Cognitive impairment is a core feature of schizophrenia, with more than 80% of patients showing significant impairments (Keefe & Fenton, 2007). The range of cognitive impairments in individuals with schizophrenia is broad, with the more robust and replicable deficits typically found in the domains of processing speed, episodic memory, working memory and executive function. These impairments have been shown to be associated with various impaired functional outcomes and thus development of new therapies to enhance cognition has become one of the most pressing challenges. Cognitive deficits persits throughout the course of the illness and as such, negatively affect daily functioning, work outcomes and treatment adherence. While anti-pscyhotic medications can control psychotic symptoms for the majority of patients, such improvements do not automatically transfer into the functional outcome, such as community functioning. Additionally, anti-psychotic drugs that are currently the main form of treatment in schizophrenia demonstrate only a modest positive effect on cognition.
Despite a large number of compelling rationales and significant body of preclinical data, there are no dramatic or consistent results that any one medication has the power to increase cognitive skills to the level of normal functioning. While a wide range of cholinergic, dopaminergic, glutamatergic and cannabinoid compounds have been developed, the Food and Drug Administration (FDA) has not yet approved any of the drug development programmes specifically aimed at treating cognitive impairments in schizophrenia.
Pharmacological
approach: Potential Cognitive-Enhancing Drugs in Schizophrenia
- Antipsychotic Drugs (APDs)
While numerous studies have demonstrated the dramatic
efficacy of APDs in suppressing psychotic symptoms and preventing
their recurrence, they have also revealed their inability to
alleviate the negative and cognitive symptoms of the illness. There
are, however, some studies that suggest that some of the newer
atypical antipsychotics e.g. aripiprazole, clozapine, quetiapine,
olanzapine, risperidone and ziprasidone, may provide minimal benefits
in certain specific areas of cognition.
- Donepezil, Rivastigmine, Galantamine
Researchers
sometimes focus on drugs that have proved effective in other
cognitively impaired conditions, such as in dementia. Several drugs
approved for dementia stimulate acetylcholine by blocking its
breakdown, which has been shown to improve cognition and slow
cognitive decline. Donepezil belongs to this type. The results in
schizophrenia field, however, are not very encouraging, with only a
few studies showing somewhat minimal memory improvement.
Rivastagime
has also been investigated but only in smaller-scale studies. No
significant findings have been reported to date.
Evidence
of cognitive benefit with galantamine has been mixed so far. The
overall trend indicates that at lower doses galantamine exerts a
positive effect on cognition but at higher doses it is consistently
associated with negative results. The most effective dosage is yet to
be established.
- Nicotine and nicotinic receptors
It
is now widely accepted that nicotinic receptor abnormalities are
present in schizophrenia. The vast majority of studies found some
positive effects, improvements were frequently recorded in working
memory and attentional/executive control functions and in episodic
memory. However, nicotine did not improve every measure examined in
each study and the magnitude of the effects was not large.
Additionally, nicotine as a therapeutic agent may be limited by
tachyphylaxis.
- Modafinil
Modafinil
is a wakefulness-promoting agent, shown to be effective in enhancing
cognition in sleep-deprived and healthy individuals, as well as in
some psychiatric disorders. While having effect on many
neurotransmitter systems, modafinil has an uncertain mechanism of
action. Results at this stage appears to be inconclusive. Benefits
demonstrated by early studies were not replicated by larger-scale
studies.
NB: Non-pharmacological applications will be reviewed in a future post
Reference
Keefe,
R. S. E., & Fenton, W. S. (2007). How should DSM-V criteria for
schizophrenia include cognitive impairment? Schizophrenia
bulletin,
33(4),
912-20. doi:10.1093/schbul/sbm046
