Improving positive and negative symptoms with dopamine D2 partial agonists

Dopamine D2 partial agonists can ameliorate both positive and negative symptoms of schizophrenia and have a good tolerability profile. The unique features of these drugs could make them a treatment of choice at every stage of treatment for schizophrenia, as outlined in this satellite symposium at EPA Virtual 2021.

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

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

  1. Stahl SM. CNS Spectr 2017; 22: 375-384
  2. Stahl SM. 4th Edition, New York. NY. Cambridge University Press 2013
  3. Lacroix LP et al. Neuropsychopharmacology 2003;28:839-49
  4. Leggio GM et al. Neuropsychopharmacology 2008;18: 271-277
  5. Stahl SM. Actra Psychiatr Scand 2020; 10.1111:acps.13266
  6. Citrome L et al. CNS Spectre 2018: 23: 228-38
  7. Pillinger T et al. Lancet Psychiatry 2020: 7: 64-77
  8. Huhn M et al. Lancet 2018: 394: 939-951
  9. Abbas A and Roth BL. Expert Opin Pharmacotherapy 2008; 9: 3251-3259 
  10. Correll. J Clin Psychiatry 2019; 80: 18m12495
  11. Németh GY. Lancet 2017: 389: 1103-1113
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