Psychopharmacological treatment of cognitive deficits in Schizophrenia and mood disorders

A. Vita 1 2, C. Mussoni 1, G. Deste 1, G. Ferlenghi 1, C. Turrina 1 2, P. Valsecchi 1 2

1 Department of Clinical and Experimental Sciences, University of Brescia, Italy; 2 Department of Mental Health, Spedali Civili Hospital, Brescia, Italy


Cognitive dysfunction is a core feature and a transdiagnostic domain of psychiatric disorders, such as Schizophrenia, Bipolar Disorder and Depression. The study of these disorders may contribute to the development of novel drugs and to the repurposing of existing agents for the treatment of cognitive impairment. This manuscript will review the literature regarding the effects of pharmachological treatment of cognitive deficits in psychiatric disorders.


PubMed was used for the search including the following terms: Schizophrenia, Major Depressive Disorder, Bipolar Disorder, pharmacological treatment, antipsychotics, antidepressants, lithium and  anticonvulsant medications.


The treatment of Schizophrenia with First Generation Antipsychotics (FGAs) has relatively little influence on cognitive symptoms. It has been indicated that Second Generation Antipsychotics (SGAs) may partially improve cognitive dysfunction, due to their relatively high affinity for serotonin 5HT2A receptors. Dysfunction of γ-aminobutyric acid (GABA) led to the “GABA hypofunction” theory and to the development of novel compounds to treat cognitive deficits. The effects of glutamatergic agents indicated benefits on cognition of a group of amino acids that act as glutamate agonists by binding to the glycine site on NMDA receptors. It was discovered that the administration of muscarinic antagonists potentiated the cognitive impairments, and the α7 nicotinic acetylcholine receptors have been shown to play an important role in cognition with potential therapeutic applications in Schizophrenia. A number of studies regarding drugs targeting neuroinflammation and oxidative stress to improve cognitive deficits emerged. 

Regarding Major Depressive Disorder (MDD), conventional antidepressants are generally associated with beneficial effects on cognitive impairment in individuals with MDD, which may be mediated at least in part by the improvement obtained in affective symptoms, suggesting a partially indirect effect. Furthermore, it has been hypothesized that vortioxetine may improve the cognitive symptoms of MDD through its effects on serotoninergic receptors which may modulate glutamatergic neurotransmission, exerting its antidepressant and beneficial effect on cognitive function via a distinct mechanism. 

The literature findings regarding the effects of lithium on cognition in Bipolar Disorder are inconclusive, while anticonvulsant medications, such as valproic acid, lamotrigine and carbamazepine, showed well-established mood stabilizing and cognitive enhancing properties.


Cognitive dysfunction in Schizophrenia, Major Depressive Disorder and Bipolar Disorder is a relevant determinant of patient clinical and functional outcomes. Clinical studies evaluated several compounds to estimate their positive impact and their efficacy profiles on cognitive domains.

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