🧵Clozapine + Cariprazine for TRS with persistent Negative Symptoms 🚨1/7

Study :
A systematic review (21 studies, 52 cases) evaluated cariprazine augmentation in clozapine partial responders.

👉Cariprazine replaced another AP in 44% or was added to clozapine in 35%

👉90% had positive symptoms;
81% had negative symptoms pre-treatment

What were the results ? 👇1/7 1/ Improvement in 66% (positive) and 83% (negative) symptom domains

-PANSS total ↓ 43.4%; negative symptoms ↓ 59.1%

-Well tolerated overall; most common AE: akathisia (6%)

-Clozapine side effects reduced in some

🧵 Humans are BAD at Probabilistic thinking - Risk Analysis of SSRIs in Pregnancy 🚨1/12

The recent FDA panel on SSRIs highlighted that clinicians often struggle with probabilistic thinking.

For most of human history, binary thinking kept us alive: safe or dangerous?

But in today’s world, risk isn’t black or white -it’s probabilistic.

When we talk about SSRIs in pregnancy, we must move beyond “all good” or “all bad” and start thinking in numbers, not instincts.

And that’s a clinical issue : because when we can’t think in risks and trade-offs, patients suffer.

Let me explain. 👇

Image from (Labelling people as ‘High Risk’: A tyranny of eminence?, Järvinen) 1/ Charlie Munger said it rather crudely 👇

“If you don’t get this elementary, but mildly unnatural, mathematics of elementary probability into your repertoire, then you go through a long life like a onelegged man in an asskicking contest."

HG Wells predicted that in modern society, statistical thinking would become as necessary as reading and writing.

But the FDA panel discussion showed us we’re not quite there.

🧵Addiction isn’t the problem.
It’s the solution the brain found. 🚨
(⚠️Long one!)

But to change it, we must first understand:

What was it trying to solve?

Let’s explore it. 👇1/21

*thanks for the thread - important

https://twitter.com/brightonpsych/status/1947243139246243855

1/“Humans are bundles of habits.” -William James

At our core, we are habitual creatures.

We develop mental, emotional, and behavioural routines to manage internal states.

Some habits are adaptive.

Others become maladaptive over time-That’s where addiction begins.

🧵Antidepressant switch or augmentation? One medication or two? 🚨1/12

Seems like a simple question.

But in psychiatry as in chess we're not just moving pieces.

We're reading configurations.

Let’s explore this clinically. 👇1/12 1/ Chess isn’t about a single move.

It’s about anticipating responses.

Likewise, psychiatry isn’t about choosing just a drug.

It’s about understanding the interaction between:

-The patient’s biopsychosocial ‘make up’
-The depression phenotype
-The response patterns

You’re not playing white alone. ❌

🧵ADHD meds reduce self-harm, crime, and traffic crashes. 🚨1/10

BUT...

as prescriptions rise, benefits seem to shrink.

Is this a sign treatment is failing - or are we looking at the wrong denominator?

Let’s explore 👇1/10 1/ A large Swedish study (N = 247,420) confirms what we already suspected:

ADHD medication is associated with lower rates of:

-Self-harm
-Unintentional injuries
-Traffic crashes
-Crime

🧵Partial agonists are misunderstood - and often misused. 🚨1/9

They’re not “milder” meds.

They’re modulators.

And if you set and forget, you’ve already missed the point.

Let’s break this down. ( Ill focus on partial D2 agonists) 👇* image concept from Dr Mattingly 1/ Here is how i explain it in teaching

We first need to understand two concepts:

1️⃣Affinity

2️⃣Intrinsic Activity

👉Affinity is how tightly a drug binds - like a person racing to claim the best seat in a crowded room.

👉Intrinsic activity is how “loudly” that person speaks once seated -

- Full agonists speak at full volume

- antagonists remain silent

- partial agonists speak at a controlled, softer volume.

Long 🧵 Great Question ✅
I'll reframe it "What’s the best way to understand rejection sensitivity in neurodivergent individuals?" 🚨 1/18

TLDR: Moving beyond labels and looking through the lens of neuropsychoanalysis.

Because this isn’t just about emotion.

It’s about prediction.

And what happens when early emotional learning gets 'wired' into the nervous system.🧵👇 1/ Rejection sensitivity refers to a heightened emotional and behavioural response to perceived or actual rejection.

It’s often rooted in early interpersonal unpredictability, when safety, attunement, or emotional availability were inconsistent.

Can you remember a time you trusted someone or something, only to realise it wasn’t true?

-A friendship that let you down?
-Feeling rejected by someone you liked
- Feeling like an outsider in the play group?
- going up to your caregiver in an anxious state and being rejected because you ‘disappointed them’.

-That pain.
-The sinking feeling.
-The moment of shock.

But there’s more beneath the surface.

🧵From 2024 👉Neuroinflammation in Depression: 10 Key Points for Psychiatrists🚨

Recognising an inflammatory subtype can make a significant difference to treatment✅”

Let’s revisit the key points ( Not exhaustive) 👇1/11 1/ Symptomatology :

👉Depression associated with neuroinflammation often includes fatigue, brain fog, cognitive dysfunction, anhedonia, hyperarousal / agitation / insomnia.

👉A mixed state is often present.

🧵What Clinicians Should Know About Psychosis in Borderline Personality Disorder (BPD)🚨1/8

Salience operates on a continuum.

Under stress, the salience system doesn’t ask for permission -it amplifies threat based on past wiring.

We can’t predict the response, but we can track how it’s expressed.

1/8👇 1/ Psychosis in BPD is Real and Prevalent :

-Auditory verbal hallucinations (AVHs) occur in up to 54% of individuals with BPD, often resembling those seen in primary psychotic disorders.

-These are not simply ‘pseudo’ or transient symptoms-they are phenomenologically similar to schizophrenia and can meet criteria for first-rank symptoms.

🧵Novel and Emerging Treatments for Agitation in Schizophrenia and Bipolar Disorder 🚀
1/7 1/ Traditional approaches :

- Haloperidol (oral/IM/IV)

Limitations: High incidence of extrapyramidal symptoms (EPS), dystonia, and risk (albeit rare) of neuroleptic malignant syndrome. 🚨

- Lorazepam (oral/IM/IV)

Limitations: Tolerance, risk of respiratory depression, cognitive impairment - particularly problematic in elderly or medically fragile populations. 🚨

🧵Ketamine and Dissociation - What’s the Mechanism? 🚨1/7

A real-world 2025 EEG study in bipolar depression patients reveals a cascade of changes across brain rhythms, complexity, and excitation-inhibition (E/I) balance.

Let’s break it down: 👇1/7 1/ Oscillatory activity:

Ketamine reduced theta (θ), alpha (α), and low beta (β) power while increasing low gamma (γ), consistent with cortical disinhibition via NMDA antagonism on GABAergic interneurons.

Translation 👉The brain’s usual slow, calming rhythms were dampened and fast, stimulating activity ramped up.

This likely reflects a release of inhibitory control. 🚨

🧵 𝑷𝑻𝑺𝑫 𝒂𝒏𝒅 𝑷𝒂𝒊𝒏: 𝑾𝒉𝒚 𝑻𝒉𝒆𝒚 𝑺𝒐 𝑶𝒇𝒕𝒆𝒏 𝑪𝒐𝒆𝒙𝒊𝒔𝒕 🚨

In clinical practice, psychological and physical pain often overlap, especially in PTSD.

This overlap is not incidental.

It is driven by shared emotional circuits and neurobiological mechanisms.👇 1/8 1/ 🧠 Shared Neural Circuits:

- The ACC projects to the thalamus, amygdala, hypothalamus, and PAG, modulating pain, fear, and autonomic responses.

- Trauma induces amygdala hyperreactivity, HPA axis dysregulation, and altered dopamine signalling, amplifying inflammation and pain sensitivity.

- The parabrachial nucleus routes pain signals directly to the amygdala, reinforcing survival responses.

🧵Why are SSRIs associated with emotional blunting- and why is that not always a bad thing? 🚀

The answer lies in their nuanced neurobiological effects.

Here's what happens 👇

https://twitter.com/psycheureka/status/1913584124696416336

1/ SSRIs reduce amygdala reactivity

This underpins their anxiolytic and reduced stress response benefits ( e.g PTSD)

Lower limbic activation = reduced fear, less hypervigilance, and blunted stress responses.

This effect is seen across anxiety disorders and PTSD.

(ref : Harmer et al., 2006)

🧵When Physical Pain Meets Psychiatry 🚨 1/15

Pain doesn’t just arise from the body -it’s constructed by the brain.

The circuits that mediate emotional and physical pain overlap.

That’s why in psychiatry, we don’t just treat pain as a symptom -we treat it as a signal.

Here’s how a shift in approach changes things. 👇1/15 1/ “Pain on both soles of feet -I can't exercise.”

“My back pain’s gotten worse.”

“My spinal cord stimulator worked initially, but now it doesn’t ;standing is painful.”

“My muscles ache all over.”

“I’ve tried coming off fentanyl, but I just can’t.”

These are varied descriptions of patients with affective disorders.

🧵Ketogenic Diets-Promising or Problematic? The Data Just Got Interesting. 🚨1/6

Ketogenic diets are gaining traction in psychiatry-early reports show promise for depression, bipolar, and schizophrenia.

But a new study in JACC (KETO-CTA) just raised eyebrows-and it has big implications for patients in psychiatry . 👀 1/ The Study

👉100 lean, metabolically healthy individuals on a ketogenic diet-with LDL-C ≥190, HDL ≥60, and triglycerides ≤80-were followed for 1 year using coronary CT scans.

Note 👉 these are lean metabolically healthy individuals ✅

🧵 The Paradox of Medication: Sometimes You Need It to Stop Needing It 🚨

Sounds paradoxical, right?

But clinicians who follow patients long-term recognise that treatment unfolds in distinct phases.

1. Short-term stabilisation
2. Long-term recovery.

Let's explore 👇 1/7 1/ When allostatic load overwhelms an individual’s control mechanisms, we see clear markers:

-Worsening symptoms
-New symptoms emerging
-Increasing effort just to function

At this stage, medication may act as a regulatory intervention, reducing allostatic load and restoring homeostatic control to the individual.

🧵The Skin as a Boundary and Container for ‘The Self’ 🚨

The skin, both literal and symbolic, offers a window into the fragmented self.

Psychodermatology in BPD 👇1/11 1/ Clinicians would have heard the statement “I feel uncomfortable in my own skin."

Psychodynamically, the skin is more than a physical boundary-it’s a container for the self.

It separates "me" from "not me," creating a sense of cohesion.

In borderline personality organisation, this boundary is fragile, leading to feelings of exposure, vulnerability, and chaos.

🧵15 Commandments of Psychopharmacology 🚀

Textbooks taught me psychopharmacology-UNTIL I stepped into real-world practice as a consultant psychiatrist. 🚨

Here’s what experience taught me that textbooks don’t (or can’t). 👇1/16 1/ Psychopharmacology without phenomenology is blind.

Meds must align with symptom constructs, functional impairment, and lived experience-not just diagnostic labels.

Treat the patient, not the category.

🧵 From Tabula Rasa to Conscious Being 1/11

We are born as a blank slate- how do we transform ‘raw’ needs into emotions, identity, and thought?

Let’s explore 👇1/11 1/ At birth, we are Tabula Rasa- a blank slate.

A newborn's only task?

To have its needs met.

Survival hinges on fulfilling homeostatic needs: warmth, nourishment, and safety.

🧵The Art of Diagnostic Understanding - Thinking Backwards in Psychiatry 1/9

We think forwards-quick, easy, and categorical. But is that what’s needed?

When psychiatric disorders involve molecular to societal influences, thinking backwards-from patterns to pathology to formulation-is the key to individualised care

Here’s how we navigate complexity 👇1/9 1/ Formulation is often misunderstood as simply writing a summary.

But diagnostic understanding is more than a summary-it’s an evaluative process.

It requires:

1. A hierarchy of differentials 📊

2. The integration of biopsychosocial, neurobiological & psychological factors ✅

3. The ability to place labels correctly without premature closure 🏷️

🧵Antidepressants & Discontinuation: Why Stopping Is a New Adaptation, Not a Rewind Button 🚨

Antidepressants are prescribed to help create stability.

But stopping isn’t just a 'reset ’- it’s a new physiological change with multiple possible trajectories. 👇 1/11 1/ The process:

A. Person has distress (symptoms).

B. Medication is prescribed.

C. Medication helps reduce distress, allowing for some stability.

D. Person decides to reduce.

*Note that at this stage, it is the shared decision-making that is important - discussing risks, benefits, short and long-term, and alternatives with their risks and benefits.