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.  

American Psychiatric Association 2017 Annual Meeting

American Psychiatric Association 2017

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

Dr White discussing the BCPP findings with Dr. John Kane, who did the first controlled trial of clozapine in North America.


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! 

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

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!

Famotidine for treatment-resistant schizophrenia

Psychiatrists regard the histamine-receptor antagonism of antipsychotics mostly as a nuisance given its relationship to sedation and weight gain. Some evidence, including research on animal models and preliminary human investigations, suggest that in fact it has a therapeutic role for schizophrenia. Recent research has found that clozapine is an inverse agonist at H2 receptors, meaning that it reduces H2 receptor activity below its baseline (1).

A Finnish team has completed a four-week randomized, controlled, and double-masked trial of famotidine, a selective H2 antagonist now marketed as an over-the-counter remedy for heartburn (2). They recruited 30 patients with treatment-resistant schizophrenia, mean age about 51 years, who were on a variety of antipsychotics and had residual functional impairment; 11 of them were on clozapine. They assessed them with the Scale for Assessment of Negative Symptoms (SANS), the Positive and Negative Syndrome Scale (PANNS), and the CGI. The active-treatment group received 100 mg of famotidine twice daily; no significant adverse reactions occurred, but 3 subjects receiving placebo dropped out “for unclear reasons.”

In comparison with the placebo group, the famotidine group had a significant reduction in mean PANSS total score and PANSS general subscale score and in mean CGI. The mean total PANSS score decreased 11% in the famotidine group and 1% in the placebo group. The researchers acknowledged that their study was too brief and had too few subjects to adequately investigate famotidine, and they suggested a follow-up trial with at least 80 subjects for 8 to 10 weeks to test the potential of this well-tolerated medication in treatment-resistant patients.


1. Humbert-Claude M, Davenas E, Gbahou F, et al. Involvement of histamine receptors in the atypical antipsychotic profile of clozapine: a reassessment in vitro and in vivo. Psychopharmacology. 2012;220:225-241.

2. Meskanen K, Ekelund H, Laitinen J et al. A randomized clinical trial of histamine 2 receptor antagonism in treatment-resistant schizophrenia. J Clin Psychopharmacol. 2013;33:472-478.

Pimozide is ineffective for clozapine augmentation

Partial or non-response to clozapine is a challenging clinical situation. For these patients, who are considered refractory or ultra-resistant, we have limited options. Available evidence for augmenting clozapine is discouraging, but even negative trial results are valuable as a guide for what not to do. Exposing patients to ineffective treatments increases both costs and risk of adverse effects.

Pimozide, a potent D2 receptor antagonist, was found to be effective in a 1997 open-label clinical trial in partial clozapine responders. In a 2011 double-blind, placebo-controlled, 12-week trial in patients with partial or non-response to clozapine, pimozide at a mean dose of 6.5 mg daily was ineffective (1). A different U.S. group just published another randomized, double-blind, placebo-controlled trial of pimozide at 4 mg daily in patients with partial clozapine response (2). Using the BPRS, the Schedule for the Assessment of Negative Symptoms, and evaluations of verbal memory, working memory and executive function, the investigators found no significant differences between the groups at 12 weeks, although both showed improvement in the BPRS over time.

With two negative trials, it seems that pimozide as a clozapine augmentation agent can be put to rest. In fact, the entire strategy of adding first-generation D2 antagonists to clozapine for partial or non-repsonse is dubious.


1. Friedman JI, Lindenmayer JP, Alcantara F, et al. Pimozide augmentation of clozapine in patients with schizophrenia and schizoaffective disorder unresponsive to clozapine monotherapy. Neuropsychopharmacology. 2011;36:1289-1295. Full text

2. Gunduz-Bruce H, Oliver S, Gueorguieva R, et al. Efficacy of pimozide augmentation for clozapine partial responders with schizophrenia. Schizophr Res. 2013;143:344-347. Abstract

Does lamotrigine augment clozapine?

Many of the patients referred to B.C psychosis Program are on clozapine or have received it in the past, and many have had a limited response. Clozapine-resistance is a big challenge for psychiatrists who manage chronic psychosis, and a recent quantitative review of clozapine augmentation strategies provides little guidance or solace. Stefan Leucht and colleagues examined randomized, masked, placebo-controlled studies

of at least two weeks duration in which another drug was added following at least four weeks of  clozapine therapy. Whenever possible, they used intention-to-treat data to calculate effect size.

The studies involved a range of medications including antidepressants, antipsychotics, glutamatergic agents, and antiepileptics. Lamotrigine is particularly of interest because Tiihonen’s group performed a meta-analysis in 2009 based on five studies that showed a significant effect for augmentation of clozapine. This group obtained unpublished data from studies that looked at lamotrigine added to a variety of antipsychotics, and intention-to-treat outcomes from the trial by Zocali, the largest study to date with 30 subjects on active therapy. Based on the 2009 meta-analysis, Goff commented that “the addition of lamotrigine in patients who remain symptomatic despite adequate clozapine treatment represents the most promising treatment option currently available.”

Although Tiihonen et al. found insignificant heterogeneity, Leucht et al. did find heterogeneity and concluded that the Zocali study was an outlier. They therefore excluded it from their final analysis. This is the crucial difference between the two meta-analyses and the reason for the sharply divergent conclusions. Four studies of lamotrigine augmentation are negative and one is positive. A closer look reveals that the Zocali trial was 24 weeks in duration, whereas the other trials were 10 to 14 weeks; could this be a crucial difference? Goff is still correct, and rather than throw lamotrigine overboard, we need a replication trial lasting 24 or 30 weeks. We know that the benefits of clozapine may take many months to be fully evident, so we should not expect that clozapine augmentation to be a quick affair.

As for other findings of the Leucht meta-analysis, sulpiride augmentation showed significant impact on both positive and negative symptoms, and citalopram showed significant impact on negative symptoms, but the findings are based on one trial each. A trial of an experimental glutamatergic agent showed a signal. This leaves us with few clear optins but some direction for further research.


Sommer IE, Begemann MJ, Temmerman A, Leucht S. Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review. Schizophr Bull. Mar 21 2011; Epub ahead of print; doi:10.1093/schbul/sbr004

Tiihonen J, Wahlbeck K, Kiviniemi V. The efficacy of lamotrigine in clozapine-resistant schizophrenia: A systematic review and meta-analysis. Schizophr Res. 2009;109:10–14.

Goff DC. Review: lamotrigine may be an effective treatment for clozapine resistant schizophrenia. Evid Based Mental Health. 2009;12:111.

Zoccali R,Muscatello MR,Bruno A, Cambria R, et al. The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: a double-blind, placebo-controlled study. Schizophr Res. 2007;93:109–116.