To the best of our knowledge, this is the first study to leverage a large dataset of Cluster B PD individuals to elucidate the nuanced variations in psychopharmacological treatment across sex and age, shedding light on critical epidemiological patterns. Our findings revealed three key insights: (i) a noticeable fluctuation in prescription patterns surrounding the point of diagnosis; (ii) a trend towards higher medication use among females, with the exception of antipsychotics; and (iii) a significant variability in prescribing practices according to both age and classes of psychotropic medications.

The data indicated a surge in medication prescriptions nearing the time of diagnosis for both sexes, followed by a decline post-diagnosis that nonetheless failed to revert to pre-diagnosis levels, suggesting complex dynamics in treatment initiation and continuation. Several hypotheses have been proposed to explain this situation, including the emergence of new comorbidities, the sudden decompensation of an individual’s health due to an adverse social situation, the limited access to affordable psychotherapy, or the dynamics in patient-doctor relation, which can affect the patient’s tolerance of symptoms and their request for medication. It seems that during periods of crisis, clinicians are more prone to identify Cluster B PD in their patients. Thus, the diagnosis may remain hidden [29] until the clinician observes certain additional behaviours commonly associated with the diagnosis, such as suicidal tendencies or impulsive actions. This should lead to two clinical reflections. Firstly, it would be beneficial to screen for PD in groups with affective disorders or ADHD who are taking psychiatric medications before adding any new drug. This proactive approach could help to identify and treat PD, possibly with psychotherapy, before a crisis occurs. Secondly, after the “diagnostic crisis,” it is recommended that clinicians initiate deprescribing, as prescriptions decreased but did not revert to previous levels, despite clinical guidelines cautioning against these prescriptions [30, 31].

The tendency for female patients to be prescribed more medications than their male counterparts echoes broader international trends, pointing towards gender-based disparities in healthcare access, as women generally receive more medical attention and treatment strategies within psychiatric settings [24, 32,33,34]. The reasons for this could stem from biological or psychological distinctions and social determinants. It is widely recognized that there are notable distinctions between women and men with Cluster B PD, such as the number of lost years of life compared with the general population [2]. Specifically, our previous research has shown that, at age 20, female patients with Cluster B PD have a life expectancy reduced by up to nine years compared to the general population, while male patients with Cluster B PD may experience a reduction of up to 13 years [2]. The presence of comorbidities differed significantly between sexes, which may account for using distinct medication approaches. Women may experience more affective, anxiety, and eating disorders, possibly resulting in a higher likelihood of being prescribed antidepressants [21]. Meanwhile, men may exhibit higher rates of antisocial personality disorder, substance use disorders, explosive behaviours, and aggressiveness, potentially leading to increased prescription of antipsychotic medications [6, 21, 35]. Moreover, the prescription of psychotropic drugs may vary depending on sex or gender, even when treating the same illness. This is partially due to the differing effect size observed between sexes [36, 37]. This may not address the gender bias that plagues the healthcare system. Due to various social and demographic factors, there may be an overemphasis on medicalizing women and a corresponding lack of attention given to men [38]. Paradoxically, this could result in advocating for a decrease in prescription rates among females while simultaneously increasing awareness of treatment options for males.

The pronounced age-related variations in prescription trends across sexes underscore the profound impact of age as a determinant of psychiatric care, warranting deeper exploration. For instance, antipsychotic medication was more frequently prescribed for individuals of both sexes between the ages of 50 and 64 years. This could be partially explained by the possible use of some antipsychotics, such as quetiapine, for insomnia, a condition that is highly prevalent in this age group [39, 40]. Indeed, in a sensitivity analysis, removing prescriptions for low doses of quetiapine (50 mg or less), which are typically used off-label for sleeping purposes rather than psychiatric disorders, resulted in a marked reduction in the overall count of antipsychotic usage, as illustrated in Supplemental Fig. 1 [39]. Despite this reduction, the use of antipsychotics after the diagnosis remained higher than before the diagnosis for all groups, albeit to a lesser extent in women aged 50–64. These results need further investigation and a specific focus on antipsychotics that goes beyond the purpose of the current paper.

Antidepressants and anxiolytics were more commonly prescribed to men between 50 and 64, while women over 65 received a higher proportion of these drugs. Finally, with regard to ADHD medications, the trend was reversed, with a greater frequency of prescriptions observed among younger individuals that decreased over time. There has been a discernible rise in the prescription of ADHD medication to young individuals, and this trend can be attributed to different discernable factors. On the one hand, the diagnosis has not been recognized enough in the past [41,42,43,44]. On the other hand, young people may require enhanced focus for their studies, which could contribute to the greater need for ADHD drugs in this population. The increasing use of ADHD medications over time may also reflect the growing evidence of their effectiveness in reducing hospitalizations, injuries and mortality in ADHD patients [45, 46], and also among patients with BPD [47]. Comprehending the peak in antidepressant and antipsychotic prescriptions and the sex-based disparities therein poses a greater challenge. Above all, it is important to remember that prescriptions may not always be associated with an officially approved indication, as medication can be used off-label [48]. By considering this perspective, we can speculate that in males with Cluster B PDs, the highest occurrence of behavioural symptoms (such as impulsive behaviours) and internal symptoms (such as anxiety and depression) is typically observed between the ages of 50 and 64. Following this period, impulsive symptoms may tend to decrease. Conversely, among females, the peak of behavioural problems precedes that of internal symptoms. It is important to note that while BPD symptoms generally diminish over time [13, 14], the overall progression of the entire Cluster B PD may not follow the same pattern.

There was no discernible difference in trends over time between the sexes. The most prevalent medication category utilized by both males and females was antidepressants, in line with the fact that depression and anxiety were the most common comorbid conditions. Indeed, the main indications for antidepressant prescriptions are depressive [49] and anxiety disorders [50]. Indeed, anxiolytic use decreased over time, partly because of guidelines recommending newer antidepressants instead of anxiolytics for both depressive and anxiety symptoms [50]. The decline in the use of anxiolytics has also been reported in other studies from Quebec [51, 52]. However, there was no increase in the use of antidepressants during the study period to compensate for the decrease in anxiolytic use. Antipsychotic use increased only slightly during the study period. However, there was a noticeable increase in usage in the year following a diagnosis of PD, suggesting higher compliance with guidelines in the latest years [17, 18]. Nevertheless, low doses of antipsychotics can be used successfully to control emotional crises, especially in BPD, and a subclass of patients may present true psychotic symptoms. However, a possible inappropriate prescription of antipsychotics once the PD is diagnosed can still be present. Finally, prescriptions of ADHD medications showed a constant rise over the study period, corresponding to the increasing number of ADHD diagnoses over the past few years, regardless of the presence of Cluster B PD [43, 44]. The data also shows that an increasing number of females are taking ADHD medication, which is a possible indicator of a positive trend in identifying and treating this condition among girls and young women.

It is important to acknowledge that our study had some limitations. First, we used the information in the QICDSS database to categorize individuals based on sex. Even if it is theoretically possible for individuals to ask for a modification in the information about sex in the database, we believe that the frequency should be low during the period considered, but we do not have this information. We are not aware of the frequency of this occurrence. This means that our results do not apply to gender differences but rather to sex differences. Moreover, we could not access all the necessary information about medication use for every patient but only for those covered by the public drug plan. Therefore, our findings may not apply to all individuals with Cluster B PDs. This is because people with private insurance tend to have higher socioeconomic status and possibly less severe cases, as they can work and access and maintain employer-provided private drug insurance. Moreover, they have access to private health insurance covering psychotherapy, which may not be affordable for those who are more disadvantaged. Additionally, we used the diagnostic ICD-9 and ICD-10 codes recorded in the QICDSS database to identify individuals with Cluster B personality disorders. Despite the choice of such codes being based on a consensus among expert clinicians working with PD patients in Quebec, some individuals may have been wrongly assigned these codes or have been misdiagnosed. Moreover, it is important to note the absence of specific ICD codes exclusively for Cluster B PDs, which led to the adoption of a general set of codes deemed appropriate by these clinicians. This methodological choice lacks a formally validated case definition, which could lead to diagnostic misclassifications. As a result, individuals with Cluster A or C personality disorders may have been mistakenly classified as having Cluster B disorders. Considering that we employed medication claims as an estimate for medication usage, it is also possible that we may have overestimated the proportion of individuals taking psychotropic medications. Nonetheless, our findings align with previous studies conducted in various countries and contexts, indicating a high prevalence of medication use among individuals with PDs. It is also important to acknowledge that the SISMACQ database, while extensive, does not encompass all the potential confounding variables that could influence the association between sex and psychotropic prescribing patterns, such as severity of symptoms or patient-reported outcomes.

Despite these limitations, our study was bolstered by the large and diverse sample size. Indeed, it used a large cohort of Cluster B PD individuals throughout the Canadian province of Quebec. Furthermore, we had access to almost two decades of data, allowing us to discern patterns and trends in psychotropic medication use and compare them according to sex and age groups. Finally, while this study provides comprehensive insights into psychotropic medication use across a large population, detailed analyses concerning specific medication dosages and their off-label use were beyond the scope of this initial investigation. Future studies could benefit from exploring these aspects to refine the understanding of treatment patterns in cluster B patients, particularly for medications frequently used off-label (e.g., quetiapine).