Improving positive and negative symptoms with dopamine D2 partial agonists

Professor Stephen Stahl, University of California, Riverside and San Diego, USA began by explaining how dopamine D₂ partial agonists may help solve a central dilemma in schizophrenia treatment whereby increases in dopaminergic activity drive positive symptoms while reductions in dopaminergic activity drive negative symptoms.

Dopamine D₂ partial agonists have the lowest propensity for weight gain, sedation and drug-induced parkinsonism of all antipsychotic medications

Dopamine D₂ partial agonists act by blockade of dopamine D₂ receptors in the limbic striatum to overcome high dopamine function. Within the class, different agents vary in their activity at different D₂ receptor subtypes, which in turn vary in their distribution throughout the brain.^1-4

Maintaining adherence is important for early-stage patients and differences in adverse event profiles are an essential aspect of treatment selection. Dopamine D₂ partial agonists have the lowest propensity of all antipsychotic medications for weight gain, sedation and drug-induced parkinsonism, explained Professor Stahl.^5-9

We may need to rethink treatment for drug-naïve patients

We don’t tend to use these agents early on, he said, but we may need to rethink that for drug-naïve patients with first-episode psychosis.

Sustained efficacy in middle and chronic stages

Professor Stephan Leucht, University of Munich, Germany, described the benefits of dopamine D₂ partial agonists on relapse and remission. In a long-term (up to 72 weeks) study of a dopamine D₂ partial agonist in patients with a diagnosis of schizophrenia of more than one year and a current psychotic episode of less than four weeks’ duration, treatment with a dopamine D₂ partial agonist significantly delayed time to relapse (326 days) compared with placebo (92 days, p=0.009).¹⁰

Forty-two percent of patients treated with a partial agonist remained in remission for up to 6 consecutive months versus only 27% of those on placebo.¹⁰

The needs of the patient come first

Later stage schizophrenia involves recurrent episodes and unremitting illness. To maximise treatment effectiveness at this stage of the illness, treatment usually involves combinations of therapy or targeting relative recovery.

Focusing on the negative symptoms of schizophrenia, Professor Peter Falkai, Ludwig-Maximilians-University, Munich, Germany, described a two-year study in patients with predominant negative symptoms of more than six months’ duration randomized to a dopamine D₂ partial agonist or a standard antipsychotic treatment. Significant benefits in favour of the dopamine D₂ partial agonist were observed for patient functionality (personal and social performance; PSP) and PSP sub-domains reflecting activities of daily living.¹¹

Treating schizophrenia must involve treating those aspects of the illness that impact on people’s real-life needs and should be individualized at every stage of the disorder.

Educational financial support for this Satellite symposium was provided by Richter-Ricordati