Reading · Rational Psychiatry

Transition time from manic and mixed episodes to depression: a retrospective cohort study
There is something compelling about the phenotype of bipolar disorder. It was described (as manic depressive insanity) by Emil Kraepelin and much of his characterisation persists today. I’ve previously argued that people who have experienced a manic episode will invariably go on to have a depressive episode but what is the temporal connection between these illness poles?
In a (*not yet peer-reviewed*) pre-print Dr Chloe Yap and colleagues at Oxford examine this question using the NeuroBlu platform of electronic health records. They found that 1/4 of manic episodes were followed by a depressive episode within a month. Lithium, other mood stabilisers, and sedating anti-histamines were associated with delayed development of depression. While antipsychotics, antidepressants and benzodiazepines were not.
The study lends support to Athanasios Koukopoulos’s view of bipolar disorder whereby depressive states are secondary to mania.
The Lithium Landscape Has Dramatically Changed
In this American Journal of Psychiatry commentary, Dr Robert Post argues that lithium’s side-effects are manageable, that it is neuroprotective and is disease-modifying for bipolar disorder. He argues it is generally underutilised and should be recommended in first episode mania - I can’t disagree.
Time to lithium: A case register study of lithium initiation in bipolar disorder
A stark demonstration of this underutilisation comes from a study led by Dr Sameer Jauhar, examining the length of time taken to prescribe lithium at South London and Maudsley NHS Trust. Median time between first assessment and bipolar diagnosis was 220 days, while the median time until lithium prescription was 659 days. There was a median 2.5 mood episodes and two antipsychotics prior to lithium.
We can do better.
Acceptability and accuracy of point-of-care monitoring of lithium levels
One potential solution is lithium point-of-care blood testing (finger-prick sampling, similar to monitoring blood sugar in diabetes). Usual initiation of lithium requires titration and checking of plasma levels until these are within the therapeutic range. Point-of-care testing is more acceptable to patients than venous blood sampling, this study shows the new method was closely correlated with conventional venous measurements.
Clozapine After 1 Failed Antipsychotic Drug Trial in First-Episode Psychosis A Randomized Clinical Trial
Another medication we probably under-use in psychiatry is clozapine. In this RCT it was shown to be superior to other antipsychotics following a single non-response to another medication (current guidance is that patients should be offered clozapine after non-response to two other antipsychotics).
I’m particularly impressed, and surprised, that clozapine had double the response rate of olanzapine.
Cutting through stigma: psychiatry and neurosurgery working together
Is functional neurosurgery underutilised in psychiatry? A British Journal of Psychiatry editorial argues it is, for refractory forms of OCD and depression. It seems that, like ECT, the history of psychosurgery (frontal lobotomies) has created stigma which inhibits its use as a therapeutic option.
Psychiatric and behavioural sequelae following encephalitis: a systematic review and meta-analysis
A stellar team of authors bookended by Drs Cameron Watson and Tom Pollak provide evidence of psychiatric complications following encephalitis. With so much focus in recent years on autoimmune psychosis, I was surprised that infective encephalitis was associated with more psychiatric symptoms. It also surprised me that, while psychiatric sequelae was common (>25%), it occurred at roughly the same frequency as in other neurological disorders.
Diminishing Returns of Novel Autoantibody Discovery in Encephalitis
Prominent autoimmune neurologists, including Professor Sarosh Irani argue that discovering novel autoantibodies has less benefit than understanding the pathophysiology behind autoimmune encephalitis. They also lament the misdiagnosis of autoimmune encephalitis based on serum autoantibodies, of questionable clinical significance.
Ethical issues in the clinical use of diagnostic technologies for rare causes of psychosis
With autoimmune psychosis in mind, I’d say the biggest ethical issue is the possibility of false positives and unnecessary immunosuppressives.
Variability and Magnitude of Choline Levels Across the Psychosis Spectrum: A Meta-analysis
There is renewed interest in the cholinergic system following the success of xanomeline (Cobenfy) for schizophrenia. The meta-analysis showed elevated choline in each patient group but interestingly the effect size increases from clinical high risk for psychosis to frank psychosis to treatment resistant schizophrenia.
Neurometabolites and Antipsychotic Response in Psychosis - A Mega-Analysis
Like London buses, you wait for one choline meta-analysis and two come along at once. Reassuringly this one also finds elevated choline in antipsychotic non-responders, as well as increased glutamate.
Risk of perinatal psychiatric disorder among women with a history of premenstrual disorder: a nationwide register-based study from Sweden
Women with a history of PMDD had increased risk of perinatal mental disorders, with the strongest association being bipolar disorder, followed by perinatal depression.

‘Drug of last resort’ gets new guidance after Times reporting
Following the death of William ‘Wim’ Northcott in 2021, the Royal College of Psychiatrists has developed a new protocol for clozapine monitoring. Wim had been prescribed the medication for a decade but collapsed and died due to myocarditis, caused by toxic levels of clozapine.
I’m wary of not prescribing clozapine when appropriate but if this initiative improves safety of the medication while not decreasing its use, it will be a net positive.
I had postnatal depression — yes, dads can get it too
Obviously depressive episodes can be triggered by stressful life events, including a new baby, but I don’t think its helpful to categorise this under the umbrella of postnatal depression. In women, we have a pretty good understanding that postpartum depression is caused, at least in part, by hormonal changes. Allopregnanolone is a hormonal treatment specifically developed for this condition (in women).
Young women now have ‘close to zero’ risk of cervical cancer death after HPV jab.
Love to see it!

Psychiatry at the Margins - Some Predictions About the Future of “Withdrawal Studies”
When it comes to controversial topics in psychiatry, Awais usually finds the right balance. Here is a good example where he acknowledges the potential harms of SSRI withdrawal, without readily accepting overly simplistic and alarmist takes on this issue. His predictions are similar to my own views (I’ve also written of the need for balance in this debate) and I hope research is done to prove him right or wrong.
Cognitive Wonderland - Blinded by Blindsight
You may have heard simplistic versions of blindsight discussed on podcasts, particularly in philosophical discussions about consciousness. It is presented as someone who says they are blind (they do not consciously have sight) but their visual system is unconsciously working (for example they are able to navigate past objects even though they don’t ’see these consciously’).
I’ve always felt a bit skeptical towards this account and in a great post, Tommy Blanchard *a neuroscientist* digs through the original research. As with many scientific stories, it’s a bit more complicated/nuanced than is commonly presented.
Asterisk Magazine - The case against randomized controlled trials
This isn’t really a case against randomised controlled trials but more the case against RCTs being the best form of evidence for every question. I wasn’t totally convinced that emulated target trials are as unbiased as the author suggests. What would convince me? ETTs being shown to predict the results of RCT, before the trials are run.
The Clinical Trials Abundance blog - Why were Covid vaccine trials so fast?
Maybe instead we should do more trials cheaper, better and faster. This is the argument of clinical trials abundance and here Saloni Dattani shows lessons can be learned from the covid vaccine trials.
The Munro Report - The truth about the shingles vaccine and dementia
The shingles vaccines protecting against dementia hypothesis is being tested, to destruction. Here Dr Alasdair Munro presents the evidence against, mainly based on a wonderful talk by Professor George Davey Smith, who failed to replicate the protective effect in a much larger sample size.
Undoubtedly, the vaccine is good at preventing shingles, which is reason to get it alone.

Triggernometry: The Truth About Depression - Dr Joanna Moncrieff
The straw man put forward by Professor Moncrieff is that depression isn’t caused by a chemical imbalance. The hosts, Francis and Konstantin (perhaps unintentionally) find that her views extend much further though:
Francis: When people talk about mental health, they conflate it with mental illness. So we talk about depression and schizophrenia as if they’re under the same umbrella when as anybody knows and I have people in my family have suffered from schizophrenia. It is a very very different condition to depression.
Prof Moncrieff: I think it’s a very different condition but there’s not very good evidence for any biological basis for schizophrenia either.
Francis: Really?!
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For your attention, July 2026

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