Sabina Abidi

From Chlorpromazine to Clozapine—Antipsychotic Adverse Effects and the Clinician's Dilemma

The pharmacotherapy of schizophrenia remains an ongoing challenge for researchers and clinicians alike. Current medications remain suboptimal to effectively treat this illness despite the recent surge of what are considered to be better antipsychotics: the atypicals. The atypicals cause fewer extrapyramidal symptoms and tardive dyskinesia, but there is growing concern regarding the significant long-term metabolic and cardiac adverse effects of these novel antipsychotics. There are differences among the atypicals in their propensity to produce these adverse effects, and clinicians should weigh the risk–benefit ratio for each drug with each individual patient. Diabetes, heart disease, obesity, and unhealthy lifestyle choices are on the rise in the general population, and individuals with chronic schizophrenia are even more at risk. The dilemma clinicians face in trying to avoid the neurological morbidity of the typicals (extrapyramidal side effects and tardive dyskinesia) is the risk of consequently exposing patients to both the morbidity and potential mortality of the atypicals (cardiovascular, endocrine, and metabolic adverse effects). The importance of baseline investigations and monitoring at regular intervals as well as identification of patients at risk for obesity, diabetes, and cardiovascular morbidity has become crucial. Informed decision making is essential for successful antipsychotic pharmacotherapy. For a condition, which often necessitates long-term pharmacotherapy, the importance of prevention and (or) minimization of morbidity and mortality related to adverse effects of such pharmacotherapy cannot be understated.

A familial risk enriched cohort as a platform for testing early interventions to prevent severe mental illness

BackgroundSevere mental illness (SMI), including schizophrenia, bipolar disorder and severe depression, is responsible for a substantial proportion of disability in the population. This article describes the aims and design of a research study that takes a novel approach to targeted prevention of SMI. It is based on the rationale that early developmental antecedents to SMI are likely to be more malleable than fully developed mood or psychotic disorders and that low-risk interventions targeting antecedents may reduce the risk of SMI.Methods/DesignFamilies Overcoming Risks and Building Opportunities for Well-being (FORBOW) is an accelerated cohort study that includes a large proportion of offspring of parents with SMI and embeds intervention trials in a cohort multiple randomized controlled trial (cmRCT) design. Antecedents are conditions of the individual that are distressing but not severely impairing, predict SMI with moderate-to-large effect sizes and precede the onset of SMI by at least several years. FORBOW focuses on the following antecedents: affective lability, anxiety, psychotic-like experiences, basic symptoms, sleep problems, somatic symptoms, cannabis use and cognitive delay. Enrolment of offspring over a broad age range (0 to 21 years) will allow researchers to draw conclusions on a longer developmental period from a study of shorter duration. Annual assessments cover a full range of psychopathology, cognitive abilities, eligibility criteria for interventions and outcomes. Pre-emptive early interventions (PEI) will include skill training for parents of younger children and courses in emotional well-being skills based on cognitive behavioural therapy for older children and youth. A sample enriched for familial risk of SMI will enhance statistical power for testing the efficacy of PEI.DiscussionFORBOW offers a platform for efficient and unbiased testing of interventions selected according to best available evidence. Since few differences exist between familial and ’sporadic’ SMI, the same interventions are likely to be effective in the general population. Comparison of short-term efficacy of PEI on antecedents and the long term efficacy for preventing the onset of SMI will provide an experimental test of the etiological role of antecedents in the development of SMI.

Stimulant Medication and Psychotic Symptoms in Offspring of Parents With Mental Illness

BACKGROUND: Stimulants, such as methylphenidate, are among the most commonly used medications in children and adolescents. Psychotic symptoms have been reported as rare adverse reactions to stimulants but have not been systematically inquired about in most previous studies. Family history of mental illness may increase the vulnerability to drug-induced psychotic symptoms. We examined the association between stimulant use and psychotic symptoms in sons and daughters of parents with major mood and psychotic disorders. METHODS: We assessed psychotic symptoms, psychotic-like experiences, and basic symptoms in 141 children and youth (mean ± SD age: 11.8 ± 4.0 years; range: 6–21 years), who had 1 or both parents with major depressive disorder, bipolar disorder, or schizophrenia, and of whom 24 (17.0%) had taken stimulant medication. RESULTS: Psychotic symptoms were present in 62.5% of youth who had taken stimulants compared with 27.4% of participants who had never taken stimulants. The association between stimulant use and psychotic experiences remained significant after adjustment for potential confounders (odds ratio: 4.41; 95% confidence interval: 1.82–10.69; P = .001) and was driven by hallucinations occurring during the use of stimulant medication. A temporal relationship between use of stimulants and psychotic symptoms was supported by an association between current stimulant use and current psychotic symptoms and co-occurrence in cases that were assessed on and off stimulants. CONCLUSIONS: Psychotic symptoms should be monitored during the use of stimulants in children and adolescents. Family history of mood and psychotic disorders may need to be taken into account when considering the prescription of stimulants.

Canadian Treatment Guidelines for Individuals at Clinical High Risk of Psychosis

Objective: Young people who are at clinical high risk (CHR) of developing psychosis are often help seeking and have significant distress and dysfunction. There are limited guidelines for the assessment and treatment for this population. The aim of this guideline was to develop treatment recommendations for this at-risk group. Method: A systematic search was conducted for published guidelines for CHR. All current guidelines for schizophrenia were reviewed for treatment guidelines on individuals at CHR. The recommendations adopted were primarily drawn from the European Psychiatric Association (EPA) guidance on the early intervention in clinical high-risk states of psychoses and the 2014 National Institute for Health and Care Excellence (NICE) guidelines on the treatment and management of those at CHR for psychosis. Results: After the guideline development process described, 9 recommendations were developed based on the quality of evidence, appropriateness for the Canadian health care system, and clinical expert consensus. Conclusions: Assessment by an expert in the field was the first recommendation. It was recommended that treatment follow a staged approach with psychological treatments being the first-line treatment and pharmacotherapy reserved for adults, those who did not respond to psychological interventions, and those who had more severe symptoms.

Psychosis in Children and Youth: Focus on Early-Onset Schizophrenia

On the basis of strong research evidence (1)(3) very early onset (VEOS) and early onset schizophrenia (EOS) carry significant morbidity and mortality risks for children and adolescents. On the basis of strong research evidence, the pathogenesis of EOS is linked to a dysregulation of dopamine and morphologic brain changes. (6)(7) On the basis of some research evidence and consensus, development of schizophrenia is the result of the interplay between genetic and environmental risk factors. (4) On the basis of strong research evidence, antipsychotic medications are the cornerstones of treatment for EOS. (11)(12)(13) On the basis of some research evidence and consensus, (13) treatment for schizophrenia should be timely, multimodal and multidisciplinary, including both pharmacologic and nonpharmacologic modalities tooptimize recovery.

Canadian Guidelines for the Pharmacological Treatment of Schizophrenia Spectrum and Other Psychotic Disorders in Children and Youth

Objective: Schizophrenia spectrum and other psychotic disorders often have their onset in adolescence. The sequelae of these illnesses can negatively alter the trajectory of emotional, cognitive, and social development in children and youth if left untreated. Early and appropriate interventions can improve outcomes. This article aims to identify best practices in the pharmacotherapy management of children and youth with schizophrenia spectrum disorders. Methods: A systematic search was conducted for published guidelines for schizophrenia and schizophrenia spectrum disorders in children and youth (under age 18 years). Recommendations were drawn from the National Institute for Health and Care Excellence guidelines on psychosis and schizophrenia in children and youth (2013 and 2015 updates). Current guidelines were adopted using the ADAPTE process, which includes consensus ratings by a panel of experts. Results: Recommendations identified covered a range of issues in the pharmacotherapy management of children and youth with schizophrenia spectrum disorders. Further work in this area is warranted as we continue to further understand their presentation in the developing brain. Conclusions: Canadian guidelines for the pharmacotherapy management of children and youth with schizophrenia spectrum disorders are essential to assist clinicians in treating this vulnerable population. Ongoing work in this area is recommended.

Disruptive mood dysregulation disorder in offspring of parents with depression and bipolar disorder

BackgroundIt has been suggested that offspring of parents with bipolar disorder are at increased risk for disruptive mood dysregulation disorder (DMDD), but the specificity of this association has not been established.AimsWe examined the specificity of DMDD to family history by comparing offspring of parents with (a) bipolar disorder, (b) major depressive disorder and (c) a control group with no mood disorders.MethodWe established lifetime diagnosis of DMDD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children for DSM-5 in 180 youth aged 6-18 years, including 58 offspring of parents with bipolar disorder, 82 offspring of parents with major depressive disorder and 40 control offspring.ResultsDiagnostic criteria for DMDD were met in none of the offspring of parents with bipolar disorder, 6 of the offspring of parents with major depressive disorder and none of the control offspring. DMDD diagnosis was significantly associated with family history of major depressive disorder.ConclusionsOur results suggest that DMDD is not specifically associated with a family history of bipolar disorder and may be associated with parental depression.

Canadian Treatment Guidelines on Psychosocial Treatment of Schizophrenia in Children and Youth

Objective: A panel of experts, including researchers, clinicians and people with lived experience, was brought together to develop the new Canadian schizophrenia guidelines for the psychosocial treatment of children and youth with schizophrenia or psychotic disorders. Method: The ADAPTE process, which relies on adapting existing high-quality guidelines, was used. Existing guidelines for children and youth (mostly from the National Institute for Health and Care Excellence [NICE]), as well as CPA adult guidelines, were reviewed and discussed in terms of their adaptability to the Canadian context and their level of recommendation for children and youth. New treatments were also considered when recent meta-analyses suggested their usefulness. Results: The children and youth psychosocial guidelines include many cross-sectional recommendations in terms of clinical and interpersonal skills needed to work with this clientele, setting and collaboration issues and needed adaptations for specific subpopulations. In terms of specific treatments, the treatments most strongly recommended are family intervention and cognitive behavior therapy. Also recommended, although with different degrees of support, are supported employment/supported education programs, patient education, cognitive remediation, and social skills training. Novel and upcoming psychosocial treatments are also briefly discussed. Conclusion: These novel Canadian guidelines for the psychosocial treatment of children and youth with schizophrenia or psychotic disorders report evidence-based treatments as well as important considerations for providers who work with this clientele. More studies with children and youth with schizophrenia and psychotic disorders are warranted. If followed, these guidelines should facilitate the recovery of children and youth with schizophrenia or psychotic disorders as well as the recovery of their families.

Paving the Way to Change for Youth at the Gap between Child and Adolescent and Adult Mental Health Services

By 2020 mental illness will be one of the 5 most common illnesses causing morbidity, mortality and disability among youth. At least 20% of Canadian youth have a psychiatric disorder the impact of which can dramatically alter their life trajectory. Focus on the factors contributing to this problem is crucial. Lack of coordination between child and adolescent mental health systems (CAMHS) and adult mental health systems (AMHS) and consequent disruption of care during this vulnerable time of transition is one such factor. Reasons for and the impact of this divide are multilayered, many of which are embedded in outdated, poorly informed approaches to care for this population in transition. This paper considers the etiology behind these reasons as potential foci for change. The paper also briefly outlines recent initiatives ongoing in Canada and internationally that reflect appreciation of these factors in the attempt to minimize the gap in service provision for youth in transition. The need to continue with research and program development endeavours for youth with mental illness whereby access to services and readiness for transition is no longer determined by age is strongly supported.

Canadian Guidelines for the Assessment and Diagnosis of Patients with Schizophrenia Spectrum and Other Psychotic Disorders

Objective: The objective of this article is to identify best practices in the diagnosis and assessment of patients with schizophrenia spectrum and other psychotic disorders. The diagnosis and assessment may occur in a range of situations from the emergency room to the outpatient clinic and at different stages of the disorder. The focus may be on acute exacerbations of illness, residual symptoms, levels of function, or changes in the response to treatment. Methods: A systematic search was conducted for guidelines published in the last 5 years for schizophrenia and schizophrenia spectrum disorders. The guidelines were rated by at least 2 raters, and recommendations adopted on the diagnosis and assessment were primarily drawn from the American Psychiatric Association practice guidelines for the psychiatric evaluation of adults and the National Institute for Health and Care Excellence guideline on psychosis and schizophrenia in adults. A number of de novo recommendations were also developed. Results: Eleven recommendations were identified that cover a range of assessment situations from diagnosis to the involvement of families in assessments. Conclusions: An accurate assessment establishes the baseline for treatment planning based on clinical decision making for both pharmacotherapy and psychosocial treatments.