Is Antipsychotic Drug Use During Pregnancy Associated with Increased Malformation Rates and Worsening of Maternal and Infant Outcomes? A Systematic Review.

There is much debate about continuing antipsychotic medication in patients who need it when they become pregnant because benefits must be weighed against potential teratogenic and malformation effects related to antipsychotics themselves. To address this, we conducted a systematic review on the PubMed, PsycINFO and CINHAL databases and the ClinicalTrials.gov register using the following strategy: (toxicity OR teratogenicity OR malformation* OR "birth defect*" OR "congenital abnormality" OR "congenital abnormalities" OR "brain changes" OR "behavioral abnormalities" OR "behavioral abnormalities") AND antipsychotic* AND (pregnancy OR pregnant OR lactation OR delivery OR prenatal OR perinatal OR post-natal OR puerperium) on September 27, 2023. We found 38 studies to be eligible. The oldest was published in 1976, while most articles were recent. Most studies concluded that the antipsychotics, especially the second-generation antipsychotics, were devoid of teratogenic potential, while few studies were inconclusive and recommended replication. Most authoritative articles were from the Boston area, where large databases were implemented to study the malformation potential of psychiatric drugs. Other reliable databases are from Northern European registers. Overall conclusions are that antipsychotics are no more related to malformations than the disorders themselves; most studies recommend that there are no reasons to discontinue antipsychotic medications in pregnancy.

The Patient's Perspective on the Effects of Intranasal Esketamine in Treatment-Resistant Depression.

The effectiveness of the esketamine nasal spray (ESK-NS) for treatment-resistant depression (TRD) has been confirmed by real-world studies. Available evidence derived from clinician-rated assessments might differ from patients' perceptions about the helpfulness of treatments. We aimed to verify the effect of ESK-NS from patients' view in 25 TRD patients (56% males, 55.1 ± 10.9 years) treated with ESK-NS (mean dose: 78.4 ± 11.43 mg) for three months and evaluated at different time-points through clinician-rated and self-administered scales, assessing changes in depression, anhedonia, sleep, cognition, suicidality, and anxiety. We observed an overall early improvement that lasted over time (endpoint total score reduction in Montgomery-Åsberg Depression Rating Scale, p < 0.001, Beck Depression Inventory, p = 0.003). Patients reported a significant self-rated decrease in anhedonia at two months (Snaith-Hamilton Pleasure Scale, p = 0.04) and in suicide ideation at endpoint (BDI subitem 9, p = 0.039) vs. earlier improvements detected by clinicians (one-month reduction in MADRS subitem 8, p = 0.005, and subitem 10, p = 0.007). These findings confirm the effectiveness of a three-month treatment with ESK-NS in TRD patients, highlighting an overall overlapping response from patients' and clinicians' perspectives, although with some differential effects on specific symptoms at given time-points. Including patients' viewpoints in routine assessments could inform clinical practice, ensuring a better characterization of clinical phenotypes to deliver personalized interventions.

The Nrf2 Pathway in Depressive Disorders: A Systematic Review of Animal and Human Studies.

There is increasing interest in the involvement of antioxidative systems in protecting from depression. Among these, Nrf2 occupies a central place. We aimed to review the role of Nrf2 in depression. For this reason, we conducted a PubMed search using as search strategy (psychiatr*[ti] OR schizo*[ti] OR psychot*[ti] OR psychos*[ti] OR depress*[ti] OR MDD[ti] OR BD[ti] OR bipolar[ti] OR Anxiety[ti] OR antidepress*[ti] OR panic[ti] OR obsess*[ti] OR compulsio*[ti] OR "mood disord*"[ti] OR phobi*[ti] OR agoraphob*[ti] OR anorex*[ti] OR anorect*[ti] OR bulimi*[ti] OR "eating disorder*"[ti] OR neurodevelopm*[ti] OR retardation[ti] OR autism[ti] OR autistic[ti] OR ASM[ti] OR adhd[ti] OR "attention-deficit"[ti]) AND nrf2, which on the 9th of March produced 208 results of which 89 were eligible for our purposes. Eligible articles were studies reporting data of Nrf2 manipulations or content by any treatment in human patients or animals with any animal model of depression. Most studies were on mice only (N = 58), 20 on rats only, and three on both rats and mice. There were two studies on cell lines (in vitro) and one each on nematodes and fish. Only four studies were conducted in humans, one of which was post mortem. Most studies were conducted on male animals; however, human studies were carried out on both men and women. The results indicate that Nrf2 is lower in depression and that antidepressant methods (drugs or other methods) increase it. Antioxidant systems and plasticity-promoting molecules, such as those in the Nrf2-HO-1, BDNF-TrkB, and cyclic AMP-CREB pathways, could protect from depression, while glycogen synthase kinase-3ß and nuclear factor κB oppose these actions, thus increasing depressive-like behaviours. Since Nrf2 is also endowed with tumorigenic and atherogenic potential, the balance between benefits and harms must be taken into account in designing novel drugs aiming at increasing the intracellular content of Nrf2.