A retrospective study of pharmacological treatment in anorexia ... - BMC Psychiatry

To our knowledge, this is the first study to retrospectively review BMI courses at five timepoints (at the beginning of treatment and at 3, 6, 9, and 12 months after treatment) in outpatients with AN receiving different medications. In our study, patients who adhered to their antidepressant or antipsychotic medication regimens had a significant BMI increase in the 6-month follow-up, compared with patients who switched medication, used combined medication or did not use medication. These findings suggest that medication adherence to a single medication may play a key role in improving BMI in both the antidepressant and antipsychotic groups. Our study highlights the importance of medication adherence, and the essential role of pharmacotherapy in the treatment of AN. The contributions of this study are further elaborated in the following sections.

First, based on the results of our study, it seems that medication adherence is more important than the specific medication in the treatment of patients with AN. Since the core symptoms of AN are in direct conflict with the medical goal of weight gain, adherence to the therapeutic recommendations presents significant clinical challenges [28]. In the 6-month follow-up, we found that patients with AN had significant BMI increase after treatment with antidepressants (p < 0.001) and antipsychotics (p = 0.01). However, no significant differences in BMI were found in patients who switched medication, used combined medication or did not use medication. The results suggest that maintaining a consistent medication regimen may be more effective at increasing BMI, compared to switching medications or using a combination of medications. On the other hand, psychoeducational interventions to enhance medication adherence among patients with AN is critical during the treatment course. Since the main treatment of AN as delineated in the current international guidelines is a form of psycho-behavioral therapy which can be provided on an outpatient basis [13,14,15], specific psychological therapies such as trans-diagnostic Cognitive Behaviour Therapy – Enhanced (CBT-E) are the first-line treatment for all eating disorders and have the greatest impact on symptom reduction and other outcomes [29]. Novick et al. [30] found that insight, therapeutic alliance, and adherence are closely related and all of these factors have an impact on clinical and functional status in patients. That being said, pharmacotherapy may only play an adjunctive role in the treatment of AN, and behavior change and medication adherence are the keys to recovery. Patients with AN have been particularly impaired by poor insight [31], as this disorder is characterized by distorted cognitions of weight and body shape as well as ambivalence in motivation to recover [32]. Level of insight has been demonstrated to be of clinical relevance in the treatment and prognosis of psychiatric disorders [33]. Based on our results, we speculate that medication adherence is mainly accompanied by better quality of insight to the disorder itself, and increased insight may lead to acceptance of weight gain in the clinical course of AN while receiving medication.

Additionally, our study found that patients treated with antidepressants had a significant increase in BMI in the first 3 months (T0-T3) and the second 3 months (T3-T6). This information may be useful for clinicians in evaluating the effectiveness of medication based on weight change in patients with AN after prescription. A study reviewed outpatient therapy for patients with AN and found that patients with the greatest early weight gain had significantly higher levels of remission [34]. Thus, close monitoring in weight change may help clinicians to adjust the treatment plan accordingly, and it must be kept in mind that the association between early weight gain trajectories and the outcome of the disorder seems to be crucial. However, our findings are inconsistent with the results of recent studies on use of antidepressants in the treatment of AN. In general, there is a lack of solid evidence that antidepressants can improve weight gain in the treatment of patients with AN [35]. In our study, the choice of antidepressants included four SSRIs, namely fluoxetine, paroxetine, escitalopram, and sertraline, and one NaSSA mirtazapine. Fluoxetine is one of the most-studied SSRIs in AN and seems to have the most evidence supporting its use in the treatment of AN in weight-restored individuals [24]. An open trial [36] investigated fluoxetine use in 6 patients with chronic refractory AN-R previously treated with tricyclic antidepressants (TCAs), trazodone, and/or monoamine oxidase inhibitors (MAOIs), and found that fluoxetine treatment (mean duration = 7.6 months) was not only associated with significant improvement of depressive symptoms in all patients, but was also associated with significant weight gain in 5 patients (83.3%) and improvement in obsessive–compulsive symptoms. Kaye et al. [37] conducted an open trial of patients with AN who were followed up for 11 ± 6 months and found a positive effect of fluoxetine on BMI development when administered after at least partial weight recovery. However, in the study no control subjects were investigated, and the results were comparable with data from the literature. In contrast, Holtkamp et al. [23] challenged the efficacy of SSRI medication in the treatment of adolescent AN. In the study, both SSRI and non-SSRI groups showed a similar course of BMI at the 3-month and 6-month follow-up. The inconsistent evidence on the effectiveness of antidepressants in treating AN patients necessitates the need for additional studies with a larger sample size and longer follow-up duration.

Antipsychotics have also been suggested as a potential treatment option for AN. In our study, the use of antipsychotics was found to result in a significant increase in BMI after 6 months, but not after 12 months. This may be due to the limited sample size in the 12-month follow-up, the choice of antipsychotics, and the fact that antipsychotics did not address the comorbid depression and anxiety associated with AN. It is worth noting that the small sample size in the antipsychotic group (n = 2) compared to the antidepressant group (n = 17) may have limited the power of this result. Additionally, the antipsychotic used in our study was sulpiride, rather than the more commonly studied second-generation antipsychotic (SGA) olanzapine. Few studies on first-generation antipsychotics (FGAs) have been conducted on AN patients due to its severe side effects, such as grand mal seizure, which may occur in patients taking chlorpromazine [38]. A double-blind, placebo-controlled, cross-over study [39], which included 18 female AN inpatients revealed that sulpiride was superior to placebo for daily weight gain, especially in the first treatment period of three weeks. However, in the cross over analysis, this effect did not reach statistical significance. The absence of supporting evidence for the effectiveness of sulpiride in treating AN patients necessitates the need for more robust and high-quality research in order to offer practical guidance to clinicians.

Second, our study found that the BMI of patients in the switching medication group did not increase. The results suggest that frequent switching of medications may not be beneficial for weight gain and may also require a re-establishment of rapport with patients with AN. Switching medications can have a significant impact on the patient-doctor relationship, as it often involves discussing the current treatment plan, evaluating its effectiveness, and making changes to better meet the patient's needs. This process requires open communication, trust, and collaboration between the patient and doctor, which can help to re-establish and strengthen the relationship between them. However, there is a possibility that the poorer outcome in the "switch medication" group may simply reflect that this group was more medication resistant, rather than the switch itself causing the poorer outcome. Unless the clinical situation requires a medication change, prescribers may take steps to optimize current medication regimens (e.g., dosage adjustments, behavioral or psychosocial interventions) before switching medications [40]. In clinical practice, taking the time to understand a patient's motivations for wanting to discontinue or switch medications and approaching medication changes with caution can be beneficial. This is because changes in medication often result in the need to re-establish the patient-doctor relationship.

Third, in our study, pharmacotherapy was found to be superior to no medication in treating AN patients..—Compared to the group without medication, the antidepressant group showed a statistically significant increase in BMI at both the 6-month and 12-month follow-up, while the antipsychotics group showed a significant increase in BMI at the 6-month follow-up. This may be due to the fact that antidepressants effectively address the underlying depression and anxiety issues in AN patients. Although recent studies on pharmacotherapy show inconsistent evidence regarding improvements in weight gain in patients with AN, a number of the symptoms frequently associated with AN, such as depression and anxiety are responsive to medications [21]. As recommended by most guidelines, it is important to consider the overall picture of the patient, including their psychiatric, medical, nutritional, and social circumstances. Medication should be prescribed on the basis of the clinical evaluation and this evaluation should always include the patient's opinion about the treatment [11]. Apart from specific psychological therapy, the treatment needs to be provided by a multidisciplinary team to address important nutritional, physical and mental health comorbidities [41].

It is important to note that, due to the naturalistic study design (different medications at different dosages, non-randomized), our findings are preliminary and should be interpreted with caution. There are also several limitations to this study that should be considered. First, although we assessed BMI, our study lacked other clinical evaluations commonly seen in AN, such as eating disorder psychopathology, depressive symptomatology, and obsessive–compulsive symptomatology. Besides, since patients with AN are prone to have other psychiatric and medical comorbidities, the complete information of these comorbidities may be further addressed in detail but it is lacking in our study. Second, our study lacked long-term BMI follow-up. The observation periods of the BMI course were short, with follow-up at 6 months and 12 months only. Third, our study encompassed a relatively limited number of subjects (n = 93 in the 6-month follow-up group and n = 36 in the 12-month follow-up group). Therefore, further well-controlled studies with a larger sample size and a longer follow-up period are required to confirm our findings. Fourth, there are many other possible factors that might be related to BMI fluctuation in patients with AN. For example, the poorer outcome in the "switch medication" group may simply reflect that this group was more medication resistant, rather than the switch itself causing the poorer outcome. Whether patients receive nonpharmacological interventions (psychotherapy, family therapy, etc.) or whether patients receive medical treatments from internal medicine specialists may contribute to BMI change. Comprehensive information of all kinds of treatment for patients with AN should be considered in the future study. Fifth, in our study, we considered patients with AN who came back to the outpatient department routinely for prescription are those patients who were taking medication regularly. However, patients with AN are notorious for their poor medication compliance, so appropriate measurement of medication adherence such as self-report questionnaires or structured interviews should be included.