From the Editor
Recently during a family meeting, a patient’s father leaned forward, looked me directly in the eye, and asked: “what would be the best for my son?”
As clinicians, we draw from many sources: personal experience, clinical guidelines, expert opinion, studies. For the latter, randomized clinical trials are considered to be the gold standard. But do such trials capture well the complexity of the patient sitting in front of you?
In the first selection, Heidi Taipale (of the University of Eastern Finland) and her co-authors offer new data to answer that question. Drawing on impressive databases (over 25 000 people diagnosed with schizophrenia spectrum disorders), they consider patients with schizophrenia in RCTs against real-world populations in a JAMA Psychiatry paper. They find: “In this study, we applied typical inclusion and exclusion criteria of RCTs to the real-world populations of individuals with schizophrenia in Finnish and Swedish national registries. We found that almost 80% of individuals with schizophrenia would be ineligible to participate in typical RCTs and are therefore not represented in them.”
In this week’s other selection, we also consider schizophrenia but with a different perspective. What could we do better to support patients and their families? Susan Inman writes: “Mothers, like me, who provide caregiving for adult children with schizophrenia do not have much of a voice.” In a thoughtful essay for Medium.com, she speaks about problems that hinder an effective mental health system, including a lack of mental health literacy campaigns.
DG
Selection 1: “Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials”
Heidi Taipale, Johannes Schneider-Thoma, Justo Pinzón-Espinosa, et al.
JAMA Psychiatry, 26 January 2022
Most evidence about efficacy and safety of medical treatments is based on randomized clinical trials (RCTs), which are highly standardized, systematic studies. RCT outcomes (efficacy) may differ from the utility of interventions in routine clinical practice (effectiveness), in what has been termed the efficacy-effectiveness gap. Efficacy-effectiveness gaps have been identified in several health care areas, including pneumology, oncology, infectology, and internal medicine; nonpharmacological interventions in psychology; and antidepressants.
A possible efficacy-effectiveness gap in effectiveness and safety of antipsychotics in individuals with schizophrenia, which, to our knowledge, has not been investigated so far, may stem from the strict exclusion criteria applied in typical RCTs aiming at marketing approval. Therefore, a broad and diverse set of individuals is excluded from these trials, such as those experiencing suicidal ideations, substance use disorders, or somatic and psychiatric comorbidities. Such excluded people may have different courses of illness and possibly also different treatment outcomes.
So begins a paper by Taipale et al.
Here’s what they did:
- The authors “applied eligibility criteria typically used in RCTs for relapse prevention in schizophrenia spectrum disorders to real-world populations.”
- Drawing from national patient registries in Finland and Sweden, they identified individuals with diagnoses of schizophrenia spectrum disorders. (They note: “We chose 2 registries to assess similarity in findings across countries and reduce the likelihood of chance findings.”)
- “Individuals who had used antipsychotics continuously for 12 weeks in outpatient care were selected.”
- “Individuals were followed up for up to 1 year while they were receiving maintenance treatment with any second-generation antipsychotic (excluding clozapine).”
- The main outcome: “Proportions of RCT-ineligible individuals with schizophrenia spectrum disorders owing to any and specific RCT exclusion criteria.”
Here’s what they found:
- Demographics. The mean age in the Finnish cohort was 47.5 years and 50.4% were women; in the Swedish cohort, the mean age was 44.8 years and 44.8% were women. Note: “There were no major differences in the distribution of age and sex between eligible and ineligible individuals”
- Medications: Ineligible individuals were more likely to be prescribed oral quetiapine and less likely to receive depot antipsychotics.
- Ineligibility. 20 060 individuals (79%) with schizophrenia spectrum disorders would be ineligible for RCTs (Finnish cohort: 79.9%; Swedish cohort, 78.3%). See figure below.
- Reasons. “Most frequent reasons for ineligibility were serious somatic comorbidities and concomitant antidepressant/mood stabilizer use.” Substance and suicide risk were less frequent reasons.
- Hospitalizations. “Risks of hospitalization due to psychosis was higher among ineligible than eligible individuals (Finnish cohort: 18.4% vs 17.2%… Swedish cohort: 20.1% vs 14.8%…).”
A few thoughts:
1. This is a good study.
2. It’s a big finding. “Only a minority (about one-fifth) of real-world individuals with schizophrenia may be eligible for typical RCTs and their clinical outcomes were estimated to differ from ineligible individuals.” Not surprisingly, they make a call for action: “in line with previous literature, future studies focusing on specific subpopulations, pragmatic trials to investigate treatment strategies, and well-designed observational studies are needed to investigate and improve the outcomes of the many individuals afflicted by schizophrenia and currently underrepresented in research settings”
3. Like all studies, there are limitations. The authors note several including: “inclusion and exclusion criteria vary between RCTs. Some RCTs apply more relaxed criteria than the ones we used, e.g., by allowing the participation of individuals with psychiatric or somatic comorbidities, with stable concomitant antidepressant or mood-stabilizing medications, history of suicide attempts (without active suicidal thoughts or behaviors), or substance use (when inactive at the time or when criteria for dependence are not met).”
4. The paper raises questions. Are RCTs too focused? Are their findings thus flawed? Or do RCTs do what they are supposed to do – look at a relatively straightforward group of patients?
5. This paper looks at people with schizophrenia. Years ago, The American Journal of Psychiatry published a paper considering antidepressant treatment trials for depression, finding that 86% of patients were excluded. Is there too great a gap between the literature and our clinical work? Certainly, much recent research has sought to close that gap, including observational studies. Has it been enough?
6. For those interested in the history of RCTs, a NEJM describes well the invention and rise of RCTs. It was considered in a past Reading: http://davidgratzer.com/reading-of-the-week/reading-of-the-week-do-the-meds-work-peter-kramers-essay-and-more/
The full JAMA Psychiatry paper can be found here: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2788266
Selection 2: “Being the Mother of Someone with Schizophrenia”
Susan Inman
The Medium, 3 January 2022
Mothers, like me, who provide caregiving for adult children with schizophrenia do not have much of a voice. An unusual opportunity to learn more about the situations of these women arose in 2015 when the European Federation of Families of People with Mental Illness (EUFAMI) conducted a large survey of family caregivers in 22 countries including Canada where I live. The survey found that the typical family caregiver is a woman around 60 years of age who believes she will be caring for her adult child for the rest of her life; she also believes that she is dealing with a larger mental health system which does not meet either the needs of her family member or her own needs.
My personal coping strategy has been to try to identify and write about the larger systemic problems that hinder the development of an effective mental health system for people with severe mental illnesses. The problems I’m focusing on here can be discussed separately, but there is tremendous overlap between them.
So begins an essay by Inman.
She focuses on five problems; here, we summarize three.
Lack of adequate public mental illness literacy campaigns
“Unfortunately, both my undergraduate and graduate school education proved to be a barrier to understanding what was happening to our daughter when she began to flounder as a teenager; this ignorance led us to seek help from a high profile therapist… I hear numerous stories from other parents who, because they lacked basic information, made the same kind of mistake that we made.
“Neither Canada nor the US has a national mental illness literacy campaign. The public isn’t learning about early warning signs of illnesses like schizophrenia, the steps to take when they see these signs, or the kinds of treatments that are evidence-based. This ignorance also contributes to stigma, since people can easily assume that the disturbing behavior they have witnessed from someone in psychosis is freely chosen.”
Inman also notes that anti-stigma campaigns “either avoid mentioning or minimize the more debilitating symptoms of schizophrenia…”
Lack of psycho-education for clients
“At family support groups, it is clear that a central problem is that too many people do not stay on anti-psychotic medications that they need. Families dealing with mental illnesses in British Columbia have access to two closely related programs, the US National Alliance on Mental Illness’s Family to Family course and the Canadian developed Strengthening Families Together. These programs provide a solid understanding of the symptoms of serious mental illnesses and the medical and psychosocial treatments that can lead to the best results. However, families complain that their family members lack this kind of basic information. Most clients, unless they are in one of the too few Early Psychosis Intervention programs (EPI), do not even learn about the common cognitive losses that may be making their daily lives much more difficult to manage nor do they learn about simple adaptation strategies.”
Increased exposure to anti-psychiatry/anti-medication beliefs
“While not receiving the kind of education about their illnesses that is needed, people with schizophrenia are increasingly exposed to the beliefs of the alternative/psychiatric survivor movement. This exposure is not just through Google searches, but through the expanding presence and influence of people with similar perspectives within the mental health system. Often this exposure comes through the peer movement.
“I believe in the usefulness of peer support workers both for clients who need a vast range of supports, but also for the workers who have a great chance to rebuild their resumes. However, we need to acknowledge the serious problems with the powerful international peer movement…
“The consequences of lack of appropriate education and guidance have been very evident in Vancouver’s mental health services. For instance, although the heavily promoted peer led Hearing Voices Network (HVN) does offer important support and some coping strategies, it also includes larger messages that undermine the belief in the value of medical approaches to severe mental illnesses.”
She notes that a study group linked to HVN “focuses on leaders in the anti-psychiatry movement.”
A few thoughts:
1. This is a good, important, and informed essay.
2. The summary doesn’t do justice to Inman’s writing.
3. Inman is practical. While she likes the idea of peer support, she worries. “There is no requirement or even a recommendation for these workers to learn anything about the actual mental illnesses that many of their clients have.” She also writes from experience: “My daughter appreciated assistance she has received from peer workers, but she has let us know about troubling interactions. At one point, the peer leading a Wellness Recovery Action Plan (WRAP) program explained to the group she was leading that they were all there because they had ‘parents who were never there for them.’ My daughter is aware of the problems with messages like this and was aware of them when she described some in the group as noticeably ill; creating greater distrust of families among this population is not in their best interest.”
4. She also recognizes a tension that exists: many people – as peer workers, yes, but also government officials – don’t embrace a medical model. Ouch.
The full Medium essay can be found here:
https://medium.com/@suinman/being-the-mother-of-someone-with-schizophrenia-62894e8f8493
Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.
Recent Comments