Reading of the Week: Bipolar & Med Adherence – the New Journal of Affective Disorders Study; Also, Sleep (QT) and Sheff on Involuntary Treatment (NYT)

From the Editor

You wrote a prescription, but did he actually take the medications? For those with bipolar disorder, pharmacotherapy is an essential part of care. Studies have noted poor adherence. 

To date, though, there hasn’t been a big cohort study. And there are good questions to ask: what drugs are more linked with adherence? Who is more likely not to take the medications? In a new paper just published in the Journal of Affective Disorders, Dr. Jonne Lintunen (of the University of Eastern Finland) and his co-authors attempt to answer these questions. They draw on Finnish data, covering more than three decades and including over 33 000 patients. “The majority of patients with bipolar disorder do not use their medications as prescribed.” We consider the paper and its clinical implications.

In the second selection, Dr. Michael Mak (of the University of Toronto) comments on sleep in a new Quick Takes podcast interview. In this sleep “update,” we talk about meds, CBT, and the mobile apps that he recommends to patients and their families. We also explore the history of sleep medicine and mull the growing role apps and wearables are playing in both diagnosis and therapy. “The lines between sleep, health, and mental health in general are blurred.”

In the third selection, author David Sheff talks about his son’s addiction and recovery – and involuntary treatment. In a New York Times’ essay, he notes the challenges of engaging those with substance problems. He sees several ways forward, including involuntary treatment. “Many people in the traditional recovery world believe that we must wait for people who are addicted to hit bottom, with the hope that they’ll choose to enter treatment. It’s an archaic and dangerous theory.”


Selection 1: “Non-adherence to mood stabilizers and antipsychotics among persons with bipolar disorder – A nationwide cohort study”

Jonne Lintunen, Markku Lähteenvuo, Antti Tanskanen, et al.

Journal of Affective Disorders, 20 April 2023  Online First

Non-adherence to medications in bipolar disorder is a common clinical problem. Its prevalence estimates vary from 20% to 60% with a median of 40%. It is associated with poor clinical outcomes, such as increased risk of relapse and hospitalizations, suicides, and mortality. In addition, because of hospitalizations and the increased need for inpatient care, non-adherence increases treatment costs significantly.

The prevalence estimates of non-adherence vary significantly, mostly due to different research methods and heterogeneous patient samples. Studies that base their estimations on patients’ self-reported drug use are problematic due to self-reporting bias and limited sample sizes. To the best of our knowledge, there are only a few previous studies that utilized larger cohorts, but these only included specific patient groups (combat veterans) rather than nationwide cohorts…

So begins a paper by Lintunen et al.

Here’s what they did:

“Nationwide sample of persons diagnosed with bipolar disorder during 1987–2018 were identified from registers. Dispensings of their electronic prescriptions during 2015–2018 were followed up to define rates of primary non-adherence. Primary non-adherence was defined as having at least one non-dispensed mood stabilizer or antipsychotic prescription during 2015–2018. In a broader definition, non-adherence was defined as having ≥ 20% of mood stabilizer and/or antipsychotic prescriptions non-dispensed. Adjusted logistic regression was used to assess risk factors for non-adherence.”

Here’s what they found:

  • “The total cohort included 33 131 persons.”
  • Demographics. The mean age was 43.8 years and the majority was female (58.0%).
  • Illness experience. Many had been diagnosed in the past 3 years (38.5%) with no hospitalizations (64.9%).
  • Prescriptions. 63.1% had benzodiazepines and 68.0% had antidepressants prescribed to them.
  • Non-adherence. “59.1% had at least one non-dispensed mood stabilizer or antipsychotic prescription during the four-year follow-up of prescriptions and their dispensings.” Also, “When non-adherence was defined as having ≥ 20% of mood stabilizer and/or antipsychotic prescriptions non-dispensed, 31.0% were non-adherent.” !!
  • Mood stabilizers. “61.8% had at least one mood stabilizer prescription. Of all mood stabilizers, 13.7% of the prescriptions were non-dispensed… Lithium had the lowest (11.3%…) and valproic acid had the highest (14.8%…) proportion of non-dispensed prescriptions.”
  • Antipsychotics. “88.6% had at least one antipsychotic prescription. Of all antipsychotics, 16.0% of prescriptions were non-dispensed… Clozapine had the lowest amount of non-dispensed prescriptions (9.0%…) and asenapine prescriptions were most often non-dispensed (31.4%…).”
  • “Young age, recent bipolar disorder diagnosis, multiple hospitalizations due to bipolar disorder, and use of benzodiazepines or antidepressants were associated with an increased risk of non-adherence.”

A few thoughts:

  1. This is a good study, drawing on a big database.

  2. A three-word summary: adherence was problematic.

  3. Ouch.

  4. A summary in two sentences: “Approximately 60% of the persons with bipolar disorder were non-adherent to mood stabilizers or antipsychotics at least once over a period of four years based on their prescription-drug dispensings. Moreover, a third of the cohort was non-adherent to ≥ 20% of their mood stabilizers/antipsychotics.” 

  5. Two medications stood out for their adherence: clozapine and lithium. The authors wonder why, noting that both require careful follow-up and blood work. But they also see advantages to them. “Their superior effectiveness may explain good adherence: lithium is the most effective mood stabilizer for bipolar disorder and it prevents both manic and depressive episodes…” The authors describe clozapine as the best antipsychotic.

  6. The clinical implications? There are many. Start here: we should probably spend more time with patients discussing their experiences with medications. 

  7. And, yes, lithium and clozapine are underappreciated medications.

  8. Like all studies, there are limitations. The authors note several, including “purchasing a drug from a pharmacy does not necessarily mean using the drug as prescribed and thus the actual non-adherence rate could be even higher.”

The full Journal of Affective Disorders paper can be found here:

Selection 2: “The big sleep update”

Michael Mak

Quick Takes, April 2023

In a recent study involving almost 90,000 people, sleep problems were reported by 80% of those with mental disorders. What should you be prescribing? What to think of newer meds? What are other options? In this episode, I speak with Dr. Michael Mak, a CAMH psychiatrist and sleep medicine specialist.  

We highlight from the discussion:

On the most common problem you hear as an inpatient psychiatrist

“Insomnia. Symptoms: problems falling asleep or staying asleep.”

On sleep meds

“In terms of new treatments for insomnia disorder, this is an exciting time. We have a whole new family of insomnia treatments: dual orexin receptor antagonists. In narcolepsy, patients are irresistibly sleepy – the hallmark symptom of that condition. They’re sleepy all the time and it’s unquenchable. When we study these patients, we know that they have a deficit of a neurotransmitter called orexin. Orexin is the main neurotransmitter that promotes alertness during the daytime for all folks. So chemists came up with the idea of blocking that transmitter and its receptor to see if it would induce sleepiness. It does. We have medications that have this exact mechanism and it shows great promise because, in comparison to older treatments, the side effects seem to be far more tolerable. There’s less risk of addiction and tolerance, but also it doesn’t seem to have that impairment to cognition the next day.”

On therapy

“At the end of the day, the best treatment for insomnia is not medications, it’s therapy, namely cognitive behavioural therapy for insomnia. And the reason why that’s the best treatment: it’s been shown to be equally as effective as any sleeping pill in existence and the gains are durable – meaning that when people complete the course of CBT for insomnia, the symptoms tend not to return.”

On apps for sleep

“Sleepio, CBT-i Coach, Sleep Ninja and Somryst. The one that’s easiest to access because it’s free: CBT-i Coach.”

The above answers have been edited for length.

The Quick Takes podcast can be found here, and is just over 15 minutes long:

Selection 3: “My Son Was Addicted and Refused Treatment. We Needed More Options.”

David Sheff

The New York Times, 12 April 2023

Fifteen years ago, I was the father of a child who was living on the street, addicted to meth, opioids and other drugs. My son was slowly dying.

When he was missing, I scoured neighborhoods where I knew he hung out. Mostly I searched in vain, but I found him a few times and tried to persuade him to enter a treatment program. He was unwilling to get help. He became angry and belligerent. He accused me of trying to control him. He insisted he was fine and said he could stop using on his own if he wanted to, but he didn’t want to. Once he was 18, I couldn’t force him. He had to decide for himself — and yet he was in no condition to do so. ‘I was completely out of my mind, unable to make rational decisions,’ he says now.

So begins an essay by Sheff.        

He argues that safety should come first. “Ideally, people with addiction would seek care. But waiting for a person to choose treatment for a disease that affects rational thought can be catastrophic, now more than ever. The ubiquity and lethality of street drugs such as fentanyl and fentanyl mixed with xylazine, a veterinary tranquilizer, mean that many people with substance use disorders are in grave and imminent danger, and most cannot simply quit on their own.

“This is excruciating for people with loved ones addicted to drugs. I spent years in abject terror waiting for the phone to ring in the middle of the night, afraid of being told, ‘Mr. Sheff, we have your son. He didn’t make it.’”

He reviews the literature:

  • He quotes Keith Humphreys (of Stanford University): “The fashionable rhetoric is that mandating people doesn’t work, but evidence points the other way.” 
  • “A study published in The Journal of Substance Abuse Treatment in 2005, followed patients one and five years after voluntary and court-mandated treatment. It concluded that ‘contrary to popular belief,’ when drug users mandated to treatment are compared with people who sought treatment themselves, those who were mandated had similar results related to drug use outcomes and reductions in crime ‘or sometimes better than those achieved by voluntary patients.’”
  • “The National Institute on Drug Abuse says the evidence for compulsory treatment is mixed. ‘Creating a climate that encourages and supports people to seek treatment voluntarily and provides access to evidence-based treatment methods is critical,’ the group said in a statement. ‘When that fails to happen, systems and organizations may begin to look to coerced treatment as an alternative.’”

In the essay, Sheff champions several ideas, including safe consumption sites. “Sites like these are greatly underfunded and technically illegal. We need more of them. Last year, 700 overdoses were reversed at New York’s OnPoint overdose prevention centers, and trained staff members were able to get some people to enter treatment.”

But Sheff feels that some need a more coercive approach. He discusses his son’s journey: “He used dangerous drugs for 10 years before he went into a program that finally helped him. He didn’t want to go, but he broke into his mother’s house and was about to be arrested. A sympathetic police officer gave him a choice between rehab or jail. He chose rehab. If he hadn’t been impelled, he says (and I believe), he probably wouldn’t be alive today. There was a time I didn’t think he would make it to 21. He turned 40 this year…”

He recognizes, however, the limitations. “One of the major problems with involuntary treatment is the poor quality of many programs. Many people forced into treatment are not given evidence-backed care. They are left to painfully detox without access to medications that can make the process easier and likely more effective. They are often not treated with respect. Many are threatened, blamed and badgered. And if people’s experiences are negative, that could make them less likely to try treatment in the future.”

A few thoughts:

  1. This is a well written essay.

  2. We may agree or disagree with the author, but we must recognize his experience as a family member of a person who struggled with substance use.

  3. Involuntary treatment is highly controversial – though much in the news as of late, with both the provinces of Alberta and British Columbia weighing proposals.

  4. Involuntary treatment is sometimes mentioned as a way of responding to violence on public transit systems like the TTC. Past Readings have considered that issue, including a Globe and Mail essay by Dr. Sandy Simpson (of the University of Toronto). You can find it here:

  5. In the coming weeks, we will return to involuntary treatment, including papers that offer different perspectives.

  6. As is always the case, the Reading of the Week welcomes letters to the editor. Agree with Sheff? Disagree? Please consider putting the pen to paper.

The full NYT essay can be found here:

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

1 Comment

  1. As the mother of a daughter with schizophrenia who doesn’t have a substance use disorder, I’d like to comment on how the current mental health system makes it more likely that people like her will go on to develop one. My criticisms are followed by suggested improvements.

    1. Problem: Lack of public mental illness literacy campaigns means that people developing schizophrenia and the community around them remain dangerously ignorant about this disorder and the best steps to take when symptoms appear. This lack of basic knowledge contributes to people remaining untreated for too long and they go on to self medicate with street drugs.

    Suggestion: Promote public mental illness awareness campaigns that include schizophrenia.

    2. Problem: Except perhaps in EPI programs, professionally facilitated psycho-education programs for clients with schizophrenia have mostly disappeared. (This psycho-education used to exist in Vancouver in the now long defunct UBC Schizophrenia Day Program where my daughter and her friends received relevant psycho-education and learned to understand, accept and manage as best they can their severe disorders.)

    Suggestion: Develop professionally delivered psycho-education for clients with severe mental illnesses.

    3. Problem: While not offering appropriate psycho-education, increasingly services are being provided by peers. Neither the Mental Health Commission of Canada nor BC required that peer training include any information about mental illnesses like schizophrenia:
    Most psychosocial rehabilitation programs at my daughter’s community mental health team are provided by peers. The most heavily promoted program is the Hearing Voices Network (HVN). This movement was initiated by psychiatrist Dr. Marius Romme who has stated that antipsychotic medications interfere with processing the meaning of the voices. The HVN Study Group focuses on approaches promoted by Mad in America; while no longer publicizing the names of the people whose beliefs the group studies, this link to Will Hall remains. Will Hall is famous for guiding people to get off of antipsychotic mediations:
    It’s also a problem that programs combine people who don’t have a SUD with those who do.

    Suggestion: Improved the training of peer support workers. In fact, use them to address the problem of the underutilization of clozapine since peers could help people get to necessary blood tests. Ensure that peers know they should never undermine medically necessary treatments.

    4. Problem: Mental health acts across the country have been influenced by the psychiatric survivor movement and misguided ideas about social justice. They have made access to involuntary psychiatric treatment almost impossible in many places.

    Suggestion: Psychiatrists can offer much needed public understanding about why some people need access to involuntary treatment. This article by Ontario psychiatrists is so helpful. I just wish it had appeared in the Globe and Mail instead of a publication with a much smaller readership:

    5. Problem: Service providers too rarely cooperate with family caregivers providing necessary support to family members living with schizophrenia. This means that the providers are missing out on information that can lead to the best medical and psychosocial rehabilitation recommendations.

    Suggestion: Improve training of service providers about why and how to work cooperatively with family caregivers. My family has been unusually lucky in mostly having service providers who have wanted to cooperate with us. It’s made all the difference.