This is sad topic for me because it highlights several problems I see in modern psychiatry.
The issue is whether particular medications can “cause” a patient’s suicide, and therefore does the prescribing physician have some kind of liability for a patient’s death.
The reason I find this topic sad is that the “original sin” is for psychiatry to imagine that it is going to deliver care without consequences. Suicide is a rare event relative to the total number of patient encounters psychiatrists engage in. Not all suicides are preceded by contact with a psychiatrist who has personal responsibility for a patient’s treatment, for example suicides may not interact with a professional , they may interact transiently with a professional for example a PCP who refers him to a psychiatrist, or he may go to an urgent care or ER and receive care that is understood to end at the patient’s departure from the care location.
In any event, rarely, a psyuchiatrist has personal responsibility for the patient’s ongoing care and the patient commits suicide. Most of these patients had psychiatric complaints preceding their suicide. The psychiatrist makes recommendations the patient adheres to or doesn’t, and even more rarely, the psychiatrist makes a “wrong” decision that is followed by a suicide. By “wrong”, I mean that the psychiatrist opted for a treatment that did not make the patient better fast enough to avert his taking his life.
The subject at hand of course isn’t just that a medication didn’t help, but that it made a patient worse than he was in the first place. That is the implication of the discussion anyway. And Aftab and others want to chip away at the concept that a psychiatric medication could “make” someone commit suicide.
What I would like to point out is that this is a distinction without a difference, and rather than rooted in actual concern for the patient’s welfare, it is rooted in concern for the psychiatrist’s liability. And that makes me sad.
Whether the medication “didn’t help”, “made the patient worse”, or “didn’t help enough”, makes no difference to the patient, he just wants to feel better and his loved ones want him to remain alive and intact. Only psychiatrists engage in such a discussion, I don’t think any other field attempts to parce out these distinctions to avoid liability, and given the already extremely small liability psychiatrists face compared to other specialties, the argument seems petty and misdirected.
I see no reason why a particular medication could not “trigger” someone’s suicide, just like a traffic ticket, an alchoholic binge, an argument, or a financial notice, might.. To suggest that this could never happen seems ridiculous. I know that the NAS has attempted to stratify the “statistical signal” of suicidality by age to suggest that certain age groups might be more vulnerable to this effect and that is fine but doesn’t help us clinically because a busy clinician will still see patients from each age group with depression and potential suicidality, as I do on a near daily basis.
The real question everyone should be asking is, is prescribing antidepressants to depressed or anxious people, protective against suicide generally: that is the only patient-centered question. And of course, absolutely no one has investigated this in a prospective way, in fact I have not even seen a chart review meta-analysis (the “garbage” of statistical analysis) that answered this specific question. I would argue this is because psychiatrists are more concerned with liability in this instance than the welfare of their patients (collectively, i don’t mean to criticize Aftab or any other individual).
I PERSONALLY (meaning this approach works for me but may not work for other people) don’t see the “big deal”. Lots of my patients complain of suicidality or emotional problems distressing enough one could imagine suicide to result. I make serious clinical decisions all day every day. I am not going to get it right every time. My solution is to know my medications extremely well and to recommend follow-up appropriate to the selected treatments.
I have never, thankfully, had a patient commit suicide while I was responsible for his treatment. This could happen at any time of course, I am not claiming special powers. But if I have decided to practice psychiatry, already one of the slower-paced, less risky specialties, I think to imagine I could never make a patient worse with a treatment choice strikes me as cowardly and self-serving. Of course I make “bad decisions” every day, hopefully the good exceeds the bad. Also, because I have ongoing responsibility, I am very focused on appropriate follow-up, I believe this remains patient-centered while protecting me from liability issues. But I won’t lie. I could get things wrong at any time. I am not different from any other doctor practicing clinical medicine. If psychiatrists have no liability for their decisions, I am not sure that they are making decisions that have any value.
The issue of liability is definitely in the background and it does distort the general discussion we see in the field. I think psychiatrists are generally reluctant to acknowledge suicidality as an adverse effect because of liability and because they don’t want to discourage people from starting the medication. I was more interested in how to think about clinical mechanisms and risk considerations once we recognize that yes, this does happen.
I appreciate the information from both you Dr. Bresch, and from Dr. Aftab's essay. There is definitely a concern for liability for doctors but also the need to do what's best for the patient in the shortest time period so that he or she can function in society. My insight comes from being a veterinarian and having to treat pets with behavioral issues, sometimes with the same SSRIs used for people, and as someone who has struggled with anxiety and depression for over 25 years.
I agree with the final thoughts Dr. Aftab mentioned in his essay. Transparency about antidepressants, even just to warn the patient about possible side effects, would definitely help with treatment as the patient could be aware of them, and thus hopefully they can inform the doctor or a trusted person if things are going awry. Honestly, I don't remember any psychiatrist or GP in the US warning me about possible side effects from these medications. My follow-ups were typically 2-4 weeks and may be a short phone call. I don't know if the doctors thought I was intelligent enough or since I was in the medical field, I would easily voice any issues. However, I would have appreciated more input on this.
His second point, acknowledging the severity of mental health conditions such that medications are warranted, that the benefits of starting medications outweigh possible risks, is critical for both patients and doctors. There is still the pressure of wanting to be "normal" not just for yourself as the patient, but also to be "normal" and not a burden on those around you. For the patient/doctor relationship, I think this acknowledgement can help build trust- Hey I'm here and I understand you have a condition that we need to treat like a serious disease to get better.
For Dr. Bresch, I hear you when you say this conversation seems to lean more on trying to remove liability from the doctor, rather than focusing on the patient. But I can understand the pressure many psychiatrists and GPs may have to struggle with logistically in order to provide some level of treatment to their patients. When I was a teenager back home in Trinidad, I used the public service to provide care as my family could not afford private care. This would mean attending a clinic where EVERYONE with varying psychiatric conditions were in one room with one doctor. I remeber having one session where a patient became dysphoric and began attacking people while naked. In spite of all this, I only have about 20 minutes with the doctor, then I got a prescription for 3 months of Prozac and a promise to recheck when he is available.
Fast forward a couple of decades, I had attended a continuing education session with a board-certified animal behaviorist. The premise was to help general practice veterinarians treat patients with behavioral issues more effectively. She went on to describe 2-3 hour behavior appointments, in-depth discussions with the clients about at-home training, how to involve professional trainers for that pet, and how to properly charge for these services. At the end of talk, her request for follow-up questions were met with laughter. Not because her information was nonsensical, but because of how unrealistic her treatment plans would be in the typical veterinary general practice model. Many vets see 15-20 pets a day, sometimes up to 30 pets a day (both scheduled exams and drop-offs), so the idea of setting aside even 2 hours to one patient seemed unfathomable. Then the pressure from clients to "fix' their pet in the quickest and most cost-effective way possible, and our own issues of "imposter syndrome" adds to the struggle. Many of us belong to corporate practices, so when something goes wrong, or a client makes a complaint, even as simple as a poor online review, or a true litigation case, can involve intense scrutiny and inquiries for the veterinarian, sometimes lasting months.
I say all this to acknowledge the faulty system both doctors and patients have to maneuver in order to achieve healing. There is a societal pressure on the patient to become "normal" as quickly as possible, but there is a stigma to use medications or even psychotherapy as a whole. The possibility of serious side effects, while rare but valid, is used to encourage more "wholesome" ways to overcome mental health issues (if one eats well, exercises, prays to God and meditates, you will heal yourself). There is the societal need to punish, rather than understand, the complications of psychiatry and psychotherapy, hence the push for legal litigations and the social media attacks. There is a severe lack of social support across the board here in America, coupled with a fast-food model for many fields, including the medical field (come in, get your service, get out ASAP) so fields where more in-depth discussions and follow up are needed feel incomplete. I don't know what the solution is, but hopefully these conversations will help move us as practitioners and patients in the best direction.
This comment was a hoot because it describes the PRECISE issues we have treating people, and yet the author is mostly describing her pet-patients.
This raises yet another unpleasant truth of psychiatric care, just because a treatment has “differentiated” in some drug trial doesn’t mean it is effective in the real world. I would guess that if we were to prescribe Prozac for example, in the conditions the author describes, whatever effect it had in drug trials, would vanish. And I bet that’s true for lots of treatments not just psychiatric. I have lots of suspicions, for example, about “tight control of glucose” and anti-coagulation, given the enormous number of ER visits they generate. Meanwhile I want to listen very carefully to the author’s experience and let it inform my care, though I continue to claim that shorter intervals of follow-up minimize the need for an exhaustive discussion of “side effects”.
They observe two different neuron populations that react in opposing directions and different timescales to SSRIs. One increases short-term stress, and with that potentially suicidality, the other provides the long-term antidepressive effect.
Still, this is a mouse study with only fluoxetine tested. So, it is unclear how this would impact different patients and age groups differently.
Thank you for sharing this. Yes, there is a fair bit of literature on the acute vs chronic biological effects of SSRI administration, and it is relevant as much of the agitation-related adverse effects we see are concentrated in the first few weeks of starting the med.
This seems to about right. For many people SSRIs are remarkably tolerable but suicidality on them is case wise problem. Luckily clinical medicine is practiced in case wise fashion. I think the precautions outlined here are shockingly simple ways of greatly reducing the risk on a case by case basis. If you have an emotionally dysregulated person, maybe don't wait a month to see how they went. It's this sort of sensible judgement that makes medicine safe.
A pilot judges what to do from the cockpit. During training they may have learned about large scale studies that examined crash data and they may use this nomothetic information to inform their judgement. But they don't stare down a looming mountain range with two stalled engines while trying to recall the statistical chances of crashing based on meta analysis of similar accidents.
I don’t know how generalisable my experience is, because a) my official diagnoses have been PDs and schizophrenic and bipolar spectrum disorders, moreso than MDD or dysthymia b) my depression was, in retrospect, situational due to gender dysphoria and ubiquitous experiences of antisemitic and xenophobic microaggressions (to the point that it felt inescapable and like I must “deserve” them, because adults in my life at the time largely did not intervene, and when I left education, my peers didn’t seem to care either) c) SSRIs did very little for me after I became habituated to citalopram in my very early twenties, and SNRIs made me very, very sick (akinetic, indifferent, unable to thermoregulate, l my arms stopped swinging when I walked, I experienced severe intention block, and my old records describe me at the time as evidencing aboulia; actually I think they provisionally diagnosed me with aboulia, even, at the second inpatient clinic).
The lack of effect on the one hand and the intolerable side-effects on the other really contributed to growing despair and I sort of became convinced I was irreparably broken. All kinds of add-on meds and re-diagnoses followed, but ultimately all I’m left taking is methylphenidate for ADHD symptoms and Tramadol XR for peripheral neuropathy and generalised musculoskeletal pain. I know Tramadol is also an SSRI, and I do wonder if that’s helping the depression, but maybe not? It’s hard to tell.
I think that lack of response to antidepressants or inadequate response can precipitate a crisis in the patient. I only didn’t attempt as it became clearer that psych meds were just not doing anything much because suicide seemed “impossible” — I was living at home and then with a partner, and I was rarely left on my own. I didn’t actually attempt until I’d lost what felt like even the chance at community. I’m doing much better now — largely thanks to a robust support network both online and offline.
But it does seem plausible to me that at least some of the experiences of suicidal feelings and behaviours in people who start antidepressants are due to the antidepressants not working as hoped — and this leads to feelings of futility and despair and “brokenness”. Especially because, unfortunately, the lay conversation regarding mood disorders often elides or even outright denies that some people just won’t experience relief from medication. When I’ve talked critically of the neurochemical hypothesis of mental illness and of the current state of psychiatric practices (as I’d experienced them in Germany), I’ve even had people get snitty and rude to me, sometimes accusing me of being some kind of crank with an agenda or trying to undermine and discredit their own recovery or the usual accusations of being one of the “bad ones” who makes people think no medication works! So I do think that some people go in expecting a magic bullet and then when it fails to work, their mental state rapidly deteriorates.
I don’t have an answer as to what to do about it, though. I agree that risk is unavoidable, and I think the problem here may well be the lack of recognition of specific risks of treatment — including the treatment just failing to work.
This perennial topic is far too broad to cover in this space, but I would like to respond with some data-based observations, and one personal reflection.
1. The term “suicidality” is not informative or useful. Conflating distinct experiences under a single, generic umbrella phrase obscures critical clinical nuances. Modern psychiatric guidelines recommend separating passive thoughts, active intent, and actual self-harming behaviors to ensure accurate risk assessments. A study in The Lancet Psychiatry notes that precise, behavioral nomenclature is necessary because grouping thoughts and actions together slows down targeted intervention research.
2. Suicidal thoughts have very low predictive value re: completed suicide. While suicidal ideation is a clear indicator of psychological distress, the vast majority of individuals (about two-thirds) who experience thoughts of suicide never attempt it. A comprehensive meta-analysis published in The British Journal of Psychiatry demonstrated that using suicidal ideation to predict future suicide deaths yields remarkably low positive predictive value (PPV), resulting in high rates of false positives. Relying on ideation alone as a red flag fails to distinguish who will transition from thoughts to fatal actions.
3. The risk factors that drive suicidal thoughts are not the same as those that drive completed suicide. The transition from thinking about suicide to acting on it requires an entirely separate set of variables, such as access to lethal means. Psychological pain and hopelessness routinely predict suicidal ideation, whereas objective factors like agitation, severe impulsivity, male sex, and substance abuse correlate much more heavily with completed suicide. This distinction forms the foundation of contemporary clinical models, such as the Three-Step Theory of Suicide.
4. Suicide is a vastly over-determined act. It is doubtful that a reaction to a medication alone can be the sole cause. Suicide typically stems from a complex, multi-layered intersection of genetic predispositions, chronic psychological vulnerabilities, and acute environmental stressors. Attributing a fatal act entirely to a single medication oversimplifies the pathology of severe major depressive disorder or bipolar illness. While a medication can act as a proximal trigger—such as causing acute agitation or akathisia—it operates as a destabilizing catalyst within an already high-risk, fragile psychosocial milieu.
5. On a population basis, antidepressants are associated with decreased rates of suicide. At worst, they have a “neutral” effect. Large-scale, multi-national ecological data reveal that as regional antidepressant prescription rates increase, overall population suicide rates consistently decline. Systematic reviews mapping global trends reinforce that broad access to these medications acts as a net positive for public health. For suicide mortality, SSRIs and older antidepressants (i.e. tricyclic antidepressants) were associated with reduced risks of suicide.
6. That said, age really does matter. Large register-based studies, including notable cohorts by Lagerberg et al. (2023) demonstrate an increased risk of suicidal behavior among individuals aged below 25 years who were treated with an SSRI after a depression diagnosis, as compared to those who were not. The study found no evidence of this effect among older age categories.
It does seem that young adults occasionally exhibit transient increases in non-fatal self-harm or suicidal ideation when first starting an SSRI. That should encourage very conservative SSRI use in young adults, and great vigilance. However, even within the historical data reviewed by the FDA, the increase is confined entirely to non-fatal behaviors, and the number of completed suicides across those initial pediatric trials was zero.
7. The FDA’s “black box” warning re: antidepressants may well have backfired. Following the 2004 mandate of the black box warning, subsequent public health data showed an immediate drop in antidepressant prescriptions for youth alongside a paradoxical, simultaneous spike in youth suicide rates. The National Bureau of Economic Research (NBER) concluded that the warning inadvertently scared families and physicians away from effective treatment, leaving severe depression untreated.
8. Psychiatrists are not alone in dealing with medication that may be associated with suicidal ideation. For example, in 2008, the FDA mandated a blanket warning for all antiepileptic drugs (AEDs) after a meta-analysis showed a doubled risk of suicidal thoughts and behaviors. Similarly, in 2020, the FDA upgraded montelukast (Singulair) to a severe Boxed Warning. The regulator cited a stark increase in serious neuropsychiatric events, including suicidal ideation and completed suicides, in both adults and children using the drug for asthma and allergic rhinitis.
9. Psychiatrists are concerned about suicide risk and antidepressants not merely because of legal liability, though, as Dr. Bresch notes, that is always lurking in the background. The loss of a patient to suicide is a profoundly traumatic experience for the attending psychiatrist and the treatment team. I can testify to this from sad personal experience, involving the one patient in my clinical practice (>25 years) lost to suicide. The impact of a patient's suicide ripples through a clinic or—in my case—the inpatient unit, causing long-lasting psychological distress, profound guilt, and professional self-doubt for the treating psychiatrist and nursing staff. Sadly, up to half of all psychiatrists will lose a patient to suicide during their careers, often experiencing a grief reaction akin to losing a family member.
Kind regards, and thanks to Awais,
Ron Pies
References:
1. Goldstein TR, Bridge JA, Brent DA. Concepts and controversies in evaluating "suicidality." Lancet Psychiatry. 2018;5(11):863-864.
2. McHugh CM, Corderoy A, Ryan CJ, Hickie IB, Large MM. Association between suicidal ideation and suicide: meta-analyses of odds ratios, sensitivity, specificity and positive predictive value. Br J Psychiatry. 2019;214(3):136-143.
3. Klonsky ED, May AM. The Three-Step Theory (3ST): a new theory of suicide rooted in the “ideation-to-action” framework. Int J Cogn Ther. 2015;8(2):114-129.
4. Mann JJ, Rizk MM. A mechanistic approach to the gene-environment interaction in the pathogenesis of suicidal behavior. Am J Psychiatry. 2020;177(10):890-901.
5. Braun C, et al. Effect of psychotropic medications on suicide-related outcomes. EClinicalMedicine. 2026;70:102457. doi:10.1016/j.eclinm.2026.102457
6. Lagerberg T, Matthews AA, Zhu N, et al. Effect of selective serotonin reuptake inhibitor treatment following diagnosis of depression on suicidal behaviour risk: a target trial emulation. Neuropsychopharmacology. 2023;48(12):1760–1768.
7. Soumerai SB, Eagle DH, Jin R, et al. Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study. BMJ. 2014;348:g3759. doi:10.1136/bmj.g3759
8. US Food and Drug Administration. Statistical Review and Evaluation: Antiepileptic Drugs and Suicidality. US Food and Drug Administration; 2008. Accessed June 28, 2026.
9. Plakun EM, Tillman JG. The impact of patient suicide on clinicians. Psychiatr Clin North Am. 2005;28(2):511-523. doi:10.1016/j.psc.2005.01.002
I think your first point that "suicidal ideation" isn't one thing is a very important insight. I recall a quote from Michael Alan Taylor to the effect that melancholics often don’t complain of “depression” and that they are very secretive in the way they plan their suicides. I hope you’ll forgive me on this occasion for not providing the exact quote or citation, but I believe the comment appears in "Clinical Neuropsychiatry". On the other hand, and this is left of field as well, one of Leonhard's bipolar cases, I'm not sure if it was in the first edition of his textbook but its in the final edition was "performative" in their suidical guesturing. In fact in my opinion its quite striking just how much Leonhard's bipolar case series shades into BPD, but I'm going way off topic.
There is another thread here, one that is very strange, speculative, and no doubt rare, forgive me because what follows is going to go at a bit of gallop. It seems that is that some rare cases of suicidality that seem to be precipitated by a substance or exogenous cause which are strikingly violent. The first time I witnessed this involved Zoloft. In these cases, it’s not even clear that they are suicidal per se, just that the individual reports an overwhelming urge or “inner tension” driving them to injure themselves or others, in my experience anyway. Aside from the obvious connection to akathisia, while trying to find analogous cases, I came across Judd’s work on cortisone psychosis and then the 1950s case series on cortisone psychosis, in particular the case of “Mrs. L. H.,” who died in an exceptionally violent way (Borman & Schmallenberg, 1951). In fact, the feature that drove me was that these cases often involved women attempting acts of violence that we would typically associate with men. I’ll go at a bit of a gish gallop and just say one thing led to another, and I made a further connection to “cycloid psychosis” and was delighted to find that Ian Brockington had also flagged the cortisone cases in connection with this (Brockington, 2014, p. 183). Ian was kind enough to tell me that he believed a bipolar diathesis was necessary for such cases and pointed me to his “tripolar” hypothesis and said he never found a zone of rarity between such cases and bipolar, but I may have misunderstood him and I’m not sure I fully comprehend his ideas. Most recently I moved on to temporal lobe epilepsy (Downs, Ward, & Farmer, 1991) and the link between descriptions of premenstrual tension and akathisia (Frank, 1931). Anyway, that is quite the gish gallop for anyone reading this. Apologies for riding roughshod over the detail.
I like your point about anticonvulsants. In my experience talking to women in a lamotrigine withdrawal support group, most cases fall into a sort of diffuse neuropathic category. I might even be tempted to link it to the ideas expressed by Kraepelin or Fish of acquired or organic neuroasthenia. Naturally this attracts ideas about hysteria and neurosis, but I think there is something distinctly exogenous about the timing and descriptions. I find them credible for the most part. A smaller minority, though, go into what is by definition a mixed state, but that is perhaps closer to Leonhard’s descriptions of the cycloid psychoses or an exogenous psychosis than to Weygandt’s mixed MDI types. Most of them are extremely agitated, some require hospitalisation, the temporal relationship between onset and medication is compelling, and the other reason I find them persuasive is that they often become exquisitely sensitive to other medications. This is a little more credible because they often become sufficiently unwell as to require hospitalisation and frequently beg for medication so in that context their seemingly becoming more sensative to a variety of substances seems to carry some believability.
The most serious cases I’ve encountered in the lamotrigine "withdrawal" group involved comorbid lupus or Lyme disease. The Lyme cases often developed full-blown confusional psychosis and quickly ended up in the IPU. I don’t consider it a withdrawal syndrome. Whatever it is seems to trigger in some people at titration, in others when the dose is adjusted or randomly one day after taking it for a year or so, while others are fine right up until the day they decide to stop taking it. No doubt the lowered seizure threshold plays some part here too, though quite what I can’t say. I think the depersonalisation often has the flavour of jamais vu about it, and olfactory hallucinations and reports of panic attacks preceded by gastric rises are not uncommon, but they also seem too diffuse and lack the stereotypy of a true seizure. The whole thing seems almost set up to evoke ideas about "hysteroid epilepsy", nervous illness, and PNES, but I don’t think that is the right answer at all, and the mimicry, I think, could be concealing something far more interesting.
I lean towards the bipolar diathesis for these extreme and rare cases myself, but explaining why is difficult. It’s little more than a gut feeling.
References
Borman, M. C., & Schmallenberg, H. C. (1951). Suicide following cortisone treatment. Journal of the American Medical Association, 146(4), 337–338. https://doi.org/10.1001/jama.1951.63670040004007b
Downs, J., Ward, J., & Farmer, R. (1991). Preoccupation with suicide in patients treated with fluoxetine. American Journal of Psychiatry, 148(8), 1090–1091. https://doi.org/10.1176/ajp.148.8.1090b
Thank you for the very rich and thought-provoking comments, Peter, and for introducing me to the term "gish gallop"--though that characterization may not do justice to your ideas. [see https://www.merriam-webster.com/slang/gish-gallop]. You cover far more ground than I can traverse here, but your reference to "cortisone psychosis" brought back memories of a case report I published many years ago (1981). This involved a 28-year-old woman who had received a single course of corticosteroids for treatment of ulcerative colitis. She subsequently became depressed; shortly thereafter, signs of mania developed. Despite discontinuation of corticosteroid therapy, the patient went on to have five bouts of mania, closely followed by severe depression, over a period of 1½ years. [see: https://pubmed.ncbi.nlm.nih.gov/6166260/].
This observation simply confirms that exogenous substances, including some medications, may have unexpected neuropsychiatric complications.
Perhaps not a "gallop" but quick enough to paper over the holes.
You know, I think “neuropsychiatric complications” is a very good way of framing it. It is often neurological, somewhat diffuse, and rare enough that clinically it can be dealt with case-wise. I do worry, though, that framing it too vaguely could discourage further investigation. I know in the IPU certain babbly terms seem to start getting thrown about when bed pressure demands a discharge. Perhaps neurologists are even more guilty of this though.
It is interesting to contemplate the possible link between apparently disparate complications. For simplicity, I will use Kraepelin's examples as the example, although he is clearly describing the ideas of others in this instance. The category of “exhaustion psychosis” that he described was a cluster of syndromes appearing from apparently disparate exogenous causes, and the proposal is that it may have some similarity to the rarer reactions seen with a seemingly disparate set of drugs. One good example of it popping up all over the armamentarium was provided just the other day by Thomas Reilly in another context when he pointed out a similar profile in cases of clozapine withdrawal: https://pmc.ncbi.nlm.nih.gov/articles/PMC8450618/. I should say, credit where credit is due, that it is really David Healy who pointed out the similarity to older and broader notions of non-infectious delirium.
Quite how this fits in with akathisia is certainly a bit of a mystery, and that term is starting to go the way of anhedonia: soon every agitated psychosis will be an akathisia. David also deserves credit for drawing attention, albeit tentatively, to the curious similarity between descriptions of more narrowly defined premenstrual mood illness, using the older term premenstrual tension, and psychic akathisia. This sounds like an incredible thing for no one to notice, but part of the trick seems to be looking through PMDD cases in which inner tension is the cardinal symptom, and then looking closely at the description given by the patient.
I also noticed that Gordon Parker recently reported that his patients have been describing mixed states as “scratchy”. Tts in a recentish paper and he mentions it in the first chapter of his new book, you know the own about poo. This stratchy description struck me as, A) a long way from Weygandt and Eliot Slater, who claimed stuporous mania was the most common form of mixed state, and B) shading close enough to akathisia to make me slightly uncomfortable.
But this is all very speculative. I think it is a good area for research, but if the cases are as rare as they seem to be, this would be a challenge.
I’ve tried to put together a case series of the women on the lamotrigine support forum, but some of these people are really quite unwell, and it is just not feasible to herd them about from the other side of the globe when their more immediate need is comfort. Plus I feel unqualified, I'm only a psychology undergrad. To be frank, in many cases a benzodiazepine wouldn’t go astray. But of course the antipsychiatry movement is a big presence in those spaces, so all talk of anything that might bring relief is a good way to be booted out. Not to mention, hyperbolic tapering is near cult-like: every symptom is blamed on a failure to adhere strictly enough to the prescribed 10% taper handed down on stone tablets by Mark Horowitz.
Do you know there are people there who have been tapering for years? Some of them grind pills into fractions of grams. It is almost like an eating disorder. Mark really needs to have his face properly rubbed in what well-meaning words can cause. I feel awful saying that, he is brave to speak out so boldly, and I don’t begrudge him speaking out with an authentic and passionate voice. It is very commendable. I just wish he’d give the dogma a bone and not harp on hyperbolic curves like they are some sort of sacred geometry. These sort of ideas really resonate with ordinary people. They latch onto them like a drowning man. Its a bit like the chemical imbalance narrative: its as much that ordinary folk connect with the image, it becomes a symbol; although I doubt many know what "hyperbolic" is, it just sounds suitably scientific. If it brings people comfort I'm not against suggesting it but it so often becomes an unhealthy obsession.
Thank you for drawing my attention to your cortisone case. The million-dollar question, though, is: was there any other followed-up past the 1 1/2 year mark? If so, was the diagnosis of bipolar upheld?
Alas, the patient was "lost to follow-up" after a year and a half. And as for hyperbolic tapering, it has not been tested "head-to-head" in controlled studies vs. more "traditional" (but very slow) tapering periods, over 2-6 months. That said, some patients may need it. --Regards, RP
That is a shame about the follow-up. It sounds like a more clear-cut case that might have helped settle things. Would you say the mania was, to your pattern recognition, very much of the typical bipolar sort? Or was the picture somewhat atypical? I would love to know your impression and how it struck you at the time.
Any proposal for a new tapering method has to be compared head to head against other methods.
If someone has trouble tapering, it is only reasonable that slowing the rate would present itself as an obvious option. Some people seem to need to go very slowly, but my feeling is that this may be better gauged by feeling out the right speed with the individual. If the first drop seemed poorly tolerated, make the next one smaller. A bit like when you go to the optometrist and they have that wonderfully scientific method of working out which lens to use: "Better... or worse? Better? Or worse? How about now? Better? Or worse?" An n of 1, within-subject approach, or, as David calls it in his book, "the Christmas tree light bulb method".
Of course, if good evidence emerged for a genuinely slower method, that would be wonderful. But in the meantime, I don't see how glacial rates can be applied as a blanket approach. It would be a crazy shift without proof. I think Nassir said it best recently regarding cross-tapering instead: "There is no need to torture the patient."
This is sad topic for me because it highlights several problems I see in modern psychiatry.
The issue is whether particular medications can “cause” a patient’s suicide, and therefore does the prescribing physician have some kind of liability for a patient’s death.
The reason I find this topic sad is that the “original sin” is for psychiatry to imagine that it is going to deliver care without consequences. Suicide is a rare event relative to the total number of patient encounters psychiatrists engage in. Not all suicides are preceded by contact with a psychiatrist who has personal responsibility for a patient’s treatment, for example suicides may not interact with a professional , they may interact transiently with a professional for example a PCP who refers him to a psychiatrist, or he may go to an urgent care or ER and receive care that is understood to end at the patient’s departure from the care location.
In any event, rarely, a psyuchiatrist has personal responsibility for the patient’s ongoing care and the patient commits suicide. Most of these patients had psychiatric complaints preceding their suicide. The psychiatrist makes recommendations the patient adheres to or doesn’t, and even more rarely, the psychiatrist makes a “wrong” decision that is followed by a suicide. By “wrong”, I mean that the psychiatrist opted for a treatment that did not make the patient better fast enough to avert his taking his life.
The subject at hand of course isn’t just that a medication didn’t help, but that it made a patient worse than he was in the first place. That is the implication of the discussion anyway. And Aftab and others want to chip away at the concept that a psychiatric medication could “make” someone commit suicide.
What I would like to point out is that this is a distinction without a difference, and rather than rooted in actual concern for the patient’s welfare, it is rooted in concern for the psychiatrist’s liability. And that makes me sad.
Whether the medication “didn’t help”, “made the patient worse”, or “didn’t help enough”, makes no difference to the patient, he just wants to feel better and his loved ones want him to remain alive and intact. Only psychiatrists engage in such a discussion, I don’t think any other field attempts to parce out these distinctions to avoid liability, and given the already extremely small liability psychiatrists face compared to other specialties, the argument seems petty and misdirected.
I see no reason why a particular medication could not “trigger” someone’s suicide, just like a traffic ticket, an alchoholic binge, an argument, or a financial notice, might.. To suggest that this could never happen seems ridiculous. I know that the NAS has attempted to stratify the “statistical signal” of suicidality by age to suggest that certain age groups might be more vulnerable to this effect and that is fine but doesn’t help us clinically because a busy clinician will still see patients from each age group with depression and potential suicidality, as I do on a near daily basis.
The real question everyone should be asking is, is prescribing antidepressants to depressed or anxious people, protective against suicide generally: that is the only patient-centered question. And of course, absolutely no one has investigated this in a prospective way, in fact I have not even seen a chart review meta-analysis (the “garbage” of statistical analysis) that answered this specific question. I would argue this is because psychiatrists are more concerned with liability in this instance than the welfare of their patients (collectively, i don’t mean to criticize Aftab or any other individual).
I PERSONALLY (meaning this approach works for me but may not work for other people) don’t see the “big deal”. Lots of my patients complain of suicidality or emotional problems distressing enough one could imagine suicide to result. I make serious clinical decisions all day every day. I am not going to get it right every time. My solution is to know my medications extremely well and to recommend follow-up appropriate to the selected treatments.
I have never, thankfully, had a patient commit suicide while I was responsible for his treatment. This could happen at any time of course, I am not claiming special powers. But if I have decided to practice psychiatry, already one of the slower-paced, less risky specialties, I think to imagine I could never make a patient worse with a treatment choice strikes me as cowardly and self-serving. Of course I make “bad decisions” every day, hopefully the good exceeds the bad. Also, because I have ongoing responsibility, I am very focused on appropriate follow-up, I believe this remains patient-centered while protecting me from liability issues. But I won’t lie. I could get things wrong at any time. I am not different from any other doctor practicing clinical medicine. If psychiatrists have no liability for their decisions, I am not sure that they are making decisions that have any value.
The issue of liability is definitely in the background and it does distort the general discussion we see in the field. I think psychiatrists are generally reluctant to acknowledge suicidality as an adverse effect because of liability and because they don’t want to discourage people from starting the medication. I was more interested in how to think about clinical mechanisms and risk considerations once we recognize that yes, this does happen.
Hello,
I appreciate the information from both you Dr. Bresch, and from Dr. Aftab's essay. There is definitely a concern for liability for doctors but also the need to do what's best for the patient in the shortest time period so that he or she can function in society. My insight comes from being a veterinarian and having to treat pets with behavioral issues, sometimes with the same SSRIs used for people, and as someone who has struggled with anxiety and depression for over 25 years.
I agree with the final thoughts Dr. Aftab mentioned in his essay. Transparency about antidepressants, even just to warn the patient about possible side effects, would definitely help with treatment as the patient could be aware of them, and thus hopefully they can inform the doctor or a trusted person if things are going awry. Honestly, I don't remember any psychiatrist or GP in the US warning me about possible side effects from these medications. My follow-ups were typically 2-4 weeks and may be a short phone call. I don't know if the doctors thought I was intelligent enough or since I was in the medical field, I would easily voice any issues. However, I would have appreciated more input on this.
His second point, acknowledging the severity of mental health conditions such that medications are warranted, that the benefits of starting medications outweigh possible risks, is critical for both patients and doctors. There is still the pressure of wanting to be "normal" not just for yourself as the patient, but also to be "normal" and not a burden on those around you. For the patient/doctor relationship, I think this acknowledgement can help build trust- Hey I'm here and I understand you have a condition that we need to treat like a serious disease to get better.
For Dr. Bresch, I hear you when you say this conversation seems to lean more on trying to remove liability from the doctor, rather than focusing on the patient. But I can understand the pressure many psychiatrists and GPs may have to struggle with logistically in order to provide some level of treatment to their patients. When I was a teenager back home in Trinidad, I used the public service to provide care as my family could not afford private care. This would mean attending a clinic where EVERYONE with varying psychiatric conditions were in one room with one doctor. I remeber having one session where a patient became dysphoric and began attacking people while naked. In spite of all this, I only have about 20 minutes with the doctor, then I got a prescription for 3 months of Prozac and a promise to recheck when he is available.
Fast forward a couple of decades, I had attended a continuing education session with a board-certified animal behaviorist. The premise was to help general practice veterinarians treat patients with behavioral issues more effectively. She went on to describe 2-3 hour behavior appointments, in-depth discussions with the clients about at-home training, how to involve professional trainers for that pet, and how to properly charge for these services. At the end of talk, her request for follow-up questions were met with laughter. Not because her information was nonsensical, but because of how unrealistic her treatment plans would be in the typical veterinary general practice model. Many vets see 15-20 pets a day, sometimes up to 30 pets a day (both scheduled exams and drop-offs), so the idea of setting aside even 2 hours to one patient seemed unfathomable. Then the pressure from clients to "fix' their pet in the quickest and most cost-effective way possible, and our own issues of "imposter syndrome" adds to the struggle. Many of us belong to corporate practices, so when something goes wrong, or a client makes a complaint, even as simple as a poor online review, or a true litigation case, can involve intense scrutiny and inquiries for the veterinarian, sometimes lasting months.
I say all this to acknowledge the faulty system both doctors and patients have to maneuver in order to achieve healing. There is a societal pressure on the patient to become "normal" as quickly as possible, but there is a stigma to use medications or even psychotherapy as a whole. The possibility of serious side effects, while rare but valid, is used to encourage more "wholesome" ways to overcome mental health issues (if one eats well, exercises, prays to God and meditates, you will heal yourself). There is the societal need to punish, rather than understand, the complications of psychiatry and psychotherapy, hence the push for legal litigations and the social media attacks. There is a severe lack of social support across the board here in America, coupled with a fast-food model for many fields, including the medical field (come in, get your service, get out ASAP) so fields where more in-depth discussions and follow up are needed feel incomplete. I don't know what the solution is, but hopefully these conversations will help move us as practitioners and patients in the best direction.
This comment was a hoot because it describes the PRECISE issues we have treating people, and yet the author is mostly describing her pet-patients.
This raises yet another unpleasant truth of psychiatric care, just because a treatment has “differentiated” in some drug trial doesn’t mean it is effective in the real world. I would guess that if we were to prescribe Prozac for example, in the conditions the author describes, whatever effect it had in drug trials, would vanish. And I bet that’s true for lots of treatments not just psychiatric. I have lots of suspicions, for example, about “tight control of glucose” and anti-coagulation, given the enormous number of ER visits they generate. Meanwhile I want to listen very carefully to the author’s experience and let it inform my care, though I continue to claim that shorter intervals of follow-up minimize the need for an exhaustive discussion of “side effects”.
Maybe this new research finding points towards a likely scenario: https://www.nature.com/articles/s41380-026-03644-x
They observe two different neuron populations that react in opposing directions and different timescales to SSRIs. One increases short-term stress, and with that potentially suicidality, the other provides the long-term antidepressive effect.
Still, this is a mouse study with only fluoxetine tested. So, it is unclear how this would impact different patients and age groups differently.
Thank you for sharing this. Yes, there is a fair bit of literature on the acute vs chronic biological effects of SSRI administration, and it is relevant as much of the agitation-related adverse effects we see are concentrated in the first few weeks of starting the med.
This seems to about right. For many people SSRIs are remarkably tolerable but suicidality on them is case wise problem. Luckily clinical medicine is practiced in case wise fashion. I think the precautions outlined here are shockingly simple ways of greatly reducing the risk on a case by case basis. If you have an emotionally dysregulated person, maybe don't wait a month to see how they went. It's this sort of sensible judgement that makes medicine safe.
A pilot judges what to do from the cockpit. During training they may have learned about large scale studies that examined crash data and they may use this nomothetic information to inform their judgement. But they don't stare down a looming mountain range with two stalled engines while trying to recall the statistical chances of crashing based on meta analysis of similar accidents.
I don’t know how generalisable my experience is, because a) my official diagnoses have been PDs and schizophrenic and bipolar spectrum disorders, moreso than MDD or dysthymia b) my depression was, in retrospect, situational due to gender dysphoria and ubiquitous experiences of antisemitic and xenophobic microaggressions (to the point that it felt inescapable and like I must “deserve” them, because adults in my life at the time largely did not intervene, and when I left education, my peers didn’t seem to care either) c) SSRIs did very little for me after I became habituated to citalopram in my very early twenties, and SNRIs made me very, very sick (akinetic, indifferent, unable to thermoregulate, l my arms stopped swinging when I walked, I experienced severe intention block, and my old records describe me at the time as evidencing aboulia; actually I think they provisionally diagnosed me with aboulia, even, at the second inpatient clinic).
The lack of effect on the one hand and the intolerable side-effects on the other really contributed to growing despair and I sort of became convinced I was irreparably broken. All kinds of add-on meds and re-diagnoses followed, but ultimately all I’m left taking is methylphenidate for ADHD symptoms and Tramadol XR for peripheral neuropathy and generalised musculoskeletal pain. I know Tramadol is also an SSRI, and I do wonder if that’s helping the depression, but maybe not? It’s hard to tell.
I think that lack of response to antidepressants or inadequate response can precipitate a crisis in the patient. I only didn’t attempt as it became clearer that psych meds were just not doing anything much because suicide seemed “impossible” — I was living at home and then with a partner, and I was rarely left on my own. I didn’t actually attempt until I’d lost what felt like even the chance at community. I’m doing much better now — largely thanks to a robust support network both online and offline.
But it does seem plausible to me that at least some of the experiences of suicidal feelings and behaviours in people who start antidepressants are due to the antidepressants not working as hoped — and this leads to feelings of futility and despair and “brokenness”. Especially because, unfortunately, the lay conversation regarding mood disorders often elides or even outright denies that some people just won’t experience relief from medication. When I’ve talked critically of the neurochemical hypothesis of mental illness and of the current state of psychiatric practices (as I’d experienced them in Germany), I’ve even had people get snitty and rude to me, sometimes accusing me of being some kind of crank with an agenda or trying to undermine and discredit their own recovery or the usual accusations of being one of the “bad ones” who makes people think no medication works! So I do think that some people go in expecting a magic bullet and then when it fails to work, their mental state rapidly deteriorates.
I don’t have an answer as to what to do about it, though. I agree that risk is unavoidable, and I think the problem here may well be the lack of recognition of specific risks of treatment — including the treatment just failing to work.
This perennial topic is far too broad to cover in this space, but I would like to respond with some data-based observations, and one personal reflection.
1. The term “suicidality” is not informative or useful. Conflating distinct experiences under a single, generic umbrella phrase obscures critical clinical nuances. Modern psychiatric guidelines recommend separating passive thoughts, active intent, and actual self-harming behaviors to ensure accurate risk assessments. A study in The Lancet Psychiatry notes that precise, behavioral nomenclature is necessary because grouping thoughts and actions together slows down targeted intervention research.
2. Suicidal thoughts have very low predictive value re: completed suicide. While suicidal ideation is a clear indicator of psychological distress, the vast majority of individuals (about two-thirds) who experience thoughts of suicide never attempt it. A comprehensive meta-analysis published in The British Journal of Psychiatry demonstrated that using suicidal ideation to predict future suicide deaths yields remarkably low positive predictive value (PPV), resulting in high rates of false positives. Relying on ideation alone as a red flag fails to distinguish who will transition from thoughts to fatal actions.
3. The risk factors that drive suicidal thoughts are not the same as those that drive completed suicide. The transition from thinking about suicide to acting on it requires an entirely separate set of variables, such as access to lethal means. Psychological pain and hopelessness routinely predict suicidal ideation, whereas objective factors like agitation, severe impulsivity, male sex, and substance abuse correlate much more heavily with completed suicide. This distinction forms the foundation of contemporary clinical models, such as the Three-Step Theory of Suicide.
4. Suicide is a vastly over-determined act. It is doubtful that a reaction to a medication alone can be the sole cause. Suicide typically stems from a complex, multi-layered intersection of genetic predispositions, chronic psychological vulnerabilities, and acute environmental stressors. Attributing a fatal act entirely to a single medication oversimplifies the pathology of severe major depressive disorder or bipolar illness. While a medication can act as a proximal trigger—such as causing acute agitation or akathisia—it operates as a destabilizing catalyst within an already high-risk, fragile psychosocial milieu.
5. On a population basis, antidepressants are associated with decreased rates of suicide. At worst, they have a “neutral” effect. Large-scale, multi-national ecological data reveal that as regional antidepressant prescription rates increase, overall population suicide rates consistently decline. Systematic reviews mapping global trends reinforce that broad access to these medications acts as a net positive for public health. For suicide mortality, SSRIs and older antidepressants (i.e. tricyclic antidepressants) were associated with reduced risks of suicide.
6. That said, age really does matter. Large register-based studies, including notable cohorts by Lagerberg et al. (2023) demonstrate an increased risk of suicidal behavior among individuals aged below 25 years who were treated with an SSRI after a depression diagnosis, as compared to those who were not. The study found no evidence of this effect among older age categories.
It does seem that young adults occasionally exhibit transient increases in non-fatal self-harm or suicidal ideation when first starting an SSRI. That should encourage very conservative SSRI use in young adults, and great vigilance. However, even within the historical data reviewed by the FDA, the increase is confined entirely to non-fatal behaviors, and the number of completed suicides across those initial pediatric trials was zero.
7. The FDA’s “black box” warning re: antidepressants may well have backfired. Following the 2004 mandate of the black box warning, subsequent public health data showed an immediate drop in antidepressant prescriptions for youth alongside a paradoxical, simultaneous spike in youth suicide rates. The National Bureau of Economic Research (NBER) concluded that the warning inadvertently scared families and physicians away from effective treatment, leaving severe depression untreated.
8. Psychiatrists are not alone in dealing with medication that may be associated with suicidal ideation. For example, in 2008, the FDA mandated a blanket warning for all antiepileptic drugs (AEDs) after a meta-analysis showed a doubled risk of suicidal thoughts and behaviors. Similarly, in 2020, the FDA upgraded montelukast (Singulair) to a severe Boxed Warning. The regulator cited a stark increase in serious neuropsychiatric events, including suicidal ideation and completed suicides, in both adults and children using the drug for asthma and allergic rhinitis.
9. Psychiatrists are concerned about suicide risk and antidepressants not merely because of legal liability, though, as Dr. Bresch notes, that is always lurking in the background. The loss of a patient to suicide is a profoundly traumatic experience for the attending psychiatrist and the treatment team. I can testify to this from sad personal experience, involving the one patient in my clinical practice (>25 years) lost to suicide. The impact of a patient's suicide ripples through a clinic or—in my case—the inpatient unit, causing long-lasting psychological distress, profound guilt, and professional self-doubt for the treating psychiatrist and nursing staff. Sadly, up to half of all psychiatrists will lose a patient to suicide during their careers, often experiencing a grief reaction akin to losing a family member.
Kind regards, and thanks to Awais,
Ron Pies
References:
1. Goldstein TR, Bridge JA, Brent DA. Concepts and controversies in evaluating "suicidality." Lancet Psychiatry. 2018;5(11):863-864.
2. McHugh CM, Corderoy A, Ryan CJ, Hickie IB, Large MM. Association between suicidal ideation and suicide: meta-analyses of odds ratios, sensitivity, specificity and positive predictive value. Br J Psychiatry. 2019;214(3):136-143.
3. Klonsky ED, May AM. The Three-Step Theory (3ST): a new theory of suicide rooted in the “ideation-to-action” framework. Int J Cogn Ther. 2015;8(2):114-129.
4. Mann JJ, Rizk MM. A mechanistic approach to the gene-environment interaction in the pathogenesis of suicidal behavior. Am J Psychiatry. 2020;177(10):890-901.
5. Braun C, et al. Effect of psychotropic medications on suicide-related outcomes. EClinicalMedicine. 2026;70:102457. doi:10.1016/j.eclinm.2026.102457
6. Lagerberg T, Matthews AA, Zhu N, et al. Effect of selective serotonin reuptake inhibitor treatment following diagnosis of depression on suicidal behaviour risk: a target trial emulation. Neuropsychopharmacology. 2023;48(12):1760–1768.
7. Soumerai SB, Eagle DH, Jin R, et al. Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study. BMJ. 2014;348:g3759. doi:10.1136/bmj.g3759
8. US Food and Drug Administration. Statistical Review and Evaluation: Antiepileptic Drugs and Suicidality. US Food and Drug Administration; 2008. Accessed June 28, 2026.
9. Plakun EM, Tillman JG. The impact of patient suicide on clinicians. Psychiatr Clin North Am. 2005;28(2):511-523. doi:10.1016/j.psc.2005.01.002
I think your first point that "suicidal ideation" isn't one thing is a very important insight. I recall a quote from Michael Alan Taylor to the effect that melancholics often don’t complain of “depression” and that they are very secretive in the way they plan their suicides. I hope you’ll forgive me on this occasion for not providing the exact quote or citation, but I believe the comment appears in "Clinical Neuropsychiatry". On the other hand, and this is left of field as well, one of Leonhard's bipolar cases, I'm not sure if it was in the first edition of his textbook but its in the final edition was "performative" in their suidical guesturing. In fact in my opinion its quite striking just how much Leonhard's bipolar case series shades into BPD, but I'm going way off topic.
There is another thread here, one that is very strange, speculative, and no doubt rare, forgive me because what follows is going to go at a bit of gallop. It seems that is that some rare cases of suicidality that seem to be precipitated by a substance or exogenous cause which are strikingly violent. The first time I witnessed this involved Zoloft. In these cases, it’s not even clear that they are suicidal per se, just that the individual reports an overwhelming urge or “inner tension” driving them to injure themselves or others, in my experience anyway. Aside from the obvious connection to akathisia, while trying to find analogous cases, I came across Judd’s work on cortisone psychosis and then the 1950s case series on cortisone psychosis, in particular the case of “Mrs. L. H.,” who died in an exceptionally violent way (Borman & Schmallenberg, 1951). In fact, the feature that drove me was that these cases often involved women attempting acts of violence that we would typically associate with men. I’ll go at a bit of a gish gallop and just say one thing led to another, and I made a further connection to “cycloid psychosis” and was delighted to find that Ian Brockington had also flagged the cortisone cases in connection with this (Brockington, 2014, p. 183). Ian was kind enough to tell me that he believed a bipolar diathesis was necessary for such cases and pointed me to his “tripolar” hypothesis and said he never found a zone of rarity between such cases and bipolar, but I may have misunderstood him and I’m not sure I fully comprehend his ideas. Most recently I moved on to temporal lobe epilepsy (Downs, Ward, & Farmer, 1991) and the link between descriptions of premenstrual tension and akathisia (Frank, 1931). Anyway, that is quite the gish gallop for anyone reading this. Apologies for riding roughshod over the detail.
I like your point about anticonvulsants. In my experience talking to women in a lamotrigine withdrawal support group, most cases fall into a sort of diffuse neuropathic category. I might even be tempted to link it to the ideas expressed by Kraepelin or Fish of acquired or organic neuroasthenia. Naturally this attracts ideas about hysteria and neurosis, but I think there is something distinctly exogenous about the timing and descriptions. I find them credible for the most part. A smaller minority, though, go into what is by definition a mixed state, but that is perhaps closer to Leonhard’s descriptions of the cycloid psychoses or an exogenous psychosis than to Weygandt’s mixed MDI types. Most of them are extremely agitated, some require hospitalisation, the temporal relationship between onset and medication is compelling, and the other reason I find them persuasive is that they often become exquisitely sensitive to other medications. This is a little more credible because they often become sufficiently unwell as to require hospitalisation and frequently beg for medication so in that context their seemingly becoming more sensative to a variety of substances seems to carry some believability.
The most serious cases I’ve encountered in the lamotrigine "withdrawal" group involved comorbid lupus or Lyme disease. The Lyme cases often developed full-blown confusional psychosis and quickly ended up in the IPU. I don’t consider it a withdrawal syndrome. Whatever it is seems to trigger in some people at titration, in others when the dose is adjusted or randomly one day after taking it for a year or so, while others are fine right up until the day they decide to stop taking it. No doubt the lowered seizure threshold plays some part here too, though quite what I can’t say. I think the depersonalisation often has the flavour of jamais vu about it, and olfactory hallucinations and reports of panic attacks preceded by gastric rises are not uncommon, but they also seem too diffuse and lack the stereotypy of a true seizure. The whole thing seems almost set up to evoke ideas about "hysteroid epilepsy", nervous illness, and PNES, but I don’t think that is the right answer at all, and the mimicry, I think, could be concealing something far more interesting.
I lean towards the bipolar diathesis for these extreme and rare cases myself, but explaining why is difficult. It’s little more than a gut feeling.
References
Borman, M. C., & Schmallenberg, H. C. (1951). Suicide following cortisone treatment. Journal of the American Medical Association, 146(4), 337–338. https://doi.org/10.1001/jama.1951.63670040004007b
Downs, J., Ward, J., & Farmer, R. (1991). Preoccupation with suicide in patients treated with fluoxetine. American Journal of Psychiatry, 148(8), 1090–1091. https://doi.org/10.1176/ajp.148.8.1090b
Frank, R. T. (1931). The hormonal causes of premenstrual tension. Archives of Neurology and Psychiatry, 26(5), 1053–1057. https://doi.org/10.1001/archneurpsyc.1931.02230110151009
Taylor, M. A. (1999). The fundamentals of clinical neuropsychiatry. Oxford University Press.
Thank you for the very rich and thought-provoking comments, Peter, and for introducing me to the term "gish gallop"--though that characterization may not do justice to your ideas. [see https://www.merriam-webster.com/slang/gish-gallop]. You cover far more ground than I can traverse here, but your reference to "cortisone psychosis" brought back memories of a case report I published many years ago (1981). This involved a 28-year-old woman who had received a single course of corticosteroids for treatment of ulcerative colitis. She subsequently became depressed; shortly thereafter, signs of mania developed. Despite discontinuation of corticosteroid therapy, the patient went on to have five bouts of mania, closely followed by severe depression, over a period of 1½ years. [see: https://pubmed.ncbi.nlm.nih.gov/6166260/].
This observation simply confirms that exogenous substances, including some medications, may have unexpected neuropsychiatric complications.
Kind regards,
Ronald W. Pies, MD
Perhaps not a "gallop" but quick enough to paper over the holes.
You know, I think “neuropsychiatric complications” is a very good way of framing it. It is often neurological, somewhat diffuse, and rare enough that clinically it can be dealt with case-wise. I do worry, though, that framing it too vaguely could discourage further investigation. I know in the IPU certain babbly terms seem to start getting thrown about when bed pressure demands a discharge. Perhaps neurologists are even more guilty of this though.
It is interesting to contemplate the possible link between apparently disparate complications. For simplicity, I will use Kraepelin's examples as the example, although he is clearly describing the ideas of others in this instance. The category of “exhaustion psychosis” that he described was a cluster of syndromes appearing from apparently disparate exogenous causes, and the proposal is that it may have some similarity to the rarer reactions seen with a seemingly disparate set of drugs. One good example of it popping up all over the armamentarium was provided just the other day by Thomas Reilly in another context when he pointed out a similar profile in cases of clozapine withdrawal: https://pmc.ncbi.nlm.nih.gov/articles/PMC8450618/. I should say, credit where credit is due, that it is really David Healy who pointed out the similarity to older and broader notions of non-infectious delirium.
Quite how this fits in with akathisia is certainly a bit of a mystery, and that term is starting to go the way of anhedonia: soon every agitated psychosis will be an akathisia. David also deserves credit for drawing attention, albeit tentatively, to the curious similarity between descriptions of more narrowly defined premenstrual mood illness, using the older term premenstrual tension, and psychic akathisia. This sounds like an incredible thing for no one to notice, but part of the trick seems to be looking through PMDD cases in which inner tension is the cardinal symptom, and then looking closely at the description given by the patient.
I also noticed that Gordon Parker recently reported that his patients have been describing mixed states as “scratchy”. Tts in a recentish paper and he mentions it in the first chapter of his new book, you know the own about poo. This stratchy description struck me as, A) a long way from Weygandt and Eliot Slater, who claimed stuporous mania was the most common form of mixed state, and B) shading close enough to akathisia to make me slightly uncomfortable.
But this is all very speculative. I think it is a good area for research, but if the cases are as rare as they seem to be, this would be a challenge.
I’ve tried to put together a case series of the women on the lamotrigine support forum, but some of these people are really quite unwell, and it is just not feasible to herd them about from the other side of the globe when their more immediate need is comfort. Plus I feel unqualified, I'm only a psychology undergrad. To be frank, in many cases a benzodiazepine wouldn’t go astray. But of course the antipsychiatry movement is a big presence in those spaces, so all talk of anything that might bring relief is a good way to be booted out. Not to mention, hyperbolic tapering is near cult-like: every symptom is blamed on a failure to adhere strictly enough to the prescribed 10% taper handed down on stone tablets by Mark Horowitz.
Do you know there are people there who have been tapering for years? Some of them grind pills into fractions of grams. It is almost like an eating disorder. Mark really needs to have his face properly rubbed in what well-meaning words can cause. I feel awful saying that, he is brave to speak out so boldly, and I don’t begrudge him speaking out with an authentic and passionate voice. It is very commendable. I just wish he’d give the dogma a bone and not harp on hyperbolic curves like they are some sort of sacred geometry. These sort of ideas really resonate with ordinary people. They latch onto them like a drowning man. Its a bit like the chemical imbalance narrative: its as much that ordinary folk connect with the image, it becomes a symbol; although I doubt many know what "hyperbolic" is, it just sounds suitably scientific. If it brings people comfort I'm not against suggesting it but it so often becomes an unhealthy obsession.
Thank you for drawing my attention to your cortisone case. The million-dollar question, though, is: was there any other followed-up past the 1 1/2 year mark? If so, was the diagnosis of bipolar upheld?
Alas, the patient was "lost to follow-up" after a year and a half. And as for hyperbolic tapering, it has not been tested "head-to-head" in controlled studies vs. more "traditional" (but very slow) tapering periods, over 2-6 months. That said, some patients may need it. --Regards, RP
That is a shame about the follow-up. It sounds like a more clear-cut case that might have helped settle things. Would you say the mania was, to your pattern recognition, very much of the typical bipolar sort? Or was the picture somewhat atypical? I would love to know your impression and how it struck you at the time.
Any proposal for a new tapering method has to be compared head to head against other methods.
If someone has trouble tapering, it is only reasonable that slowing the rate would present itself as an obvious option. Some people seem to need to go very slowly, but my feeling is that this may be better gauged by feeling out the right speed with the individual. If the first drop seemed poorly tolerated, make the next one smaller. A bit like when you go to the optometrist and they have that wonderfully scientific method of working out which lens to use: "Better... or worse? Better? Or worse? How about now? Better? Or worse?" An n of 1, within-subject approach, or, as David calls it in his book, "the Christmas tree light bulb method".
Of course, if good evidence emerged for a genuinely slower method, that would be wonderful. But in the meantime, I don't see how glacial rates can be applied as a blanket approach. It would be a crazy shift without proof. I think Nassir said it best recently regarding cross-tapering instead: "There is no need to torture the patient."