Can We Predict Antipsychotic Response in Psychosis? – Highlights from RCPsychIC 2019
This article is based on the talk by Dr Sameer Jauhar at the RCPsych IC 2019
The question of, ‘what is antipsychotic response?’ is addressed through a dopamine lens and the relevance of PET imaging studies within clinical situations.
1. Epidemiological data show that around 20% of people who present to first-episode psychosis with schizophrenia will have a treatment-resistant illness from the onset, and this increases with secondary treatment resistance to around 33-40% of people.
2. PET imaging shows the presynaptic system as having more abnormalities in people with schizophrenia.
The locus of the largest dopaminergic abnormality in schizophrenia is presynaptic, which affects dopamine synthesis capacity, baseline synaptic dopamine levels, and dopamine release. Current drug treatments, which primarily act at D(2/3) receptors, fail to target these abnormalities. [Howes O, 2012]
3. Dopamine cannot be measured directly in the brain. Enzyme systems are measured, namely aromatic L-amino acid decarboxylase (AADC), which is part of the presynaptic system. It is not the rate-limiting step in dopamine production but is a reasonably good measure of dopamine synthesis, and validated by Parkinson disease studies. With schizophrenia, an excess of presynaptic dopamine may be in the striatonigral pathway, and antipsychotics seem to have a post-synaptic effect.
4. A meta-analysis showed that the degree of dopaminergic dysfunction varies across the striatum, and identifies the dorsal striatum (as opposed to the limbic subdividion of the striatum) as the predominant locus of dopamine dysfunction in psychosis; findings that are inconsistent with the mesolimbic hypothesis of schziophrenia. [McCutcheon R et al., 2018]
5. Evaluation of people with first-episode illness scanned before antipsychotic treatment and measured prospectively over time, showed that baseline dopamine synthesis capacity correlated with response to antipsychotics. Also, patients with an elevated dopamine synthesis capacity were more likely to have a response to positive psychotic symptoms.
Differences in dopaminergic function between responders and non-responders are present at first episode of psychosis, consistent with dopaminergic and non-dopaminergic sub-types in psychosis, and potentially indicating a neurochemical basis to stratify psychosis. [Jauhar S et al., 2018]
6. What do we know clinically from the antipsychotic response?
If a response is going to happen, it will be within the first two weeks and essentially predicts any response at all regarding antipsychotics.