June 20, 2026

Top News
Clozapine’s Superior Efficacy May Stem From Muscarinic Agonism, Not Just Dopamine Blockade
Podcast Summary
[Podcast] Side Effect Mastery in Psychopharmacology: Rawlings–Thompson A-F Classification, Low Slow Titration & Real-World Management with Dr. Michael Cummings & Dr. Blaire Heath

This podcast provides practical strategies for managing psychopharmacology side effects using the Rawlings–Thompson A-F classification system and low-slow titration techniques.

Pharmacogenomics
Discovery of a potential novel pharmacogenomic biomarker on ANK3 gene for liafensine, a triple reuptake inhibitor for treatment-resistant depression

A pharmacogenomic study identifies an ANK3 gene variant as a predictive biomarker for treatment response to liafensine, a triple reuptake inhibitor, in patients with treatment-resistant depression.

Mechanism of Action
A computational pipeline for a neurotransmitter-centric analysis of the effects of psychiatric medication on EEG spectral power

This study validates a neurotransmitter-centric computational pipeline for analyzing EEG spectral power changes in patients taking psychotropic medications, offering a more mechanistic framework for understanding drug effects than traditional class-based approaches.

Drug Development
Centanafadine Study: New ADHD Drug Effective for Adults and Kids - ADDitude

Centanafadine demonstrates efficacy in clinical studies for treating ADHD in both adult and pediatric populations, representing a new pharmacological option for this condition.

Mechanism of Action
The unique efficacy of clozapine is attributable to muscarinic receptor agonism

A recent hypothesis suggests clozapine's superior efficacy in treatment-resistant schizophrenia may be driven by muscarinic receptor agonism rather than its traditional dopaminergic profile.

Clinical Pearls

Bite-sized clinical takeaways from today's literature (sources from Dec 01 – Jun 19)

  • Consider prescribing centanafadine as a novel pharmacological option for ADHD in both adult and pediatric populations when standard therapies are insufficient.
  • Utilize the new PBPK/PD model that integrates genetic polymorphisms to optimize precision dosing of clozapine for treatment-resistant schizophrenia.
  • Monitor metabolic safety closely when prescribing cariprazine for affective disorders, as recent meta-analyses provide updated evidence-based data on its profile.
  • Evaluate xanomeline and other cholinergic modulators as emerging efficacy options for schizophrenia, supported by recent Bayesian network meta-analysis.
  • Apply the Rawlings–Thompson A-F classification system to systematically manage psychopharmacology side effects during clinical practice.
  • Use low-slow titration techniques alongside the Rawlings–Thompson framework to mitigate adverse effects when initiating or adjusting psychotropic medications.
  • Consider roflumilast as a potential off-label strategy to enhance memory network activity and address cognitive deficits in schizophrenia patients.
  • Recognize that muscarinic receptor agonism may be a key driver of clozapine's superior efficacy in treatment-resistant schizophrenia, beyond its traditional dopaminergic profile.
  • Liafensine response in treatment-resistant depression may be predicted by the presence of an ANK3 gene variant, suggesting a role for pharmacogenomic testing.

Mechanism of Action 1

Precision dosing of clozapine: A physiologically based pharmacokinetic/pharmacodynamic model integrating genetic polymorphisms and clinical outcomes

A new PBPK/PD model integrates genetic polymorphisms to optimize clozapine precision dosing for treatment-resistant schizophrenia.

Journal Article 4

Enhancement of memory network activity in schizophrenia patients by phosphodiesterase-4 (PDE4) inhibitor, roflumilast: A pilot study

A pilot study suggests the PDE4 inhibitor roflumilast may enhance memory network activity in schizophrenia patients, highlighting a potential off-label strategy for treating cognitive deficits associated with the disorder.

Effect of cariprazine on metabolic parameters in patients with affective disorders: A systematic review and meta-analysis

This systematic review and meta-analysis evaluates the metabolic safety profile of cariprazine in patients with affective disorders, providing evidence-based data for clinicians prescribing this second-generation antipsychotic.

Efficacy and safety of pharmacological and non-pharmacological interventions for antipsychotic-induced weight gain in individuals with schizophrenia: A systematic review and network meta-analysis of 55 clinical trials

A network meta-analysis of 55 trials evaluates pharmacological and non-pharmacological interventions for managing antipsychotic-induced weight gain in schizophrenia.

A Bayesian network meta-analysis of randomized controlled trials comparing the efficacy and safety of cholinergic modulators in schizophrenia

A Bayesian network meta-analysis evaluates the efficacy and safety of cholinergic modulators, including xanomeline, for treating schizophrenia.

Neuroscience 1

Associations between glutamate and cerebral blood flow in treatment-resistant schizophrenia during clozapine treatment

A study examines the relationship between glutamate levels and cerebral blood flow in patients with treatment-resistant schizophrenia during clozapine therapy.