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

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

Schizophrenia is not a progressive brain disease

DSC_0072 1 (2)Despite Emil Kraepelin’s early characterization of dementia praecox, the disorder or disorders that we now call schizophrenia are not characterized by dementia, or inevitable loss of cognitive ability and function. Dr. Robert B. Zipursky, Professor of Psychiatry and Behavioural Neurosciences at McMaster University in Hamilton, Ontario, said that psychiatrists may share Kraepelin’s impression of a malignant illness because of the clinician’s illusion, which arises from the biased sample of patients that psychiatrists treat, i.e. people with chronic, relapsing illness and multiple co-morbidities who come to hospitals (1). According to Professor Zipursky, who spoke at the 9th Annual Pacific Psychopharmacology Conference in Coquitlam, BC on September 18, 2015, available studies indicate that about 70% of people with first-episode psychosis will achieve remission within a year; he defined remission as having positive symptoms no greater that mild in severity and negative symptoms no greater than moderate in severity.

First-episode psychosis includes patients with various diagnoses including bipolar disorder, schizoaffective disorder, brief psychotic disorder as well as schizophrenia. Patients who achieve functional recovery, however, represent a smaller group, especially in those confirmed to have schizophrenia. In long-term outcome research, 20% or fewer of people with schizophrenia meet criteria for recovery defined as sustained remission of symptoms and success in social relations and competitive employment.
Some psychiatrists have concluded that this long-term functional impairment is due to progressive cognitive deterioration which may occur with untreated or chronic positive psychotic symptoms. A related hypothesis is the “neurotoxicity of psychosis” which posits that persisting psychosis leads to ongoing loss of cerebral tissue as manifested by enlarged ventricles and cortical atrophy on neuroimaging, accompanied by worsening deficits on neuropsychologic testing. Consequently, many clinicians working in first episode psychosis accept that the duration of untreated psychosis is an important determinant of long-term outcome.

While he acknowledged that deficits in grey matter volumes observed with MRI are more prominent in chronic patients, Dr. Zipursky asserted that many factors may contribute to this such as sampling bias; concurrent substance use including cannabis, tobacco and alcohol; lack of physical activity; and chronic antipsychotic therapy. The latter is controversial, but he cited a meta-analysis of longitudinal MRI studies in which change in grey matter volumes was correlated with antipsychotic exposure but not illness duration or severity (2). However, he emphasized that relieving suffering and improving function are the goals of treatment, not specifically increasing cerebral volume, which is affected by various factors mentioned before. Furthermore, Dr. Zipursky showed compelling evidence that following a first episode of schizophrenia, antipsychotic discontinuation is by far the most important cause of relapse.

Duration of untreated psychosis (DUP) has a small correlation with treatment outcome, likely accounting for less than 5% of the variance in clinical outcome measures, and questionable association with cognitive functioning and structural brain measures, according to Dr. Zipursky. He presented evidence that it is a risk marker for poor outcome in schizophrenia as opposed to a causative risk factor. “It’s not certain that it relates to improving outcomes, but it does relate to reducing suffering,” Zipursky said.
He concluded that to improve outcomes and promote functional recovery, antipsychotic medication is crucial but so are psychosocial interventions to manage substance use, educate families, provide adequate housing and income support when needed, and engage patients in vocational rehabilitation and supported employment.

References

Zipursky RB, Reilly TJ, Murray RM. The myth of schizophrenia as a progressive brain disease. Schizophr Bull. 2013;39:1363-1372. Full text

Fusar-Poli P, Smieskova R, Kempton MJ, Ho BC, Andreasen NC, Borgwardt S. Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neurosci Biobehav Rev. 2013;37:1680-1691. Full text

The Canadian Psychiatric Association’s Annual Conference Welcomes Dr. Randall White at its 65th Annual Conference

65th Canadian Psychiatric Association’s Annual Conference banner

Every year, more than 1,200 psychiatrists and other mental health care professionals attend the Canadian Psychiatric Association’s conference to educate themselves on the latest research in the field, exchange ideas, and network with colleagues from across the country. This year, Dr. Randall White is honoured to be presenting a symposium on the diagnostic and therapeutic advances in Schizophrenia along with several of his esteemed colleagues.

As the largest psychiatric professional development program in Canada, the CPA is an invaluable resource. 2015 marks a new direction for its annual conference with several changes to usual programming:

  • Pre-conference courses will be offered Wednesday, September 30
  • Thursday, Friday, and Saturday mornings will each offer an all-delegate keynote plenary
  • The AGM and President’s Gala have been moved to Friday morning and evening, respectively
  • Refreshment stands with coffee and tea will now be available at both venues

The conference will be held October 1st – 3rd at both The Fairmont Hotel Vancouver and the Hyatt Regency Vancouver. For location and room rates, visit fairmont.com/hotel-vancouver and vancouver.hyatt.com/en/hotel/home.html or book online 2015 CPA FHV and 2015 CPA HRV.

Conference Details:

  • Pre-Conference Courses (scheduled on Wednesday, 30 September, 13:00 – 17:00)
    These four-hour sessions were the most highly rated courses from peer reviewers. Space is limited, so register early.
    -Member/Affiliate: $150
    -Non-member: $225
  • Registration Package (CPA Members/Affiliates only)
    Includes three discounted scientific days, admittance to the exhibit hall, daily coffee breaks, admittance to the co-developed symposium, and the option to purchase a ticket(s) to the President’s Gala (all events have limited seating).
    $900
  • Daily Registration
    Each day of registration includes scientific sessions, admittance to the exhibit hall, daily coffee breaks, admittance to the co-developed symposium, and the option to purchase a ticket(s) to the President’s Gala (all events have limited seating).

    Resident & Medical Student Member registrations include all 3 days for $75.

    Thursday
    -Member/Affiliate: $320
    -Non-Member: $550
    -Nurse, Research Assistant, Psychologist, Social Worker: $380

    Friday
    -Member/Affiliate: $320
    -Non-Member: $550
    -Nurse, Research Assistant, Psychologist, Social Worker: $380

    Saturday
    -Member/Affiliate: $320
    -Non-Member: $550
    -Nurse, Research Assistant, Psychologist, Social Worker: $380

Attend the CPA President’s Gala!

Friday October 2, 7:00-11:00pm
The President’s Gala is an exceptional four-course dinner where we honour CPA award winners, congratulate our outgoing president, and conduct the exchange of office. It offers a great opportunity in a beautiful setting for networking with your friends, colleagues, mentors, and may even see you on the dance floor. The dress for this event is business attire.

-Residents: $35
-Members/affiliates: $75
-Non-members: $95

Dr. White’s Symposium Details:

Thursday, October 1 at 4:30pm – 6:00pm
Randall White*, MD, FRCPC; Geoffrey Smith, PhD; William Honer, MD, FRCPC; Marnie MacKay, BScN, PhD (c); Serdar Dursun, MD, PhD, FRCPC; Mahesh Menon, PhD, RPsych; Gary Remington, MD, PhD, FRCPC

 

For a complete schedule of the scientific programming, click here.

For updates, follow @BCPsychosis on twitter & use #cpaconference to follow conference highlights.

Dr. Randall White at the 9th Annual Pacific Psychopharmacology Conference

Dr. Randall White is pleased to be attending the 9th Annual Pacific Psychopharmacology Conference this September where he will be Co-chairing the pre-conference and moderating many of the conference sessions. Join us to learn what’s new in evidence-based research on the pharmacotherapy of psychiatric illness.

This year’s conference theme is: Balancing Risks and Benefits to Improved Adherence

The pre-conference workshop title is: Strategies for Managing Mood and Anxiety Disorders in Primary Care at the workshop. The workshop will also cover the following topics in the format of brief presentations with cases:

  • Incorporating Measurement-Based Care for Mood Disorders into Clinical Practice
  • The BC Practice Support Program Adult Mental Health Module: Implications for Primary Care
  • Use of Antidepressants in Ambulatory Settings

Key speakers for the conference:

Martha Sajatovic, MD
Treatment Adherence in Bipolar Disorder
Dr. Martha Sajotovic, is a professor of Psychiatry and Neurology at Case Western Reserve University. She is also a director of the Geropsychiatry Program, and Neurological and Behavioral Outcomes Center, University Hospitals Case Medical Center, and a Willard Brown Chair in Neurological Outcomes Research, Cleveland. Her research focus is on treatment adherence in Bipolar Disorder and Improving Outcomes for People with Schizophrenia.

Robert Zipursky, MD, FRCPC
Improving Outcomes for People with Schizophrenia
Dr. Zipursky is a professor, Department of Psychiatry & Behavioural Neurosciences. ‘s research interests have been in investigating the biology of schizophrenia and its treatment using brain imaging techniques (CT, MRI, PET), the treatment of first episode psychosis, prevention of schizophrenia, and clinical outcomes from schizophrenia. He has served on the editorial boards of Schizophrenia Research and Schizophrenia Bulletin. He is a recipient of the John Cleghorn Memorial Award for Excellence and Leadership in Clinical Research from the Canadian Psychiatric Association and the Michael Smith Award from the Schizophrenia Society of Canada.If you are planning to attend, please introduce yourself to Randall! And if you’re coming from out of town, Be sure to ask for the “Annual Pacific Psychopharmacology Conference 2015” rate or quote booking ID #15906 at time of booking.

Pre-conference Workshop Information
September 17, 2015
Time: 1-4pm, lunch provided prior to course at 12:30pm
Cost: $119 for delegates, $69 for residents, apply a $25 discount if you register for the Sept. 18 conference as well

This workshop will be great for nurse practitioners, pharmacy/therapeutics, psychiatrists, registered nurses, residents and students.

Conference Details:
September 18, 2015
Executive Plaza Hotel and Conference Centre

Social Media:
Follow Dr. Randall White @BCPsychosis on Twitter, use #CPDpppc to follow the conference.

Transcranial direct current stimulation (tDCS) for treatment-resistant psychosis

Neurostimulation techniques are a growing aspect of psychiatric treatment especially as advances in pharmacotherapy have slowed down. Although electroconvulsive therapy (ECT) remains the best studied and perhaps most efficacious form of neurostimulation for treatment-resistant psychosis and mood disorders, it is invasive, requires considerable resources, and remains stigmatized. tDCS by contrast is noninvasive, requires few resources, and has never been portrayed as a form of punishment in novels and films. Although its efficacy for psychosis is yet to be fully established, evidence is accumulating. Because tDCS is relatively easy to administer, controlled experiments with active and sham treatment groups are feasible.

tDCS involves the passage of an electrical current of 1-2 milliamperes across the cerebral cortex by means of 2 electrodes placed on the scalp. To diminish auditory hallucinations, electrodes are placed on the left fronto-temporal region; for negative symptoms, bifrontal placement has been used. The treatment is typically given for 20 minutes twice a day for at least 5 days. Adverse effects are minimal but may include tingling or itching at the site of electrode placement and short-lived somnolence.

According to a review by Mondino, Fecteau and colleagues, 32 studies have examined the effects of tDCS in schizophrenia. Most studies involved patients who were also receiving medication, and several case reports have described safe combination with clozapine. For auditory hallucinations, 14 studies exist including 2 randomized controlled trials (RCTs) which included a total of 54 patients. One RCT found a 30% reduction in treatment-resistant auditory hallucinations after 10 sessions, significantly greater than in the sham-treatment group. The second RCT, however, did not find a significant reduction in auditory hallucinations. The treatment parameters differed between the studies, which confounds interpretation; for instance, in the positive trial, subjects received tDCS twice daily whereas in the negative trial, tDCS was once daily.

In the review, the authors also describe investigations of tDCS on such parameters as functional MRI, auditory and motor evoked potentials, and cognitive measures including executive function. Questions yet to answered include the appropriate duration of each tDCS session, 20 minutes being the most usual; the total duration of treatment, i.e. days or weeks; and the placement of electrodes. The duration of beneficial effect is uncertain, although data to date suggest it may endure for several months, and the role of maintenance treatment requires considerable investigation.

Reference

Mondino M, Brunelin J, Palmc U, Brunonid AR, Pouleta E and Fecteau S. Transcranial direct current stimulation for the treatment of refractory symptoms of schizophrenia: current evidence and future directions. Current Pharmaceutical Design. 2015;21:3373-3383. Abstract

Refugees in Canada have a high incidence of psychosis

A recent article which I reviewed found evidence for an increasing incidence of schizophrenia in Canada. The researcher speculated that Canada’s high rate of immigration may contribute to this finding. Studies from other industrialized countries have found that immigrants, both in the first and second generation, have an elevated risk of developing schizophrenia, but evidence of this in Canada is lacking. A group from the Centre for Addictions and Mental Health in Toronto estimated the incidence of schizophrenia and schizoaffective disorder in Ontario, the most populous and immigrant-rich province of Canada, by examining hospital and billing records with the records maintained by Canadian immigration authorities.

The identified cohort was all Ontario residents who were age 14 to 40 years at the beginning of the 10-year period from 1999-2008. Because of the universal health-care system, all people who come to medical attention have their diagnosis recorded in a provincial data set. All those listed as an immigrants by the federal ministry of citizenship were classified as such whereas all those not listed were classified as non-immigrants. The investigators also noted which immigrants were admitted under refugee status, an indication of a more vulnerable and likely trauma-exposed group.

The rate of new-onset psychosis in the general population was 55.6 (95% CI 54.9–56.4) per 100 000 person-years and 51.7 (95% CI 49.2–54.4) per 100 000 person-years in first-generation immigrants; these rates are not significantly different. Among the immigrants classified as refugees, the rate was higher: 72.8 (95% CI 67.1– 78.9) per 100 000 person-years, but this is not significantly different from the other rates. Closer examination found that immigrants of various origins had differing rates; those from the Caribbean and Bermuda had significantly higher risk whereas those from northern and southern Europe and east Asia had significantly lower risk than the general population. Among refugees, those from east Africa and south Asia had significantly greater risk of psychosis than the general population.

The shortcomings of this kind of study are considerable, mainly the retrospective design and the reliance on administrative-level diagnostic data. Furthermore, the general population included second-generation immigrants who could not be identified by the study methods but who also probably have a higher risk of psychosis. Moreover, the researchers mention that refugees often have other mental illnesses such as posttraumatic stress disorder which may be misdiagnosed as psychosis. Despite these sources of bias, the findings support an emerging theoretical framework in which those immigrants most subject to discrimination, often because of their race, may be most vulnerable to onset of psychosis. Socioeconomic factors and trauma also likely play a role. Early intervention programs may increase their effectiveness by taking this into consideration. The findings also underline the significance of the federal role in health-care funding for refugees, a highly vulnerable population.

Anderson KK, Cheng J, Susser E, McKenzie KJ, Kurdyak P. Incidence of psychotic disorders among first-generation immigrants and refugees in Ontario. CMAJ. 2015;17:e279-e286. Article