From the Editor
Is new really better?
With several new antipsychotic medications on the market, this question is very relevant clinically. For the patient in your office, should you opt for a new antipsychotic or something older?
In the first selection, Dr. Mark Weiser (of the Stanley Medical Research Institute) and his co-authors draw on a large database – and the experience of tens of thousands of people – to compare antipsychotics. “Among veterans with schizophrenia, those who initiated antipsychotic treatment with clozapine, long-acting injectable second-generation medications, and antipsychotic polypharmacy experienced longer episodes of continuous therapy and lower rates of treatment discontinuation.” We consider this paper, and the clinical implications.
Is new better – or just eye catching?
In the other selection, Dr. Rebecca Lawrence, a practicing psychiatrist, writes for The Guardian. In her essay, she distinguishes between mental health and mental illness, noting that they are not the same thing, and worrying that we are increasingly as a society focused on the former at the expense of the latter. She thinks about her work as a physician: “As a doctor, I can talk with someone and give them pills, but I can’t easily get them any help with losing weight or trying to exercise. I can tell them it would be good for them, but I don’t necessarily have any practical ways to help.”
Selection 1: “Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs”
Mark Weiser, John M. Davis, Clayton H. Brown, et al.
The American Journal of Psychiatry, 14 July 2021 Online First
Randomized controlled trials are the gold-standard design used to test the efficacy of antipsychotics but only reflect effectiveness in patients who volunteer for such trials. Despite the obvious shortcomings, an alternative approach is to carefully analyze data from available health care databases, including medication and hospitalization data on large samples of individuals. This may offer insight into antipsychotic prescribing practices in clinical practice, enable comparison of the effectiveness among all medications used, and allow direct comparisons between oral and long-acting injectable (LAI) formulations of the same medications. The majority of extant observational studies of administrative databases were performed outside of the United States, used smaller and regional samples from the Veterans Administration system and Medicaid, and/or focused on the use of specific, rather than all, antipsychotics. Hence, there is a need to study all-cause discontinuation of all oral and LAI antipsychotics, as well as psychiatric hospitalization, in a large nationwide study in the United States, including comparison of LAI formulations with the same oral medication, using a comprehensive health care database.
The U.S. Department of Veterans Affairs (VA) health care system maintains a large, comprehensive health care service utilization database on all veterans who receive their care within the VA system. The database includes information on diagnosis, demographic characteristics, prescriptions, and service utilization, including psychiatric hospitalizations. Thus, the database provides a unique opportunity to examine the relative effectiveness of oral and LAI antipsychotics in a real-world setting. In this study, we analyzed all-cause discontinuation of antipsychotic medications and psychiatric hospitalizations for 37,368 people with schizophrenia treated in the VA health care system. To our knowledge, this is the largest study comparing all-cause discontinuation of antipsychotics and psychiatric hospitalizations in the United States and the first to compare LAI formulations with the same oral medication in a nationwide, multiyear U.S. sample using nonprofit funding. Based on findings from previous studies, we hypothesized that clozapine and LAI antipsychotics would be associated with longer time to discontinuation and fewer psychiatric hospitalizations compared with oral olanzapine and that LAI formulations would be associated with longer time to discontinuation and fewer psychiatric hospitalizations than oral formulations of the same medication.
So begins a paper by Weiser et al.
Here’s what they did:
- They did an observational study, drawing on VA health care service utilization data from October 1, 2010, to September 30, 2015.
- They included users of health care who had at least one inpatient and outpatient contact, with a diagnosis of schizophrenia. They considered outpatient antipsychotic prescriptions, and did comparisons with olanzapine.
- “Outcomes were assessed by examining time to all-cause discontinuation of an antipsychotic medication and time to psychiatric hospitalization.”
- Statistical analyses were done, including the Cox proportional hazards regression model.
Here’s what they found:
- 37,368 individuals with schizophrenia were included in the study.
- Demographics: patients tended to be male (91%), white (59%) with a mean age of 54.3 years.
- The Cox proportional hazards regression results yielded a hazard ratio of 0.42 for clozapine, a hazard ratio of 0.71 for aripiprazole LAI, a hazard ratio of 0.76 for paliperidone LAI, and a hazard ratio of 0.91 for risperidone LAI. (!!) See figure below.
- “Oral first-generation antipsychotics, oral risperidone, oral aripiprazole, oral ziprasidone, and oral quetiapine had a statistically significant higher hazard probability of discontinuation than olanzapine…”
- “Compared with oral olanzapine and adjusting for covariates, no drug was associated with lower risk for psychiatric hospitalization…” (!!) But quetiapine was associated with a 36% worse outcome in terms of hospitalizations compared with olanzapine.
A few thoughts:
- This is a good study.
- It also offers a big result, published in an important journal, drawing on an impressive database (with an n of more than 37 000).
- The authors summarize well the major findings: “[W]e found that in a nationwide sample of veterans, clozapine and LAI second generation antipsychotics were less likely to be discontinued, on average, than oral olanzapine and other oral antipsychotic medications. In addition, we observed that antipsychotic polypharmacy was associated with a longer time to discontinuation…”
- How do the findings compare to past work? The clozapine and LAI second-generation antipsychotics findings are consistent with previous studies – including the one done drawing on Swedish data – “Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia” by Tiihonen et al. (That paper was considered in a past Reading, and can be found here: https://davidgratzer.com/reading-of-the-week/reading-of-the-week-is-new-overrated-antipsychotics-in-the-real-world/.)
The authors note the importance of replication when non-randomized trials are involved which “greatly strengthens the validity and generalizability of the results.”
- The clinical relevance? A handful of medications are linked to better compliance. By this standard, not all antipsychotics are equal. And to return to the original question: is new really better? Weiser et al. offer a split decision, with an older medication (clozapine) doing well, as did some very new medications (LAI second-generation antipsychotics).
- But the other major finding is interesting. No antipsychotic appeared to bestow an advantage in terms of preventing hospitalizations. Two cheers then for clozapine and LAI second generation antipsychotics? One interpretation: these meds work, but need to be part of a larger care plan.
- Like all studies, there are limitations. The authors note: “[T]he analyses performed on some of the newer antipsychotics (oral paliperidone and aripiprazole LAI) include a relatively small number of veterans, although each sample did include several hundred veterans.”
The full AJP paper can be found here:
Selection 2: “Mental illness is a reality – so why does ‘mental health’ get all the attention?”
The Guardian, 14 July 2021
We talk a lot about ‘mental health’ these days, and references to mental illness are becoming rarer. The focus is on being well, and on recovery, which is very encouraging. But it’s not so good if you don’t actually manage to recover. Cancer services, accident and emergency departments and fracture clinics are fairly blunt about what they are addressing – but if you become mentally ill, you will usually be directed to services designed to help you with your mental health.
Does this difference in nomenclature reduce the stigma around mental illness, or does it actually make it worse? There is an implication that saying mental illness out loud would be too painful, and that we cannot admit to the possibility that people might not get better. To me, it feels like denying the severity of a problem, indeed denying the existence of an illness, and I’m not sure that’s right.
So begins an article by Dr. Lawrence.
She writes that she considers the concept of mental health to be important: “I would like to be very clear that I’m not rubbishing the concept of mental health here. I think it’s really important to consider both our own and that of other people. Lifestyle choices can be changed, often before they lead to illness, and also to stop any further progression. It’s not always possible, of course – for example, it is not usually a lifestyle choice to slip from heavy to dependent drinking – but we can try to eat better, sleep better, drink less and exercise, at least some of the time.”
But she sees mental illness as being something different. “I see many patients in the hospital setting who are clearly ill, but maybe, only months before, they were well but struggling, trying to maintain their mental health before it slipped away.”
She continues: “I think that both states exist, and co-exist, and actually we’re probably not helping people enough with their mental health. As a doctor, I can talk with someone and give them pills, but I can’t easily get them any help with losing weight or trying to exercise. I can tell them it would be good for them, but I don’t necessarily have any practical ways to help. Even so, I would like us all to be more honest about mental illness.”
She also discusses her own mental illness: “Why do I – still – feel slightly embarrassed to say I have bipolar disorder? Because mental illness remains rather unacceptable, with some diagnoses more so than others. ‘Mental health’ is not only less unpleasant, it actually feels quite wholesome, implying a healthy mind and healthy living. ‘I must look after my mental health’ sounds far better than ‘I fear becoming mentally ill.’”
She notes the problems of confusing mental health with mental illness: “People who are experiencing mental illness can, understandably, become upset and angry when they meet with platitudes around mental health. Advising a hot bath can be particularly insulting, and it isn’t hard to see why. It’s not that a hot bath would be a bad thing, it’s more that the severity of their distress and suffering is being completely missed.”
Likewise, she warns about the converse: “[I]t can sometimes be better not to medicalise life’s difficulties. There may be times when people get stuck in a situation where, for example, they have come to believe they have a definite chemical imbalance in the brain that will only respond to the right pill. The causes of mental illness remain complex, however, and a rigid conception of the problem can disempower people and blind them to the steps they might be able to take to help themselves.”
She closes: “I would say embrace mental health by all means, but don’t forget that people get ill as well.”
A few thoughts:
- This is a good essay.
- This is also a very timely essay.
- The author does a solid job of distinguishing between mental health and mental illness.
- Increasingly, we speak about mental health. Dr. Lawrence would argue that we are being distracted. Playing the Devil’s advocate: are we finally starting to think about larger issues like mental health in the way that we think about physical health?
- “We talk a lot about ‘mental health’ these days, and references to mental illness are becoming rarer.” Is that true? Again, to play the Devil’s advocate: aren’t we speaking more about mental illness and mental health?
- Dr. Lawrence has lived experience. In a previous Reading, we considered an essay she wrote on psychiatric diagnoses. That Reading can be found here: https://davidgratzer.com/reading-of-the-week/reading-of-the-week-alcohol-use-ed-visits-also-dr-lawrence-on-diagnoses-and-her-diagnosis-guardian/.
The Guardian article can be found here:
Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.