How to improve cognition in Schizophrenia? Eur Neuropsychopharmacol. Aug 2013.


Individuals with schizophrenia suffer from marked impairment in cognition. This is well established by the time of the first episode and  shows limited relation to positive psychotic symptoms and is largely unaffected by antipsychotics and often predicts the functional outcome.  Cognitive-enhancing drugs  and  cognitive remediation approaches are attempted to address cognitive defects.

Panayiota G. Michalopouloua, Shon W. Lewisb, Til Wykesc, Judith Jaegerd and Shitij Kapur  review these approaches in this paper.

Cognitive remediation (CR) :  2011 meta-analysis of the controlled studies showed a modest improvement in overall cognitive performance  with some durability of effects. These help in increasing the prefrontal cortical function and may protect against grey matter loss. many studies were negative. Functioning is better when CR is coupled with rehabilitation input.

Cognition enhancing drugs: 17 controlled trials of add-on potential cognitive-enhancing compounds were identified (2011).Most were underpowered.Minocycline, modafinil and galantamine have shown promising results over isolated cognitive domains.Nicotinic alpha-7 agonist (EVP-6124) has demonstrated a significant effect on global cognitive function.

Animal data support the idea that combining the above two may be more beneficial. The remediation activity can  induce plasticity and the drugs could enhance these changes to reach functional significance. There is also evidence to suggest that the combination might reactivate the plastic changes of earlier critical periods of brain development, giving a chance to correct the ‘basic’ defect. Restoring plasticity of neural network appear to be the key change here.

Combining amphetamine/methyl phenidate/ levodapa with motor rehabilitation has shown to  accelerate the rate of motor recovery in hemiplegic stroke patients. Similarly D-cyclo- serine (DCS) with exposure behavioural therapy  is  effective in phobias , as DCS increases the efficacy of  exposure therapy by enhancing NMDA receptor function during fear extinction or by reducing NMDA receptor function during fear memory consolidation.

Many drugs are under scrutiny to see whether they would benefit in cognitive problems in schizophrenia. Amphetamine, levodopa, modafinil, DCS ,ampakine CX516 and memantine are among those being tried. Some of these could worsen psychosis at higher dose or if taken for longer periods. It is expected that we will see more research in near future  on Pharmacologically- Augmented Cognitive Therapies (PACT).

Summary of the article.

Treating impaired cognition in schizophrenia: The case for combining cognitive-enhancing drugs with cognitive remediation.

Michalopoulou PG, Lewis SW, Wykes T, Jaeger J, Kapur S.Eur Neuropsychopharmacol. 2013 Aug;23(8):790-8

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