Serious Mental Illness

Annotated Abstracts of Journal Articles
2013, 4th Quarter

Serious Mental Illness

Annotations by Lydia Chwastiak, MD, MPH, FAPM and Oliver Freudenreich, MD, FAPM
December 11, 2013

  1. Drug-Induced Long QT in Adult Psychiatric Inpatients: The 5-Year Cross-Sectional ECG Screening Outcome in Psychiatry Study
  2. Antipsychotics and the risk of type 2 diabetes mellitus in children and youth
  3. A comparison of assertive community treatment fidelity measures and patient-centered medical home standards
  4. Integrated care: the evolving role of psychiatry in the era of health care reform

PUBLICATION #1 — Serious Mental Illness
Drug-Induced Long QT in Adult Psychiatric Inpatients: The 5-Year Cross-Sectional ECG Screening Outcome in Psychiatry Study

R Girardin F, Gex-Fabry M, Berney P, Shah D, Gaspoz JM, Dayer P
Am J Psychiatry 2013 Dec; 170(12):1468-76

This article is also reviewed this quarter by Freudenreich & Cohen under HIV Psychiatry.

ANNOTATION (Chwastiak & Freudenreich)

The Finding: In this large study of 7000 patients admitted to a psychiatric hospital in Geneva during a 5-year period, 0.9% met the criteria for drug-induced long QTc (> 500 msec). Almost 20% of these patients subsequently had torsades de pointes or sudden death. (More than half of the patients with these severe outcomes were also receiving methadone opioid substitution therapy.)  Clinical factors associated with drug-induced long QT were hypokalemia, HIV, HCV and morphological T wave abnormalities on ECG. There was wide variability across medications with respect to risk , with haloperidol, sertindole and phenothiazines associated with increased risk.

Strength and Weaknesses: Strengths of the study include a systematic review of a large number of ECG recordings upon admission to a psychiatric hospital over a 5-year period.  Long QT is a relatively rare event and this study utilized a pharmacovigilance program that thoroughly documented a large sample.
Weaknesses of the study include its cross-sectional design, which provides no information about temporal relationship between exposure and outcome. The relatively small numbers of patients on specific medications provided limited statistical power to detect associations with long QT, and precluded the evaluation of dose-related effects. Finally, associations based on data collected from inpatients may not reflect associations in the general population

Relevance: White blood cell count monitoring is required for patients receiving clozapine therapy, for which 0.2 events of agranulocytosis per 1000 patient-years has been reported. By contrast, no formal risk-management program has been established to detect prolonged QT at psychiatric hospitals—even though the incidence of sudden cardiac death in patients taking antipsychotic medications is about 2.9 events per 1000 patient-years.  The detection of QTc > 500 ms should lead to prompt action in a psychiatric hospital, including correction of electrolyte abnormalities, discontinuation of offending drug, and careful cardiac monitoring.


Objective: The authors aimed to determine the prevalence of drug-induced long QT at admission to a public psychiatric hospital and to document the associated factors using a cross-sectional approach.

Method: All ECG recordings over a 5-year period were reviewed for drug-induced long QT (heart-rate corrected QT ≥500 ms and certain or probable drug imputability) and associated conditions. Patients with drug-induced long QT (N=62) were compared with a sample of patients with normal ECG (N=143).

Results: Among 6,790 inpatients, 27.3% had abnormal ECG, 1.6% had long QT, and 0.9% qualified as drug-induced long QT case subjects. Sudden cardiac death was recorded in five patients, and torsade de pointes was recorded in seven other patients. Relative to comparison subjects, patients with drug-induced long QT had significantly higher frequencies of hypokalemia, hepatitis C virus (HCV) infection, HIV infection, and abnormal T wave morphology. Haloperidol, sertindole, clotiapine, phenothiazines, fluoxetine, citalopram (including escitalopram), and methadone were significantly more frequent in patients with drug-induced long QT. After adjustment for hypokalemia, HCV infection, HIV infection, and abnormal T wave morphology, the effects of haloperidol, clotiapine, phenothiazines, and citalopram (including escitalopram) remained statistically significant. Receiver operating characteristic curve analysis based on the number of endorsed factors per patient indicated that 85.5% of drug-induced long QT patients had two or more factors, whereas 81.1% of patients with normal ECG had fewer than two factors.

Conclusions: Drug-induced long QT and arrhythmia propensity substantially increase when specific psychotropic drugs are administered to patients with hypokalemia, abnormal T wave morphology, HCV infection, and HIV infection.

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PUBLICATION #2 — Serious Mental Illness
Antipsychotics and the risk of type 2 diabetes mellitus in children and youth
Bobo WV, Cooper WO, Stein CM, Olfson M, Graham D, Daugherty J, et al
JAMA Psychiatry 2013 Oct; 70(10):1067-75

ANNOTATION (Chwastiak & Freudenreich)

The Finding: Among this large sample of children and youth (ages 6-24) in a Tennessee Medicaid population, antipsychotic users had a 3-fold increased risk for type 2 diabetes. (87% of antipsychotic users were treated with an atypical antipsychotic medication.) This increased risk was apparent within the first year of treatment with antipsychotic medication. Risk did not vary significantly with baseline dose, but did increase with cumulative dose. The risk remained elevated for up to 1 year following discontinuation of antipsychotic use.

Strength and Weaknesses:This large epidemiologic study addresses a gap in the literature about the risk of antipsychotic medications among children and youth. This study addresses the limitations of previous studies: the inability to distinguish type 1 from type 2 diabetes, and lack of an appropriate comparison group.
Weaknesses include somewhat limited generalizability of the findings, as the incidence of type 2 diabetes among children covered by Medicaid may be elevated due to economic and social factors and a higher prevalence of behavioural factors. 40% of the children in TN are covered by Medicaid, however, and this study addresses a particularly vulnerable subgroup of children and youth.  In addition, misclassification of diabetes may have affected the results, with a bias toward increased detection of diabetes among those children treated with antipsychotic medications (due to ADA-APA recommendations for screening patients treated with SGA for diabetes).

Relevance: The majority of antipsychotic prescriptions among children are for indications other than psychotic disorders, including bipolar disorder, affective disorders and symptoms related to behavior and conduct. Children (as young as 6 years old) and youth who are prescribed an antipsychotic medication have an increased risk of type 2 diabetes that increases with cumulative dose and persists for up to a year after discontinuation of medication.


Importance: The increased prescribing of antipsychotics for children and youth has heightened concerns that this practice increases the risk of type 2 diabetes mellitus.

Objective: To compare the risk of type 2 diabetes in children and youth 6 to 24 years of age for recent initiators of antipsychotic drugs vs propensity score-matched controls who had recently initiated another psychotropic medication.

Design, Setting, and Participants: Retrospective cohort study of the Tennessee Medicaid program with 28 858 recent initiators of antipsychotic drugs and 14 429 matched controls. The cohort excluded patients who previously received a diagnosis of diabetes, schizophrenia, or some other condition for which antipsychotics are the only generally recognized therapy.

Main Outcomes and Measures: Newly diagnosed diabetes during follow-up, as identified from diagnoses and diabetes medication prescriptions.

Results: Users of antipsychotics had a 3-fold increased risk for type 2 diabetes (HR = 3.03 [95% CI = 1.73-5.32]), which was apparent within the first year of follow-up (HR = 2.49 [95% CI = 1.27-4.88]). The risk increased with cumulative dose during follow-up, with HRs of 2.13 (95% CI = 1.06-4.27), 3.42 (95% CI = 1.88-6.24), and 5.43 (95% CI = 2.34-12.61) for respective cumulative doses (gram equivalents of chlorpromazine) of more than 5 g, 5 to 99 g, and 100 g or more (P < .04). The risk remained elevated for up to 1 year following discontinuation of antipsychotic use (HR = 2.57 [95% CI = 1.34-4.91]). When the cohort was restricted to children 6 to 17 years of age, antipsychotic users had more than a 3-fold increased risk of type 2 diabetes (HR = 3.14 [95% CI = 1.50-6.56]), and the risk increased significantly with increasing cumulative dose (P < .03). The risk was increased for use restricted to atypical antipsychotics (HR = 2.89 [95% CI = 1.64-5.10]) or to risperidone (HR = 2.20 [95% CI = 1.14-4.26]).

Conclusions and Relevance: Children and youth prescribed antipsychotics had an increased risk of type 2 diabetes that increased with cumulative dose.

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PUBLICATION #3 — Serious Mental Illness
A comparison of assertive community treatment fidelity measures and patient-centered medical home standards
Vanderlip ER, Cerimele JM, Monroe-Devita M
Psychiatr Serv 2013 Nov 1; 64(11):1127-33

ANNOTATION (Chwastiak & Freudenreich)

The Finding: High-fidelity ACT teams are equipped with the infrastructure necessary to support the requirements of a medical home for individuals with severe mental illness, as demonstrated by the significant overlap between NCQA medical home criteria and ACT program standards and fidelity criteria. The major gaps between ACT and medical homes include deficiencies in health information technology, tracking of laboratory and imaging test results, and quality improvement.

Strength and Weaknesses: This analysis systematically compared NCQA standards defining a PCMH to ACT fidelity standards, and identified the extent to which the infrastructure of high-fidelity ACT teams overlaps with PCMH criteria. No such comparison of these evidence-based models has been previously reported.
Limitations include the inability to account for “real-world” ACT practices, specifically that many ACT-like programs may fall short of full implementation of the ACT model. A 2010 survey of state mental health program directors, however, demonstrated that 38 of the 42 states with ACT programs require monitoring of services with a fidelity instrument. In addition, ACT represents a resource-intensive intervention for a very high risk subgroup of patients with serious mental illness, so it may not be feasible to scale this model up to be a PCMH for all or most community mental health center clients.

Relevance: The medical home concept was developed in primary care to provide accessible and accountable services for individuals with chronic medical conditions, but this model does not adequately address the unique needs of patients with serious mental illness. Without specific attention to their unique needs, persons with serious mental illness will continue to fall through the cracks of a fragmented system. ACT is an existing evidence-based model that might be extended to address chronic medical illness management for a vulnerable population.


Objective: This study compared program measures of assertive community treatment (ACT) with standards of accreditation for the patient-centered medical home (PCMH) to determine whether there were similarities in the infrastructure of the two methods of service delivery and whether high-fidelity ACT teams would qualify for medical home accreditation.

Methods:  The authors compared National Committee for Quality Assurance PCMH standards with two ACT fidelity measures (the Dartmouth Assertive Community Treatment Scale and the Tool for Measurement of Assertive Community Treatment [TMACT]) and with national ACT program standards.

Results: PCMH standards pertaining to enhanced access and continuity, management of care, and self-care support demonstrated strong overlap across ACT measures. Standards for identification and management of populations, care coordination and follow-up, and quality improvement demonstrated less overlap. The TMACT and the program standards had sufficient overlap to score in the range of a level 1 PCMH, but no ACT measure sufficiently detailed methods of population-based screening and tracking of referrals to satisfy “must-pass” elements of the standards.

Conclusions: ACT measures and medical home standards had significant overlap in innate infrastructure. ACT teams following the program standards or undergoing TMACT fidelity review could have the necessary infrastructure to serve as medical homes if they were properly equipped to supervise general medical care and administer activities to improve management of chronic diseases.

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PUBLICATION #4 — Serious Mental Illness
Integrated care: the evolving role of psychiatry in the era of health care reform

ANNOTATION (Chwastiak & Freudenreich)

Psychiatric Services has launched a new column on integrated care, focusing on service delivery and policy issues at the medical-psychiatric interface. This column by Lori Raney, a national leader in the integration of medical care into community mental health settings, provides a vision and a roadmap for the role of psychiatrists in the era of health care reform. Dr. Raney identifies areas of opportunity and new competencies that may be required for the practicing psychiatrist. She challenges psychiatrists to be catalysts for change in a rapidly changing healthcare environment.


Health care reform offers psychiatrists, who are trained in both general medical and behavioral health care, many opportunities to assume leadership roles on collaborative care teams and improve patient outcomes. This column describes such opportunities in primary care and public mental health settings and outlines new competencies, such as enhanced primary care skills, that will allow psychiatrists to expand their scope of practice in new models of care in the era of reform. These changes will require training, and the author calls on leaders of the American Psychiatric Association to help psychiatrists obtain new skills and undertake new roles.

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