Prescribing antidepressants and anxiolytic medications to pregnant women: comparing perception of risk of foetal teratogenicity between Australian Obstetricians and Gynaecologists, Speciality Trainees and upskilled General Practitioners

Abstract

Depression and anxiety are common disorders, however their occurrence during pregnancy has the potential to significantly impact the health and wellbeing of both mother and child [ 1 , 2 ]. Negative outcomes of mental health disorders in pregnancy include a variety of serious complications. Inadequately treated depression is associated with a substantial risk of maternal, fetal and neonatal morbidity and mortality [ 3 ]. In addition to subjective distress, the impact on relationships can be very significant, particularly when attachment to the newborn is disrupted. This may lead to enduring detrimental effects on the child extending into adulthood [ 4 ]. Depression also leads to suicide, with it being the second largest cause of indirect maternal mortality in the perinatal period in Australian women [ 1 ]. Unclear messages contribute to pregnant women being reluctant to take psychotropic medication, including antidepressants and anxiolytics with many fearing foetal harm [ 5 , 6 , 7 , 8 ]. Medical personnel including O&Gs and GPs form an important part of a pregnant woman’s network of information sources during pregnancy and can impact patient decision-making around medications in pregnancy [ 7 , 8 , 9 ]. The Australian clinicians’ own perception of teratogenicity of antidepressants (AD) and anxiolytics (AX) may influence counseling and care of vulnerable women and is largely unexplored. It is, however, likely to align with the international community where perceived teratogenicity is overestimated by physicians of all medical specialties, except psychiatrists [ 10 , 11 , 12 ]. Professional bodies such as the RANZCOG publish statements and recommendations to provide advice on management of perinatal anxiety and depression, serious mental illness and bipolar disorder. The target audience is all health professionals who are engaged in providing maternity and mental health care to these patients [ 13 ]. This study hypothesised that differences exist in the perception of risk of teratogenicity of AD and AX medication commonly prescribed to pregnant women, by differing clinicians, namely O&Gs and GPs. It also explored medication counselling and prescription practices, clinician resources and base knowledge of risk of AD and AX when used in pregnancy. Utilising the RANZCOG database, current Obstetrics and Gynaecology Fellows, trainees and “GP diplomates” (upskilled General Practitioners with additional qualifications in Women’s Health) were invited to participate in a nation-wide cross-sectional observational study of practices relating to prescription of AD and AX in pregnancy and provided a link to an anonymous ten-minute online questionnaire ( www.surveymonkey.com ) (Additional file 1 ). Participation was voluntary and consent was implied with completion and submission of the questionnaire. The responses submitted by the participants were de-identified. GP affiliates included in the study from New Zealand were virtually unrepresented, as they do not undertake the Diploma and were therefore not captured by this survey. Our novel questionnaire was developed after researching questionnaire design and a directed literature search. Feedback was obtained from professional peers on the content and relevance of questions. A small pilot group of doctors ( n = 10) tested the coherence of the questions, and the time frame to complete the questionnaire. The 34 questions were designed to elicit clinician attitudes about AD and AX including their prescription during pregnancy, medication counseling practice, perceptions of the level of patient concern regarding their use during pregnancy and the risk perceptions of the stakeholders who influenced a pregnant woman’s decision making. Demographic data was collected about the clinicians aligned specialty including their proportion of public and private practice, age, training, experience, interest in mental health and educational exposure. Clinician confidence in prescribing, managing adherence issues and perceived adequacy of training to manage depression and anxiety in pregnancy were also surveyed. Questions relating to attitudes and confidence were measured using Likert scales. Similar to published literature, we also included a series of questions to gauge basic AD and AX knowledge [ 2 ]. The survey was adminstered through the RANZCOG and a reminder email was sent out 4 weeks after the initial invitation, reminding clinicians of the survey closure date. All data was analysed using the SPSS version 23 (IBM Corp., Armonk, NY). To aid with the interpretation of the questionnaire results, the following collapse of the Likert scale categories was made for Questions 21, 24 and 34: Agree = agree, strongly agree and Disagree = Strongly disagree, disagree and neutral. Categorical variables were summarised by frequency and percentage and continuous variables by mean and standard deviation (SD). Mean differences were reported with 95% confidence intervals (CI). Categorical variables were examined using Pearson Chi-squared test or Fisher’s exact test, where more than 20% of the expected values were less than 5. Continuous variables were checked for normality and examined using the Student t-test. Data was summarised for clinicians overall and separately by O&Gs and GPs. P values for the comparison of O&Gs and GPs were reported, with p < 0.05 considered to be statistically significant. Overall, the RANZCOG database identified 5409 eligible clinicians, all of whom received a standardised invitation by email. This comprised of 2120 Fellows, 769 FRANZCOG trainees and 2520 Diplomates. A total of 545 valid responses were received and submitted for analysis (10.1%), less than the predicted response rate for medical personnel (32.8%) [ 12 ]. The response rate for O&G affiliates (12.9%) was consistent with gynaecologist rates from a similar risk perception study by Csajka et al. (13%) [ 2 ]. The response rate for GP affiliates was 6.8%. Three hundred and seventy-three clinicians aligned with RANZCOG (68.4%) and 172 were affiliated with RACGP (31.6%). The demographic characteristics of the respondents are shown in Table 1 . Seventy-two percent of respondents were trained in Australian medical colleges with 60.9% having over 10 years’ experience in their area of speciality. Twenty-six percent of O&Gs and 12.3% of GPs respondents had not yet attained their fellowship. Majority of the clinicians (98%) saw pregnant women in their clinical practice on a regular basis. Seventy-eight percent of O&Gs spent 11 h or more per week caring for pregnant women compared to 18.7% of GPs. In general, respondents had no particular interest in perinatal mental health disorders (36.7%), however more GPs (46.7%) were interested than O&Gs (32.1%). The vast majority of clinicians (96.9%) had not conducted any perinatal mental health research in the last 5 years. Also, fewer than half (46.4%) of all clinicians had attended a conference or read a journal article where AD or AX medication use in pregnancy had been reviewed. In general, only a small percentage of clinicians (15.3%) were involved in the provision of education to trainees about psychotropic prescription during pregnancy. Self-reported perception of concern around prescribing AD or AX medications was not significantly different between the groups ( p = 0.38), with O&Gs ( n = 368) apportioning a mean score of 3.7 (SD 2.3) and GPs ( n = 169) a mean score of 3.9 (SD 2.4). This indicated a relatively low level of concern on a 0–10 scale, with 0 being no concerns. The perceived proportion of patient non-compliance was also not significantly different ( p = 0.36) between the groups. Both of these estimated that just over a third of patients on a 0 to 100 scale would be non-compliant with their AD or AX treatment: O&Gs ( n = 367) mean 34.8% (SD 18.7) and GPs ( n = 170) 36.4% (SD 19.3). When asked to share their perceptions, GPs ( n = 172) estimated their patients’ anxiety regarding AD and AX medication decision making in pregnancy as higher on a 0 to 100 scale: mean 73.7% (SD 21.3) compared with mean 63.1% (SD 24.1) for O&Gs ( n = 372), a mean difference of 10.6% (95% CI 6.4–14.8). Only 10.5% of all clinicians ( n = 545) “very often” provided pregnant women with written information about the intended prescription AD or AX. (6% of O&Gs compared to 14.5% of GPs). Sources of written information were varied and the overall numbers were small. Most of the O&Gs sourced UpToDate (32.2%), followed by MIMS (26.8%) and Mother Risk (13.4%). For GPs, the most commonly used resource was MIMS (27.9%) followed by “other” (19.2%) and Drug Company leaflets (15.1%). Less than 10% of all clinicians had their own practice pamphlets or relied on the pharmacists as their main source of written information. Thirty-two percent of O&Gs provided no written information compared with 16.3% of GPs ( p < 0.001). If seeing a pregnant patient with mental health illness for the first time, the time spent discussing potential maternal and foetal side effects of AD or AX treatment differed between clinician group ( p < 0.001, n = 541). More than half of GPs (52.6%, n = 171) reported spending 15 min discussing potential maternal and foetal side effects of AD or AX treatment compared with O&Gs (48.6%, n = 370) spending less than 5 min. There was a statistically and clinically significant difference ( p < 0.001) in prescription practice where AD or AX initiation was surveyed: 84.8% of 171 GPs initiated these medications compared to 52.2% of 372 O&Gs. The GPs ranked “prior response to the medicine” as being an influential reason (60.5%) for prescribing a particular AD or AX. O&Gs ( n = 372) on the other hand, were more influenced by a medication “a mental health practitioner had previously prescribed” (50.5%). This preponderance for O&Gs to rank a specialist mental health clinicians’ opinion highly was also demonstrated later in the questionnaire, where 55.7% O&Gs ( n = 357) would rely on the original prescriber’s management plan comapred to 11.7% of GPs ( n = 162) ( p < 0.001). Responses to the question relating to discontinuation of fluoxetine in a hypothetical pregnant patient signified varying practices between clinician groups. Fifty-nine percent of GPs indicated that they would initiate a patient consultation compared to only 18.0% O&Gs. Furthermore, 48.8% of O&Gs suggested that they would seek referral to a mental health specialist compared to 5.3% of GPs. The questionnaire revealed that overall, clinicians’ main concerns regarding AD and AX medication prescription to women of reproductive age in order of perceived influence are: medical safety profile including teratogenicity (86.9%, n = 543), medical efficacy (75.2%, n = 537), neonatal adaption syndrome (70.0%, n = 543), and medication addiction potential (48.6%, n = 537). Of note, 57.4% of GPs ( n = 169) were concerned about maternal side effects compared to 47.3% of O&Gs ( n = 368) ( p = 0.029) (Fig. 1 ). Comparison of self-reported knowledge and confidence in prescribing AD and AX medications by clinical affiliation There were differences in levels of reported confidence in being up-to-date with medication recommendations and safety profile with 57.6% of GPs feeling confident compared to 44.2% of O&Gs ( p = 0.004). In general, GPs consider themselves to be more confident in their knowledge (mean difference 0.9 (95% CI 0.5–1.3) and ability to prescribe (mean difference 2.2 (95% CI 1.7–2.6) and manage (mean difference 2.1 (95% CI 1.7–2.6) AD and AX medications than O&Gs. Respondents were tested on their knowledge of five well-known AD and AX medications and their potential teratogenicity. As demonstrated in Table 2 , GPs knowledge was generally similar to that of O&Gs, with the majority of respondents recognising that these medications had no significant proven teratogenicity. However, up to 22.3% respondents in both clinician groups incorrectly ascribed recognised teratogenicity to a commonly used AD or AX. Around 13% ( n = 118) trainees were incorrect for sertraline, venlafaxine and diazepam while 28.2% ( n = 117) were incorrect for amitriptyline and 21.2% ( n = 118) for mirtazapine. Twelve percent of O&Gs considered “Sertraline” teratogenic compared to 3.5% of GPs ( p = 0.001). GPs were more likely to agree that training and education had been adequate for them to feel confident in prescribing AD and AX to pregnant women (56.1%) compared to only a third of O&Gs (29.0%), p < 0.001. When asked what would be more useful to daily practice of caring for pregnant patients, 71.0% of all 541 respondents chose increased clinician education and training (71.1% O&Gs versus 70.8% GPs) in preference to increased technological supports such as apps for smart phones. Interestingly, 67.4% of a total of 543 clinicians agreed that completion of the study questionnaire had increased their interest in pursuing more information regarding AD and AX use in pregnancy.

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