When should clinicians consider agomelatine in depression?

Agomelatine is not simply “another antidepressant”.

Its clinical fit usually comes down to two practical questions:

1/ Is the presentation shaped by circadian rhythm disruption?

2/ Are standard antidepressants limited by tolerability? 🧵👇 Agomelatine has two key receptor actions:

- MT1/MT2 melatonergic agonism
- 5-HT2C antagonism

That combination is what gives it a different clinical profile from antidepressants explained mainly through serotonin or noradrenaline reuptake.

BPD and bipolar disorder are not the same.

The two can look alike...

But they are not unstable in the same way.

Here are 6 practical distinctions to tell them apart: 🧵👇 1/ Affective-Interpersonal Pattern 

In BPD, mood shifts are often rapid and linked to interpersonal stressors.

In bipolar disorder, mood episodes are usually less reactive to the immediate environment.

Borderline Personality Disorder (BPD) isn’t just “emotion dysregulation.”

It can be usefully conceptualised as a predictive-processing problem where salience, reward prediction errors (RPEs), and the endogenous opioid system (EOS) bias social learning.

Here’s how clinicians can help patients update predictions and reduce volatility. 🧵👇 Prediction errors = expectation vs outcome

Rapid, phasic dopamine/serotonin signalling in reward/salience networks encodes PEs, guiding attention, belief updating and affect regulation.

A patient may genuinely want recovery and still struggle to move toward it.

Because if the brain cannot predict what recovery feels like...

The familiar pattern may remain easier for them to recognise as 'safe'...

Even when it is what continues to harm them.🧵👇 The brain is predictive by nature.

It does not passively perceive reality.

Instead, it builds a model of what is likely to happen next.

Then it compares that prediction with incoming signals from the world and the body.

BPD is not simply complex PTSD.

Yes, the two can overlap…

But they differ in 5 key clinical ways. 🧵👇 At ‘face value’, BPD can look a lot like cPTSD.

They overlap across:

- emotional dysregulation
- shame
- trauma history
- dissociation
- relational disturbance

But unlike cPTSD, BPD is not defined by trauma alone.

It has a different organising pattern.

ADHD and ASD are often treated as separate diagnoses. 

Technically, they are.

But their developmental roots may not be as far apart as the labels suggest. 🧵👇 Diagnostic labels separate ADHD and ASD.

But aetiology does not always adhere to diagnostic boundaries.

The overlap may even start early:

- genes
- molecular pathways
- brain development
- gene–environment interaction

Long before the overlap appears clinically as behaviour.

Reward does not automatically become action.

The brain has to translate it:

past pleasure → future value → effort calculation → planning → goal-directed behaviour

In schizophrenia, this translation process may be impaired.

This is why avolition may be more than just the absence of motivation. 🧵👇 In schizophrenia, reward processing is not only about pleasure.

It is about whether reward information can organise behaviour.

So the problem may appear as reduced activity…

But the breakdown may begin before action starts.

The drug may start the addiction.

But over time, the cue can begin to drive it.

A place. A person. A smell. A mood. A time of day.

This is how the brain learns to seek the drug before the drug is even present. 🧵👇 To understand why, start with what repeated drug use teaches the brain.

The substance is not experienced in isolation.

It happens in a context:

* where the person is
* who they are with
* what they feel
* what they expect
* what their body has learned to anticipate

Psychodynamic psychotherapy is built on 2 core processes.

Take one away, and therapy may not progress.

Here are those 2 processes and how they apply in practice: 🧵👇

(scroll through to see number 2) 1/ Attachment

The connection between therapist and patient.

In psychodynamic psychotherapy, it is this therapist-patient bond that forms the foundation of the entire therapeutic process.

Without enough connection, mentalisation has less room to develop.

Gabapentin and pregabalin are often described as “GABA-like.”

But clinically, that can be misleading.

They do not act by binding to GABA receptors.

To understand their role in psychiatry, let's start with what gabapentinoids actually do. 🧵👇 Despite their structural similarity to GABA, gabapentin and pregabalin do not bind to GABA-A or GABA-B receptors.

Their main target is the α2δ subunit, especially α2δ-1, of voltage-gated calcium channels.

Psychiatric disorders are not explained by genetic vulnerability alone.

Stress, trauma, substance use, nutrition, infection, and medication can also shape gene expression.

That is where epigenetics becomes clinically relevant. 🧵👇 Let’s start with the definition.

Epigenetics refers to changes in gene activity and expression that occur without changing the DNA sequence itself.

The genetic code may stay the same.

But how that code is read can change.

Methylphenidate is not simply “a stimulant.”

Its clinical effect depends on how dopamine and noradrenaline are increased, released, sustained, and worn off.

That is where formulation choice becomes clinically important. 🧵👇 Methylphenidate blocks the reuptake of:

* dopamine via DAT
* noradrenaline via NAT

This increases dopamine and noradrenaline in the synaptic cleft, supporting dopaminergic and noradrenergic transmission.

It’s not just: 

“Is psychosis improving?”

It’s also:

“Is the patient returning to daily life?”

Clinical care often focuses on reducing psychosis.

But recovery also means rebuilding function. 🧵👇 This is the recovery gap in schizophrenia.

Positive symptoms may improve:

* hallucinations
* delusions
* thought disorder

But the patient may still struggle with motivation, expression, social connection, and goal-directed behaviour.

Depression is not one biological pathway.

For some patients, monoamines may be only part of the story.

Here’s how new developments in the biology of depression are reshaping antidepressant treatment: 🧵👇 For decades, antidepressants have largely targeted monoamine systems:

* serotonin
* noradrenaline
* dopamine

This model changed depression care.

But it also left major gaps:

* delayed onset
* treatment resistance
* tolerability problems
* incomplete response

Guanfacine and clonidine are often grouped together as alpha-2 agonists.

But that shared mechanism doesn’t make them clinically interchangeable.

So the question is not simply:

“Which one should I prescribe?”

It is:

“What symptom or problem am I trying to address?” 🧵👇 Both medications can be useful in ADHD when stimulants are:

* unsuitable
* not tolerated
* ineffective
* only partly effective

They can be used as monotherapy or as adjunctive agents.

But their clinical fit is not the same.

Psychiatric labels are useful.

But in complex presentations, they often don’t explain enough.

The better clinical question is not only:

“What diagnosis fits?”

But:

“Which neural circuit is driving the presentation?” 🧵👇 This is where the Tripartite Model of Fronto-Striato-Limbic Circuits becomes useful.

Rather than organising symptoms only by diagnosis, it helps clinicians map symptoms onto 3 core loops:

1. Affective loop
2. Cognitive loop
3. Motor loop

Not all PTSD reflects the same neurobiological pattern.

Some presentations are predominantly hyperaroused. Others are predominantly dissociative. 

This distinction has direct clinical implications:🧵👇 Around 13–30% of individuals with PTSD meet criteria for the dissociative subtype.

So treating all PTSD as one neurobiological pattern risks clinical oversimplification.

This suggests that hyperaroused and dissociative PTSD may reflect different underlying regulatory patterns.

Schizophrenia is often framed through the mesolimbic dopamine model.

But recent neuroimaging suggests dopaminergic dysfunction may be more pronounced in the dorsal striatum than previously emphasised.

That distinction matters clinically. Here’s why: 🧵👇 The dorsal striatum is not just a motor structure.

Its associative striatal region acts as an integrative hub linking cortical, limbic, and motor systems.

So dysfunction here can affect not only psychosis, but also cognition, action selection, and behaviour.

Autoimmune Encephalitis (AE) is a relatively rare neuroinflammatory disorder.

However, what makes AE so hard for clinicians to spot isn't just its rarity.

Rather, it is that it can look psychiatric early.

To avoid misdiagnosis, here’s a 3-point AE diagnostic criteria clinicians should know:🧵👇 AE diagnosis can be considered when all three of the following criteria are met.

1/ Subacute Onset

The first criterion is a subacute onset, defined as a rapid progression over less than 3 months.

Clinically, this may present as:

- working memory deficits or short-term memory loss
- altered mental status
- psychiatric symptoms

The key signal is not just symptom type, but how quickly the syndrome evolves.

Schizophrenia is often conceptualised across 3 domains:

- Reality distortion: delusions and hallucinations

- Disorganisation: formal thought disorder, disorganised behaviour, inappropriate affect 

- Negative symptoms: alogia, avolition, anhedonia, asociality

But this framework doesn’t fully capture clinical complexity.

Here are 3 additional features that remain clinically relevant in schizophrenia, even if they are not specific to it alone:🧵👇

(Click through to see all 3 additional clinically relevant features) 1/ Catatonia

Catatonia is a psychomotor syndrome that can occur in schizophrenia.

Catatonic stupor may be a recognisable presentation, but immobility, mutism, staring, and rigidity are also described clinical signs.

Although DSM frameworks have reclassified catatonia from a core feature of schizophrenia to a specifier across several disorders, it remains clinically relevant and still manifests in around 9% of schizophrenia cases. (Solmt et. al., 2018)

Why do some patients not improve, despite the “right” medication?

Because prescribing is not purely biological…

It is not only metabolised by the body.
it is also filtered through trust, ambivalence, and transference.

To minimise avoidable treatment limitations, here are 7 psychodynamic principles in pharmacotherapy every clinician should understand 🧵👇 1/ Avoid the Mind–Body Split

Psychopharmacology and psychotherapy are not separate.

Medication acts on biology…

But the mind shapes how it is experienced, tolerated, and adhered to.