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https://www.dailymail.com/news/royals/ar...viour.html

SARAH VINE: Harry and Meghan's new life is already starting to unravel. What a pair of quitters and these are the real poor victims of their behaviour

By SARAH VINE, COLUMNIST
Published: 01:01, 16 September 2026 | Updated: 10:51, 16 September 2026 

Was there ever such a pair of quitters as the Duke and Duchess of Sussex? 

First, they leave Britain after just 18 months of royal life; then they abandon practically every project they embark on Stateside; now they’re back here again for unknown reasons and already, just a few weeks into their new life, things are starting to unravel.  Do they never look before they leap? 

Do they always act on impulse, like headstrong teenagers? 

Do they never plan a few moves ahead, or try to solve their problems instead of flouncing from one place to the next?

Every decision they make seems to be taken on a whim, with little or no thought for the long-term consequences for them or those around them.  But this time they have surpassed even themselves. They’ve pulled the children, Archie and Lilibet, out of their new prep school after just two days. Two days! Barely time for the poor mites to work out which peg is theirs and find their way to the loo and already they’re being whisked away.  Security concerns around the school run, apparently. Ha. More like bad planning, as usual, coupled with Harry and Meghan’s characteristic impulsiveness. And, as some have pointed out, this time it might well work in their favour.  After all, isn’t Ravec (the body that oversees VIP and royal security) currently ‘re-evaluating’ the Sussexes’ security status? 

The safety of the children would no doubt be an important consideration.  Either way, it’s done. The kids are moving schools and all the time, expense and effort that presumably went into preparing parents, children and staff at the first place for their arrival has now been wasted. The whole process will now have to be repeated elsewhere.  As for Archie, seven, and Lilibet, five, their poor little heads must be spinning.  Not only have they just been pulled out of the only life they’ve ever known in sunny California and dumped in the middle of the Cotswolds just in time for the English winter, they’ve now also had to endure all the stresses of starting a new school in a new country, only to have the rug pulled out from beneath them.  It’s one thing for Harry and Meghan to blindside their staff and other members of the Royal Family, as they have time and time again.  Only this summer, they suddenly announced their return, shocking everyone from the King down he reportedly found out about their move the Sunday before they announced it.  But it’s quite another to do that to their own children. How anxiety-inducing must it be for poor Archie and Lilibet? 

Their parents’ behaviour has already excluded them from getting to know their cousins or having a meaningful relationship with their British relatives, and now this. What a mess.  Children look to their parents for stability and wisdom. Harry and Meghan are supposed to be the grown-ups and yet they are behaving like children themselves, chopping and changing at the first sign of the slightest obstacle. Besides, kids understand so much more than we give them credit for.  They will likely be feeling very scared and confused by this sudden decision, especially if they’ve picked up that it’s a security issue.  Talking of which, if the duke and duchess were really so worried about their own safety and that of the children, why would they post pictures of family life in their new countryside idyll?

Isn’t that kind of thing completely counterproductive and a gift to anyone with bad intentions towards them? 

There is no need for it, and it serves no purpose other than to expose them to unnecessary scrutiny and potentially attract unwanted attention.  No one in the Press has identified either the Sussexes’ new home or the children’s school, out of respect for their right to privacy and safety and yet they themselves have strongly hinted at their location to anyone with even basic local knowledge.  That is no one’s fault but their own. And no doubt if, God forbid, something were ever to happen, the couple would blame everyone except themselves. It’s such classic Sussex denial.  One can only conclude that they are either very stupid or they like causing a melodrama.  Let’s not forget that time in New York in 2023 when they issued a dramatic statement claiming to have been involved in a ‘near-catastrophic car chase’ (a highly loaded term given Harry’s family history) which, on closer inspection, turned out to be them getting stuck in a traffic jam.  Granted, they were snapped by a few paparazzi but never in a manner that put anyone in any danger.  As for their school-run complaint, I won’t reveal the name of the establishment, but I have several friends whose children have attended that school over the years, and I would say two things. Firstly, it is a brilliant, very well-established institution, and more than capable of dealing with the security concerns of high-profile parents. Second, even the most cursory enquiries would have revealed its one and only disadvantage: The local traffic, which is famously murderous.  It’s so bad I have one friend who used to leave the house at 6.30am just to get her kids there on time. Houses within walking distance are fought over by millionaires and exchange hands for eye-watering prices.  Parents endure it because the school is so good. But it is notoriously a nightmare traffic-wise.  So why, if they were going to uproot the entire family and send their children there, didn’t the Sussexes check the practicalities of their decision with some of the few remaining friends and supporters they have in Britain?

After all, Princess Beatrice and her husband, Edoardo Mapelli Mozzi, own a six-bedroom converted farmhouse in the Cotswolds complete with ‘party barn’, tennis court and swimming pool, which they purchased in 2021 for around £3.5million.  Edo (as he’s known) attended schools in the area. By all accounts the Sussexes remain on very good terms with the Mapelli Mozzis. They would have been more than able to tell them the lie of the land and flag up any potential pitfalls concerning school runs.  Perhaps they didn’t bother to ask. Or perhaps the fact the decision to return to Britain was taken so on the hoof just meant there was no time.  It seems they did the dry run in August, when everyone is on holiday and the roads are relatively clear which makes you wonder about the quality of some of the security advisers they’re using.  Or perhaps Prince Harry is just so used to the VIP treatment he simply forgot that as mere mortals there are no motorcycle outriders to clear the way through civilian traffic. Well, all I can say is welcome to the real world, Sir. Not always as fun or as easy as it looks, is it?

I loved school up until I left primary school as it was a small school and ju  Myst from my street there were seven of us in the same year.  My problems started when I started at a local comprehensive as I was separated from my girl friends and I only knew a couple of boys from the primary school.  Thankfully I made new friends and still saw friends out of school.

Unfortunately I started getting bullied by older girls and never found out why so I started dreading going to school.  It was okay during lessons, it was lunchtime, morning and afternoon breaks that were difficult.  My friends always had my back but it was the times when they weren't with me.

I was incredibly shy and was scared to tell my parents and teachers as I thought it would make it worse.  My parents knew something was wrong ad tried to get me to talk.  I was also afraid they would think I was being silly or was trying to get out of going.  It only started to ease a bit as a couple of girls were laughing about what they were doing - she and I went to different schools as she was in the last year of the 11+ where we lived.  My sister overheard the conversation, I don't know where they were other than they were out, and she had words with them.  Whatever was said worked but by this time my mental health was already suffering.

I joined last night as I am struggling to find anybody I can trust enough to talk honestly about how I am feeling.

https://www.dailymail.com/news/royals/ar...D-KAY.html

Decoding the King's striking declaration on Harry and Meghan and why royal insiders tell me they are already 'exasperated' by couple's behaviour since returning to Britain: RICHARD KAY

By RICHARD KAY, SENIOR EDITOR-AT-LARGE
Published: 01:00, 8 September 2026 | Updated: 16:55, 8 September 2026 

Some will see it as an act of kingly statecraft, a timely shot across their quasi-royal bows. To others it is a vital sign that Prince Harry’s and Meghan’s presence in Britain will not be allowed to destabilise the monarchy.  What is unquestionably clear, however, is that less than two weeks after their return to British shores, one thing remains unchanged: Megxit still means Megxit.  The decisive move by the King strongly supported, I am told, by Prince William means that just because the couple are home there will be no softening of attitudes nor any dilution of the uncompromising view of the late Queen Elizabeth that they could never be ‘half-in, half-out’ royals.  That the unprecedented announcement should come on the eve of the fourth anniversary of the Queen’s death will be lost on no one, including her grandson, Harry.  This official affirmation of his and Meghan’s continued status as non-working royals is the first since their bitter departure more than six years ago.  It is also timely, with a flurry of key royal events imminent, including Prince George’s first day at Eton College.  The letter, issued in the name of the Lord Chamberlain, Lord Benyon, the King’s most senior aide, is a rigid reminder that the Duke and Duchess of Sussex are to be treated as ‘private citizens’ while in Britain, and do not represent the Royal Family.  Nor can they use their HRH titles which, Lord Benyon emphasises, ‘remain in abeyance’.

Should there be any lingering doubts among Sussex supporters or indeed the couple themselves that returning to the UK might lead to a more flexible approach, with the couple wanting to ramp up their charity work, such hopes look wildly misplaced.  The Lord Chamberlain may have drafted the official communique, which has been sent to members of the Government, the military and Lord Lieutenants, but the content is very much in line with Charles’s sentiments.  In practical terms, it was designed to make clear to those who are involved with royal visits that any engagements carried out by the Sussexes will be in a private capacity.  And it shows that the outcome of the so-called Sandringham Summit in 2020, which led to their departure, still stands.  The language and the icily formal tone of the draft are striking. Stressing that the purpose of the letter was to ‘avoid doubt or confusion’, it says the couple do not represent the sovereign.  While any charity work they do ‘is a personal matter for them both and undertaken in their private capacity’.

One passage gives the most distinct view of how this once-golden couple are viewed. ‘In short,’ the letter says, ‘their position is akin to private citizens with commercial and charitable interests.’

Reading between the lines, the only way to divine the directive on how they are to be treated is as a command.  Royal aides may insist that there is nothing controversial, nor new, about the letter’s contents adding that it merely sets out the position for all parties.  But the fact that Buckingham Palace needed to send the letter in the first place illustrates the degree of confusion and uncertainty Harry and Meghan’s sudden return to the UK has caused.  As one long-term friend of the King told me: ‘They didn’t need to issue guidance about Andrew Mountbatten-Windsor when he ceased his royal life and gave up public duties, which suggests they have been spooked by the Sussexes.’

One factor that has raised concern at the highest levels, has been the way friends of Harry and Meghan have been spoon-feeding friendly publications with details about their plans. ‘They’ve only been back a matter of days and can have barely unpacked but we keep hearing how they want to step up their charity work which would inevitably raise their public profile,’ says one figure. ‘It’s exasperating.’

Talk, too, of the couple establishing some kind of rival court has also irritated figures close to the King.  The Lord Chamberlain’s letter, which he says was a response to ‘a number of requests for guidance’, should indeed be viewed therefore as a shot across the Sussex bows or at least across the bows of those pushing their agenda.  The problem, however, is that it is all very well telling organisations that any visits Harry and Meghan undertake should not be treated as royal engagements, but in the years since they left Britain that is precisely the way their appearances have been treated. Even their visits overseas have been crafted to resemble the kind of duties they carried out before they abandoned their royal life, often with the same protocols, such as paying respects in war cemeteries.  As Harry himself has often chosen to remind people not least in his battle to obtain taxpayer-funded security he has always been a royal.  Yesterday’s intervention will be seen as an essential move by the King to preserve the cohesion of an institution which was undermined in the first place by the Sussexes flouncing off to California.  And while it may not prevent the couple seeking out public-facing opportunities, it may change the way people react to them.  Of course, the letter leaves many questions unanswered. It does not address the issue of family events and when and where Harry, Meghan and their children might join private House of Windsor gatherings.  Nor does it offer any insight into the police protection Harry so passionately wants, with his children about to start at school and the potential risks of shuttling them to and from the same place each day.  Aware that such concerns may be raised, the Lord Chamberlain dodges it, writing: ‘Any operational security issues should continue to be directed to the relevant police authorities.’

However, he does acknowledge that accommodating the couple may be contentious and suggests that any questions ‘where recourse to public funds may be required, should be directed to Buckingham Palace’.

A sign, perhaps, that the King will intervene if he does feel Harry and Meghan’s conduct may not be in the monarchy’s best interests.  Many critics believe that although the letter was designed to draw a line under speculation about the couple’s future, there was a missed opportunity.  Removing them from the royal website [where they still feature but without their HRH titles] would have been the most significant gesture to separate them as non-working royals from the rest of the family,’ a former aide to the King said.

After their tours of Africa, Central America and Australia, where they were treated as huge royal stars, it might have been useful if the Lord Chamberlain had also sent a copy of his letter to world leaders too.

https://www.nhs.uk/mental-health/conditi...-disorder/

Bipolar disorder 

Bipolar disorder is a mental health condition where you have extreme mood changes. Medicines and talking therapy can help manage it.

Symptoms of bipolar disorder

The main symptom of bipolar disorder is extreme changes to your mood.

You sometimes have either:

• high moods (mania or hypomania) – for example, feeling very happy, excited or energetic
  
• low moods (depression) – for example, feeling sad, tired or hopeless
  

• you have extreme changes in your moods that last a long time or impact your everyday life
  
• you've been diagnosed with bipolar disorder and treatments are not helping (or speak to your mental health specialist if you have one)
  

• medicines to help stabilise your moods
  
• talking therapy such as cognitive behavioural therapy (CBT)
  

• try to have a regular routine
  
• get plenty of sleep
  
• eat a healthy diet
  
• exercise regularly
  
• try to avoid and manage stress
  

• do not take recreational drugs
  
• do not smoke
  
• do not drink too much alcohol
  
• do not do shift work or work very long hours if you can avoid it
  
• do not fly at night or across time zones if you can avoid it
  
• do not drink lots of caffeinated drinks such as coffee, tea or cola
  
  

• Local and specialist support groups (Bipolar UK)
  
• Online and local support groups (Mind)
  
• eCommunity online forum (Bipolar UK)
  
• Blogs sharing stories and experiences about living with bipolar disorder (Bipolar UK)
  
  

• Supporting someone with bipolar disorder (Bipolar UK)
  
• Helping someone else (Mind)
  
• Carers hub (Rethink Mental Illness)
  
  

• Bipolar UK
  
• Mind: bipolar disorder
  
• Rethink Mental Illness: bipolar disorder
  

• childhood trauma or abuse
  
• a stressful event such as relationship problems, abuse, the death of someone close to you or money problems
  
• recreational drugs such as cannabis or cocaine
  
• a parasite called toxoplasma gondii (which causes toxoplasmosis)
  

https://www.psychiatrictimes.com/view/ho..._source=hs

How to Approach Conversations With Adult Patients Who Might Have ADHD: New Tools and Insights
Author(s)Leah Kuntz, Nona Kocher, MD, MPH

Key Takeaways

• Quintessence Psychiatry uses Mentavi's Diagnostic Evaluation to enhance ADHD assessments, offering a structured, objective alternative to traditional testing.
  
• Dr. Nona Kocher highlights the importance of open, exploratory conversations with patients, focusing on understanding rather than criticism. 
  

https://www.nhs.uk/conditions/alcohol-use-disorder/

Alcohol-use disorder 

Alcohol-use disorder is drinking alcohol in a way that's harmful. People sometimes call this alcoholism. Treatment and support is available to help you cut down or stop.

Signs of alcohol-use disorder

Signs of alcohol-use disorder include:

• regularly drinking more alcohol than you mean to
  
• difficulty stopping or reducing the amount you drink, even if you want to
  
• feeling guilty or remorseful after drinking
  
• people you know being concerned about your drinking
  
• continuing to drink even when it's causing problems for your health, work or relationships
  
• craving alcohol, for example, needing a drink when you wake up in the morning
  
• needing increasing amounts of alcohol to get the same effect
  
• getting withdrawal symptoms when you stop or reduce drinking
  

• anxiety
  
• difficulty sleeping
  
• feeling and being sick (nausea and vomiting)
  
• a racing heartbeat, sweating and shaking (tremor)
  
• seeing, hearing or feeling things that are not there (hallucinations)
  
• confusion
  
• seizures
  

• you're worried about your drinking
  
• you want help to stop drinking
  
• you get symptoms like anxiety, difficulty sleeping, sweating or feeling and being sick when you try to stop drinking
  
• you're worried about someone else's drinking
  

• shaking visibly
  
• being unusually restless, irritable or upset
  
• confusion (for example, not knowing what day it is)
  
• seeing, hearing, or feeling things that are not there
  
• having a seizure
  

• talking therapies such as cognitive behavioural therapy (CBT)
  
• medical help for withdrawal symptoms when you stop drinking alcohol, either at home or in hospital
  
• help to prevent relapses (where you start drinking again), such as medicines to reduce alcohol cravings
  
• support to make positive changes in other areas of your life, such as your relationships
  
• help accessing other forms of support, for example with employment or housing
  

• acamprosate or naltrexone, which help reduce alcohol cravings
  
• disulfiram, which causes unpleasant effects (such as a headache, feeling sick, high body temperature and heart palpitations) when combined with alcohol
  

• serious accidents or injuries while drunk
  
• alcohol poisoning
  

• liver damage such as alcohol-related liver disease
  
• increased risk of many different types of cancer
  
• high blood pressure and stroke
  
• heart problems including cardiomyopathy and heart failure
  
• acute pancreatitis and chronic pancreatitis
  
• mental health conditions such as anxiety and depression
  
• alcohol related brain damage
  

• The risks of drinking too much
  
• Drinking alcohol while pregnant
  

• keep a daily diary of how much you're drinking, or try a drink tracking app
  
• to cut down, try alternating alcoholic drinks with soft drinks, or choose lower strength (ABV in %) drinks
  
• tell people you're stopping drinking so they can help keep you on track
  
• avoid situations where you know you're likely to drink
  
• find different activities to do when you'd usually drink, such as trying a new hobby
  
• try joining a support group
  

• NHS Drink Free Days – App Store
  
• NHS Drink Free Days – Google Play
  

• Alcoholics Anonymous
  
• SMART Recovery
  

• Al-Anon UK
  
• SMART Recovery: family and friends programme
  
• Adfam
  

• Help for family and friends (Alcohol Change UK)
  
• Caring for someone with alcohol or substance misuse issues (Carer's Trust)
  

https://www.nhs.uk/mental-health/feeling.../overview/


Overview – Eating disorders 

An eating disorder is a mental health condition where you use the control of food to cope with feelings and other situations.

Unhealthy eating behaviours may include eating too much or too little or worrying about your weight or body shape.

Anyone can get an eating disorder, but teenagers and young adults are mostly affected.

With treatment, most people can recover from an eating disorder.

Types of eating disorders

The most common eating disorders are:

• anorexia nervosa (often called anorexia) – trying to control your weight by not eating enough food, exercising too much, or doing both
  
• bulimia – losing control over how much you eat and then taking drastic action to not put on weight
  
• binge eating disorder (BED) – eating large portions of food until you feel uncomfortably full
  
  

• negative feelings over the smell, taste or texture of certain foods
  
• a response to a past experience with food that was upsetting, for example, choking or being sick after eating something
  
• not feeling hungry or just a lack of interest in eating
  

• spending a lot of time worrying about your weight and body shape
  
• avoiding socialising when you think food will be involved
  
• eating very little food
  
• making yourself sick or taking laxatives after you eat
  
• exercising too much
  
• having very strict habits or routines around food
  
• changes in your mood, such as being withdrawn, anxious or depressed
  
  

• feeling cold, tired or dizzy
  
• pains, tingling or numbness in your arms and legs (poor circulation)
  
• feeling your heart racing, fainting or feeling faint
  
• problems with your digestion, such as bloating, constipation or diarrhoea
  
• your weight being very high or very low for someone of your age and height
  
• not getting your period or other delayed signs of puberty
  

• anorexia symptoms
  
• bulimia symptoms
  
• binge eating disorder and its symptoms
  

• dramatic weight loss
  
• lying about how much they've eaten, when they've eaten, or their weight
  
• eating a lot of food very fast
  
• going to the bathroom a lot after eating
  
• exercising a lot
  
• avoiding eating with others
  
• cutting food into small pieces or eating very slowly
  
• wearing loose or baggy clothes to hide their weight loss
  

• Beat: get information and support
  
  

• Beat: what to do if you're worried about a friend or family member
  
• Beat: what to do if you're worried about a colleague
  
  

• anorexia
  
• bulimia
  
• binge eating disorder
  
  

• you or a member of your family has a history of eating disorders, depression, or alcohol or drug misuse
  
• you've been criticised for your eating habits, body shape or weight
  
• you're really worried about being slim, particularly if you also feel pressure from society or your job, for example, ballet dancers, models or athletes
  
• you have anxiety, low self-esteem, an obsessive personality or are a perfectionist
  
• you've been sexually abused
  

• Beat: eating disorders information and support
  
• Health for Teens: information and advice about eating disorders
  

https://www.psychiatrictimes.com/view/wh...e=hs_email

When Treatment-Resistant Depression Means Mismatched: Rethinking Difficult-to-Treat Depression
Author(s)Walter Paganin, MD, PhD

Much of what we call "treatment-resistant" depression may be mismatched, not resistant. A psychiatrist makes the case for trading the failed-drug tally for a difficult-to-treat framework clinicians can act on Monday morning.

Case Study
“Cheryl,” a woman in her early 60s, is referred to you with “treatment-resistant depression.” Her chart lists 4 antidepressants across 2 classes over 18 months, 2 of them stopped early for adverse effects, one abandoned without explanation. What dominates the picture is not sadness but a flat, effortful anhedonia: she moves slowly, tires within an hour of waking, complains that her memory “isn’t there anymore.”Buried in her intake, easy to skim past, is a history of early-life trauma, a childhood of chronic adversity and fear, that no prior note has connected to the adult in front of you. Her inflammatory status has never been checked, because why would it be? She is, after all, simply treatment resistant. But before you reach for a fifth agent, it is worth asking a different question: is this resistance, or is it a mismatch?
That question sits at the heart of a shift now underway in the depression literature, one that has not yet reached most of us at the bedside. It is the move away from “treatment-resistant depression” (TRD) toward the broader, more clinically honest construct of difficult-to-treat depression (DTD) and, within it, toward stratifying patients by the biology and the circumstances that are actually driving their illness.

The Trouble With “Resistant”
A systematic review identified 155 distinct definitions of treatment-resistant depression (TRD) currently in use.1 This is not merely a pedantic concern. It means that the same patient may qualify as “treatment-resistant” in one clinic but not in another, depending on how many failed treatment trials are required, how long those trials must last, and whether psychotherapy or neuromodulation are considered at all. The label influences decisions regarding access to advanced treatments and reimbursement, yet it rests on no universally accepted definition.
Worse still, much of what we call resistance may not be resistance at all. A substantial proportion of apparent nonresponders, estimated at between 30% and 60% in some studies, reflects pseudoresistance: inadequate dosing, insufficient treatment duration, poor adherence, unrecognized comorbidities, or pharmacokinetic variability that renders standard doses subtherapeutic in a meaningful minority of patients.1 When treatment adequacy is not rigorously assessed and documented, the prevalence of “resistance” is artificially inflated, leading to potentially inappropriate clinical decisions.
The clinical consequences of this label are far from neutral. Fava and Rafanelli have described a process of “cascade iatrogenesis,” whereby clinicians reflexively move from one pharmacological strategy to another, switching, escalating, and augmenting treatment, before adequately addressing adherence, psychosocial determinants, or considering whether psychotherapy and neuromodulation should already be part of the treatment plan.2 A construct originally intended to identify patients in need of alternative approaches too often results in more of the same.

From Counting Failures to Understanding Difficulty
DTD reframes the problem (Figure). Rather than tallying pharmacological failures, it asks what is actually sustaining the burden.1 The international consensus defines DTD as depression that continues to cause significant burden despite usual treatment efforts, and it shifts the therapeutic target from symptom reduction alone to functioning and quality of life.3 That burden is never the patient’s alone: it is carried by families, who absorb the caregiving, the lost income, and the vigilance about relapse, and by clinicians and services, who accumulate repeated visits, escalating polypharmacy, and their own demoralization when nothing works.3,4 Rush et al make the same move explicit: when remission proves elusive, the goal becomes optimal symptom control and a disease-management approach rather than an endless pursuit of the next agent.5
This is more than semantics. DTD integrates the things the TRD frame tends to push aside: treatment adequacy, functional impairment, psychiatric and medical comorbidity, trauma history, symptom profile, patient goals, and even organizational barriers such as access and continuity of care.4 It abandons the binary responder/nonresponder logic for a spectrum, and it treats chronic depression the way we treat other chronic illnesses, as something to be managed across domains rather than cured in one. For the clinician, the practical consequence is a change in the first question you ask. Not “which drug next?” but “what is making this depression difficult, and have I addressed it?”

Inflammation: A Worked Example of Why Stratification Matters
Among the determinants the DTD frame brings into view, the inflamed subgroup is the clearest illustration of what stratification buys us. Roughly a quarter of patients with major depressive disorder show low-grade systemic inflammation (high-sensitivity C-reactive protein, hs-CRP, ≥3 mg/L).6 These patients respond more poorly to standard monoaminergic antidepressants independent of how severe their depression.7 The phenotype is recognizable: marked anhedonia, psychomotor slowing, fatigue, cognitive complaints—like Cheryl, the woman in the vignette.
The reframing is the important part. Their poor response is not stubbornness of the illness; it is a mechanistic mismatch between the driver (neuroinflammation acting on reward circuitry) and the mechanism of the drug (monoaminergic modulation).8 Calling such a patient “resistant” misnames the problem. They are mismatched, and mismatch is potentially actionable. The logic is simple enough to use: screen with hs-CRP, a test you already order, interpreted during clinical stability and against BMI, smoking, and intercurrent infection; where it is elevated, phenotype further with a parsimonious cytokine panel (IL-6, TNF-α, IL-1β); then align the intervention to the biology rather than escalating blindly.
Here honesty is essential. At present, inflammatory stratification is a tool for phenotyping, prognosis, and enriching clinical trials, not a validated trigger for routine anti-inflammatory prescribing. The evidence for immunomodulatory agents is genuinely mixed: a large trial of infliximab in TRD found no overall benefit, yet in an exploratory analysis a subgroup with elevated baseline hs-CRP (>5 mg/L) improved, which is precisely the argument for enrichment rather than unselected treatment.9 So the near-term value of measuring inflammation is not that it tells you to prescribe a biologic. It is that it tells you why a patient may not be responding, flags those for whom lifestyle, behavioral, and psychosocial interventions are biologically rational early choices, and keeps you from a sixth monoaminergic switch that mechanism predicts will fail.

What to Do on Monday Morning
None of this requires specialized infrastructure. It requires a change in sequence, summarized in the Table. Before you accept “resistant,” verify adequacy of the dose, start a trial of at least 6 to 8 weeks, ensure adherence, and complete therapeutic drug monitoring where pharmacokinetics are in doubt.1 Reconsider the diagnosis, screen for comorbidity, and take a brief trauma history. In the patient who is stalling rather than responding, measure hs-CRP. Assess function and cognition explicitly, not by impression. The Sheehan Disability Scale takes a minute, and a brief cognitive screen, such as the THINC-it battery, captures the deficits patients rate as most disabling.10 Bring psychotherapy and psychosocial intervention forward rather than reserving them for after the pharmacological options are exhausted.3 In everyday clinical practice this is concrete rather than aspirational: a brief trauma history,even a handful of adverse-childhood-experience questions, fits inside a standard visit, can be documented in the shared record and flagged to the collaborating primary care clinician, and turns an apparent “resistance” into a life-course vulnerability that makes trauma-focused psychotherapy a rational early move rather than a last resort. It is also essential to work collaboratively with primary care, social supports, family, and conduct periodic reassessments of the diagnosis itself.

Back to the Patient
Let’s return to Cheryl. Read through the DTD lens, she stops being a dead end and becomes a short list of concrete moves.
First, confirm adequacy: were those 4 trials actually delivered at therapeutic dose for 6 to 8 weeks, with adherence verified? Given the 2 early discontinuations for adverse effects, is tolerability the real story rather than resistance?
Second, rediagnose: her early-life trauma history, the early discontinuations, the prominent anhedonia and psychomotor slowing all warrant a fresh look at comorbidity, including posttraumatic presentations, bipolarity, and medical contributors before another switch.
Third, read the phenotype rather than the failure count: the anergic, anhedonic, cognitively blunted presentation is exactly the profile in which an hs-CRP, a test already on the order set, earns its place, not as a verdict but as one more piece of information.
Fourth, measure what matters: an SDS and a brief cognitive screen turn "she isn't better" into a functional baseline you can track.
Fifth, widen the plan now, not after the next failure: bring psychotherapy, structured psychosocial support, and family involvement forward alongside whatever pharmacological adjustment follows.
The point is not that an inflammatory marker would have "explained" her, or that an anti-inflammatory would have fixed her. It is that "treatment-resistant" closed her case, while "difficult-to-treat" reopens it with a sequence of actions any clinician can run on Monday. The label described our frustration; the framework gives us something to do with it. That is the whole of the shift and it is available now, in the clinic you already work in, with the tests you already order and the colleagues you already have.

Dr Paganin is a psychiatrist and psychotherapist in the public mental health service and holds a PhD in neuroscience at the University of Rome Tor Vergata, Rome, Italy; he also collaborates with Studio Psicologia Signorini, Guidonia, Italy. His research focuses on difficult-to-treat depression and the neurobiology of psychiatric disorders, with particular attention to the role of childhood trauma, and he works with multifamily and interfamilial therapy approaches.

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