Tag Archives: treatment-resistant psychosis

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

Dr. Randall White at the APA IPS in Chicago
Posted on
Reply

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

Abstract:

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

Methods:

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

Results:

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

Conclusion:

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

Dr. Simon Bow at the CPA meeting in Toronto

Dr. Simon Bow at the CPA meeting in Toronto

Orphan patients research poster

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

The B.C. Mental Health Act Protects My Daughter

Posted on
3

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.  

Long-term benzodiazepine use is associated with increased mortality in people with schizophrenia

Posted on
Reply

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.

Find the full article here!

Twenty percent of schizophrenia may be treatment-resistant from onset

Posted on
4

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

Posted on
1

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

Posted on
Reply

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.

Vitamin D deficiency in treatment-resistant schizophrenia

Posted on
Reply

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

Cognition in treatment resistance

Posted on
Reply

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

Supersensitivity psychosis in treatment resistance

Posted on
1

Guy Chouinard proposed the concept of dopamine supersensitivity psychosis (DSP) in 1978, a consequence of chronic antagonism of dopamine D-2 receptors which also is posited to cause tardive dyskinesia (1). The proposed mechanism is upregulation of D2 receptors in the basal ganglia, and tardive dyskinesia is itself considered one of the markers of the condition, also characterized by tolerance to increasing doses of antipsychotic. Supersensitivity psychosis patients may therefore represent a subtype of treatment resistance. In this study from Japan, the investigators examined this hypothesis in a group of patients with chronic psychosis (2).

The 147 patients enrolled had treatment-resistant schizophrenia or schizoaffective disorder as defined by failure of at least 2 antipsychotics at a dose equivalent to 600 mg chlorpromazine for 4 weeks. Although specifics of antipsychotic therapy were not provided, none of the patients was on clozapine. Their mean duration of illness was about 23 years. Supersensitivity was diagnosed if a patient met one of 3 criteria, which were adopted from Chouinard:

  • Antipsychotic tolerance indicated by relapse while on medication and failure to improve despite 20% or more increase in dosage
  • Rebound psychosis manifested by swift relapse with reduction or discontinuation of medication; the psychosis may involve new symptoms for a patient
  • Presence of tardive dyskinesia

The investigators found that 106 or 72.1% of the patients met at least one criterion for DSP; 56% had tolerance, 44% had tardive dyskinesia, and 42% had rebound psychosis. The patients were also classified by the presence or absence of deficit syndrome, defined by prominent negative symptoms assessed by standardized rating instruments. Of 55 patients judged to have deficit syndrome, the majority did not meet criteria for DSP; hence, DSP was significantly negatively associated with prominent deficit symptoms.

Although the researchers evaluated the present state of each subject, the main limitation of the study was reliance on chart reviews for the longitudinal course of patients’ illness. Furthermore, relapse of symptoms due to nonadherence could not be reliably distinguished from antipsychotic tolerance. The findings however suggest that supersensitivity psychosis may be an important contributor to treatment resistance, and that investigations using functional imaging and other techniques are warranted to validate the concept of DSP.

References Continue reading →

Riverview Refractory Psychosis Data Presented at International Psychiatry Congress

Posted on
Reply

WIN_20150329_113434

 

View the poster in a PDF file here

Abstract

Treatment-resistant psychosis is a challenge to psychiatry and a substantial burden to health-care systems. The province of British Columbia in Canada has publicly funded, universal health care, and patients with treatment-resistant psychosis may receive care in a specialized residential program. Between 1993 and 2011, 663 patients were admitted to this program; this cohort contains one of the largest known series of patients with treatment-resistant schizoaffective disorder.

All patients were evaluated by a psychiatrist, social worker, pharmacist, nurse, general physician, and neuropsychologist. Records from previous hospital admissions were reviewed and all information was presented at a multidisciplinary conference. This resulted in a consensus DSM-III or -IV multiaxial diagnosis and a detailed treatment plan. Ratings of symptoms and functioning at admission and discharge included the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning Scale, the Social and Occupational Functioning Scale, and the Clinical Global Impression of Severity. A research psychologist compiled all data at the time of each patient’s hospitalization.

Patients who did not complete treatment or had a diagnosis other than schizophrenia (SZ), schizoaffective (SZA) or mood disorder (MD) were excluded; the following describes 551 included patients (SZ = 63%, SZA = 29%, MD = 8%). More than half were male (59%), and the mean duration of hospitalization was 30 weeks. The proportion receiving clozapine increased from 21% at admission to 61% at discharge. Those with a MD were less likely to receive clozapine than either SZ or SZA (SZ = 64%, SZA = 61%, MD = 41%). In each diagnostic group, both antipsychotic polypharmacy and the ratio of prescribed daily dose to defined daily dose (PDD/DDD) of antipsychotic medication decreased during hospital stay (polypharmacy: SZ: 52% to 16%, SZA: 52% to 14%, MD: 43% to 0%; PDD/DDD: SZ: 2.1 to 1.6, SZA: 2.1 to 1.4, MD: 1.6 to 1.1). The use of mood stabilizers declined in all groups, but antidepressant use declined only in SZ and SZA. Mean total PANSS score declined in all diagnostic groups, but most in MD, least in SZ, and intermediate in SZA.

In an intensive inpatient program for treatment-resistant psychosis, aggregate improvement occurred despite global reduction in medications while clozapine use nearly tripled. Lower total antipsychotic dose correlated with greater improvement at discharge.