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.

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

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

Cognition in treatment resistance

Patients with treatment-resistant schizophrenia or schizoaffective disorder have the most severe form of the illness at least as determined by persistence of positive symptoms, but the other aspects, including negative and cognitive impairments, are typically not as well assessed clinically or in research. Most clinicians may assume that treatment-resistant patients, who often have profound functional deficits, have worse cognition than patients who respond to non-clozapine antipsychotics. This is an hypothesis that requires investigation, and a team from New Zealand have recently published such a study. They went further and also looked at the cognitive status of a group of clozapine-resistant (ultra-resistant) patients.

The 51 patients were recruited from outpatient and inpatient settings; 5 had schizoaffective disorder and the rest had schizophrenia. The control group comprised 22 healthy adults matched for age and sex. The mean age of the subjects was about 33 years. The researchers classified the patients into 3 groups based on treatment response: first-line antipsychotic responders (n=16), treatment-resistant but clozapine responders (n=20), and clozapine nonresponders (ultra-resistant; n=15). The latter group had a 8-week trial of monotherapy, and all ended up on at least 2 antipsychotics, most often clozapine and a another second-generation antipsychotic. Despite the designations, the 3 groups had no significant difference in PANSS total or subscale scores at the time of evaluation. The mean antipsychotic dose as measured in chlorpromazine equivalence was significantly greater in the clozapine-resistant group, but the mean duration of illness did not differ among groups. The control group had slightly greater mean educational attainment than the treatment-resistant group.

The cognitive assessments consisted of neuropsychologic tests covering the domains of the MATRICS Consensus Cognitive Battery developed by the U.S. National Institutes of Mental Health, considered the standard in psychosis cognitive evaluation. In this study, the testing was computerized and included such domains as executive function, social recognition, processing speed, and verbal and nonverbal learning and memory. The raw scores were converted to Z-scores normalized for age, sex and education.

The results showed that the patients overall had significant impairment in cognitive performance compared with healthy subjects, but the differences among the 3 patient groups were minimal. The treatment-resistant group, however, had a mean verbal fluency Z-score equal to that of the control group whereas the other patient groups had significantly worse performance in this domain, but subsequent analysis did not support a significant difference in verbal fluency performance in patient groups or controls. The researchers mention that pre-existing work has found that clozapine is associated with improvement in verbal fluency, an intriguing finding especially since in this study, verbal fluency was correlated with the negative-symptoms subscale of the PANSS in patients who responded to clozapine monotherapy.

The study is small, and the equivalent positive symptoms scores in the 3 patient groups raises questions about the distinctions based on treatment response, the findings tend to disconfirm the hypothesis that treatment resistance as defined by antipsychotic response necessarily indicates greater cognitive impairment.

Anderson VM, McIlwain ME, Kydd RR, Russell BR. Does cognitive impairment in treatment-resistant and ultra-treatment-resistant schizophrenia differ from that in treatment responders? Psychiatry Res. 2015; published online Oct 2015; http://dx.doi.org/10.1016/j.psychres.2015.10.036