Neuroprotective effects of the second generation antipsychotics

In contrast to over 30 studies reporting neurotoxicity associated with the first-generation antipsychotics (FGAs), several published studies have reported multiple neuroprotective effects associated with the second generation antipsychotics (SGAs). This prompted us to conduct a review of the reported neuroprotective mechanisms of the SGA class of antipsychotics compared to the FGAs.

A PubMed search was conducted using the keywords antipsychotic, neuroprotection, neuroplasticity, neurogenesis, neurotoxicity, toxicity, brain volume, neuroinflammation, oxidative stress, myelin, and oligodendrocyte. No restrictions were placed on the date of the articles or language. Studies with a clearly described methodology were included.

Animal, cell culture, and human clinical studies were identified. Twenty-four reports met the criteria for the search. All studies included at least one SGA (aripiprazole, clozapine, lurasidone, olanzapine, paliperidone, perospirone, quetiapine, risperidone, and/or ziprasidone). A few also included FGAs as a comparator (predominantly haloperidol). All studies demonstrated at least one neuroprotective mechanism of one or more SGAs, while some studies also showed that FGAs ranged from having no neuroprotective effects to actually exerting neurotoxic effects leading to neuronal death.

A review of the literature suggests that in addition to their antipsychotic efficacy and low motoric side effects, SGAs exert measurable neuroprotective effects mediated via multiple molecular mechanisms and often in a dose-dependent manner. The neuroprotective effects of SGAs range from preventative to restorative and may play a salutary role in ameliorating the neurodegenerative effects of psychosis.