There is growing concern regarding teratogenic effect of antipsychotics. Previous research assessing association between antipsychotics and congenital malformations (CMs) yielded mixed results and were all derived from Western countries. We aimed to examine risk of major and organ/system-specific CMs associated with prenatal antipsychotic exposure in Hong Kong.

This population-based study identified women aged 15–50 years who delivered their first/singleton child between 2003–2018 from public healthcare service database. Propensity score (PS)-weighted logistic-regression analyses were performed to examine risk of CMs following first-trimester exposure to antipsychotic classes (second- and first-generation antipsychotic; SGA and FGA) and six most frequently-prescribed individual antipsychotics.

Of 465,069 women, 419 and 420 redeemed ≥1 prescription of SGA and FGA during first-trimester, respectively. Prevalence of any CMs was 4.9% (95%CI:4.9–5.0%) in unexposed-infants, 9.1% (6.7–12.3%) in SGA-exposed infants, and 6.2% (4.3–9.0%) in FGA-exposed infants. SGA exposure (adjusted-odds-ratio: 2.11 [95%CI:1.19–3.86]) was associated with increased risk of CMs. This finding was consistent with sensitivity analyses addressing exposure misclassification and confounding by treatment indication, but not with PS-matched sensitivity analysis. Elevated risk of CMs was observed in infants exposed to high-dose olanzapine (7.50 [1.65–36.13]) and high-dose quetiapine (15.03 [4.86–56.72]), but with wide-CIs. Organ/system-specific malformations were not associated with SGA, FGA or individual antipsychotics.

We observed a small increased risk of major malformations associated with SGA, but was not consistently affirmed in sensitivity analyses, precluding firm conclusions. Research with large sample size clarifying comparative safety of individual antipsychotics on specific malformations is warranted.

Accumulating studies have assessed mortality risk associated with mood-stabilizers, the mainstay treatment for bipolar disorder (BD). However, existing data were mostly restricted to suicide risk, focused on lithium and valproate and rarely adequately adjusted for potential confounders. This study aimed to assess comparative mortality risk with all, natural and unnatural causes between lithium, valproate and three frequently prescribed second-generation antipsychotics (SGA), with adjustment for important confounders.

This population-based cohort study identified 8137 patients with first-diagnosed BD, who had exposed to lithium (n = 1028), valproate (n = 3580), olanzapine (n = 797), quetiapine (n = 1975) or risperidone (n = 757) between 2002 and 2018. Data were retrieved from territory-wide medical-record database of public healthcare services in Hong Kong. Propensity-score (PS)-weighting method was applied to optimize control for potential confounders including pre-existing chronic physical diseases, substance/alcohol use disorders and other psychotropic medications. PS-weighted Cox proportional-hazards regression was conducted to assess risk of all-, natural- and unnatural-cause mortality related to each mood-stabilizer, compared to lithium. Three sets of sensitivity analyses were conducted by restricting to patients with (i) length of cumulative exposure to specified mood-stabilizer ≥90 days and its medication possession ratio (MPR) ≥90%, (ii) MPR of specified mood-stabilizer ≥80% and MPR of other studied mood-stabilizers <20% and (iii) monotherapy.

Incidence rates of all-cause mortality per 1000 person-years were 5.9 (95% confidence interval [CI]: 4.5–7.6), 8.4 (7.4–9.5), 11.1 (8.3–14.9), 7.4 (6.0–9.2) and 12.0 (9.3–15.6) for lithium-, valproate-, olanzapine-, quetiapine- and risperidone-treated groups, respectively. BD patients treated with olanzapine (PS-weighted hazard ratio = 2.07 [95% CI: 1.33–3.22]) and risperidone (1.66 [1.08–2.55]) had significantly higher all-cause mortality rate than lithium-treated group. Olanzapine was associated with increased risk of natural-cause mortality (3.04 [1.54–6.00]) and risperidone was related to elevated risk of unnatural-cause mortality (3.33 [1.62–6.86]), relative to lithium. The association between olanzapine and increased natural-cause mortality rate was consistently affirmed in sensitivity analyses. Relationship between risperidone and elevated unnatural-cause mortality became non-significant in sensitivity analyses restricted to low MPR in other mood-stabilizers and monotherapy. Valproate- and lithium-treated groups did not show significant differences in all-, natural- or unnatural-cause mortality risk.

Our data showed that olanzapine and risperidone were associated with higher mortality risk than lithium, and further supported the clinical guidelines recommending lithium as the first-line mood-stabilizer for BD. Future research is required to further clarify comparative mortality risk associated with individual SGA agents to facilitate risk-benefit evaluation of alternative mood-stabilizers to minimize avoidable premature mortality in BD.

Older age bipolar disorder (OABD) is commonly defined as bipolar disorder in individuals aged 60 or more. General principles of pharmacotherapy in guidelines for treating OABD are greatly like those for younger adults. We aimed to investigate prescription changes among OABD patients discharged from two public mental hospitals in Taiwan from 2006 to 2019.

OABD patients discharged from the two study hospitals, from 1 January 2006 to 31 December 2019 (n = 1072), entered the analysis. Prescribed drugs at discharge, including mood stabilizers (i.e., lithium, valproate, carbamazepine, and lamotrigine), antipsychotics (i.e., second- and first-generation antipsychotics; SGAs & FGAs), and antidepressants, were investigated. Complex polypharmacy was defined as the use of 3 or more agents among the prescribed drugs. Temporal trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test.

The most commonly prescribed drugs were SGAs (72.0%), followed by valproate (48.4%) and antidepressants (21.7%). The prescription rates of SGAs, antidepressants, antidepressants without mood stabilizers, and complex polypharmacy significantly increased over time, whereas the prescription rates of mood stabilizers, lithium, FGAs, and antidepressants plus mood stabilizers significantly decreased.

Prescribing patterns changed remarkably for OABD patients over a 14- year period. The decreased use of lithium and increased use of antidepressants did not reflect bipolar treatment guidelines. Future research should examine whether such prescribing patterns are associated with adverse clinical outcomes.

Long-acting injectable antipsychotics (LAIs) have emerged as a new therapeutic option to treat patients suffering a psychotic disorder. To date, there is a lack of studies regarding safety and clinical use pattern of LAIs in pregnant women.

Provide evidence and real world clinical data of pregnant women with schizophrenia who have been treated with long-acting aripiprazole monohydrate (aripiprazole once monthly [AOM] condition) during their pregnancy.

Descriptive real-world clinical experiences of pregnant women in treatment with AOM. The information was obtained by reviewing electronic medical records and by direct clinical observation management.

The first six case-series describing the pregnancy course of women with schizophrenia treated with AOM. All of them remained psychopathologically stable through pregnancy, and their infants became healthy with normal developmental milestones (Table 1).

Table 1.

Clinical characteristics of six case-reports.

The favorable results in this case-series suggest that despite the lack of evidence on reproductive safety and treatment with AOM during pregnancy, this therapeutic option should be considered in pregnant women with schizophrenia. However, further research on the use of long-acting antipsychotics in pregnant women is needed.

No significant relationships.

Use of second-generation antipsychotics (SGA) has increased in recent years; however, their use and effect on metabolic outcomes has been poorly characterised in population-level studies.

This study aimed to determine the associations between SGA use and metabolic indicators in a general population.

We used data from the Canadian Health Measures Survey, a cross-sectional survey of Canadian households. Participants were Canadians aged 3–79 years, living in one of the ten provinces. Several metabolic indicators were examined, including weight, body mass index, waist circumference, hypertension, diabetes and two definitions of metabolic syndrome.

The proportion of Canadians taking an SGA tripled over the study period. SGA use was significantly associated with hypertension (odds ratio 1.94, 95% CI 1.07–3.55) and abdominal obesity in adults, as defined by the National Cholesterol Education Program–Adult Treatment Panel III (odds ratio 2.62, 95% CI 1.45–4.71).

Evidence of metabolic dysfunction with SGAs is seen in the Canadian population, along with a rapid increase in prevalence of use since 2007.

None.