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There is limited knowledge about the effects of antipsychotic exposure on the development of gestational diabetes mellitus (GDM) in women with mental illness. Studies have demonstrated an association between antipsychotic medications and metabolic problems such as weight gain and diabetes mellitus in non-pregnant patients with psychiatric disorders. GDM increases the risk of adverse maternal outcomes, including pregnancy-induced hypertension, antepartum and postpartum haemorrhage, and caesarean delivery. The National Register of Antipsychotic Medication in Pregnancy (NRAMP) is a prospective Australian cohort study that observed women who took antipsychotics during pregnancy. Data from 205 women were extracted for the final analysis and included women who took first or second-generation antipsychotics (FGA,SGA) during the first trimester of pregnancy (at minimum) and had a diagnosis of a psychotic disorder (n = 180). The comparison (non-exposed) group (n = 25) were women with psychosis who chose not to take any antipsychotic during the first trimester (at minimum). The comparison groups were not matched, although groups were homogenous in terms of sex, age range, diagnosis and perinatal status. The results of logistic regression analysis revealed that women who were exposed to FGAs, SGAs were seven and five times, respectively, more likely to develop GDM compared to non-exposed groups. When adjusted for confounding variables such as BMI and family history of diabetes, the potential of developing GDM decreased for women taking SGAs. In conclusion, the risk of developing GDM is lower in women taking SGAs compared with women taking FDAs. In addition, family history of diabetes and BMI adds to the risk., Competing Interests: Declaration of competing interest The authors report no potential conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rationale: Hyperprolactinemia is a highly prevalent adverse effect of many antipsychotic agents, with potentially serious health consequences. Several guidelines have been developed for the management of this condition; yet, their concordance has not been evaluated., Objectives: The objectives of this paper were (1) to review current clinical guidelines; (2) to review key systematic evidence for management; and (3) based on our findings, to develop an integrated management recommendation specific to male and female patients who are otherwise clinically stabilised on antipsychotics., Methods: We performed searches of Medline and EMBASE, supplemented with guideline-specific database and general web searches, to identify clinical guidelines containing specific recommendations for antipsychotic-induced hyperprolactinemia, produced/updated 01/01/2010-15/09/2016. A separate systematic search was performed to identify emerging management approaches described in reviews and meta-analyses published ≥ 2010., Results: There is some consensus among guidelines relating to baseline PRL screening (8/12 guidelines), screening for differential diagnosis (7/12) and discontinuing/switching PRL-raising agent (7/12). Guidelines otherwise diverge substantially regarding most aspects of screening, monitoring and management (e.g. treatment with dopamine agonists). There is an omission of clear sex-specific recommendations. Systematic literature on management approaches is promising; more research is needed. An integrated management recommendation is presented to guide sex-specific clinical response to antipsychotic-induced hyperprolactinemia. Key aspects include asymptomatic hyperprolactinemia monitoring and fertility considerations with PRL normalisation., Conclusion: Further empirical work is key to shaping robust guidelines for antipsychotic-induced hyperprolactinemia. The integrated management recommendation can assist clinician and patient decision-making, with the goal of balancing effective psychiatric treatment while minimising PRL-related adverse health effects in male and female patients.

Importance: A substantial proportion of women with schizophrenia experience debilitating treatment-refractory symptoms. The efficacy of estrogen in modulating brain function in schizophrenia has to be balanced against excess exposure of peripheral tissue. Raloxifene hydrochloride is a selective estrogen receptor modulator (mixed estrogen agonist/antagonist) with potential psychoprotective effects and fewer estrogenic adverse effects., Objective: To determine whether adjunctive raloxifene therapy reduces illness severity in women with refractory schizophrenia., Design, Setting, and Participants: This 12-week, double-blind, placebo-controlled, randomized clinical trial with fortnightly assessments was performed at an urban tertiary referral center and a regional center from January 1, 2006, to December 31, 2014. Participants included 56 women with schizophrenia or schizoaffective disorder and marked symptom severity despite substantial and stable antipsychotic doses. Data were analyzed using intention to treat as the basis., Interventions: Adjunctive raloxifene hydrochloride, 120 mg/d, or placebo for 12 weeks., Main Outcomes and Measures: The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score. Clinical response (defined as a ≥20% decrease in PANSS total score from baseline) and change in PANSS subscale scores, mood, cognition, reproductive hormone levels, and adverse events were also assessed., Results: Of the 56 participants (mean [SD] age, 53 [7.7] years; age range, 40-70 years; mean [SD] duration of psychotic illness, 24 [11] years), 26 were randomized to raloxifene and 30 were randomized to placebo. Raloxifene produced a greater reduction in the PANSS total score relative to placebo (β = -6.37; 95% CI, -11.64 to -1.10; P = .02) and resulted in an increased probability of a clinical response (hazard ratio, 5.79; 95% CI, 1.46 to 22.97; P = .01). A significant reduction was found in the PANSS general symptom scores for the raloxifene compared with the placebo (β = -3.72; 95% CI, -6.83 to -0.61; P = .02) groups. For patients who completed the full 12-week trial, there was not a statistically significant treatment effect on PANSS positive symptom scores (β for change in raloxifene vs placebo, -1.92; 95% CI, -3.83 to 0.00; P = .05). Change in mood, cognition, and reproductive hormone levels and the rate of adverse events did not differ between groups., Conclusions and Relevance: Raloxifene hydrochloride, 120 mg/d, reduces illness severity and increases the probability of a clinical response in women with refractory schizophrenia. This large trial of raloxifene in this patient population offers a promising, well-tolerated agent that has potential application in clinical practice., Trial Registration: clinicaltrials.gov Identifier: NCT00361543.

Introduction: Antipsychotic medications are being prescribed for a growing number of women with mental illnesses. However, evidence regarding their safety in pregnancy is still insufficient to provide adequate support for clinical practice, creating increasing concern among pregnant women and clinicians., Areas Covered: The aim of this article is to review published data regarding the safety of antipsychotic medications in pregnancy with a focus on the most commonly used atypical antipsychotics., Expert Opinion: Given the potential harm of not treating severe psychiatric illnesses during pregnancy, careful administration of antipsychotics is recommended for pregnant women who suffer from severe mental disorders. The most frequently used antipsychotics in pregnancy are olanzapine, risperidone and quetiapine, and do not appear to cause consistent, congenital harm to the fetus. No specific patterns of fetal limb or organ malformation related to these drugs have been reported. There is some evidence suggesting an association between antipsychotic use in pregnancy and the development of gestational diabetes. Also there appears to be an association between antipsychotic medication use in pregnancy and increased neonatal respiratory distress and withdrawal symptoms. Further studies are needed for clinicians to balance good maternal mental health, healthy pregnancies and good infant health outcomes.

Background: Many women diagnosed with varying psychiatric disorders take antipsychotic medications during pregnancy. The safety of antipsychotic medications in pregnancy is largely unknown., Methods: We established the National Register of Antipsychotic Medications in Pregnancy in 2005. Women who are pregnant and taking an antipsychotic medication are interviewed every 6 weeks during pregnancy and then followed until their babies are one year old. The baby's progress is closely followed for the first year of life., Findings: As of April 18 2012, 147 pregnancies had been followed through to completion. There were 142 live births and data is available for 100 one year old babies. 18% of babies were born preterm, with a higher dose of antipsychotic medication correlating to an increased likelihood of premature delivery; 43% of babies required special care nursery or intensive care after birth; 37% had any degree of respiratory distress and 15% of babies developed withdrawal symptoms. Congenital anomalies were seen in eight babies. Most pregnancies resulted in the birth of live, healthy babies. The use of mood stabilisers or higher doses of antipsychotics during pregnancy increased the likelihood of babies experiencing respiratory distress or admission to Special Care Nursery or Neonatal Intensive Care Units., Conclusion: There is a great need for safety and efficacy information about the use of antipsychotic medications in pregnancy. Live, healthy babies are the most common outcome following the use of antipsychotic medication in pregnancy, but clinicians should be particularly mindful of neonatal problems such as respiratory distress.

The total number of reported drugs in Table 2 exceeds the total number of pregnancies because some participants were prescribed more than one medication and for some participants there were changes to prescribed medication during follow-up. The original title, abstract, Table 2, Table 3, and results section of this article state that 147 pregnancies had been followed through to completion during this study. Reference 1 Kulkarni J, Worsley R, Gilbert H, Gavrilidis E, Van Rheenen TE, Wang W, et al. (2014) A Prospective Cohort Study of Antipsychotic Medications in Pregnancy: The First 147 Pregnancies and 100 One Year Old Babies. [Extracted from the article]

Objective: Oestradiol has been implicated in the pathogenesis of schizophrenia. Women with schizophrenia often suffer with menstrual dysfunction, usually associated with low oestradiol levels, but whether menstrual dysfunction has an effect on their psychiatric symptoms is not well researched. The aim of this study is to document the menstrual characteristics of women with chronic schizophrenia with focus upon menstrual regularity, menstrual cycle length and menstrual symptoms. To determine which patient characteristics are associated with irregular menses and whether irregular menses are associated with the severity of psychotic symptoms, menstrual symptoms or depressive symptoms. Method: Cross-sectional analyses using baseline data of women enrolled in a clinical trial. Inclusion criteria include Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective or schizophreniform disorder; aged between 18 and 51 years; residual symptoms of psychosis despite treatment with a stable dose of antipsychotic medication for at least 4 weeks. Menstrual cycle characteristics including regularity, cycle length and menstrual associated symptoms were documented. Symptoms of schizophrenia were measured using Positive and Negative Syndrome Scale, cognition was measured using Repeatable Battery for the Assessment of Neuropsychological Status and depression was assessed using the Montgomery–Asberg Depression Rating Scale. Blood samples were collected at baseline for hormone assays. Results: Of the 139 women, 77 (55.4%) had regular menses, 57 (41%) had irregular menses and 5 (3.6%) women had missing data on their menstrual cycle. Use of atypical antipsychotics associated with hyperprolactinaemia was positively associated with irregular menses (odds ratio = 4.4, 95% confidence interval = [1.8, 10.9], p = 0.001), while age more than 30 years was negatively associated (odds ratio = 0.3, 95% confidence interval = [0.1, 0.6], p = 0.004). Women with irregular cycles had significantly lower oestradiol levels than women with regular cycles (213.2 ± 25.0 vs 299.0 ± 27.3, p = 0.03), but there was no difference in Positive and Negative Syndrome Scale, Montgomery–Asberg Depression Rating Scale or Repeatable Battery for the Assessment of Neuropsychological Status between those with regular and irregular cycles. The most common menstrual associated symptoms were decrease in mood with the menstrual cycle (64.8%), bloating (64.8%), cramps (59.7%), back pain (37.6%) and worsening of psychosis symptoms (32.4%). Conclusion: Regular menses are associated with higher oestradiol levels and higher rates of cyclical mood symptoms but are not associated with Positive and Negative Syndrome Scale scores. Understanding the effect the menstrual cycle can have on psychiatric illness, such as premenstrual exacerbations, is important for the holistic care of women with schizophrenia. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Raloxifene for schizophrenia and symptoms of hyperprolactinaemia?" published in previous issue of the journal.