientific observations. Analysis
of the reported cases of recovery, with particular attention paid to the condition
of the patients and to the association of their improvement with the
start of drug administration, suggests that these treatments might have promoted
the clinical improvement of some patients. These drugs are from various
and diverging classes, but can be grouped into two main categories, CNS
stimulants and CNS depressants. Some of these treatments seem to directly
encourage a consciousness restoration, while others play a more determinant role in improving cognitive domains, especially in patients with residual
cognitive impairment, than in the field of consciousness.
Given the great interest recently generated in the scientific community by
the increasing number of papers addressing this issue, further investigation of
the above treatments, with particular attention paid to their mechanisms of
action, the neurotransmitters involved and their effects on cortico-thalamocortical
circuitry, is needed.