🧵Medications in Borderline Personality Disorder (BPD)🚨1/15

A common belief persists: “medications don’t work in BPD.”

This false split 👉psychotherapy vs. pharmacology👉prevents optimal outcomes.

Here’s why that view is misleading, and how to think differently. 👇

#BPD #medications #psychiatry 1/ Psychotherapy is essential in BPD.

No question.

But dismissing medications outright ignores neurobiology.

Patients with BPD often carry comorbid psychiatric and physical conditions.

Emotional dysregulation is not split from biological processes underpinning it

Leaving those untreated means leaving suffering unaddressed.

🧵Difficult-to-Treat Depression: What’s Resistant- and What’s Misunderstood?🚨1/14

In psychiatry, we often label complex cases as treatment-resistant.

But that term suggests the illness is the problem.

What if the issue lies in how we think-not just what we treat?

Let’s shift from labels to clinical reasoning. 👇 1/ Depression is frequently reduced to sadness or low mood.

But these symptoms, while common, are not central to every presentation.

Instead, depression involves dysfunction across three core domains:

Activity, Cognition, and Emotional Hedonics (ACE)

🧵Clonidine vs Zopiclone in Sleep and Pain - Who’s the Winner ? 🚨1/7

Zopiclone - A z drug acting via allosteric modulation at GABA-A receptor

Clonidine - an Alpha-2 agonist .

Let’s explore 👇1/7 1/ Clonidine is an alpha 2 agonist.

-α2A (tonic) = stabilises attention, calms hyperarousal

-Presynaptic α2 = reduces noradrenaline release

🧵It’s Not All GLP-1: Why Psychiatrists Shouldn’t Forget Metformin 🚨1/7

GLP-1 agonists are getting all the hype in psychiatry.

But we shouldn’t forget metformin -less dramatic upfront, but still effective long-term in many patients.

Here’s why psychiatrists should look closer 👇 1/ Metformin’s relevance in psychiatry goes beyond glucose control.

It acts on:

1. Peripheral insulin sensitivity → improves glycaemia

2. AMPK activation → ↓ systemic inflammation & oxidative stress

3. Brain insulin resistance (BIR) → a mechanism now linked to psychosis, mood disorders & treatment resistance

🧵New JAMA paper: GLP-1 agonists show metabolic benefits in psychiatric patients. 🚨1/7

Weight ↓ | HbA1c ↓ | QoL ↑ | No adverse MH outcomes.

The question isn’t if these work.

It’s whether we implement them in psychiatry. 👇 1/ For over a decade, psychiatry has recognised the metabolic burden of antipsychotics.

We’ve known about

-Metformin
-Topiramate

And now:

-GLP-1 receptor agonists (Semaglutide, Liraglutide, Tirzepatide etc )

The data keep coming.

Yet metabolic outcomes?…

🧵Psychiatry as a Scapegoat-And the Mirror We’d Rather Not Face 🚨1/11

‘Psychiatry isn’t real medicine.’
‘Psychiatry medicalises normal life.’
‘Psychiatry is pseudoscience.’
‘Psychiatry is dangerous.’
‘Psychiatry is built on lies’

Psychiatry is the perfect object of projection.

Let’s explore 👇 1/ For physicians

It is where bias, feelings of helplesness, the medically unexplained (and uncertain) and inadequate (MH) training are displaced.

A refuge that protects the ego against the threat of incompetence,
while clinging to the false comfort of the mind–body split.

🧵What Doctors Do When the Evidence Runs Out 🚨

Evidence-based medicine is the mantra.

But what happens when there’s no evidence?👇1/9 1/ Prof David Isaacs & Dr Dominic Fitzgerald wrote a tongue-in-cheek classic categorising how clinicians actually make decisions.

❌ Why We’ve Got Prescribing Exercise All Wrong 🚨1/10

There’s endless debate about “exercise” in mental health.

This evidence shows movement helps depression.

However, it doesn’t mean that medications or CBT aren’t useful.

The key is movement - matched to the right time, for the right person.

The aim is to get the brain moving!

So rather than say “go exercise, it’s good for you,”

👉 Here’s how I actually prescribe it 👇 1/10 1/ When I “prescribe exercise,” I’m not asking patients to suddenly become gym junkies.

The real target isn’t exercise. ❌

It’s movement. ✅

Because movement → cognition → emotional regulation.

🧵Could this single image help us understand PSSD? 🚨 1/14

PSSD - Post-SSRI Sexual Dysfunction can follow SSRIs, finasteride (PFS) or isotretinoin.

It’s often discussed as a peripheral problem.

But the genitals have a huge cortical footprint, deeply connected to emotion and salience networks.

Could functional brain changes be a key part of the puzzle?

Let’s explore 👇

*image from Dr Khaldoon Al Saee presentation on the Academy on The Neuroscience of Pain
#PSSD 1/ In the sensory homunculus, the genitals take up huge cortical real estate.

That’s not about anatomy size -it’s about sensitivity and signal importance.

🧵The Brain as a Predictive Organ: Why You Think You Know More Than You (may) Do 🚨1/10

You think you know it.

Wrong.

Your brain predicts that you know, SO you can feel like you know it.

Read it again

This is not a trick.

It’s the fundamental operating system of the brain-boxy connection

Diagram from article : Sammons M et al, Brain-body physiology: Local, reflex, and central communication. Cell. 2024 👇1/11 1/ The brain is an organ of prediction.

It doesn’t just react to reality - it rehearses it.

Prediction gives the body a head start.

A sense of certainty = reduced arousal = sense of the world

It’s why you salivate before food touches your lips.

🧵Vortioxetine in SSRI-Resistant OCD – Early Clinical Signals 🚨1/4

Study :

-64 adults with DSM-5 OCD
-SSRI non-responders
-Vortioxetine monotherapy ≥20 mg/day
-≥8 weeks treatment

👉Primary outcome: Y-BOCS

👉Secondary: HAM-D, HAM-A, adverse events

Results 👇1/4 1/ Results:

- 39.1% met responder criteria (≥25% ↓ Y-BOCS)

-Y-BOCS ⬇️from 27.1 → 20.7

-HAM-D and HAM-A improved significantly

-Most common SEs: nausea (29.7%), sedation (18.8%)

-No serious adverse events

🧵When Patients Feel Harmed by Treatment - Is There More to the Story? 🚨 1/21

This will get backlash.

It’s not about denying harm.

It’s about understanding how harm is experienced, amplified, encoded, and communicated and

how that understanding can help people move forward in a world that’s flawed and uncertain.

1/21👇 1/You’ve heard stories like:

“I was harmed by antidepressants.”
“These medications ruined my life.”
“I’m a shell of who I used to be.”

These experiences are real and often tragic.

But to truly understand them, we need to look beyond pharmacology - into personality, pain, and developmental templates.

🧵 Protracted SSRI Withdrawal and the Problem of Causality 🚨1/11

Much of the debate around “protracted SSRI withdrawal” stems from a misunderstanding of causality.

Let’s explore it using Rothman’s model: causality consists of

1️⃣Necessary causes
2️⃣Sufficient causes
3️⃣Component causes

Let’s apply it directly to this debate 👇1/11 1/ Necessary Cause = A cause that must be present for the outcome to occur.

In protracted SSRI withdrawal, the SSRI itself is a necessary cause.

You cannot have SSRI withdrawal without prior SSRI use.

But necessary ≠ sufficient.

🧵SSRI Withdrawal Is Real But So Are Other Possibilities 🚨1/11

This slide shows the withdrawal (discontinuation) symptoms from SSRIs-based on the Horowitz & Taylor paper (2019).

It’s a helpful summary. Right?

But now imagine this:

Someone stops their SSRI... and these symptoms continue for months or even years.

Protracted withdrawal? Easy ? Not quite 👇 1/ Protracted withdrawal.

It sounds clear, right?

But what actually makes it “protracted withdrawal”?

Let’s think clinically.

🧵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.