Neural Correlates of Treatment Response in First Episode Psychosis – Highlights from the RCPSychIC 2019
This article is based on the talk by Dr Sameer Jauhar at the RCPsych IC 2019.
1. Treatment response to an initial antipsychotic in first-episode schizophrenia is generally very good. Results of the OPTiMiSE trial confirmed that most patients achieved symptomatic remission when treated sequentially with amisulpride and clozapine.
For most patients in the early stages of schizophrenia, symptomatic remission can be achieved using a simple treatment algorithm comprising the sequential administration of amisulpride and clozapine. Since switching to olanzapine did not improve outcome, clozapine should be used after patients fail a single antipsychotic trial-not until two antipsychotics have been tried, as is the current recommendation. [Kahn et al., 2018]
2. A meta-analysis of molecular imaging of the dopaminergic system in schizophrenia reveals greater dysfunction in dorsal vs limbic areas of the striatum, inconsistent with the mesolimbic hypothesis and highlighting the dorsal striatum as a potential therapeutic target. [McCutcheon R et al., 2018]
3. An investigation of D2 receptor availability in patients with schizophrenia before and during treatment-induced acute dopamine depletion provides direct in vivo evidence of an association between D2 binding and clinical efficacy. [Abi-Dargham A et al., 2000]
4. In an 18F-DOPA PET study, baseline dopamine synthesis capacity was associated with positive symptom change. The voxel-based analysis revealed dopamine synthesis capacity was elevated in responders vs non-responders with the most significant increase in voxels in right caudate and left putamen. [Jauhar S et al., 2018].
5. Data from a study of antipsychotic treatment resistance in schizophrenia suggest that neurochemical imaging might be useful in stratifying patients according to antipsychotic response. These data also support existing evidence that the glutamate system could be a therapeutic target for residual symptoms in schizophrenia. [Demjaha A et al., 2014]
6. There is variability in antipsychotic response, but molecular imaging appears to show the clearest findings. An inverse relationship exists between cortical glutamate concentrations and striatal dopamine synthesis capacity in first-episode psychosis and demonstrates that dopaminergic and glutamatergic function is associated with psychotic symptoms. Thus modulating cortical glutamate may be a potential therapeutic target. [Jauhar S et al., 2018]
7. Clinical response to antipsychotic medication requires a therapeutic threshold of D2 occupancy, but even at that threshold, a proportion of people will not have an antipsychotic response. Future studies could test the effect of modulating cortical glutamate in the treatment of psychosis.
Jauhar S, McCutcheon R, Borgan F, et al. The relationship between cortical glutamate and striatal dopamine in first-episode psychosis: a cross-sectional multimodal PET and magnetic resonance spectroscopy imaging study. Lancet Psychiatry. 2018;5(10):816-823. Erratum in: Lancet Psychiatry. 2018 Dec;5(12):e28.