British Columbia Schizophrenia Society

By Dr. Richard Williams

Schizophrenia is a serious and debilitating disease that affects 1 in 100 Canadians. The first signs and symptoms of the illness usually appear during late adolescence or early adulthood. [i]

Schizophrenia is characterized by the presence of positive symptoms such as delusions and hallucinations, negative symptoms such as the lack of motivation and social withdrawals, and cognitive deficits. Many individuals suffering from schizophrenia live with a number of co-morbidities, such as depression (25%) and substance abuse (50%). There is a greater degree of obesity amongst these patients[ii]and a 2 to 2.5 times greater chance of smoking 2,[iii][vii].,[iv]. Patients with schizophrenia have a two-fold increased chance of developing diabetes 4,[v] or a metabolic syndrome 2,[vi] and a two-fold increased chance of dying from cardiovascular disease

The goal of therapy for schizophrenia is to effectively treat both positive and negative symptoms, prevent relapse, improve cognition, and restore functionality. Antipsychotic medications are a fundamental part of the treatment of schizophrenia. Newer antipsychotic medications (atypical antipsychotics such as risperidone, olanzapine and quetiapine) have shown improved tolerability and efficacy compared to traditional treatments and are recommended as first-line agents.[viii] Although these newer agents have many notable benefits, their use has been associated with reports of weight gain, and metabolic abnormalities, which may be distressing and dangerous to patients.[ix],[x],[xi]

Zeldox* is a new atypical antipsychotic medication indicated for the treatment of schizophrenia and related psychotic disorders.[xii] It is available as an oral capsule in 20mg, 40mg, 60mg and 80mg strengths. Zeldox is administered initially at a daily dose of 80mg, taken as 40mg twice daily with food – dosage may be adjusted on the basis of clinical status up to 160mg (80mg twice daily). It has been noted that patients may be agitated at initial doses, but this disappears as dose is increased.

The clinical efficacy and safety of Zeldox has been established in numerous controlled studies. Active comparator studies have demonstrated equivalent efficacy to risperidone[xiii],[xiv] and olanzapine[xv],[xvi] in short and long term settings. Switch studies have documented significant improvement in some patients transitioned to Zeldox following failure on other antipsychotics (olanzapine, risperidone, conventional agents). [xvii],[xviii]

Zeldox is a safe and well tolerated atypical antipsychotic for the treatment of schizophrenia. The most commonly observed adverse events associated with the use of Zeldox (incidence of 5% or greater) and observed at a rate at least twice that of placebo were somnolence, extrapyramidal symptoms, and respiratory tract infection (8%). The incidence of postural hypotension was notably low, with no pattern of laboratory abnormalities or apparent weight gain. Overall, side effects were generally of mild to moderate severity and rarely led to discontinuation of the drug. Zeldox is associated with modest QTc prolongation, an adverse event that appears to be common to the atypical antipsychotic class. As a result, Zeldox is contraindicated in patients at greater risk for QTc prolongation (those with a known history of QT prolongation, recent acute myocardial infarction, or uncompensated heart failure).

The favourable metabolic profile of Zeldox is what distinguishes it the most from other atypical antipsychotic agents. Individuals suffering from schizophrenia are at greater risk of developing diabetes, metabolic syndrome or cardiovascular disease. The risk is further exacerbated with the use of atypical agents due to their association with weight gain and metabolic abnormalities. [xix] Zeldox has a better metabolic profile and a lower incidence of weight gain versus risperidone. 13,14 The CATIE trial has also shown that Zeldox has a favourable metabolic profile relative to olanzapine with regard to its effects on weight and the lipid and glucose metabolism. In general, patients switched to clozapine for non-response to other antipsychotic should not be switched to Zeldox.

Zeldox is available at competitive prices, and is currently under review in BC.

Dr. Richard Williams is Director of Schizophrenia Service, Vancouver Island Health Authority; Adjunct Professor of Psychology, University of Victoria; and Clinical Professor, Department of Psychiatry, UBC