The use of antiepileptic drugs in pregnancy always presents challenges to doctors and their patients as it may have deleterious effects on the developing embryo. Lamotrigine is most commonly-prescribed drug among the newer antiepileptic drugs; hence, it has been selected for the present review. A number of studies pertaining to the safety of lamotrigine use during pregnancy have been reported, with differing results. Contradictory results have been reported in animals regarding lamotrigine teratogenicity, and human studies have also proven inconclusive. In many countries, human pregnancy registries are maintained to establish the safety of antiepileptic drugs during pregnancy, as all the different suggestions favour some over others, with specific antiepileptic combinations still being questioned. It is our hope that the present work may integrate the available disparate relevant facts into a directed effort towards minimising the risk of foetal compromise.
Abnormalities, Drug-Induced ; Animals ; Anticonvulsants ; adverse effects ; therapeutic use ; Epilepsy ; drug therapy ; Female ; Folic Acid Deficiency ; chemically induced ; Humans ; Pregnancy ; Teratogens ; pharmacokinetics ; pharmacology ; Triazines ; adverse effects ; therapeutic use

INTRODUCTIONWe aim to study and elucidate the safety profile of the antiepileptic doses of gabapentin during pregnancy, and to evaluate gabapentin-induced murine fetotoxicity at different dose levels.

METHODSA total of 60 pregnant mice, divided into 12 groups of five mice each, were exposed to gabapentin in four different doses of 0 (control), 113, 226, or 452 mg/kg body weight per day, at three different gestational stages including early gestation (1-6 days), mid-gestation (7-12 days), and late gestation (13-17 days). The pregnant mice were euthanized on day 18 of gestation, and foetuses were examined for teratogenic manifestations. Their brains were dissected and examined for gross changes, malformations, histological changes, and quantitative protein estimation.

RESULTSFoetal resorptions were observed in all treated groups with gabapentin administration at early gestation (1-6 days), and mid-gestation (7-12 days). On the other hand, growth retardation along with stunting in size of live foetuses were observed in all the mid-gestation (7-12 days), and late gestation (13-17 days) treated groups. Various gross malformations were observed with all the three doses (113, 226, and 452 mg/kg body weight per day) when gabapentin was administered at mid-gestation (7-12 days). The same trends were confirmed by gross and microscopic examination of brains along with quantitative protein estimation.

CONCLUSIONGabapentin should not be prescribed during pregnancy, as no therapeutic dose of gabapentin is safe during this period as far as the foetal well-being is concerned.

Abnormalities, Drug-Induced ; Amines ; adverse effects ; Animals ; Anticonvulsants ; adverse effects ; Body Weight ; Congenital Abnormalities ; prevention & control ; Cyclohexanecarboxylic Acids ; adverse effects ; Dose-Response Relationship, Drug ; Female ; Mice ; Mice, Inbred ICR ; Models, Chemical ; Pregnancy ; Pregnancy, Animal ; drug effects ; Teratogens ; gamma-Aminobutyric Acid ; adverse effects

Objective: Pharmacotherapy including mood stabilizers and antipsychotics are frequently used in bipolar disorder (BD); however, the lack of consensus regarding the definition of polypharmacy hinders conducting comparative studies across different settings and countries. Research on Asian Prescription Pattern (REAP) is the largest and the longest lasting international collaborative research in psychiatry in Asia. The objective of REAP BD was to investigate the prescription patterns of psychotropic medications across Asian countries. The rates of polypharmacy and psychotropic drug load were also analyzed. Methods: The data collection was web-based. Prescription patterns were categorized as (1) mood stabilizer monotherapy: one mood stabilizer; (2) antipsychotic monotherapy: one antipsychotic; (3) simple polypharmacy: one mood stabilizer and one antipsychotic; and (4) complex polypharmacy: ≥ 2 mood stabilizers or/and antipsychotics. The psychotropic drug load in each patient was calculated using the defined daily dose method. Results: Among 2003 patients with BD (52.1% female, 42.4 years) from 12 countries, 1,619 (80.8%) patients received mood stabilizers, 1,644 (82.14%) received antipsychotics, and 424 (21.2%) received antidepressants, with 14.7% mood stabilizer monotherapy, 13.4% antipsychotic monotherapy, 48.9% simple polypharmacy, 20.3% complex polypharmacy, and 2.6% other therapy. The average psychotropic drug load was 2.05 ± 1.40. Results varied widely between countries. Conclusion Over 70% of psychotropic regimens involved polypharmacy, which accords with the high prevalence of polypharmacy in BD under a permissive criterion (2 or more core psychotropic drugs) worldwide. Notably, ≥ 80% of our sample received antipsychotics, which may indicate an increasing trend in antipsychotic use for BD treatment.