Psychopharmacolojourney: A look at how we have come and where we might go

Keynote Address

• Title: Psychopharmacolojourney: A Look at How Far We Have Come and Where We Might Go

• Speaker: Stephen M. Stahl, MD, PhD, DSc (Hon.), DMedSci (Hon. Cambridge)

  • Distinguished Health Sciences Clinical Professor of Psychiatry and Neuroscience at UC Riverside

  • Adjunct Professor at UC San Diego

  • Director of Psychopharmacology Services, California Department of State Hospitals

  • Editor-Emeritus of CNS Spectrums

  • Presented at 2024 NEI Congress

Learning Objectives

1. Evaluate the historical pharmacological treatment of mental illness.

2. Describe the evolution in understanding neuropathology of psychiatric conditions and advances in psychopharmacological treatment.

Historical Context of Psychopharmacology

• 1985: Review of the future of psychopharmacology for the Royal Society of Medicine.

• 2016: Lecture titled "Future of Psychopharmacology—Is New Treatment Innovation Dead?" presented to the Society for Neuroscience.

• 2022: Lecture on the post-COVID future of psychopharmacology.

Timeline of Psychopharmacology Developments

• 1950-2020: Evolution of psychiatric medications.

  • 1970s-1980s: 1st Generation Antipsychotics, SSRIs, SNRIs, and the impact of DSM classifications (I-V) from 1952 to 2013.

  • Generational Phases:

    • 1st Generation: Serendipity of monoamine targets;

    • 1st Age of Darkness: Lack of new targets;

    • 2nd Generation: Target refinement;

    • 2nd Age of Darkness: Panic due to absence of targets;

    • 3rd Generation: Introduction of new targets such as psychedelics, neurosteroids, GlyT1 inhibitors.

New Strategies in Discovery of Treatments

1. Focus on symptoms in circuits rather than categorical approaches.

2. Emphasis on nodes in networks as opposed to just receptors in the brain.

3. Integration of serendipity with neuroscience.

Understanding Psychiatric Disorders

• Psychiatric disorders viewed as syndromes based on symptom collections, not purely neurobiological.

• Symptoms hypothesis: arise from inefficient processing in brain circuits.

• Common symptoms across multiple disorders may response to similar treatments:

  • Pain management in various conditions

  • Cognitive and attentional impairments

  • Sleep disruptions across disorders

  • Psychotic manifestations

  • Mood disorders similar manifestations and treatment responses.

ADHD Symptom Deconstruction

• Categories of Symptoms:

  • Inattention: Sustained attention issues, selective attention.

  • Hyperactive and impulsive symptoms present differently.

• Neural Correlates: Association with specific brain regions involved in attention and functioning (DLPFC, prefrontal cortex).

Major Depression Disorder (MDD) Symptoms and Brain Regions

• Symptoms: Concentration problems, mood disturbances, sleep irregularities, and physical fatigue.

• Associated brain regions: VMPFC, NA, and their roles in the emotional and cognitive domains.

Beyond Treating Symptoms

• Treatments should focus on potential disease modification and prevention.

• Emphasis on recognizing symptoms early and applying aggressive presymptomatic treatments.

Nodes in Networks and Psychosis

• Neuroscience perspective shift from receptor-focused approaches to network dynamics.

• Dopamine and NMDA Receptors: Essential players in understanding the psychosis network.

Muscarinic Modulation in Psychosis

• Cholinergic Influence: Acetylcholine regulation of dopamine pathways in psychosis.

• M1 and M4 Receptors: Key roles in psychotic disorders and therapeutic targets.

Neuroplasticity and Psychopharmacology

• Plastogens: Inducing neuronal plasticity.

• Psychoplastogens: Neuroplasticity agents that induce specific mental states.

• Exploration of how to harness neuroplasticity without undesirable psychological effects.

Neuroplasticity Triggers

• Development and maturation play critical roles in neuroplasticity.

• Median age at onset for psychiatric disorders reflecting developmental trajectories.

Neuroprogression in Mental Health

• Factors contributing to neuroprogression include:

  • Inflammation

  • Treatment resistance

  • Cognitive decline

  • Structural and functional brain abnormalities.

Conclusion and Future Focus

• The future of psychopharmacology hinges on innovative treatments targeting information processing in brain circuits.

• Emphasis on therapies that modify conditions rather than merely suppressing symptoms.

• Continuing education efforts through NEI Congress and related materials.