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.

Benzodiazepines may increase the risk of death in people with schizophrenia

Patients with psychosis often accumulate medications during hospitalizations and changes in prescribers. The use of multiple medications, often with uncertain benefit, is called polypharmacy. The use of more than one antipsychotic is considered problematic and may increase the risk of adverse effects such as weight gain and diabetes, but other kinds of psychiatric medications often accumulate as well, including antidepressants and benzodiazepines. The latter are used for a variety of reasons, often for acute agitation in an emergency setting, but also for insomnia or chronic anxiety. They may be associated with tolerance, escalating dosage and dependence, although overall are considered safe medications.

Population-based studies from Finland and Denmark have revealed that patients with schizophrenia, however, may be at elevated risk for death when treated with a benzodiazepine.  Now the same has been found in a US cohort. Researchers from Ohio State University examined outpatients covered by US Medicaid, age 18 to 58 years old, who had received a diagnosis of schizophrenia during 2007 to 2009. They looked at prescription claims for benzodiazepines, antipsychotics, antidepressants and mood stabilizers from time of diagnosis through 2013. They then examined death certificate files for deaths among the 18,953 identified subjects and calculated hazard ratios for all-cause mortality, death from suicide and accidental poisoning, and death by natural causes.

Of 18,953 patients with schizophrenia, 3,476 received a benzodiazepine, and those subjects were more often Caucasian females who were separated or divorced. The top 3 benzodiazepines prescribed were, in order, lorazepam, clonazepam and alprazolam. In patients taking an antipsychotic, in comparison with those who had no added benzodiazepine, the adjusted hazard ratio after initiating a benzodiazepine was 1.48, i.e. a 48% increased risk of death during the time of cotreatment. For patients who received only a benzodiazepine and no antipsychotic or other medication, the adjusted hazard ratio was 3.08. The calculated mortality rate per 1000 person-years was significantly elevated in every examined combination of medications, e.g. for a mood stabilizer alone, or for an antidepressant plus an antipsychotic, when a benzodiazepine was added. Furthermore, the risks of death from suicide, accidental poisoning and natural causes were all elevated.

The investigators caution that this is an association, and that benzodiazepines cannot yet be implicated as a definite cause of premature mortality in people with schizophrenia. However, this evidence adds to existing epidemiologic findings to make the risk-benefit ratio of benzodiazepine prescription less favorable. The possible mechanisms behind the risk could be multiple, and the researchers mention lower mood and impulsiveness which may occur during benzodiazepine use along with withdrawal-related anxiety as factors that could elevate risk of suicide. As for natural causes, some evidence exists for heightened incidence of infectious diseases concomitant with benzodiazepine use. Prospective studies and larger epidemiologic investigations are required to understand this association, but prescribers should always keep in mind the maxim “do no harm” and attempt to eliminate unnecessary medications.

Reference

Fontanella CA, Campo JV, Phillips GS, Hiance-Steelesmith DL, Sweeney HA, Tam K, Lehrer D, Klein R, Hurst M. Benzodiazepine use and risk of mortality among patients with schizophrenia: a retrospective longitudinal study. J Clin Psychiatry. 2016;77(5):661-667. Abstract

Topirimate as augmentation for antipsychotic treatment

With modulating dopamine as the primary pharmacotherapeutic option to treat schizophrenia, we are left unable to adequately treat at least 30% of our patients, Dr. Christoph Correll told the audience at the 2016 Pacific Psychopharmacology Conference in Vancouver. The evidence for combining dopamine antagonists, whether first- or second-generation antipsychotics, is not favorable according to a meta-analysis he described which is in review for publication. When only high-quality studies were included, which involved 14 trials with 938 subjects, the evidence for combining antipsychotics melted to nothing. Although it makes sense that using two medications with the essentially the same mechanism of action would not be synergistic, many practitioners nevertheless do just that.

Dr. Christoph Correll at the 2016 Pacific Psychopharmacology Conference

Dr. Christoph Correll at the 2016 Pacific Psychopharmacology Conference

Dr. Correll, who is Professor of Psychiatry at Hofstra Northwell School of Medicine and Medical Director of the Recognition and Prevention Program at the Zucker Hillside Hospital in Queens, New York, said that adding agents with a different mechanism of action may be more promising. Topirimate acts to inhibit activity in the glutamate-NMDA receptor complex and is approved as an anticonvulsant. It also counters the weight gain of psychotropic medications by reducing appetite and enhancing insulin sensitivity. He and six coauthors have recently published a meta-analysis of 16 randomized, controlled trials including a total of 934 patients who received topirimate adjunctive to antipsychotic therapy; outcome data included PANSS or BPRS total scores and body weight, and secondary outcomes included positive and negative symptoms and various metabolic measures including waist circumference and serum glucose.

The benefit for augmentation was significant as measured by total PANSS or BPRS for the entire group, and sensitivity analyses showed it held true with a dose of 150 mg per day or less, in first and multi-episode patients, and either with clozapine or non-clozapine antipsychotics. The effect was independently significant for positive and for negative symptoms. Topirimate was associated with a significant reduction in weight with a mean reduction of 2.75 kg; other metabolic measures were unchanged except for significant reduction in serum triglycerides and fasting insulin. Although discontinuation for adverse effects or inefficacy did not differ with topirimate or placebo, notable adverse effects of topirimate included concentration problems and paresthesias.

These studies were all short-term with a mean duration of 11.8 weeks, a problem with many clinical trials in psychiatry  given that schizophrenia is a chronic disorder and patients remain on  medication for months to years. Cognitive problems including word-finding difficulty are a known effect of topirimate, and in an illness in which cognitive impairment is inherent, this could be a major liability. Longer-term effects on cognition, metabolic outcomes and psychosis are needed. Will topirimate be the NMDA-modulating treatment that makes a difference or end up like lamotrigine, abandoned after a brief dalliance?

Reference

Zheng W, Xiang Y-T, Xiang Y-Q, Li X-B, Ungvari GS, Chiu HFK, Correll CU. Efficacy and safety of adjunctive topiramate for schizophrenia: a meta-analysis of randomized controlled trials. Acta Psychiatr Scand. 2016:1–14. Published online 1 Sep 2016. Abstract

The overdose crisis in British Columbia

Dr. Arlene King of Fraser Health Authority and former chief medical officer of health of Ontario gave an update on the evolving overdose epidemic in Fraser Health region, which covers communities from White Rock to Hope, British Columbia.  On September 21, the chief coroner of BC had announced 488 overdose deaths to date in BC, a 62% increase compared to the same time in 2015. According to Dr. King, who gave a plenary presentation on September 23 at the 2016 Pacific Psychopharmacology Conference in Vancouver, more than 60% of deaths in Fraser region were related to fentanyl, and if the current trend continues through 2016, 258 people will have died of overdose in the region. Although most people who die of overdose have a chronic substance-use disorder, young, naïve users are at high risk because of the presence of fentanyl in a wide variety of substances sold in the black market in BC. Fentanyl is a potent legal opioid, but the street form is mostly imported from clandestine markets in Asia. Fraser Health Authority is undertaking a variety of measures to prevent lethal drug overdoses; more information is available on Fraserhealth.ca .

On the previous day, Dr. Annabelle Mead, lead physician for Heartwood Centre for Women and an addiction medicine consultant for Vancouver Coastal Health, described the evidence for providing take-home naloxone kits and overdose education to prevent deaths. Naloxone kits are available in communities across BC, and specific outlets are posted on the Web site Toward the Heart which is maintained by the BC Centre for Disease Prevention. The site offers information about a variety of harm reduction approaches including a link to Insite, North America’s first legal safe-injection site in the Downtown Eastside of Vancouver. In other Canadian cities, efforts are underway to open safe-injection sites, which have strong evidence for preventing disease transmission and fatal overdoses, but no site has yet been announced in the Fraser region.

Drs. Ric Procyshyn, Christoph Correll, and Bill MacEwan visit the Downtown Eastside of Vancouver

Drs. Ric Procyshyn, Christoph Correll, and Bill MacEwan visit the Downtown Eastside of Vancouver

Vitamin D deficiency in treatment-resistant schizophrenia

Vitamin D deficiency is associated with schizophrenia, although cause and effect are undetermined. Various published findings include low serum levels of vitamin D in people with chronic schizophrenia, elevated risk for schizophrenia in people who as neonates had low blood levels, and increased risk and higher symptom burden in early-psychosis cohorts (1). In a recent study from the Netherlands, whose population resides at latitudes similar to that of most Canadians, 28 people with treatment-resistant schizophrenia, 77% men and 61% Caucasian, who resided in a mental-health facility, underwent plasma vitamin D3 (calcidiol) analysis in April and June of the same year (2). A control group of 29 staff at the residence, mostly Caucasian women, also underwent testing. People using vitamin supplements were excluded. The researchers estimated the amount of time each participant spent outdoors daily was 2.3 hours for patients and 0.8 hour for staff.

The mean plasma level of vitamin D3 in April and June was significantly lower in the patients than in the staff, and the increase in plasma concentration during the spring was much less robust in the patients. The prevalence of vitamin D deficiency (as determined by plasma concentration) was 90% in April and 79% in June in the cohort of people with severe schizophrenia; in staff it was 17% in June. Because Caucasians have a greater capacity to synthesize vitamin D when their skin is exposed to sunlight, the investigators did subanalyses and found that non-Caucasian patients had lower mean plasma vitamin D than Caucasian patients, and the non-Caucasian patients’ mean plasma value did not increase during the spring.

The significance of these finding for the mental health of people with schizophrenia is unknown, and the researchers did not describe the medication treatments or the diet of the patients, other than to say it was healthy. Vitamin D is naturally available in eggs, some seafood, and is added to milk in some countries including Canada. The effects of vitamin D deficiency in general are most prominent on bone health. The central nervous system is however rich with vitamin D receptors, and deficiency has been linked to neuropsychiatric illness including depressive disorders and multiple sclerosis. Given that supplementation is recommended for Canadians, especially in the winter when it is impossible for most of us to obtain adequate vitamin D from sunlight, ensuring adequate intake for people with schizophrenia, in particular those in chronic care, is justifiable. The possibility that those with chronic illness cannot synthesize vitamin D with more-than-adequate sunlight exposure suggests that year-round oral supplementation is necessary to prevent or treat deficiency.

References

1. Chiang M, Natarajan R, Fan X. Vitamin D in schizophrenia. Evid Based Mental Health. 2016;19:6-9. Abstract

2. Bogers J, Bostoen T, Broekman TG. Low levels of vitamin D poorly responsive to daylight exposure in patients with therapy-resistant schizophrenia. Nordic J Psychiatry. 2016;70:262-266. Abstract

Join Dr. Randall White at the 11th Annual Family Conference: From Crisis to Hope

11th family conference poster 2016

Dr. Randall White is pleased to be presenting at the 11th Annual Family Conference in mental healthy and substance services. Please join us Saturday, April 23, 2015, 9:00am-4:30pm in the Paetzold Theatre at the Vancouver General Hospital. Admission is $25 per person, and limited financial assistant for admission cost is available –just contact Becky Hynes via email (or call 604-714-3771 ext. 2300 for details.

Keynote Presentations Include:

  • Access & Assessment Centre (AAC): A New Service for Vancouver Residents to Access Mental Health and Substance Use Services in Vancouver
    • Monica McAlduff (Director, Vancouver Mental Health & Substance Use Acute, Tertiary & Urgent Services)
    • George Scotton (Manager, Vancouver Access & Assessment Centre, ACT & AOT)
  • Finding Clarity in Chaos: Principles for Developing Health and Recovery
    • Dr. Diane Fredrikson (Physician Lead, Early Psychosis Intervention Program, Vancouver Coastal Health)
  • When Treatments are Inadequate – New Hope for Patients
    • Dr. Randall F. White (Medical Director, B.C. Psychosis Program, Clinical Associate Professor, UBC)

Panel Discussions:

  • Support for Families in Need
  • Family Panel: How Families Can Advocate for Improved Mental Health Care

For the complete program schedule, click here!

Have questions about 11th Annual Family Conference in Mental Health and Substance Use Services? Contact Annual Family Conference: Family Involvement in Mental Health and Substance Use Services

11th family conference poster 2016

 

 


 

Is treatment-resistant schizophrenia fundamentally different?

The Danish have comprehensive data bases that have allowed wide-ranging epidemiologic findings. A group from Denmark and the UK interrogated Danish national registries to create a cohort of 8624 people with schizophrenia born after 1955 and who were at least 18 years old as of 1996.  The registries allow for determination of ICD diagnosis and inpatient treatment for schizophrenia, but not treatment-resistant schizophrenia (TRS), which is not a diagnosis recognized in ICD or DSM. To determine which patients were treatment resistant, they applied 3 criteria:

  • Treatment with clozapine
  • An 18-month period during which a patient was treated non-concurrently for 6 weeks with 2 distinct nonclozapine antipsychotics and subsequently required admission to hospital (clozapine eligible)
  • 90 days of polypharmacy, i.e. treatment with two or more antipsychotics

Although the use of clozapine may be the best proxy criterion for treatment resistance, the investigators estimate that only a third of Danish patients with TRS receive clozapine, hence the need for other proxy criteria.

The total number of treatment-resistant patients as fulfilled by any of the 3 criteria was 5900. The largest group was those who received 90 days of polypharmacy (n = 3773), which is the least specific criterion. The researchers used a Cox proportional hazards regression to compare the patients who met any of the TRS criteria to those who met none and found the following characteristics more prevalent in the TRS group:

  • Younger age at onset
  • Residence in less urban area
  • Hospital admission at time of diagnosis
  • Comorbid mental disorders
  • Paranoid subtype
  • Early parental loss
  • History of substance use disorder
  • Receiving disability benefit
  • Any psychotropic medication prescribed during the year preceding diagnosis
  • At least one suicide attempt

Sensitivity analyses examined the subcohorts of clozapine-treated plus clozapine-eligible patients (n = 1703). This combined group was more likely to have educational attainment beyond primary level but had the same likelihood of receiving a long-term disability benefit as the non-TRS group.

Characteristics that did not differ in the broad TRS cohort (n = 5900) compared with the non-TRS cohort included:

  • Sex
  • Season of birth
  • Paternal age
  • Living with a partner
  • History of a violent offense
  • Employment

The recognized risk factors for schizophrenia such as sex and season of birth did not distinguish TRS in this Danish cohort, but urban residence is a well-known risk factor which surprisingly was less common in the TRS subcohort. Other known risk factors that could not be explored in the registry-based design include birth complications, prenatal infections, and duration of untreated psychosis. The data presented however point to a more severe illness from the outset as reflected by medication use prior to, younger age, and hospital admission at the time of diagnosis.

The strength of the study is its size, which the population-based method permits, but this is also a basis for its weakness, namely the inability to precisely define a cohort of people with TRS. Unfortunately, none of the factors identified here would allow a prospective determination of TRS, i.e. who should receive clozapine. For that we require patient-specific biological markers.

Wimberley T, Støvring H, Sørensen HJ, Horsdal HT, MacCabe JH, Gasse C. Predictors of treatment resistance in patients with schizophrenia: a population-based cohort study. Lancet Psychiatry. Published online Feb 24, 2016. Abstract

Fluvoxamine

In some patients, achieving a therapeutic serum clozapine concentration requires a high dose entailing a prolonged series of dose increases. This may be more common among smokers, and people with schizophrenia are more likely to smoke and to smoke more cigarettes per day than the population at large. One short cut to achieving a therapeutic level is adding fluvoxamine, a serotonin reuptake inhibitor used to treat anxiety and depression. Clozapine is converted by cytochrome enzyme 1A2 to the metabolite N-desmethylclozapine, known as norclozapine in clinical settings. Fluvoxamine inhibits this process which shifts the ratio of clozapine to norclozapine upward and prolongs the half life of clozapine. Fluvoxamine also inhibits CYP2C19 and in some people, CYP3A4 as well. The clinical effect is to permit a lower total dose of clozapine, and it may make once-daily dosing more tolerable. Furthermore, fluvoxamine can be used to treat concurrent anxiety and depression while maximizing clozapine serum levels. The evidence for the safety and benefits of these uses of fluvoxamine was reviewed in a recently published article.

The authors identified 24 case reports and series comprising 29 patients, and 9 prospective studies comprising 212 patients; 2 of these were randomized trials. Most patients had a primary diagnosis of schizophrenia, and the rationales for the various studies were diverse.

  • Increasing clozapine plasma level
  • Treating negative symptoms
  • Treating positive symptoms
  • Treating depressive symptoms
  • Treating obsessive-compulsive symptoms
  • Reducing metabolic adverse effects

The available evidence for most of these indications is mediocre or poor except for increasing plasma levels; according to the authors, fluvoxamine increases clozapine, norclozapine, and clozapine N-oxide plasma levels in a dose-dependent manner. The data among smokers is supportive but surprisingly limited. One point they raise is that the effects of changing the ratios of metabolites other than norclozapine is not understood. The evidence for reducing metabolic adverse effects is relatively good as it comes from a 12-week RCT, but long-term efficacy is unknown. As for treating depression or obsessive-compulsive symptoms, the authors conclude that it is safer to use an appropriate antidepressant without the pharmacokinetic complications of fluvoxamine given the risk of toxicity if clozapine levels rise abruptly.

Safety concerns addressed in studies include the risk of agranulocytosis and seizures for which there is no evidence of a protective or facilitative effect; the available evidence correlates increasing clozapine dose and not plasma level with risk of seizures. (2) The reports reviewed mention frequent occurrence of common adverse effects including sedation, sialorrhea with drooling, and constipation in fluvoxamine-treated patients. Clinicians and patients should be aware that prescribing fluvoxamine to enhance clozapine effects is not approved by Health Canada or the US Food and Drug Administration.

References

Polcwiartek C, Nielsen J. The clinical potentials of adjunctive fluvoxamine to clozapine treatment: a systematic review. Psychopharmacology. Published online Dec 2, 2015. Abstract

Remington G, Agid O, Foussias G, et al. Clozapine and therapeutic drug monitoring: is there sufficient evidence for an upper threshold? Psychopharmacology. 2013;225:505–518. Abstract