Saturday, October 14, 2017 | 8:30 AM – 4:30 PM
Paetzhold Education Centre | Vancouver General Hospital
899 West 12 Avenue, Vancouver, B.C.
People living with schizophrenia and other psychotic disorders often develop profound and
disabling cognitive deficits. Even more than positive or negative symptoms, cognitive deficits can impair daily functioning and are a major factor in chronic disability and unemployment. (Hurford, 2011)
Come learn more about these cognitive difficulties and about evidence-based cognitive
remediation programs. Hear about an efficient strategy for training staff to deliver programs, and hear from people in B.C. working on related initiatives.
Dr. Alice Medalia (Director, Lieber Recovery Clinic, Columbia University)
Dr. Christopher Bowie (Director, Cognitive & Psychotic Disorders Lab, Queen’s University)
Dr. Medalia and Dr. Bowie are co-editors of the recently published anthology, Cognitive
Remediation to Improve Functional Outcomes (Oxford University Press, 2016).
8:00 Registration Opens
9:00 Opening Comments – Dr. John Gray Welcome – Dr. Bill Honer Why and How This Conference Came to Be – Susan Inman
9:30 Keynote Speaker: Dr. Christopher Bowie “Cognition in Mental Disorders: Impairments, Implications and Opportunities for Treatment”
10:45 Coffee/Nutrition Break
11:00 Keynote Speaker: Dr. Alice Medalia “How to Make Cognitive Health Services a Part of Mental Health Care”
12:30 Lunch (Not included)
1:30 Panel 1: “Cognition: A Brief Scan of B.C. Initiatives”
Moderator: Dr. Ashok Krishnamoorthy
Dr. Tom Ehmann “Guided Self-care for Cognitive Problems Associated with Psychotic Disorders”
Dr. Mahesh Menon and Dr. Ivan Torres “Adapting Cognitive Remediation for the Refractory Psychosis Population”
Dr. Amy Burns “Isn’t it Ironic? Social Cognition in Schizophrenia”
Dr. Todd Woodward “Treatment of Symptoms vs. Cognitive Remediation in Psychotic Disorders”
Dr. Randall White “The (limited) Role of Medications in Improving Cognition in Schizophrenia”
2:45 Coffee/Nutrition Break
3:00 Panel 2: “Next Steps in Implementing Cognitive Remediation in B.C.”
Moderator: Monica McAlduff
Dr. John Higenbottam
Dr. Regina Casey
Dr. Tom Ehmann
Dr. Chris Bowie
Dr. Alice Medalia
4:15 Closing Remarks: Susan Inman and Gerrit van der Leer
4:45 Conference Ends
This conference will be of great interest to clinicians, families, consumers, mental health
administrators and educators.
Professional, Clinician, Researcher, etc. $100 + GST
Family Member $50 + GST
For a full schedule, speaker bios and to register, visit www.bcss.org
Saturday, October 14, 2017 | 8:30 AM – 4:30 PM
Paetzhold Education Centre | Vancouver General Hospital
899 West 12 Avenue, Vancouver, B.C.
While many factors are blamed as contributing factors in North America’s opioid crisis and overdose, Canadian hospitals and clinics are handing out naloxone kits as a stop-gap measure for at-risk opioid users. But it can be a tricky time at any point to deal with a loved one’s addiction, whether it be to Vicodin or heroin.
What does existing science say you can do to help someone you care about? For over three decades, Maia Szalavitz, author of “Unbroken Brain: A Revolutionary New Way of Understanding Addiction,” has presented the evidence that should play a vital role when weeding through conflicting advice in a field that she states is largely unregulated. Searching out care based on scientific fact as opposed to personal and clinical experience can improve recovery chances.
Her article “What Science Says To Do If Your Loved One Has An Opioid Addiction” is an excellent, evidence-based guide derived from the best research available on addictions, including systematic reviews and clinical medication trials. Szalavitz lays out how to accurately assess the problem, delves into the psychology of addictive behavior, and suggests how to intervene gently. Then, most importantly, she explains how to choose a treatment that is research-based.
Studies suggest that most people with addiction eventually recover, a far cry from the bleak picture portrayed in the media. Recovery from an opioid addiction can look different for different people, but no doubt is rooted in two key aspects: medical assessment and a long-term maintenance program. At least, so says the World Health Organization and the Institute of Medicine, for starters. Read on for more on the science to help you help your loved one on the road to recovery.
For patients whose psychosis doesn’t adequately respond to antipsychotics, especially clozapine, treatment options include electroconvulsive therapy, cognitive-behavior therapy, and augmentation with another medication. Investigators have done cotreatment trials with other antipsychotics, anticonvulsant/mood stabilizers, and even the antibiotic minocycline and anti-inflammatory agents such as aspirin. The trials are small in many cases, so meta-analyses allow various trials to be pooled. Two recent publications give some new guidance but also may sow confusion.
One team examined clinical trials of the anticonvulsants lamotrigine, topirimate and valproate added to clozapine. They included 22 randomized controlled trials (RCTs) comprising 1227 subjects; 613 received clozapine alone, whereas the others received, in order of frequency, valproate, lamotrigine or topirimate. The primary outcome was change in Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) total score. The analysis showed no significant effect for lamotrigine, confirming a previous meta-analysis, but also confirming a prior analysis, topirimate was superior to clozapine alone for reduction in total, positive and negative psychotic symptoms ratings. Sodium valproate, but not magnesium valproate, was superior to clozapine alone in reducing total and positive psychotic symptom scores; it was not effective for negative symptoms. In terms of tolerability, topirimate but not valproate had a significant all-cause discontinuation rate compared to clozapine monotherapy.
One of the limitations of this pooled data set was that many of the patients were not clearly designated as having clozapine resistance; for instance, clozapine serum levels were not recorded. Another concern was that all the trials for valproate augmentation were done in China, and the generalizability to other settings and ethnic groups is uncertain.
The anticonvulsant meta-analysis is one of many that has examined antipsychotic augmentation, which prompted a group led by Christoph Correll to do a meta-meta-analysis. Summarizing this article will not do it justice, so I recommend reading it in its entirety. The investigators looked at 29 existing meta-analyses of trials of augmentation of any antipsychotic with any of 42 medications including, mood stabilizers, anticonvulsants, antidepressants, minocycline, a second antipsychotic, or various hormones such as estrogenic agents. They applied a novel method to assess the quality of the meta-analyses, AMSTAR-Plus Content. Five of the meta-analyses looked at augmentation of clozapine.
In combination with clozapine for positive symptoms of psychosis, only glycine, an amino acid which modulates the NMDA glutamate receptor, had a significant effect size. No treatments showed efficacy in combination with clozapine for total psychopathology or negative symptom scores. In combination with non-clozapine antipsychotics, lamotrigine, estrogenic agents, mirtazapine and a few others showed efficacy.
An important finding is buried in the discussion: “When all this metanalytic literature was compared regarding the quality of its meta-analyzed content, the effect sizes were inversely correlated with the study quality, reducing confidence in these affirmative recommendations.” In other words, many of the studies in this uber-study were small or contained biases, and those studies tended to overrate the effects of the adjunctive treatments. They point out that individual patients may benefit from specific interventions, but the evidence to guide treatment selection is lacking. This leaves the clinician without clear direction for the most difficult-to-treat patients. In an accompanying editorial, however, Wolfgang Fleishhacker suggests that this meta-analysis does not necessarily invalidate all preceding analyses.
Zheng W, Xiang YT, Yang XH, Xiang YQ, de Leon J. Clozapine Augmentation with Antiepileptic Drugs for Treatment-Resistant Schizophrenia: A Meta-Analysis of Randomized Controlled Trials. J Clin Psychiatry. 2017;78(5):e498-e505. Abstract
Correll CU, Rubio JM, Inczedy-Farkas G, Birnbaum ML, Kane JM, Leucht S. Efficacy of 42 Pharmacologic Cotreatment Strategies Added to Antipsychotic Monotherapy in Schizophrenia: Systematic Overview and Quality Appraisal of the Meta-Analytic Evidence. JAMA Psychiatry. 2017;74(7):675-684. Astract
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.
This article previously appeared in Huffington Post Canada.
A panel of five investigators discussed an emerging concept in psychiatry which integrates findings in epidemiology, pathophysiology and cell biology. Dilip V. Jeste, Distinguished Professor of Psychiatry and Neurosciences at the University of California at San Diego, described “inflammaging” as the low-level inflammatory tissue derangement that accompanies aging and which seems to be accelerated in people with chronic mental illness, whether major mood disorders or schizophrenia. Inflammaging can be measured by biomarkers such as C-reactive protein (CRP), tumor necrosis factor-alpha, F2-isoprostanes, chemokines, and leukocyte telomere length. The latter, which refers to the tips of chromosomes which slowly shorten over the lifespan, is a well-recognized measure of cellular senescence.
Although psychiatrists seldom examine these biomarkers in their patients, they know that on a population basis, people with schizophrenia have a high prevalence of metabolic disorder, diabetes, and atherosclerotic vascular disease. Compared to age-matched controls, people with schizophrenia and bipolar disorder have a high rate of morbidity and mortality from these disorders, which are partially inflammatory in nature and age-related.
Dr. Jeste and his research team have studied 140 patients with schizophrenia, ages 26-65 with a mean age of 49, half women, and they confirmed the higher prevalence of metabolic and vascular disorders in this cohort. Moreover, in comparison to a group of 120 non-mentally-ill age-matched subjects, they found elevations in six inflammation-related biomarkers including CRP and the chemokine eotaxin-1. In patients and control subjects, telomere length inversely correlated with age, but only in women with schizophrenia was telomere length significantly reduced compared to controls. According to Dr. Jeste, younger women seemed most at risk for metabolic disturbances: they had the highest rates of obesity, insulin resistance, and elevated inflammatory markers. The researchers will follow the cohort longitudinally to observe what they hypothesize is an accelerated aging process.
Jeste DV, Wolkowitz O, Harvey P, Eyler L, Nasrallah H. Accelerated biological aging in serious mental illness: are these disorders of the whole body and not of the brain only? American Psychiatric Association Annual Meeting, San Diego, California, May 20-24, 2017.
Hong S, Lee EE, Martin AS, et al. Abnormalities in chemokine levels in schizophrenia and their clinical correlates. Schizophr Res. 2017;181:63-69. Abstract
Dr Randall White was presenting a research poster at the American Psychiatric Association 2017 Annual Meeting in San Diego, CA.
Session: New Research Posters 1
Date: Monday, May 22
Time: 10:00 AM–12:00 PM
Poster Number: P5-020
Poster Hall: Exhibit Hall A, Ground Level, San Diego Convention Center
Although clozapine is the standard for treatment-resistant psychosis, 40-60% of those treated with clozapine do not have an adequate response as measured by a 20% or greater reduction in the BPRS, PANSS or other assessments. This condition is known as clozapine resistance, ultra-resistance or refractory psychosis. At the publicly funded BC Psychosis Program, at UBC Hospital in Vancouver, Canada, we have developed criteria to identify clozapine resistance (CR) and an algorithmic approach to treatment based on available evidence. This involves assuring adequate clozapine treatment verified by dose and serum level, including addition of fluvoxamine when appropriate; offering ECT to CR patients, and/or antipsychotic augmentation preferably with sulpiride or aripiprazole. All patients admitted since program inception in February 2012 had failed at least 2 antipsychotic trials. A psychiatrist, social worker, pharmacist, nurse, general physician, and neuropsychologist evaluated each patient. All available summaries of previous psychiatric admissions were reviewed, and medical, pharmacological, social and behavioural histories were recorded.
All information is presented at a case conference and a DSM-IV or -5 multiaxial diagnosis reflects agreement among at least 2 psychiatrists and a psychologist. Symptom ratings included the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Psychopathology (GAPS), and the Clinical Global Impression-Severity and Improvement scales (CGI). Clozapine resistance is defined by an adequate trial, that is, at least 500 mg daily dose for ≥60 days; and continued symptoms manifested by PANSS with 2 positive scale items rated ≥ 4 (moderate) OR 1 item ≥ 6 (severe).
Of 114 patients with schizoaffective disorder or schizophrenia on clozapine at admission, 89 had received it for≥ 60 days; 23 were on at least 500 mg; and 20 met criteria for clozapine resistance (i.e., 17 men and 3 women). Of these, 17 had schizophrenia and 3 schizoaffective disorder; the mean age was 39.6 years. The mean PANSS scores at admission were Positive=28.3, Negative=26.2, General=50.0, Total=104.4; the mean CGI-S was 6.3. Of 16 patients with complete data, 8 were offered ECT and 3 accepted a course; the number of ECT treatments ranged 19-46. Of 19 patients discharged to date, 17 remained on clozapine with a mean dose of 463.2 mg; to obtain a therapeutic clozapine level, 6 received fluvoxamine, dose range 37.5-200 mg. Seven patients received adjunctive antipsychotics: 3 sulpiride, 2 aripiprazole, 4 first-generation agents. At discharge, the mean PANSS were Positive=20.8, Negative=22.1, General=40.0, Total=82.9; the mean CGI-S was 5.1.
Find full info on the American Psychiatric Association 2017 Annual Meeting here!
What I did before
When psychiatric patients are treated in an emergency department, they are often hypervigilant, manic, or otherwise in an excited, agitated state. The current standard of care to manage acute agitation in adults is using an antipsychotic medication and a benzodiazepine, often loxapine or haloperidol and lorazepam. For patients who have schizophrenia, antipsychotic medication alone often treats such symptoms in the longer term, yet many patients are discharged with a benzodiazepine prescription continue long-term benzodiazepine use possibly because the community clinician hopes to avoid triggering a relapse in discontinuing the medication. As a psychiatrist who has worked on acute and tertiary inpatient units, I have discharged patients on benzodiazepines with the expectation it would eventually be discontinued, but I have also seen many patients for whom it never was.
What changed my practice
Then, in 2013 while at the 7th Annual Pacific Psychopharmacology Conference, I was introduced to research showing that people with schizophrenia on chronic benzodiazepine therapy have an increased risk for suicide and all-cause mortality. I kept these observations in the back of my mind and was further alarmed in 2016 when another article from the same researchers found high-dose benzodiazepine use, but not lesser doses, was associated with increased suicide and cardiovascular mortality.
What I do now
Based upon these studies, I find the evidence compelling that benzodiazepines are contraindicated for long-term use in people with schizophrenia. When appropriate, I continue to use lorazepam for acute agitation amongst other reasons, I also educate patients about the risk of long-term use, including dependence and cognitive impairment in addition to mortality.To raise awareness of this issue among my colleagues, I mention the rationale and include recommendations for tapering benzodiazepines in consultation reports and discharge summaries.
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.
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
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