Quetiapine

FAERS adverse event reports were obtained from the FDA website (http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/). Duplicated reports (among a total of 5,821,354 reports) from the first quarter of 2004 through the second quarter of 2014 were filtered by applying the FDA’s recommendation of adopting the most recent case number. Consequently, 4,547,841 remaining reports were analysed in this study. Arbitrary drug names, including trade names and abbreviations, were mapped into unified generic names via text mining. Adverse event risk was evaluated by calculating the reporting ORs with a 95% CI according to methods described in the literature34 (link).
Briefly, individuals in the FAERS database were divided into the following four groups: (a) individuals who received the drug of interest (i.e., quetiapine or vitamin D) and exhibited DM-related adverse events; (b) individuals who received the drug of interest, but did not exhibit DM-related adverse events; (c) individuals who did not receive the drug of interest and exhibited DM-related adverse events; and (d) individuals who did not receive the drug of interest and did not exhibit DM-related adverse events. The OR with 95% CI was defined as follows:

where a, b, c and d refer to the number of individuals in each group, and log refers to the natural logarithm. If the lower limit of the 95% CI was >1, a significant association was assumed between use of the drug of interest (i.e., quetiapine) and the increased occurrence of DM-related adverse events. Contrarily, if the upper limit of the 95% CI was <1, a significant association was assumed between use of the drug of interest (i.e., vitamin D) and the decreased occurrence of DM-related adverse events.
The search terms for “DM” and “vitamin D” are described in Supplementary Tables 1 and 2, respectively. We regarded drug indication data as the patients’ primary diseases. To search for concomitant drugs associated with a decreased occurrence of quetiapine-induced, DM-related adverse events, the number of individuals treated with the concomitant drug of interest was restricted to a minimum of 1000, because ORs are prone to fluctuation when the sample size is small.

Families were recruited through internet and newspaper services, local clinics, and patient support groups in Montréal, Québec. Families were mostly of white, middle-class, intact, and French-Canadian. Inclusion criteria for all families consisted of having at least one child between the ages of 6 and 11 years, and fluency in either English or French. General demographic information presented by risk status can be found in Table 1. Control families were excluded if either parent presented with a current axis-I disorder or reported a history of affective disorders. Inclusion criteria for families having a parent with BD consisted of have one parent with a BD1 or BD2 diagnosis. Psychopathology in parents was assessed with the Structured Clinical Diagnostic Interview for DSM-IV-R (SCID-I; 24). The sample consisted of 25 families with a parent having BD (72% mothers) and 28 families with parents having no mental disorders (90% mothers).Table 1

Demographic characteristics presented by risk-status

Variable	OBD	Control Offspring
Offspring age at first timepoint	7.77 years (SD = 1.74)	8.67 years (SD = 1.68)
Offspring sex
Girls	17	18
Boys	17	14
Family ethnicity
Aboriginal (e.g., First Nations, Inuit, Metis, Native American, Native Australian)	1	0
Black (e.g., African–American, Nigerian, Haitian, Jamaican, Somali)	0	4
East Asian, South-East Asian, Pacific Islander (e.g., Chinese, Japanese, Korean, Vietnamese, Thai, Filipino, Indonesian)	1	2
Hispanic/Latino/Latin-American (e.g., Brazilian, Chilean, Mexican, Cuban)	1	3
Middle Eastern, North African, Central Asian (e.g., Jordanian, Saudi, Egyptian, Moroccan, Iranian, Afghan, Tajikistani)	2	3
White (Caucasian)	20	16
Parental marital status
Single	5	2
Married	18	18
Separated	2	5
Divorced	0	3
Parental educational attainment
Highschool Diploma	1	0
CÉGEP Diploma	4	4
Some university achievement	1	3
University Degree	19	21
Family annual income
Less than $25,000	4	4
$25,001 to $50,000	8	8
$50,001 to $75,00	5	5
$75,001 to $100,000	1	7
More than $100,000	7	3
Family SES compositea	9.44 (SD = 2.10)	9.48 (SD = 1.67)

^aSES Composite = socioeconomic composite score, which combines both parental educational attainment and family annual income

Within families having a parent with BD, most affected parents presented with BD-I (90%), and all reported a history of depression. At the start of the study, most parents with BD were asymptomatic, while two were in a current manic episode. While the latter two individuals were included in the study on the basis of their diagnosis, it was their partners who completed the RUSH program and all accompanying assessments. For the other 23 families, the affected parents attended the program and completed all assessments. All parents with BD were receiving pharmacological treatment at the time of the study, which included various combinations of antidepressant (bupropion, citalopram, escitalopram, sertraline, venlafaxine; n = 6), anticonvulsant (divalproex, lamotrigine, topiramate, valproate, n = 12), antipsychotic (chlorpromazine, lurasidone, olanzapine, quetiapine, ziprasidone; n = 12) and mood stabilizing medication (lithium; n = 9).
There were 66 children across the 53 families (34 OBD; 32 control; 48% female), aged between 6 and 11 years (M = 8.20 years, SD = 1.20 years). None of the control offspring met criteria for a psychological disorder, while ten OBD had a current diagnosis at T1, including an anxiety disorder (n = 1), enuresis (n = 2), oppositional defiant disorder (n = 1), and attention deficit/hyperactivity disorder (n = 6; all of whom were being treated with psychostimulants). None of the OBD were receiving any psychosocial treatments throughout the duration of the study. Psychopathology in offspring was assessed with the parent-version of the Kiddie-Schedule of Affective Disorders and Schizophrenia-Present and Lifetime Version [K-SADS-PL; (Kaufman and Schweder 2004 ). Children were excluded on the basis of presenting with pervasive developmental disorder, an intellectual or chronic physical disorder, or any history of an affective or psychotic disorder. Groups of children did not significantly differ on any key demographic variable (e.g., sex, ethnicity, or socioeconomic status) (all p > 0.05).
Of the initial 25 families having a parent with BD who underwent the T1 assessment, 20 completed the RUSH program. Of the 20 families who completed the RUSH program, all returned for T2 and T3 assessments, but only 17 families were retained at T4. Families most commonly reported a lack of time as the reason for dropping out at T4. No differences were observed between the original sample and those who dropped out prior to participating in the RUSH program or at T4 with regards to various demographic variables (offspring and parent sex and age, socioeconomic status), parental diagnosis (BD-I v. BD-II), offspring psychopathology at T1, as well as parents’ baseline scores across all four scores of parenting stress (all p > 0.05).