Reading of the Week: Is ‘New’ Overrated? Antipsychotics in the Real World

From the Editor

Is new better?

You may be reading this on an iPhone 7, having driven to work this morning in a 2017 Hybrid Prius. So should your patients be taking a medication that became available four-and-a-half decades ago – when people drove gus-gusling 8-cylinder Oldsmobiles and smartphones didn’t even exist in science fiction novels.

This week, we look at a just-published JAMA Psychiatry paper which promises to look at the “real-world” effectiveness of antipsychotics. The authors tapped Swedish databases to consider outcomes for nearly thirty thousand people with schizophrenia.

Sweden: elaborate welfare state, beautiful historic buildings, and – yes – rich databases

Spoiler alert: the authors found that new wasn’t better. That is, newer antipsychotics tended to underperform clozapine and depot medications.

We also look at similar “real-world” work drawing from a Finnish database considering treatment of depression.



Antipsychotics and Outcomes

“Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia”

Jari Tiihonen, Ellenor Mittendorfer-Rutz, Maila Majak, Juha Mehtälä, Fabian Hoti, Erik Jedenius, Dana Enkusson, Amy Leval, Jan Sermon, Antti Tanskanen, Heidi Taipale

JAMA Psychiatry, 7 June 2017 Online First


“The comparative effectiveness of antipsychotic treatments for patients with schizophrenia has remained controversial despite extensive research. Results from randomized clinical trials (RCTs) suggest that clozapine, olanzapine, and amisulpiride are superior to other antipsychotic medications in terms of efficacy. However, the most efficacious drugs such as clozapine and olanzapine frequently induce adverse effects, such as weight gain and dyslipidemia, which may result in severe deterioration of health after long-term treatment. Investigation of these adverse effects or associated outcomes such as hospitalization and death requires thousands of patients and several years of follow-up to achieve enough statistical power, which is not possible for RCTs.


“Another major issue in RCTs is the selection of patients. Those included in RCTs represent an atypical minority of the patient population because up to 80% to 90% of patients are excluded because of refusal, substance abuse, suicidal or antisocial behavior, or mental or physical comorbidity. Especially problematic is the comparison of oral antipsychotic medications vs long-acting injections of antipsychotic medications because patients with the poorest adherence (ie, those who would receive the greatest benefit from long-acting injectable antipsychotic medications) are excluded from RCTs because participation is fully voluntary. Because RCTs include only an atypical fraction of the most adherent patients, they do not provide information on the real-world effectiveness of the antipsychotic treatments.”

Jari Tiihonen

So opens a new paper by Tiihonen et al. In this paper, the authors make an observational study, drawing on national databases. This approach isn’t unique – the authors acknowledge past work shows better outcomes for clozapine, olanzapine and long-acting depot medications – but such work has had the problem of selection bias.

They attempt to address this:

“We aimed to overcome this problem by using within-individual analysis, in which each person is his or her own control. In this approach, the exposure periods of each individual are compared with the nonexposure periods of the same individual. Therefore, the only factors that need to be adjusted are those that change as a function of time, such as time since cohort entry, temporal order of exposure periods, and concomitant medications.”

Here’s what they did:

  • “We used nationwide register-based data to conduct a prospective population-based cohort study of patients with schizophrenia…”
  • Drawing on Swedish databases, they looked at people with a diagnosis of schizophrenia between July 1, 2006, to December 31, 2013. Inclusion criteria included “all individuals residing in Sweden who were 16 to 64 years of age in 2006.”
  • Data on medication use was drawn from the Prescribed Drug Register – which includes outpatient medication, though no inpatient prescriptions. (!)
  • They considered outcomes as follows: “psychiatric rehospitalization” and “treatment failure” (defined as rehospitalization, discontinuation or switch to other antipsychotic medication, or death).
  • They did a more complicated statistical analysis – that is, they used within-individual Cox proportional hazards regression model. “The within-individual model is a stratified Cox proportional hazards regression model in which each individual forms his or her own stratum.” They also looked at covariables.


Here’s what they found:

  • There were 29,823 patients.
  • Demographically: more men than women (12,822 women and 17,001 men). The mean age was 44.9.
  • “13,042 of 29,823 patients (43.7%) experienced psychiatric rehospitalization and 20,225 of 28,189 patients (71.7%) had treatment failure.”
  • In terms of drugs used: Oral olanzapine was the most frequently used drug, and zuclopenthixol the most frequently used as a long-acting injectable antipsychotic medication.”
  • In terms of rehospitalization: “The lowest risk of rehospitalization was observed for once-monthly long-acting injectable paliperidone (HR, 0.51), long-acting injectable zuclopenthixol (HR, 0.53), clozapine (HR, 0.53), long-acting injectable perphenazine (HR, 0.58), and long-acting injectable olanzapine (HR, 0.58).” See figure below.
  • In terms of treatment failure: “The lowest risk of treatment failure was observed for clozapine (HR, 0.58), and the second lowest was seen for all long-acting injectable antipsychotic medications (HRs, 0.65-0.80), whereas the highest risk was seen for levomepromazine (HR, 1.15).” See figure below.


Adjusted Hazard Ratios (HRs) and 95% CIs for Psychiatric Rehospitalization During Monotherapy Compared With No Use of Antipsychotic in Within-Individual Analyses in the Prevalent Population


Adjusted Hazard Ratios (HRs) and 95% CIs for Treatment Failure During Each Monotherapy Compared With Oral Olanzapine Use

“Our results from a large nationwide cohort show that clozapine and long-acting injectable antipsychotic medications are substantially more effective than other antipsychotics in reducing the risk of rehospitalization or any treatment failure. The most consistent findings were observed for clozapine, being the first in rank order in most of the analyses. These results are in line with those of previous cohort studies using traditional between-individual analyses, although the effect sizes differed to some extent, especially for comparisons between long-acting injectable antipsychotic medications and corresponding oral formulations. Our results showed that the risk of rehospitalization was 22% lower during treatment with long-acting injectable antipsychotic medications compared with treatment with equivalent oral formulations in the total cohort and 32% lower in the incident cohort of newly diagnosed patients.”


A few thoughts:

  1. This is a good study, drawing on a huge dataset – not dozens of people with schizophrenia, or even hundreds, but tens of thousands.


  1. The findings are strong. Let’s not mince our words: new isn’t necessarily better. Of the five best performing medications for treatment failure that were studied, four were old. And, yes, clozapine topped that list. Depot medications were very strong in terms of rehospitalizations, with robust results for drugs that pre-date Atari’s Pong (the first and only video game in 1972), like perphenazine; though it should be added that paliperidone (new) did the best.


  1. There are implications here for practice – how many newly diagnosed patients are on depot medications? There are also implications in terms of health systems – does funding and billing schedules reward depot choices over non-depot choices? Dare I ask about clozapine?!?


  1. Has similar work been done for depression? Actually, Lancet Psychiatry has a solid paper with a very similar analysis. That’s not exactly surprising since Tiihonen is the first author. (Wow, he’s having a good month, at least compared to Theresa May.) In this study, he and his co-authors tap Finnish databases. I will quickly summarize “Pharmacological treatments and risk of readmission to hospital for unipolar depression in Finland: a nationwide cohort study”: they looked at the risk of readmission for all patients who had at least one hospitalization for depression, with data from almost 125,000; exclusion criteria included schizophrenia and bipolar. They found: “Lithium use was associated with a lower risk of re-admission to hospital for mental illness than was no lithium use.” Yes, lithium – speaking of older medications, this one is as old as the earth.6
  1. In the accompanying editorial, Allan H. Young of King’s College is enthusiastic about the findings, but calls for more investigation into lithium:


“Replication of these findings is needed, and should be possible given that similar databases exist in other countries (e.g., Denmark and Taiwan). These data could be easily assessed to establish whether they replicate the Finnish findings or not. The findings of Tiihonen and colleagues are particularly noteworthy because of recent disquiet about the use of antidepressants in unipolar mood disorders, and they suggest that lithium monotherapy might be the best long-term prophylactic drug.”


  1. Big data is changing psychiatry.


Reading of the Week. Every week I pick articles and papers from the world of Psychiatry. 

Dr. David Gratzer



Reading of the Week: Better Treatment, Safer Roads? The New JAMA Psychiatric Paper on ADHD & Driving

From the Editor

How can we reduce the number of car accidents?

We often speak about treating mental illness in terms of reducing personal suffering. Recent selections have looked at the economic cost of mental illness. But what are the implications to public health?

This week, we look at a new JAMA Psychiatry paper; this national cohort study involved more than 2.3 million people with ADHD, and considered motor vehicle crashes (as measured by emergency department visits) and whether or not they were taking medications.

Yes, he has a plaid shirt, but should he be taking his prescription meds?

Spoiler alert: The authors find “medication use for the disorder was associated with a significantly reduced risk” of car accidents.

We also look at an editorial that finds “clinical pearls” in this paper.


Driving and ADHD

 “Association Between Medication Use for Attention-Deficit/Hyperactivity Disorder and Risk of Motor Vehicle Crashes”

Zheng Chang, Patrick D. Quinn, Kwan Hur, Robert D. Gibbons, Arvid Sjolander, Henrik Larsson, Brian M. D’Onofrio

JAMA Psychiatry, 10 May 2017 Online First


“Approximately 1.25 million people die each year globally as a result of motor vehicle crashes (MVCs). In the United States, more than 33 700 individuals died from MVCs in 2014 alone, with an additional 2.4 million visiting the emergency department as a result. In addition, MVCs are a major cause of the gap in life expectancy between the United States and other high-income countries.

“Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder comprising symptoms that include poor sustained attention, impaired impulse control, and hyperactivity. The disorder affects 5% to 7% of children and adolescents and persists into adulthood in a substantial proportion of affected individuals. Previous studies have demonstrated that individuals with ADHD are more likely to experience MVCs. However, the magnitude of this association has varied substantially because of differences in outcome measures, sample selection, and confounding adjustment.

“Pharmacotherapy is considered the first-line treatment for ADHD in many countries, and rates of ADHD medication prescription have increased significantly during the last decade in the United States and other countries. Evidence from controlled trials has shown that pharmacotherapy has marked beneficial effects on core symptoms of ADHD; to some extent, it also improves driving performance in virtual reality driving simulators. The use of population-based health record data and self-controlled designs provides an innovative and informative approach to evaluate the effect of medication use on important outcomes in real-world situations. A Swedish register-based study found that ADHD medication use was associated with lower risk of traffic crashes in men. However, the association in women was not clear. Moreover, there are cross-national differences in ADHD treatment practices and rates of MVCs between Sweden and the United States. In addition, it is unclear whether ADHD medication treatment will change the long-term course of the patients and lower the risk of MVCs. Therefore, additional population-based studies in the United States are needed to evaluate the effect of ADHD medication use on MVCs.

“In the present study, we followed up a national cohort of patients with ADHD between January 1, 2005, and December 31, 2014, using data from commercial health care claims in the United States.”

Zheng Chang

 Here’s what they did:

  • The data was drawn from the Truven Health Analytics MarketScan Commercial Claims and Encounters databases – “one of the largest collections of deidentified patient data and includes inpatient, outpatient, and filled prescription claims for more than 100 insurers in the United States.” This covers 146 million people.
  • The study period was January 1, 2005, to December 31, 2014.
  • Patients were 18 and older, and had received an ADHD diagnosis (on an inpatient or outpatient basis) or a filled ADHD medication (the list of medications included amphetamine salt combination and methamphetamine hydrochloride).
  • The outcome event was an ED visit for an MVC, defined by the appropriate code (ICD-9 codes E810-E825).
  • Statistical analysis was done to find the risk of at least one MVC between patients with ADHD and controls. Additionally, to understand the association between medication use for those with ADHD and MVCs, the authors made “a monthly person-time data set” that considered the use of medications (if they filled a prescription in that month or there was a carryover prescription from a prior month). They also looked at 2-year follow ups.


Here’s what they found:

  • “The study cohort consisted of 2,319,450 patients with ADHD… observed for a total of 50,667,665 person-months.”
  • Demographically: the median age was 32.5, with a roughly equal gender distribution (1,121,053 men and 1,198,397 women). 83.9% (1,946,198) of those with ADHD had received at least one prescription for an ADHD medication.
  • “Patients with ADHD had a significantly higher risk of an MVC than their matched controls (OR, 1.49) and untreated patients with ADHD had the highest risk of an MVC compared with medicated patients with ADHD and controls…”
  • “At the population level, months with ADHD medication were associated with a 12% (OR,0.88) lower risk of MVCs in male patients with ADHD relative to unmedicated months and a 14% (OR, 0.86) lower risk of MVCs in female patients with ADHD… More important, the within-individual analyses showed that men with ADHD were 38% (OR, 0.62) less likely to have MVC events during medicated months relative to unmedicated months, suggesting that, within an individual (i.e., after controlling for all unmeasured static and measured time varying confounding factors), ADHD medication use was associated with a significant reduction in the risk of MVCs. Our PAF estimated that 22.2% of the MVCs among male patients with ADHD were attributable to lack of medication treatment, assuming that the association was causal.” The results were similar for female patients.
  • “At the population level, there were no significant associations between ADHD medication use and MVC events 2 years later. However, the within-individual analyses showed that ADHD medication use was associated with a 34% (OR, 0.66) lower risk ofMVCs 2 years later inmate patients with ADHD and a 27% (OR, 0.73) lower risk of MVCs in female patients with ADHD.”


“In this large, nationwide cohort study over 10 years, patients with ADHD had a higher risk of MVCs compared with controls without ADHD. However, in male and female patients with ADHD, medication use for the disorder was associated with a significantly reduced risk of MVCs. Similar reductions were found across all age groups, across multiple sensitivity analyses, and when considering the long-term association between ADHD medication use and MVCs.”

 The paper runs with a short and readable editorial by the University of Virginia Health System’s Vishal Madaan and Daniel J. Cox.

You can find the editorial here:

 Vishal Madaan

 The Editorial opens:

 “While driving is a ubiquitous functionality and an important activity of independent daily living, it also represents a complex neurobehavioral task involving an interplay of cognitive, motor, perceptual, and visuospatial skills. As a result, patients with neurodevelopmental disorders often have limitations in such skills. Although there has been a recent interest in understanding driving concerns in individuals with other neurdevelopmental disorders such as autism spectrum disorders, substantial research has reviewed the influence of attention-deficit/hyperactivity disorder (ADHD) on driving safety, especially given how pharmacotherapy may affect inattention, impulsivity, and executive dysfunction.”

 They praise the study, noting that: “The findings in the study by Chang et al in this issue of JAMA Psychiatry confirm and extend existing experimental studies and have impressive implications for judicious use of ADHD medication.”

 Madaan and Cox see “clinical pearls” for clinicians. The “management of ADHD is not limited to one’s school, college, or workplace: it extends to several other aspects of life, such as driving, which may be ignored to the clinician’s and patient’s peril.” They also comment that “health care professionals should be aware that MVCs in individuals with ADHD often happen later in the evening when their medications may have worn off.”

 A few thoughts:

  1. This is a good study.
  2. The topic is important.
  3. The findings are a gentle reminder of the importance of our work – literally keeping our patients safe. “The within-individual analyses showed that men with ADHD were 38% (OR, 0.62) less likely to have MVC events during medicated months relative to unmedicated months…” Wow.
  4. The paper isn’t without limitations, of course. The authors make some big assumptions: they equate medication compliance with pharmacy compliance (that is, if the prescription is filled, the patient is taking the medication); they only look to ED visits (post-MVC, a patient may seek care with his or her primary care physician); medication compliance doesn’t mean proper medication management (as Madaan and Cox note in their editorial, many stimulants have shorter half-lives, leaving patients under-medicated during evening and night-time driving). Still, it’s difficult not to be impressed with the incredible database that Chang et al. have drawn from – involving millions of people.
  5. If public health and psychiatry catches your fancy, the American Economic Review has an interesting paper on using CBT for crime reduction in Liberian men. Spoiler alert: it worked.


You can find that study here:

(Nice surprise: the paper on CBT and its public health implications ran in an economics journal.)

  1. Mental illness casts a long shadow over our society. Yes, we can see this in terms of absenteeism and presenteeism. Yes, we can see this in terms of personal tragedy and loss. But, as the authors of this paper argue, yes, we can see this in terms of car accidents and general safety.

Reading of the Week. Every week I pick articles and papers from the world of Psychiatry. 

-Dr. David Gratzer

Reading of the Week: Is Psychoanalysis Relevant? Paris vs. Ravitz

From the Editor

“Today, psychoanalysis has been marginalized and is struggling to survive in a hostile academic and clinical environment. This raises the question as to whether the paradigm is still relevant in psychiatric science and practice.”

This week, we consider the relevance of psychoanalysis.

Drawing from the May issue of The Canadian Journal of Psychiatry, we look at two papers.

Freud and analysis: debating his relevance

In a Perspectives piece, Dr. Joel Paris argues that psychoanalysis is part our legacy – but not much more. In an Editorial, Dr. Paula Ravitz responds. She opens by writing: “My concern is that by unnecessarily pitting psychiatry against psychoanalysis, we may throw out the baby with the bathwater.”

It’s a great and important debate.



Paris on Therapy

“Is Psychoanalysis Still Relevant to Psychiatry?”

Joel Paris

The Canadian Journal of Psychiatry, May 2017



“Psychoanalysis is a theory of psychopathology and a treatment for mental disorders. Fifty years ago, this paradigm had great influence on the teaching and practice of psychiatry. Today, psychoanalysis has been marginalized and is struggling to survive in a hostile academic and clinical environment. This raises the question as to whether the paradigm is still relevant in psychiatric science and practice.


“In a difficult climate for the theory and practice of psychoanalysis, several responses have emerged, either by attempting to bridge the gap with science or by redefining the field as lying outside of science. Thus, some analysts have supported revised paradigms, such as attachment theory, that are better supported by evidence. Others have taken the view that Freud’s ideas concerning the unconscious mind are compatible with modern neuroscience. Still others have moved in the opposite direction, arguing that it is sufficient to offer a coherent interpretation of psychological phenomena. This review will briefly examine all these attempts to revive psychoanalysis.”

Joel Paris

So opens McGill’s Joel Paris in his paper. He predicts a “continued and lingering decline” for psychoanalysis. In a sweeping essay that draws heavily from the literature, he makes several points.


  • Psychoanalysis has been undermined by a lack of scientific study. “The absence of solid and persuasive evidence for the theory may be the consequences of self-imposed isolation from the empirical sciences.” (He notes that attachment theory is the “notable exception.”)
  • Even psychoanalysts, he writes, concede there is limited evidence. “Peter Fonagy, a psychoanalyst who is also a respected researcher, has acknowledged that ‘the evidence base for psychoanalytic therapy remains thin.’”
  • Though there is evidence for time-limited dynamic psychotherapies, Dr. Paris argues that this isn’t generalizable to psychoanalysis. With psychoanalysis, “a few reports have attempted to examine” outcomes, but there have been serious limitations.
  • Attempts to tap brain imaging to confirm analytic theories – such as using REM activity – have been “incompatible with empirical data.” Some, like Norman Doidge, have argued that the “brain can change itself” – but Doidge’s books are bestsellers, but “have had little impact in medicine.”


“Whatever its limitations, psychoanalysis left an important legacy to psychiatry. It taught a generation of psychiatrists how to understand life histories and to listen attentively to what patients say. In an era dominated by neuroscience, diagnostic checklists, and psychopharmacology, we need to find a way to retain psychotherapy, whose basic concepts can be traced back to the work of Freud, as part of psychiatry.”



Ravitz Responds

“Contemporary Psychiatry, Psychoanalysis, and Psychotherapy”

Paula Ravitz

The Canadian Journal of Psychiatry, May 2017

“In his Perspective, ‘Is Psychoanalysis Still Relevant to Psychiatry?’ Paris presents a critical perspective on psychoanalysis in the context of evidence-based care. Scientific discourse demands critical dialogue, and so in this editorial, I provide alternative perspectives on some of Paris’s arguments and further thoughts on psychoanalytic training, research, and treatment. My concern is that by unnecessarily pitting psychiatry against psychoanalysis, we may throw out the baby with the bathwater.”

Paula Ravitz

So responds the University of Toronto’s Dr. Paula Ravitz to the Paris paper. She forwards several arguments.


  • She notes that psychoanalytic thought is traced to various theories – and that a typical scientific consideration isn’t necessarily appropriate. “[C]urrent psychoanalytic thought is informed by theory of mind, feminist theory, queer theory, sociology, cognitive psychology, nonlinear dynamics, evolutionary biology, political science, anthropology, Buddhism, evolutionary psychology, and ethology. Many aspects of this rich interdisciplinary landscape of influences lie outside the domain of science and its standards of evidence, but not all.”
  • That said, she observes “the strength of evidence” for different psychotherapies. “Canadian position papers and working group papers on psychotherapy published over the past 4 decades highlight that psychotherapy treatments are integral, core components of psychiatric practice.”
  • And she taps the literature, “Although there are fewer controlled studies of psychoanalytic treatment, there is in fact evidence for the efficacy of both short- and long-term psychodynamic psychotherapy (LTPP). Leichsenring and Rabung’s systematic review of 23 studies conducted between 1984 and 2008 identified 11 prospective RCTs and 12 observational studies of >1000 patients receiving LTPP in which there was a large within group effect size of 0.96… for pre- to posttreatment overall outcomes, and for the 8 studies that included a comparison group, the overall between-group effect size was even larger at 1.8…”


“Psychotherapy treatments can effectively address suffering and enhance outcomes and the quality of care of mental illnesses across a spectrum of health care settings. As evidence-based practitioners and psychiatrists, we must use what is best for our patients and be trained in a broad range of effective treatments, including psychotherapies and psychoanalytic principles. Based on 40 years of outcome and process research, it is clear that psychotherapy treatments are helpful for patients with psychiatric disorders and therefore a critical component to be preserved in the training and practice of psychiatrists of the 21st century.”


A few thoughts:

  1. What a terrific exchange.
  1. Congratulations to the authors – and to The Canadian Journal of Psychiatry for publishing this debate. (And I would encourage readers to look at the papers themselves, since this summary is just that – a summary.)
  1. Though these two psychiatrists take different positions, there is clearly common ground. Note, for instance, that they both acknowledge the contribution of psychoanalysis to current care, including attachment theory. And both acknowledge the incredible importance of psychotherapy in terms of evidence-based care.


  1. A past Reading considered this topic, drawing on a clever Guardian essay, and then discussing an American Journal of Psychiatry paper that showed that CBT helped patients with bulimia achieve symptom relief faster than those treated with analysis – though the study did show that neither psychotherapy was particularly effective.


You can find the Reading here:

ROTW: Freud is Dead are his Ideas Dead Too?


  1. In a publicly-funded system, there are larger questions. Does analysis justify its cost given the system’s limited resources? Is it problematic to think in these terms, with government officials then trying to pick winners and losers in treatment, potentially micro-managing patient care?


  1. These two selections, then, touch on a broader discussion – the relevance of psychoanalysis has implications for education, clinical practice, and health care financing. I’ll close the way I started: by noting that it’s a great and important debate.



Reading of the Week. Every week I pick articles and papers from the world of Psychiatry. 


-Dr. David Gratzer

Reading of the Week: Schizophrenia & Diabetes: The Gap in Care; Also, Swedish Health Care

From the Editor 

“The pain in my feet. It’s killing me.”

That’s what John told me when I asked him what he needed help with. It’s not quite the answer I thought he’d give – John has schizophrenia and he has significant side effects from his medications. But, like many people with mental illness, he also struggles with physical illness (diabetes and the accompanying neuropathy).

Many of our patients have both physical and mental illnesses. When faced with these twin challenges, how do they fair?

In this week’s first selection, we look at a new paper that considers people with schizophrenia and diabetes. The study authors find a significant gap between the care received by those with and without mental illness.

An old drug, an old illness, and a big problem for those with mental illness


In our second selection, drawing from a lively blog written by medical student Ali Damji, we look at Swedish health care.


 Diabetes and Care

“Diabetes quality of care and outcomes: Comparison of individuals with and without schizophrenia”

Paul Kurdyak, Simone Vigod, Raquel Duchen, Binu Jacob, Thérèse Stukel, Tara Kiran

General Hospital Psychiatry, May-June 2017 (Published Online First)


“Diabetes is common among individuals with schizophrenia, with a median prevalence rate of 13%, and documented prevalence rates as high as 50%. Diabetes is more common among individuals with schizophrenia than among those with other mental illnesses, and much more common than in the general population. Individuals with schizophrenia have more diabetes risk factors such as obesity, poor diet, and reduced physical activity relative to individuals without schizophrenia. Additionally, second-generation antipsychotics, a mainstay of treatment for schizophrenia, contribute to the high prevalence of diabetes through weight gain and insulin resistance. The substantial mortality gap between individuals with and without schizophrenia is largely explained by an increase in cardiovascular deaths, for which diabetes is a significant risk factor.

“Careful monitoring of blood pressure, cholesterol and glycemic control reduce morbidity and mortality for individuals with diabetes, and diabetes care guidelines have been developed in multiple jurisdictions to encourage optimal care. When diabetes is comorbid with schizophrenia, there are patient, provider, and system-level factors that make it challenging to follow evidence-based guidelines. Patients with schizophrenia have a significant level of cognitive disorganization and social instability that makes engaging in care difficult. Providers may be overwhelmed by the complexity and may not have the time or resources needed to provide optimal care. Finally, mental health care and primary care can be fragmented and there is relatively little evidence on how to design care that involves multiple health care providers when one of the comorbidities is a serious mental illness.”

Dr. Paul Kurdyak


So begins a paper by Kurdyak et al. that uses a retrospective cohort study to compare the diabetic care of those with schizophrenia and diabetes, and those with only diabetes.

Here’s what they did.

  • The authors drew data from several databases covering different aspects of health service delivery including the Ontario Health Insurance Plan (outpatient physician billing, as well as diagnostic codes and procedures) and CIHI Discharge Abstract Database (acute hospitalizations).
  • The participants were adults eligible for the Ontario Health Insurance Plan, with the study covering a period of two years, from April 1, 2011.
  • Diabetic care was based on participants getting the care recommended by the Canadian Diabetes Association 2013 Clinical Practice Guidelines – at least 4 Hb1AC tests, one cholesterol test, and one retinal exam.
  • They looked at demographic information, and other co-variables: residential instability, maternal deprivation, etc.
  • Statistical analysis was done, including an ANOVA analysis.


Here’s what they found:

  • On April 1, 2011, there were 1,131,415 individuals with diabetes age 19 to 105; of these, 26,259 (or 2.3%) had schizophrenia.
  • Demographically: those with schizophrenia were significantly more likely to be female and younger. They were significantly more likely to live in an urban setting, and in lower income neighbourhoods.
  • In terms of health care use: individuals with schizophrenia were more likely to use health care: they were more likely to have at least one ED visit for a diabetes complication (8.1% vs. 5.9%), and at least one ED visit for any reason excluding trauma (55.5% vs. 40.2%), and to be hospitalized for a diabetes complication (6.0% vs. 4.7%).
  • In terms of diabetic care: “Individuals with schizophrenia were less likely to receive guideline-level screening for diabetes.” They received the recommended number of cholesterol tests less than those without schizophrenia (72.4% vs. 80.3%) and the recommended number of eye exams (56.8% vs. 67.4%). “There was a smaller, but significant difference in the proportion of individuals who received the recommended number of HbA1c tests between the two groups (35.8% vs. 37.7%…).”
  • In terms of an adjusted odds ratio: “Individuals with schizophrenia were less likely to be guideline-concordant with one of the 3 recommended tests (aOR = 0.84 95% CI 0.81–88), two tests (aOR = 0.71 95% CI 0.68–0.74) and three tests (aOR = 0.60 95% CI 0.57–0.62) in comparison to individuals without schizophrenia.” See the following graph:

Relative risk


They note:

They also have approximately 30% more visits with their primary care physician. Despite this frequent primary care contact, individuals with schizophrenia are less likely to have cholesterol testing and eye exams, and are one third less likely to receive all three guideline-based tests (HbA1c, cholesterol testing and eye exams). Finally, individuals with schizophrenia are about one third more likely to have diabetes-related hospitalizations and ED visits.”

The authors go on to consider ways that diabetic care could be improved for those with major mental illness. They note evidence in the literature for co-location of specialists, as well as the use of diabetic nurses in primary care.


A few thoughts: 

  1. This is a good study. It speaks to the gap in care – but, at the same time, the strikingly high costs of that gap (greater utilization of primary care, more visits to the ED, and more hospitalizations).


  1. We often speak about access issues when talking about mental health problems. But it’s important to recognize the full needs of those with major mental illness – yes, there are issues in terms of access to mental health services, but physical health needs must be considered and addressed too.


  1. The paper asks a good question and finds the answer that we suspect it would. But the contribution here is the actual data. Drawing on databases that cover millions of Ontarians, the authors are able to demonstrate the difference between the diabetic care of those with and without schizophrenia.


  1. Once again, Dr. Paul Kurdyak pushes us.


Lessons from Sweden

“Guest Post: Ali Damji (Canada) – Snapshots of Patient Co-Produced Care”

Ali Damji

Co-learning with Qulturum, 5 March 2017


“Time really flies when you’re having fun!

“This is my second reflection, from when I participated in a Study Visit with a team from Singapore Institute for Mental Health (all of us pictured above). It was co-learning at its finest, where I not learned about quality improvement and healthcare in Jonkoping, but also a great deal about Singapore too!

“One of the main reasons that I traveled to Jonkoping was to learn about patients as partners, and patient-led care. This blog post will focus on a few encounters where patients co-produced better care that I witnessed firsthand.”

Ali Damji


In this essay, University of Toronto medical student Ali Damji describes his experience learning about health care in Sweden.

He notes several aspects of the Swedish health care system that are different from the Canadian system.

  • Patients are invited to attend and participate in ward rounds.
  • Self-management includes self-dialysis.
  • Hospital staff wear a similar uniform as it’s been shown to reduce infection rates. (Ali is wearing this uniform in the picture above).

He discusses at some length the inclusion of “Esther” in discussions.

“In Jonkoping, one of the key ingredients to their successes is a flipped perspective when thinking about quality improvement and change. Rather than thinking about, ‘What’s best for the system? Or what’s best for me, the provider?’, the question always is, ‘What is best for Esther?’ Esther is a hypothetical patient that many of us in healthcare are familiar with. She is a person with a life beyond the walls of the institution, not purely a patient. She is elderly and frail. She has complex health needs. She lives alone. If she lacks effective primary care or transitions from the hospital back to home without support, she does not do well. She’s called a ‘frequent flyer’. But what about the other elements of her life? What drives her? What motivates her? And most importantly, what matters to her? And how is her problem, our problem (not long term care’s problem or the hospital’s problem – our collective problem!)? How can connections be developed and the system be built so it can respond to the things that matter most to her, beyond simply her medical needs?”

Ali notes that Esther is considered at various levels of decision-making, even with program funding

A few thoughts:

  1. This is a fun and lively blog. It doesn’t directly tie into psychiatric care, but does tie into patient care.


  1. There are a couple of other blogs in the series and the observations on Swedish health care are worth reading. So often we look at other health care systems through the narrow prism of funding; this blog is broader in perspective.


  1. Ali has just been accepted into the University of Toronto’s Family Medicine program. Congratulations. We look forward to reading more health-care insights from him in the coming years.


  1. You can find his other Swedish blogs here:


Reading of the Week. Every week I pick articles and papers from the world of Psychiatry. 

-Dr. David Gratzer

Reading of the Week: Are Cats Making Us Sick? The Solmi et al.

From the Editor 

A few years ago, Czech scientist Jaroslav Flegr made a splash by arguing that our feline friends were causing psychosis in people – The Atlantic provocatively titled their article on him: “How Your Cat is Making You Sick.” Flegr’s argument was based in part on several papers (including by prominent researcher E. Fuller Torrey) noting that cat ownership confers an increased risk of psychotic disorders like schizophrenia.

So, are cats safe for household use?

In our first selection, we look at a new Psychological Medicine paper that, with a cohort study, finds no connection between cat ownership and psychotic symptoms.


Good news, tabby: you can stay

How to help the homeless? In our second selection, drawing from The Guardian, we look at a Hawaiian effort to prescribe the housing to the homeless – literally.

Please note that there will be no Readings for the next two weeks. Enjoy the March break.

-David Gratzer


 Pets and Problems

“Curiosity killed the cat: no evidence of an association between cat ownership and psychotic symptoms at ages 13 and 18 years in a UK general population cohort”

  1. Solmi, J. F. Hayes, G. Lewis, J. B. Kirkbride

Psychological Medicine, 22 February 2017 Online


“House cats are the primary hosts of Toxoplasma gondii, a protozoan parasite that can infect various warm-blooded animals, including humans. Infection can occur in utero or postnatally, via ingestion of either the parasite’s oocysts–which might be present in soil, water, or food–or tissue cysts from infected animals (e.g. in raw or undercooked meat). In intermediate hosts (e.g. humans or animals other than cats), the parasite exploits lymphocytes to encroach in muscle tissues and, importantly, the brain, where it can form tissue cysts in neurons, microglia, and astrocytes.

“Although the evidence is not unequivocal, data from several epidemiological, experimental, and animal studies suggests that T. gondii infection may be implicated in the aetiology of psychosis. For example, dopaminergic dysfunction and cognitive impairments – similar to those observed in people with schizophrenia–have been observed in infected rodents and humans; these people may also experience hallucinations during acute infection with the parasite. A recent meta-analysis of 38 studies found that compared with controls, people with schizophrenia were nearly three times more likely to be seropositive for T. gondii antibodies [odds ratio (OR) 2.71, 95% confidence interval (CI) 1.93– 3.80]. Higher seroprevalence and serointensity of T. gondii IgG (but not IgM, an indicator of recent infection) in people with schizophrenia and their mothers suggest that either early life exposure to the parasite, congenital infection, or transmission of maternal antibodies could alter neuro-development of subsequent offspring.

“Assuming a causal relationship between T. gondii infection and later psychosis, some researchers have hypothesized that cat ownership should confer an increased risk of psychotic disorders…”

Francesca Solmi

So begins a paper by Solmi et al. that seeks to test this hypothesis by looking at cat ownership in pregnancy and childhood, and whether ownership is associated with psychotic experiences (PEs) in early and late adolescence.

Here’s what they did.

  • The authors drew data from the Avon Longitudinal Study of Parents and Children (ALSPCA) study, which had “invited 16734 pregnant women expected to deliver between 1 April 1991 and 31 April 1992 resident in the former county of Avon (England) to participate.”
  • Information on pet ownership was reported “by mothers via postal questionnaires during pregnancy, and subsequently when their child was aged 8, 21, 31 and 47 months.”
  • “At approximately ages 13 and 18 years, children attended clinic visits where they were administered the psychotic-like symptoms interview (PLIKSi), a semi-structured interviewer-rated screening assessment for PEs [psychotic experiences].”
  • Statistical analysis was done. The authors used logical regression to consider if cat ownership had an association with psychotic experiences, and adjusted for socioeconomic factors (like overcrowding).


Here’s what they found:

  • The sample: 6,705 at age 13 and 4,676 at age 18 had complete data on psychotic symptoms. Of those, 776 (11.57%) and 370 (7.91%) had psychotic symptoms that were suspected or definite at 13 and 18 years, respectively.
  • Demographically: The youth included in the study included slightly more female than male (51.03% at age 13), were overwhelmingly white (96.05%), and had a mother who has married (81.24%).
  • “Cat ownership in pregnancy was not associated with psychotic symptoms at age 13 or 18 years in either univariable (age 13: OR 1.15; age 18; OR 1.08) or in multivariable (age 13: adjusted OR 1.15; age 18; OR 1.08) models…”
  • “Owning a cat at age 4 years was associated with higher odds of having PEs at age 13 years in univariable models (OR 1.23), but this effect was no longer significant after multivariable adjustment (OR 1.18).
  • “There was no evidence that cat ownership at age 4 years was associated with PEs at age 18 years (univariable OR 1.11; adjusted OR 0.97).”


In sum:

We found no evidence that cat ownership in pregnancy or childhood was associated with PEs in early and late adolescence using prospectively collected data from a large population-based cohort, following control for several confounders and methods that investigate the likely impact of missing data.”


A few thoughts:

  1.  This is a good study.
  2.  The research question is topical and catchy. This paper was picked up widely, including CNN.
  3.  On the results, lead author Francesca Solmi commented: “The message for cat owners is clear: there is no evidence that cats pose a risk to children’s mental health…” But why do these results differ so greatly from the earlier literature? This paper had a significantly different methodology – among other things: they did a cohort study with data stretching for years; in the statistical analysis, the authors also sought to rule out other factors.
  4. The authors did weigh this, and argue for the strength of their approach. They also question earlier studies: “Previous reports of positive associations between cat ownership and schizophrenia may therefore have been attributable to Type I error, particularly given the small sample sizes and lack of control for confounders inherent to some studies.” But by attempting to statistically eliminate confounders, did they end up compromising the data? In a CNN interview, researcher E. Fuller Torrey – who was the lead author on several papers on schizophrenia and cat ownership – suggested as much (specifically about overcrowding). The CNN article can be read here:


Cat ownership not linked to mental health problems, study says – CNN


Housing and Homelessness

 “Doctors could prescribe houses to the homeless under radical Hawaii bill”

-Liz Barney

guardian, 28 February 2017 Online


“One day last month, Stephen Williams asked a passerby for help and then collapsed on the sidewalk. When the ambulance arrived in downtown Honolulu, his temperature was well over 104F.

“A life-threatening staph infection had entered his bloodstream. Williams, who lives on the dusty streets of Chinatown, spent seven days hooked to an IV, treatment that can cost $40,000, according to the hospital that admitted him. But Williams didn’t pay: the bill was covered by government dollars in the form of Medicaid. Over the past four years, he has been to the hospital for infections 21 times, he said, a consequence of psoriasis flare-ups in a humid climate and unsanitary conditions.

“Cases such as these have prompted a groundbreaking new proposal in Hawaii. Instead of prescribing medication to homeless patients like Williams, what if doctors could prescribe something else that might ameliorate their health problems more effectively? The prescription would be housing.”

Liz bamey
Liz Barney

So begins a Guardian article by Liz Barney. The article describes the effort of State Senator Josh Green, who is a physician, to classify homelessness as a medical condition. People then could be “prescribed” housing.

The article notes the connection between homelessness and health costs.

  • In a recent study by a Hawaiian insurer, a small percentage of Medicaid users account for over half of the $2 billion of annual spending; high needs users were often dealing with homelessness.
  • Housing reduces health care costs for the homeless by 43%.
  • Green notes that health spending on some homeless is $120,000 but housing would be just $18,000.

 The article continues by noting supporters and critics of the approach. Kimo Carvalho of the Institute for Human Services notes the need for targeted funding, particularly in light of people “walking out” of housing.


A few thoughts:

  1.  The debate in Hawaii, like much of North America, has changed dramatically in recent years. A few years ago, Hawaii had strict laws on homelessness; today, Housing First is discussed. The Economist wrote about Hawaii and homelessness here:   Homelessness in Hawaii: Paradise Lost – The Economist
  2. Housing First is an active area of research. I’ll note the incredible work done in the area – and the Canadian connection. And, of course, we have looked at this in past Readings. See, for example:  Reading of the Week:  Housing First and At Home/Chez Soi – David Gratzer
  3. What a great public-policy debate to watch unfold. #Progress


Reading of the Week. Every week I pick articles and papers from the world of Psychiatry. 


Dr.  David Gratzer

Reading of the Week: Do Markets work for (Mental) Health Services? The Arrow Paper

Dr. David Gratzer is a Toronto-based psychiatrist and physician.

He works at The Scarborough Hospital, where he is physician-in-charge of Mental Health inpatient services, and is the physician co-lead for consultation-liaison services. He is active in teaching, and has received the specialist teacher of the year award twice, and nominated six times for University of Toronto teaching awards. He is a member of the national editorial board of CAMH’s Portico and serves on the OMA’s Section on Psychiatry Executive. He recently joined the editorial board of The Canadian Journal of Psychiatry.

Dr. Gratzer writes widely. His articles have been published in The Globe and Mail and Maclean’s. He is the author of two books and the editor of a third. His first book was awarded the Donner Prize in 2000. His research interests include psychiatry and technology.

We are proud to include his Reading of the Week posts here on Mental Notes.


Do Markets work for (Mental) Health Services? The Arrow Paper

From the Editor 

His New York Times obituary opens: “Kenneth J. Arrow, one of the most brilliant economic minds of the 20th century and, at 51, the youngest economist ever to win a Nobel, died on Tuesday at his home in Palo Alto, Calif. He was 95.”

Kenneth J. Arrow


As a tribute to Kenneth Arrow, this week’s paper is his “Uncertainty and the Welfare Economic of Medical Care.”

This paper was published decades ago. Our selections try to be current. But we’ll make an exception for a good reason: Kenneth Arrow, one of the most significant economists of the 20th Century, died last week; his work on health care and economics remains deeply influential. Indeed, whether we are discussing the Choosing Wisely campaign or debating the expansion of public coverage under Obamacare, we are essentially weighing in on Arrow’s 1963 health economics paper – which makes this paper a natural choice for this week’s Reading.

Arrow didn’t mention mental health in his 1963 paper. But as we seek to better mental health services, his observations on the problems of health-care information are worth considering.



Economics and Health Care

“Uncertainty and the Welfare Economic of Medical Care”

Kenneth J. Arrow

The American Economic Review, December 1963


“This paper is an exploratory and tentative study of the specific differentia of medical care as the object of normative economics. It is contended here, on the basis of comparison of obvious characteristics of the medical-care industry with the norms of welfare economics, that the special economic problems of medical care can be explained as adaptations to the existence of uncertainty in the incidence of disease and in the efficacy of treatment.

“It should be noted that the subject is the medical-care industry, not health. The causal factors in health are many, and the provision of medical care is only one. Particularly at low levels of income, other commodities such as nutrition, shelter, clothing, and sanitation may be much more significant. It is the complex of services that center about the physician, private and group practice, hospitals, and public health, which I propose to discuss.

“The focus of discussion will be on the way the operation of the medical-care industry and the efficacy with which it satisfies the needs of society differ from a norm, if at all.”

Kenneth J. Arrow

So begins a paper written by Kenneth J. Arrow. Many consider it the first important paper written on health economics.

“Uncertainty and the Welfare Economic of Medical Care” is one of his most cited and significant work. The paper forwards one key argument: that health care is different (economically speaking) from other aspects of the economy. Whereas markets may be functional outside of health care, he argues that market forces don’t work within health care.

“It is the general social consensus, clearly, that the laissez-faire solution for medicine is intolerable.”

He identifies several ways that health care is different:

Unpredictability. People’s needs for health care are unpredictable, unlike other basic needs like food or clothing.

Barriers to entry. Medicine must be practiced with a licence, requiring years of training, limiting the supply of services.

The importance of trust. Trust is a key component in the doctor-patient relationship.

Asymmetrical information. Doctors know more about medicine than do their patients, leaving the consumers of medical services at a disadvantage.

Picking up on the last point about asymmetrical information: providers of health care have far more information than patients. While Arrow acknowledges that we doctors are supposed to act in the patients’ best interest (we aren’t “barbers,” as he notes), he still argues that physicians are “sellers of health care” and that we can exploit the lopsided relationship.

 A few thoughts:

  1.  Despite being decades old, Arrow’s paper is cited, discussed, and debated. (It yields almost a million hits on Google.)

 For example, blogging on Obamacare, economist and writer Paul Krugman (himself a winner of the Nobel Memorial Prize in Economics) notes:

 “One of the most influential economic papers of the postwar era was Kenneth Arrow’s ‘Uncertainty and the welfare economics of health care,’ which demonstrated – decisively, I and many others believe – that health care can’t be marketed like bread or TVs.”

 He goes on to frame his views on health reform around Arrow’s paper.

You can find his blog here:  Why markets can’t cure healthcare


  1. Let’s focus on information asymmetry. Arrow wrote his paper before the Internet. In an information age, how to think about information asymmetry? Economist Deborah Haas-Wilson of Smith College weighs in with an essay noting: “There has been explosive growth in the amount of health information available online.” By 2001, for example, “there were approximately 26,000 health-related Web sites.”


You can find the full paper here:  Arrow and the Information Market Failure in Health Care: The Changing Content and Sources of Health Care Information


  1. Pushing further on the idea that health information has significantly changed over time, columnist David Brooks argues for more market reforms in health care (and changes to Obamacare):


There’s much research to suggest that people are able to behave like intelligent health care consumers. Work by Amitabh Chandra of Harvard and others found higher-performing hospitals do gain greater market share over time. People know quality and flock to it.”


Brooks’ argument provides something of a counter-point to Krugman’s – but it still begins by mentioning Arrow.

You can find his article here:  Do Markets Work in Health Care?



  1. Tying back to mental health services: regardless of our views on health care reform, we can see that asymmetric information is deeply problematic for people trying to access mental health services.


  1. In light of Arrow’s work, we can appreciate the importance of Choosing Wisely, a campaign which seeks to provide patients and providers with relevant information in order to reduce unnecessary care. The recommendations for psychiatry are thoughtful and practical – and ultimately attempt to address information asymmetry.


  1. It’s fantastic that employers are beginning to offer more robust mental health benefits, but there is still the information divide. Starbucks Canada recently began offering employees up to $5,000 a year for private psychological services. But how does a barista in Scarborough or Saskatoon find a good therapist for CBT?


CBT Associates, which runs 6 clinics in the GTA, uses validated scales to measure outcomes, thereby monitoring the quality of their therapists’ work. Some online services are posting their therapists’ ratings, empowering patients with provider reviews – Uber meets psychotherapy.


  1. Internationally, some countries have experimented with providing information directly to patients and their families, beyond the reach of industry and research biases. In the UK, as an example, mental health information is available on the National Institute for Health and Care Excellence’s website. Quick thought: wouldn’t it be nice for Canada to have a NICE?


I suspect that Arrow would think so.


 (Many thanks to Paul Tuns for calling my attention to some of the articles referenced in this Reading.)

Reading of the Week. Every week I pick articles and papers from the world of Psychiatry. 

Dr. David Gratzer