Topiramate

The meta-analysis was conducted and reported according to recommendations of the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group [36] (link). A review protocol was construed following the MOOSE guidelines. This was not published but only for internal use of this study.
A PubMed and Embase search was conducted for articles on metabolic side effect profiles of antipsychotic medication. The search term used was: ((“weight gain” OR “BMI” OR “7% weight”) AND (chlorpromazine OR haloperidol OR bromperidol OR fluphenazine OR zuclopenthixol OR pentixol OR flupentixol OR levopromazine OR perphenazine OR pimozide OR penfluridol OR sulpiride OR amisulpride OR amoxapine OR asenapine OR aripiprazole OR blonanserine OR clozapine OR iloperidone OR melperone OR olanzapine OR risperidone OR paliperidone OR quetiapine OR sertindole OR lurasidone OR ziprasidone)) NOT (addition OR additive OR adjunctive OR augmentation OR lithium OR valproate OR carbamazepine OR metformin OR topiramate OR ramelteon OR rimonabant OR modafinil OR sibutramine OR genetics OR pharmacokinetics OR vomiting OR nausea OR review OR “cognitive behavioural therapy” OR “cognitive behavioral therapy” OR delirium OR steroids OR ropinirole OR sleep OR “brain volume”)
Limits Activated: Humans, Clinical Trial, Randomized Controlled Trial, Clinical Trial, Phase IV, Controlled Clinical Trial, English, German, All Adult: 18+ years, Publication Date from 1999/01/01 to 2011/12/31.

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).

As the etiologically relevant exposure window, the outcome assessment window, and the covariate assessment window differ by study outcome, we created two separate study cohorts. First, cohort 1 was constructed for the analysis of congenital malformations by setting the window of interest between the last menstrual period (LMP) to LMP+90 (hereafter, first trimester), and we excluded the following: (1) pregnancies with exposure to known teratogenic drugs (e.g., antineoplastic agent, warfarin, lithium, systemic retinoids, misoprostol, thalidomide, androgens, antiepileptic medications [valproate, topiramate, carbamazepine, oxcarbazepine, phenobarbital, phenytoin]); (2) infants with chromosomal abnormalities, genetic syndromes, and malformation syndromes with known causes; (3) pregnancies with no NSAID prescription during the first trimester, but with ≥1 NSAID prescription within 3 months before the LMP (LMP-90 to LMP-1); and (4) pregnancies with only 1 NSAID prescription during the first trimester to minimize potential for misclassification of exposure. Second, cohort 2 was constructed for the analysis of nonmalformation outcomes of low birth weight, antepartum hemorrhage, and oligohydramnios, by setting a broader window to evaluate the effects of exposure prior to the outcome assessment period (LMP to 19 week of gestation [hereafter, early pregnancy]), where we excluded (1) pregnancies with no NSAID prescription during early pregnancy, but with ≥1 NSAID prescription within 3 months before the LMP, and (2) pregnancies with only 1 NSAID prescription during early pregnancy.