The effect of first- and second-generation antipsychotics on brain morphology in schizophrenia: A systematic review of longitudinal magnetic resonance studies with a randomized allocation to treatment arms

Schizophrenia manifests as loss of brain volume in specific areas in a progressive nature and an important question concerns whether long-term treatment with medications contributes to this. The aim of the current PRISMA systematic review was to search for prospective studies involving randomization to treatment. PROSPERO ID: CRD42020197874. The MEDLINE/PUBMED was searched and it returned 2638 articles; 3 were fulfilling the inclusion criteria. A fourth was published later; they included 359 subjects, of whom 86 were healthy controls, while the rest were first-episode patients, with 91 under olanzapine, 93 under haloperidol, 48 under risperidone, 5 under paliperidone, 6 under ziprasidone, and 30 under placebo. Probably one-third of patients were suffering from a psychotic disorder other than schizophrenia. The consideration of their results suggested that there is no significant difference between these medications concerning their effects on brain structure and also in comparison to healthy subjects. There does not seem to be any strong support to the opinion that medications that treat psychosis cause loss of brain volume in patients with schizophrenia. On the contrary, the data might imply the possible presence of a protective effect for D2, 5-HT2, and NE alpha-2 antagonists (previously called SGAs). However, the literature is limited and focused research in large study samples is essential to clarify the issue, since important numerical differences do exist. The possibility of the results and their heterogeneity to be artifacts secondary to a modification of magnetic resonance imaging (MRI) signal by antipsychotics should not be easily rejected until relevant data are available.