Schizophrenia and Impaired Cardiovascular Fitness

Schizophrenia and Impaired Cardiovascular Fitness

We’re pleased to announce Randall’s work has been released in a recent publication in the journal Psychiatric Research:

Studies show that individuals with schizophrenia have impaired cardiovascular fitness (i.e., low peak aerobic power (VO2peak)). It is speculated that antipsychotics with adverse cardiovascular and metabolic profiles, in particular clozapine, have a significant impact on VO2peak. In this cross-sectional study, we examined whether exposure to clozapine was associated with further reduced VO2peak compared with non-clozapine antipsychotics. Thirty participants with chronic schizophrenia or schizoaffective disorder were divided into clozapine and non-clozapine groups. Mean daily doses of antipsychotics were standardized to chlorpromazine equivalents and haloperidol equivalents for antagonism of alpha1– and alpha2-adrenergic receptors. Participants completed an incremental-to-maximal symptom-limited exercise test on a cycle ergometer for the assessment of VO2peak. The clozapine group demonstrated significantly lower VO2peak than the non-clozapine group. Haloperidol equivalents for alpha-adrenergic receptor antagonism, but not chlorpromazine equivalents, demonstrated significant inverse associations with VO2peak. The clozapine group had a significantly higher amount of antagonistic activity at alpha-adrenergic receptors than the non-clozapine group. In conclusion, exposure to clozapine was associated with further reduced cardiovascular fitness, which may be explained by the drug’s greater antagonistic activity at alpha-adrenergic receptors. Cardiovascular fitness needs to be promoted in individuals treated with antipsychotics, particularly clozapine, to prevent the risk of cardiovascular disease and mortality.

Kim DD, Lang DJ, Procyshyn RM, Woodward ML, Kaufman K, White RF, Honer WG and Warburton DER. Reduced cardiovascular fitness associated with exposure to clozapine in individuals with chronic schizophrenia. Psychiat Res. 2018;262:28-33.

Orphan Patients: A Case Series of Patients With Treatment-Resistant Psychosis Requiring Alternatives to Clozapine

Dr. Randall White at the APA IPS in Chicago

Dr. Simon Bow presented a research poster at the The Canadian Psychiatric Association’s 68th Annual Conference, September 27-29, 2018 in Toronto, and Dr Randall White presented it at the American Psychiatric Association Institute on Psychiatric Services, October 4-7, 2018 in Chicago. Here is the research represented on the poster:

Abstract:

Background: Clozapine is the gold standard for managing treatment-resistant psychosis (TRP). Despite superior efficacy, some patients do not tolerate or stop it, and research on this population is scarce. Here we describe inpatients with TRP, treated at the British Columbia Psychosis Program (BCPP) from 2012 to 2017, who required alternative interventions to clozapine.

Methods:

In a retrospective analysis of 275 patient records, 78 with TRP were not receiving clozapine at discharge. Data collected included demographics, standardized ratings (Positive and Negative Syndrome Scale [PANSS], Social and Occupational Functioning Assessment Scale [SOFAS], Gut and Psychology Syndrome [GAPS], Clinical Global Impression [CGI]), comorbidities, reasons for clozapine discontinuation, and alternative treatments.

Results:

A total of 85% of patients had previously taken clozapine; the remainder were not offered or refused it. Reasons patients could not have a clozapine trial at BCPP included a history of myocarditis (13%), agranulocytosis (5%) or neutropenia (8%), refusal (18%), poor compliance (12%), poor response (6%), or other severe side effects [JT1]. Antipsychotics at discharge included oral monotherapy (40%), injectable monotherapy (15%), oral polypharmacy (19%), or oral-injectable combination (23%). Additional medications included mood stabilizers (45%), antidepressants (26%), and/or sedative hypnotics (26%). Electroconvulsive therapy (ECT) was used in 13%. Psychotherapy showed benefit in 17%. Mean PANSS total score reduction was 18% and CGI scale score reduction, 1.3, with 32% and 5% of patients achieving response and remission, respectively.

Conclusion:

Clozapine may not be feasible for many reasons, but we have documented several alternatives for managing TRP. We are continuing subgroup analyses, along with a comparator group successfully started on clozapine during admission. These results may inform clinical decision making in this difficult-to-treat population.

Dr. Simon Bow at the CPA meeting in Toronto

Dr. Simon Bow at the CPA meeting in Toronto

Orphan patients research poster

Download the poster here: Dr. Randall White Final 2.

Join Me at the 5th Annual Music For The Hearts Concert

Music For The Hearts Concert

Want to show support toward mental health and make a difference? Interested in a night of live performances and food?

Join me for the 5th Annual Music For The Hearts (MFTH) charity event on Saturday, September 15th. It will be a night of celebrations, with music, great talent, and health advocacy, at the Evergreen Cultural Centre.

MFTH is a non-profit charity dedicated to supporting various causes that benefit health care in Metro Vancouver. They are made up of a group of university students, who have combined their interest in music with their passion for health. Their mission is to organize annual fundraising musical concerts to implement positive changes for our community.

This year, MFTH’s committee members unanimously decided to further contribute to mental health, specifically severe mental illness. All funds raised from ticket sales and further contributions will be donated to BC Schizophrenia Society (BCSS) in order to help families in need.

Schizophrenia is a form of severe mental illness that, for most, is a life-long, debilitating disease. Despite its complexity, it is still manageable. However, the costs associated with seeking treatment and other means of aid are quite expensive. By collaborating with BCSS, all their donations will be used to directly support those coping with schizophrenia, educate the public, and contribute to research and awareness for better medical services.

Don’t miss out on an event that supports an important cause close to my heart!

Buy your tickets today for $15.

12th Annual Pacific Psychopharmacology Conference

12th Annual Pacific Psychopharmacology Conference Banner

Dr. Randall White will be co-chairing the 12th Annual Pacific Psychopharmacology Conference which will will take place on September 21st, 2018 at the Pinnacle Hotel Harbourfront, Vancouver. This popular annual conference features a wide range of topics presented by renowned speakers, with a focus on pharmacological interventions for people with mental health problems.

Key Speakers at the 12th Annual Pacific Psychopharmacology Conference

One of the keynote speakers will be Dr. Don Goff., an expert on schizophrenia from New York University.

12th Annual Pacific Psychopharmacology Conference Dr. Jon Goff

Some of Dr. Goff’s recent publications include:
1) “The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project.” Read it here.

2) “Association between catechol-O-methyltransferase genetic variation and functional connectivity in patients with first-episode schizophrenia.” Read it here.

3) “Association of Hippocampal Atrophy With Duration of Untreated Psychosis and Molecular Biomarkers During Initial Antipsychotic Treatment of First-Episode Psychosis.” Read it here.

Another highlight of the event will feature Dr. Lakshmi Yatham, the Regional Head of Psychiatry and Regional Program Medical Director for Vancouver Coastal Health and Providence Healthcare. He is also a Professor in the Department of Psychiatry at the University of British Columbia.

12th Annual Pacific Psychopharmacology Conference Dr. Lakshmi Yatham

Dr. Lakshmi Yatham’s presentation will cover the CANMAT & ISBD Guidelines for the Management of Bipolar Disorder. Read and learn more about the recent publication of the CANMAT bipolar disorder treatment guidelines here.

Join Dr. Randall White and many other experts this September for the 12th Annual Pacific Psychopharmacology Conference, and register today! 

Genetic Counselling Research at the BC Psychosis Program

By Prescilla Carrion and Ashley DeGraaf

Genetic counselling is, according to the National Society of Genetic Counsellors, the process of helping people understand and adapt to the medical, psychological, and familial implications of the genetic contributions to disease. Psychiatric genetic counselling is a specialized field of genetic counselling that aims to help people with a personal or family history of mental illness understand the causes so that they may better adapt to and cope with the illness. This involves providing information about the environmental and genetic causes of mental illness and discussing evidence-based strategies for promoting mental health such as lifestyle modifications, nutrition, managing stress, and the role of medications. As this conversation unfolds, the genetic counsellor addresses the psychological impact of the illness and the information shared, provides support and suggests resources. If desired by the patient, the genetic counsellor can also discuss the chances of recurrence of the disorder in the family

Psychiatric genetic counseling services in British Columbia are available to all residents of British Columbia with a personal or family history of mental illness through The Adapt Clinic in the Department of Medical Genetics at BC Women’s Hospital and are fully covered by the BC Medical Services Plan. In 2015, an evaluation of The Adapt Clinic by Inglis et al. demonstrated that psychiatric genetic counseling enhances empowerment and self-efficacy in people with psychiatric disorders and their family members. Empowerment can be defined as one’s sense of control over an illness and hope for the future, while self-efficacy is one’s confidence in the ability to manage an illness. In other words, the study suggests that psychiatric genetic counseling gives patients and family members a greater sense of control over the illness and hope for the future, as well as increased confidence in managing their illness.

Prescilla Carrion and Ashley DeGraaf are certified genetic counselors at UBC Hospital who have been integrated into the BC Psychosis Program to provide psychiatric genetic counseling to patients and their family members through research.  Prescilla Carrion is a UBC genetic counselor and clinician investigator within the UBC Institute of Mental Health Centre for Care and Research. She is leading this research aimed to build evidence for psychiatric genetic counseling among patients with treatment-resistant psychosis and their family members.  As the principal investigator on the study titled “Evaluating the value of integrating genetic counseling into mental health services,” she is using validated clinical outcome measures to assess the impact of psychiatric genetic counseling in this population and aims to identify whether similar increases in empowerment and self-efficacy in mental health management can be observed and maintained as compared to the findings in the evaluation of The Adapt Clinic. She has also developed a survey, in collaboration with Drs. Jehannine Austin and William Honer, to assess clinician perspectives on how genetic counseling may have impacted the care they provide to their patients and interactions with the family members with the goal of understanding how best to engage mental health clinicians in recommending genetic counseling for their patients/clients. This research will provide the first outcome data on the effect of genetic counseling for inpatients with treatment-resistant psychosis, and on outcomes of genetic counseling when integrated into a multidisciplinary mental health program outside of a medical genetics clinic setting.

If you have a personal or family history of mental illness and are interested in psychiatric genetic counseling, you may self-refer to The Adapt Clinic by calling Angela Inglis at 604-875-2726, or Emily Morris at 604-875-2000 ext. 6787, or you may request a referral through your family doctor, psychiatrist, or other mental health clinician. A searchable directory of genetic counselors and genetic counseling services in Canada and the United States is available through the Canadian Association of Genetic Counsellors and the National Society of Genetic Counselors.

Clinical Trials Test a Psychedelic Drug as a Cure for Depression

The largest-ever clinical trial of a psychedelic drug will soon begin in Europe and North America to find a cure for depression.

Psychedelic Drug Chemistry

The psychedelic drug is psilocybin – the active ingredient in magic mushrooms. The target is treatment-resistant depression. In the episode 27 of the After On Podcast, listeners are introduced to George Goldsmith and Katya Malievskaia. They are a married couple whose startup – Compass Pathways – will soon launch the largest triple-blind clinical trial ever of a psychedelic drug. The drug is psilocybin, an active ingredient derived from psychedelic mushrooms. And the condition is treatment-resistant depression. A condition that affects over a hundred million people worldwide. The term “treatment-resistant” implies, it lacks a cure.

While this may sound implausible, the individuals that have been drawn to this company’s work is quite remarkable. Their Board of Directors includes Thomas Lonngren, who spent ten years running Europe’s equivalent of the FDA (the European Medicines Agency). Also on their board is the former Chief Medical Officer of Bristol Meyers Squibb – one of the world’s largest pharmaceutical companies. In addition, they have raised roughly $20 million for their company from some extremely savvy investors.

This podcast showcases Katya and George’s their expansive knowledge in medical research. Their efforts are focused heavily on the drug approval process. Also, they have designed their trial in consultation with the top drug regulators of multiple countries.

Psychedelic drug as a potential cure for treatment-resistant depression

Katya and George express their strong sentiments against treatment-resistant depression. They describe how the illness has severely afflicted an individual very dear to them. Listeners will learn about Katya and George’s backgrounds, along with their motivations. As well as, the trial they are architecting and their company: Compass Pathways. The discussion the long clinical history certain psychedelics and other recreational drugs have had, and the major promise several of them are now showing against a diversity of afflictions.

Click here for some helpful resources on how to support individuals with depression or other mental health issues.

Understanding Schizophrenia and Psychosis with Randall White

May 24th marks the National Schizophrenia and Psychosis Awareness Day.

On Thursday May 24th, Dr. Randall was featured on Breakfast Television in a segment to change how individuals talk and think about Schizophrenia and Psychosis.

Explaining the difference between Schizophrenia and Psychosis.

Psychosis is a generic term of a mental disorder. It occurs in several conditions, and schizophrenia is one of them, in addition to bi-polar disorder along with other brain diseases. It is a rupture with reality. People with psychosis are often paranoid with thoughts of other people trying to harm them. Other symptoms include hearing voices and as a result these individuals do not perceive the world as others typically do. They perceive the world in an augmented reality, which can be extremely scary. Also with schizophrenia, there are components of basic human function that are taken away from individuals. For example, they can lose the ability to connect with people emotionally, begin to feel withdrawn, or even lose certain cognitive abilities. These include but are not limited to the ability to plan for the future and memory function.

Highlighting common misconception about aggression for individuals with Schizophrenia and Psychosis.

There is a common misconception that people with psychosis are dangerous and aggressive or violent. While that can happen, it is actually pretty rare. People with chronic mental illness are more likely to be victims than perpetrators.

Treatment and Rehabilitation plans for patients with Schizophrenia and Psychosis and their families.

As far as treatment goes, medication is used to control the voices, scary ideas, and the anxiety. However, a patient’s recovery process is also dependent on additional factors beyond the medicinal treatment. In order for individuals to regain their basic function and ability to relate to other people, services such as counselling and cognitive remediation are crucial to aid in the recovery process. This can help with patients’ memory and problem solving skills. Another big factor is support from peers and families. Mental illnesses like Schizophrenia and Psychosis can affect entire families. It is crucial to get as much support from the whole family, if possible. As this has been shown to significantly impact the individuals healing process.

Click here for a list of helpful resources and organizations for individuals impacted by Schizophrenia and Psychosis.

What Happens to First-Episode Patients After 5 Years?

Following a first episode of psychosis, patients always want to know when they can stop taking medication. Adverse effect such as weight gain or sedation may play a role, but the need to take a daily pill or receive an injection may be inconvenient or stigmatizing no matter the side effects. Existing evidence suggests a high risk of relapse during the first 5 years if medication is discontinued, up to a 5-fold compared to continuous medication treatment, although longer-term outcomes remain uncertain. Two new studies provide further evidence about outcomes longer than 5 years.

In 2003, Drs. Eric Chen, Bill Honer and collaborators in Hong Kong initiated a randomized trial with 178 first-episode patients in several clinics. To be eligible, patients had to be free of positive symptoms during at least 12 months on medication; the mean was 21.9 months. They then received either quetiapine 400 mg daily or placebo for a year or until relapse. Following the RCT, the patients returned to the community for usual clinical care.

Ten years later, the research team followed up the 178 patients; they performed a chart review on all and interviewed 142 of them. A poor outcome was defined as death by suicide, need for clozapine treatment, or persistent positive symptoms measured by the Positive and Negative Syndrome Scale (PANSS). Of 138 patients with adequate follow-up data, 110 were taking antipsychotic medication; the mean dose was 355 chlorpromazine equivalents.

Of those subjects assigned to a year of quetiapine treatment in the RCT 10 years before follow-up, 21% had a poor outcome; of those assigned to placebo in the RCT, 39% had a poor outcome. The relative risk was 1.84 (P = 0.012). Six patients died by suicide and 11 required clozapine; the incidence of these outcomes individually did not significantly differ between the groups. The investigators also found that among subjects originally assigned to medication discontinuation, i.e. placebo, relapse of psychosis during the first 2-3 years of diagnosis seemed to mediate the elevated risk of poor outcomes.

In Finland, Dr. Jari Tiihonen and his group performed a 20-year follow up on all persons hospitalized for schizophrenia for the first time during 1972–2014. Given that everyone in Finland has health and pharmacy services recorded in a national data registry, it was possible to determine who was readmitted to hospital and who filled prescriptions for antipsychotics. Based on this data, the researchers looked at whether subjects were taking medication or had been rehospitalized at various time points and then classified them as either antipsychotic users or nonusers. I suggest readers go to the original article to gain a full understanding of the methods.

Treatment failure was defined as rehospitalization or death. The table below shows the interesting finding that patients who continued antipsychotic treatment throughout the follow-up period had the lowest risk of relapse or death, but those risks rose as a function of the duration of treatment preceding discontinuation. In other words, stopping medication after several years of stability may be more associated with poor outcome than stopping it very soon after the first episode. However, compared to those who were treated continuously, the groups that discontinued treatment at any interval had a higher rate of poor outcome.

Adjusted Hazard Ratio chart

FIGURE: Adjusted hazard ratios as a function of duration of antipsychotic use prior to discontinuation.

The number of deaths was relatively small, but available data allowed the calculation of hazard ratios in 3 matched groups: those who discontinued antipsychotic treatment within the first year, those who remained on antipsychotics throughout, and those who did not use antipsychotics.  In 3057 subjects, 91 deaths occurred; compared with continuous antipsychotic users, nonusers had a 214% higher risk of death (hazard ratio, 3.14; 95% CI, 1.29–7.68), and those who discontinued within a year had a 174% higher risk of death (hazard ratio, 2.74; 95% CI,1.09–6.89).

These studies have important limitations, given their retrospective nature and the lack of details about important outcomes related to function and comorbidities. Nonetheless, they bring new understandings to the role of antipsychotic therapy after the first few years of psychotic illness: patients who go untreated have a higher risk of remaining psychotic and of dying. But the finding that discontinuation after 5 or more years of antipsychotic therapy is highly associated with relapse suggests that stopping medication in chronic patients is risky.

References

Hui CLM, Honer WG, Lee EHM, Chang WC, et al. Long-term effects of discontinuation from antipsychotic maintenance following first-episode schizophrenia and related disorders: a 10 year follow-up of a randomised, double-blind trial. Lancet Psychiatry. 2018;5(5):432-442.

Tiihonen J, Tanskanen A, Taipale H. 20-Year nationwide follow-up study on discontinuation of antipsychotic treatment in first-episode schizophrenia. Am J Psychiatry. Published online Apr 6, 2018:

Research Study: Health Professional Mothers of Adult Children with Schizophrenia

Research Study

The University of New England School of Health is looking for health professionals to participate in a research study. The health professional must be a mother of an adult child who has been diagnosed with schizophrenia.

The purpose of the research study is to look at these mothers’ stories to see how they have negotiated care for adult children with schizophrenia.

Participation will involve:

  • Answering questions on the phone to see if you meet the inclusion criteria
  • Signing a consent form with your agreement to participate (with the proviso that you can withdraw at any time for any reason)
  • Participating in an interview in which the audio will be taped.

The research is conducted by PhD student Debra Klages from the School of Health at the University of New England.

For more information about participating in this study, please contact Debra Klages by email at dklages@myune.edu.au. The principal investigator Professor Kim Usher may also be contacted by kusher@une.edu.au.

 

Ms. Debra Klages RN, BScN, Cert Case Mgmt., M Adv Nurs Prac (Mental Health), MACN

Study Title: Health Professionals as Mothers of Adult Children with Schizophrenia

This project has been approved by the Human Research Ethics Committee of the University of New England (Approval No HE17-028, Valid to 23/03/2019)

A Family Caregiver Listens to Gerrit van der Leer

Gerrit van der Leer

By Susan Inman

Gerrit van der Leer, BC’s Director of Mental Health and Substance Use, was the closing speaker at the recent sold-out conference at Vancouver General Hospital on Bringing Cognitive Remediation to British Columbia. Van der Leer has decades of experience in developing recovery-oriented programs for people with severe mental illnesses; these include BC’s Early Psychosis Intervention (EPI) programs and Assertive Community Treatment teams.

A ground breaking resource that’s been developed for the EPI programs is the Dealing with Psychosis ToolkitIn the section on “Understanding Cognition,”the Toolkit contains essential information about the common cognitive losses experienced by people with psychotic disorders. These problems include difficulties with attention, learning and memory, critical thinking skills (e.g., planning, organizing, problem solving, abstract thinking) and social cognition. Too rarely do clients, families or many clinicians learn about these cognitive problems.

The Toolkit also contains numerous cognitive adaptation strategies that can help people manage these cognitive problems. Adaptation strategies are a useful component in cognitive remediation (CR) programs, but CR programs have a much broader mandate. Much of the conference described common components of evidence-based CR programs. These components include intensive, supervised computer based work designed to improve cognitive functioning in areas such as processing speed and concentration, and also include professionally facilitated small group discussions. These sessions operate as bridging mechanisms designed to assist clients to bring their new skills to meeting the challenges of daily living, education and work.

Van der Leer expressed his support for incorporating cognitive remediation into BC’s psychosocial rehabilitation services. He discussed the kinds of next steps that need to occur and reminded the audience that these had also been discussed earlier in the conference in a presentation by Dr. John Higenbottam and Dr. Tom Ehmann.   Policy documents need to be developed that address which populations should be included, what kinds of sites should be selected for delivery of services, which remediation programs should be used, how staff should be trained and how programs should be monitored for fidelity and outcomes.

Van der Leer also reminded audiences that cognitive remediation programs are basically inexpensive and relatively easy to implement.

We learned that BC’s new Ministry for Mental Health and Addictions is looking for input in developing a new whole-of-government approach for responding to mental health and substance use. There are vital roles for ministries involved with health, corrections, housing, education, transportation, and children and families to play in developing comprehensive strategies.

As a family caregiver, I’m hoping that certain key issues can be addressed. Here are just three of these issues:

  • BC (and Canada as a whole) needs improved mental illness literacy programs. Inadequate knowledge among the public leads to inadequate responses to psychotic disorders like schizophrenia and bipolar disorder. For instance, delay in treatment of psychosis leads to worse outcomes, and families play a crucial role in getting health care for their family member. Furthermore, inadequate psycho-education programs for clients lead to relapses that are expensive for the health care and criminal justice systems. People are better able to accept and manage their illnesses when they understand them.
  • Many programs training credentialed mental health clinicians do not require any science-based curriculum on psychotic disorders. This is one reason that clients, families and many clinicians have not been learning about the cognitive losses associated with these illnesses; it’s these losses that are considered to be a major factor in ongoing disability.
  • Though contemporary neuroscience and psychiatry no longer blame parents for the development of schizophrenia and bipolar disorder, this blame is still common among other clinical practices. It is an obstacle in creating the kind of cooperative relationships that need to exist between family caregivers and clinicians in order to best help people who develop these illnesses. Standards of training need to be raised. As well, mental health authorities need to provide professional development to help staff learn new ways of interacting with family caregivers.

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