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.

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.

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)

The B.C. Mental Health Act Protects My Daughter

The author of the original article, Susan Inman, wrote this piece for the Huffington Post from personal experience. Susan’s daughter has suffered from schizophrenia for the past 16 years, and Susan has seen first hand how involuntary hospitalization and medication have helped her daughter have years of stability.

Susan discusses how provisions in B.C’s Mental Health Act which protect people with severe mental illnesses are currently under attack. This came when a challenge was filed with B.C’s Supreme Court which states both inpatient and outpatient involuntary treatment are violations of people’s human rights. The challenge does not deal with involuntary hospitalisations, rather it proposes changes that would mean people can avoid involuntary treatment no matter how ill they are. Two of the plaintiffs themselves have received involuntary treatment.

Some may feel that the most morally responsible position is to allow people to choose whether they want to be treated, but Susan highlights how this ignores some vital information about psychotic orders. In psychosis, a person loses the ability to differentiate between what is real and what isn’t. Even as some of its symptoms begin to subside, people can be left with anosognosia, a brain-based inability to understand that they are or have been ill.

As Susan argues, mental illness policy changes can be dangerous when they ignore the impact of the most severe mental disorders, such as suicide, aggression or neglect of one’s most basic personal needs. In their challenge, the plaintiffs fail to address the consequences of the changes they propose on people with profound or life-threatening illness. Any policy changes of this nature must be looked at in depth, looking not only at the change itself but also the consequences that will follow.

Let us know your thoughts on the proposed changes to B.C’s Mental Health Act, join the discussion on our twitter page. Click here to read the full article.

This article previously appeared in Huffington Post Canada.  

Raloxifene as adjunctive treatment for chronic psychosis

Psychosis and mood symptoms are sometimes exacerbated  during times of hormonal flux in women such as postpartum and during menopause. Research from Australia has suggested that estradiol may ameliorate psychosis in women with schizoaffective disorder or schizophrenia. The same Australian team has recently published a randomized controlled trial of raloxifene in postmenopausal women with those diagnoses; raloxifene is an estrogen receptor modulator that may be safer than estradiol as it is less likely to provoke hormone-influenced cancers. However, it does entail an increased risk of thromboembolism.

The 56 subjects had a mean age of 53 years and a mean illness duration of 24 years, all were on antipsychotic therapy, and none was deemed at baseline to have elevated risk for thrombotic disease or evidence of reproductive cancers. They were randomly assigned to receive 120 mg of raloxifene or placebo for 12 weeks as cotreatment with their psychiatric medications; 8 patients were taking clozapine, 5 in the active treatment group. The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS); the investigators also monitored depression, movement disorder, cognitive function, and safety measures.

At the end of 12 weeks, the women receiving raloxifene had a significant reduction in the PANSS total and general scores, whether the diagnosis was schizophrenia or schizoaffective disorder; the PANSS positive and negative symptom subscales showed no significant improvement with raloxifene. Significantly more subjects who received raloxifene had a clinical response defined as a 20% reduction in PANSS total score (P = 0.01).  Measures of depression and cognition did not show any difference between the groups and adverse events were minimal; no thromboembolic events occurred in either group.

Raloxifene may help prevent osteoporosis and breast cancer, so it confers benefits beyond ameliorating symptoms of chronic psychosis. It has also been trialed in men cotreated with risperidone during an 8-week study in Iran; compared with placebo, the active treatment resulted in improvement in the PANSS total score and the negative and general subscale scores (2). Adverse effects did not occur more often with raloxifene, although the researchers admit that with longer-term treatment, gynecomastia and infertility would be possible which would greatly limit its utility in men.

References

1.Effect of adjunctive raloxifene therapy on severity of refractory schizophrenia in women: a randomized clinical trial. Kulkarni J, Gavrilidis E, Gwini SM, et al. JAMA Psychiatry. 2016;73(9):947-354. Abstract

2.Khodaie-Ardakani MR, Khosravi M, Zarinfard R, et al. A placebo-controlled study of raloxifene added to risperidone in men with chronic schizophrenia. Acta Med Iran. 2015;53(6):337-345. Full text

 

Twenty percent of schizophrenia may be treatment-resistant from onset

About 30% of people with schizophrenia do not have adequate response to antipsychotic medications other than clozapine. Treatment-resistant psychosis has no well-established predictors although early-onset psychosis and prolonged duration of untreated psychosis may be risk factors. The Genetics and Psychosis study based in South London, UK, enrolled 283 patients with schizophrenia-spectrum disorders in their first episode who underwent assessments including the Positive and Negative Syndrome Scale, Global Assessment of Functioning, and the Weschler Adult Intelligence Scale. The cohort had follow-up investigations 5 years after first assessment by means of the WHO Life Chart Schedule, intended for documenting the longitudinal course of schizophrenia.

Patients were determined to have treatment-resistant schizophrenia (TRS) if they were either treated with clozapine or failed to respond to 2 consecutive, adequate trials of non-clozapine antipsychotics. Remission of psychosis was defined as absence of overt psychotic symptoms for 6 months or more. The investigators classified the TRS as either early-onset or late-onset. Early onset TRS occurred when no remission occurred at any time whereas late-onset occurred when resistance developed after an interval of remission.

Of the original cohort, 246 or 87% had follow-up data. Four patients had died, and their mean age was significantly older than the cohort as a whole. In 33.7%, TRS had developed and their only distinguishing characteristic was a younger age of contact for treatment of psychosis: 25.2 years versus 27.9 years in the non-TRS group. Family history of psychosis, use of alcohol or cannabis, cognitive performance, and duration of untreated psychosis (DUP) did not differ between TRS and non-TRS groups. Those patients who were younger than 20 years at the time of first contact had an odds ratio of 2.49 for developing TRS, and men and Black people were also more likely to have TRS at follow-up.

About 70% of TRS patients had early-onset treatment resistance. Compared to the non-TRS group, those with early-onset TRS had a higher mean total PANSS score at baseline; 74% were male compared to 46% in the late-TRS group.

In the TRS cohort, about half the patients received clozapine, and they had on average a greater burden of total psychopathology and negative symptoms compared to the TRS patients who never received clozapine. The clozapine patients were also more likely to reside with family or friends.

According to the investigators, this is the largest first-episode cohort followed for onset of treatment resistance. They estimate that 23% of their patients had resistance to antipsychotic therapy from the onset of illness, and given the mean DUP of 4.5 weeks, which is quite brief, factors other than delayed treatment seem to be at play. If this study is generalizable, only a third of treatment resistance develops after the  onset of illness, and understanding that process could lead to prevention strategies. Furthermore, availability of biomarkers for TRS in early psychosis populations might help determine which patients would benefit from receiving clozapine immediately.

Lally J et al. Psychol Med. 2016;46(15):3231-3240. Abstract

Partnership: People with schizophrenia, family members and clinicians talk about schizophrenia

Schizophrenia is a long-term but treatable brain condition. 1 in 100 people worldwide live with schizophrenia.

Dr. Diane Fredrickson is a psychiatrist who treats psychosis-related conditions including schizophrenia.

Gerhart Pahl is the father of four sons—three of whom it turns out suffer from schizophrenia.

Bryn Ditmars has a form of schizophrenia known as schizoaffective disorder.

Schizophrenia occurs most commonly between people between the ages of 15-25. It is the result of physical and biochemical changes in the brain. Symptoms may include:

  • Disordered thinking
  • Changes in emotion
  • Bizarre behaviour
  • Catatonia
  • Paranoia
  • Hallucinations
  • Delusions

60% of people with schizophrenia live with their families. Recovery takes time, a team, medication, and a healthy lifestyle.

Research has improved with brain imagery, but a cause and cure are still unknown.

Statistics about schizophrenia and suicide:

  • 50% attempt suicide.
  • 10-15% of people commit suicide.
  • Self-harm is more common than harm to others.

50% of people with schizophrenia have anosognosis, a condition in which they don’t know they’re ill. Early psychosis intervention (EPI), early diagnosis and treatment improve outcomes.

Stigma contributes to discrimination, which limits access to education, housing and employment. The media contribute to perpetuating myths that create skewed perceptions and unfounded fears.

The B.C. Schizophrenia Society (BCSS) Partnership Program provides mental health literacy. To increase your knowledge, book a presentation.
Call 604-270-7841
Toll Free: 1-888-888-0029
Email: community@bcss.org

Dr. Xavier Amador Talk on Helping People with Mental Illness at Cambridge, MA

Dr. Xavier Amador
President and Founder
The LEAP Instititute
(Listen, Empathize, Agree, Partner)

Dr. Amador lays out pathways to build trust, heal relationships and partner with someone who is suffering from mental illness but is resisting help.

“I’m going to tell you a little bit about something that is very important to me from a professional perspective… but is also very personal. I have a brother with schizophrenia who really is the one who gave me the title for this talk and book by the same name: I’m not sick. I don’t need help.

“This is a very very common problem. I will talk about just how common it is”


Dr. Xavier Amador, founder of The LEAP Institute giving a public talk on how to help people with mental illness who don’t realize they are sick. Sponsored by the NAMI (National Alliance on Mental Illness) Cambridge Chapter. The lecture was given on the evening of October 2, 2012 at the Cambridge Public Library in Cambridge, Massachusetts.

For more information, visit leapinstitute.org.

Anosognosia

Anosognosia

“I think that’s exactly what he had. I believe that my son Chris, over the course of repeated breakdowns, lost his capacity to understand his illness so he went off his meds. That’s when we lost him for good. He never took meds again. He ultimately chose to take his life rather than take medication.” — Cathy Weaver, Austin, Texas

People with anosognosia have a real neurological condition caused by damage to the brain, most likely in the frontal and parietal lobes.

Because of this condition, they can’t recognize that they are sick.

Anosognosia is associated with many diseases.

Some people with strokes, brain tumours, Alzheimer’s disease, and Huntington’s disease suffer from this same lack of insight.

It’s very clear that about half the people with schizophrenia and roughly 40% of people with bipolar disorder have some degree of anosognosia. In other words, they don’t recognize their own illness. We recognize this for Alzheimer’s disease but we seem to have trouble recognizing that this is also common for people with schizophrenia and bipolar disorder.

Russell Weston is one tragic example. Mr. Weston came to Washington D.C. to “save the world from cannibals” and killed two Capitol Police officers while in this delusional state.

Weston was not taking medication because he did not believe he was sick.

County judge, Polly Jackson Spencer developed the first-of-its-kind outpatient commitment program in Texas. She saw the devastation caused when the severely mentally ill are too sick to seek treatment and end up trapped in a revolving door of incarceration, homelessness, hospitalization and victimization.

“You can’t simply tell someone who has a mental illness and is disorganized in their thinking, ‘Hey, you’ve got a doctor’s appointment in three weeks and it’s ten miles from here, these are the different buses you need to take to get there, and don’t forget to go’ and assume that they’re going to make that. That’s just not going to happen.” —Polly Jackson Spencer, County Judge

Judge Oscar Kazen supervises the day-to-day operations of Bexar County’s court-ordered outpatient treatment program. He meets regularly with patients, psychiatrists, and staff.

“When I sit in that little courtroom, down in the basement of that abandoned hospital, the guy who sits at the end of the chair—that mentally ill patient—didn’t have a choice. He didn’t wake up one morning and say ‘I want to lose my life, I want to lose my sanity.’ These people had no choice in the matter and it’s our responsibility to bring them back to sanity.” — Oscar Kazen, Judge

Anosognosia is the number one reason why people fail to seek treatment.

It’s up to the rest of us to make sure that they are able to get treatment.

Learn more about anosognosia at treatmentadvocacycenter.org

Video by the Treatment Advocacy Center.