Anorexia refers to a psychological condition whereby someone has an extreme evaluation of their body weight and shape which leads to the development of the physical capacity to tolerate self-imposed weight loss (NICE, 2017). The latest psychiatric classification manuals such as the Diagnostic and Statistical Manual, fifth edition (DSM V-TR) as well as the International Classification of Diseases (ICD-10) guide the diagnosis of anorexia based on the following criteria a) refusing to maintain weight based on the normal Body Mass Index (BMI) (b) fear of gaining weight (C) disturbance of body image and (d) the lack of menstrual cycles or amenorrhea in women which can be coupled with a loss of interest in the opposite gender (Kaye et al., 2001). In anorexic patients, body image is turned into a measure of self-worth coupled with denial of the existence of the gravity of the situation (Del Barrio, 2016). It should be noted that food restriction is one of the major aspects of the practice that is employed to lose weight. In anorexia, patients over-exercise themselves and get overly active to burn calories. Therefore, they generate opportunities to be active through for example choosing to stand instead of sitting. Individuals with anorexia are sport, athletics and dance enthusiasts. Additionally, they indulge themselves in purging activities such as self-induced vomiting, misuse of laxatives, diuretics and “body slimming substances” (Marvanova & Gramith, 2018). The majority of the patients tend to body checking which entails multiple weighing, measuring, gazing at their images in the mirror as well as other obsessive for self-reassurance that they look thin.
According to a meta-analysis conducted by Martínez-González et al. (2020) there were high rates of Anorexia Nervosa among young women than males. For example, there were 120 per 100,000 person-years in the Swedish female’s population aged 20-32 years, 200 out of 100,000 person-years among the Spanish females who were between the ages of 12 and 22 years as well as 270 per 100,000 person-years in Finnish twin females at the age of 15-19 years (Sebaaly et al., 2013). Among the European women, less than 3% are grappling with anorexia nervosa with another less than 2% suffering from bulimia nervosa (Garner et al., 2016). Among the young females in Western Europe and the United States of America, the mean prevalence approximations stand at 0.3% for Anorexia nervosa with the clinical conditions that do not reach the threshold being more prevalent (Ruggiero et al., 2003). Anorexia Nervosa presents huge mortality rates among eating disorders and there has been no improvement in the recent past despite the plethora of options available to psychiatrists (Berends et al., 2016). It stems from the fact that few patients utilize healthcare facilities. It should be noted that the rates of anorexia nervosa appear stable while those of bulimia nervosa are reducing. However, an insignificant number of eating disorders are detected by healthcare professionals (Giel et al., 2021). It is essential to bear in mind that more than 70% of people with eating disorders are suffering from psychiatric comorbidity (Hay et al., 2014). The risk of suicide is increased in eating disorders despite comorbidities being constant.
However, in the majority of the reported cases of Anorexia, there is a simultaneous presentation with other psychiatric and medical conditions which can make treatment complicated. It should be noted that mood and anxiety disorders are significantly common in a large clinical database of Swedish eating disorders (Garner et al., 2016). The most prevalent comorbid disorders include anxiety (53) and mood problems (43%) (Sebaaly et al., 2013). Substance use disorders were present in 10% of the patients with the most common diagnoses being major depression (33%), generalized anxiety disorder (31%) and particular phobias (17%) (Kaye et al., 2001). Students are at increased risk of eating disorders. In Serbia, 7.6% of the randomly selected students at the age of between 18-35 years reported eating disorders using the Eating Attitudes Test (EAT-40) with a low 2.6% of low body mass index (17.5 kg/m2) even though a single student (0.2%) reported having experienced the symptoms of eating disorders and a low body mass index (Walsh et al., 2006a). However, contrasting findings were reported in the Canary Islands whereby 33% of the females and 21% of the male students had scores of 20 in EAT-40 (Gwirtsman et al., 1990).
The most commonly used plethora of treatment options available for the management of Anorexia Nervosa include nutritional rehabilitation and pharmacological management. According to Del Barrio (2016), Hay et al. ( 2014) and NICE (2017), nutritional/weight restoration is the first-line treatment in anorexic patients that are underweight and malnourished. There is evidence that it improves cognitive function and enhances the effectiveness of psychological interventions (Berends et al., 2016). Additionally, malnutrition worsens depression and anxiety symptoms which can be fully or partially ameliorated by nutritional rehabilitation and weight restoration. The National Institute for Health and Care Excellence encourages a regular or daily intake of multivitamin and multi-mineral supplements to the point of dietary intake being able to offer sufficient supplies (Giel et al., 2021). Pharmacological treatment involves the use of antidepressants such as selective serotonin reuptake inhibitors such as fluoxetine and citalopram, tricyclic antidepressants such as amitriptyline, antipsychotics (olanzapine and quetiapine) and hormones (growth hormone, testosterone and estrogen) (Gwirtsman et al., 1990). Psychosocial interventions such as psychoeducation, individual therapy, family therapy and family therapy are the mainstay for the management of anorexia nervosa.
The use of antidepressants in the management of Anorexia nervosa is well documented. From the pathophysiologic point of view, antidepressants qualify for clinical evaluation and consideration in Anorexia Nervosa (AN) based on the pharmacological actions on the serotonin (5-HT) neurotransmitter system. It should be noted that antidepressants have been the mainstay of therapy for anxiety, depression and obsessive-compulsive behaviours that are common in AN (Marvanova & Gramith, 2018). Scholars have made efforts to tie the agents to eating disorders that stem from their underlying neurobiological abnormalities concerning catecholamine metabolism, more specifically serotonergic dysfunction, significant shared comorbidity, shared genetic risk as well as personality traits (Ruggiero et al., 2003).
The most recent treatment guidelines do not recommend employing antidepressants as monotherapy for AN because of their limited efficacy. On top of that, the use of tricyclic antidepressants and monoamine oxidase inhibitors is limited because of insufficient and reliable efficacy data coupled with narrow safety margins. However, Garner et al. (2016) show evidence of the multiple prescriptions of antidepressants among adults and adolescent anorexic patients despite the contrary recommendation by the treatment guidelines. Fluoxetine, the selective serotine reuptake inhibitor, was the most prescribed antidepressant (87.9% of study participants). Notably, depression and anxiety are the major factors implicated in the development of anorexia nervosa meaning that anorexic patients can benefit from antidepressant drugs such as fluoxetine. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) which blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane and thereby amplifying the actions of serotonin on 5HT1A autoreceptors (Walsh et al., 2006b). SSRIs have an insignificant affinity for the histamine receptors, acetylcholine, as well as norepinephrine receptors as compared to the tricyclic antidepressant drugs. It is the first SSRI to be introduced and it has the longest duration of action with a plasma half-life of 2 days while the demethylated metabolite has 7-10 days (Ruggiero et al., 2001). It is now approved for use in children less than 7 years or older for depression as well as OCD on the grounds of similar efficacy and side effects profile as in adults (NICE, 2017). However, fluoxetine should only be administered to children when psychotherapy fails. The most common side effects include agitation and dermatological reactions are more frequent as compared to other SSRIs. Because of its slower onset of antidepressant action, it is best suited for patients that do not require rapid effect and is more appropriate for poorly compliant patients. It is contraindicated in patients showing agitation.
Research evidence exists for the use of fluoxetine in the management of AN. De Zwaan (2003a) conducted a systematic literature review on the pharmacotherapy of ANS and evidence from uncontrolled studies showed that antidepressants have a major role in weight gain (Gwirtsman 1990; Pallanti 1997; Frank 2001a). Non-randomized trials drawing a comparison between the SSRIs treatment (together with other interventions) and placebo had a mixture of findings (Strober 1999; Ferguson 1999; Santonastaso 2001; Ruggiero 2003). For example, Ruggiero (20003) found significant weight gain in AN patients treated with fluoxetine and nutritional management in stark contrast to those on only nutritional management. On the other hand, Strobber (1999) did not find any benefit of including fluoxetine in the inpatient’s management in terms of weight gain or AN symptom in contrast to matched historical records that were subjected to the same interventions without adjunctive pharmacotherapy. However, the scholars argued that confounding variables, for example, other adjuvant treatments limited the confidence in the findings meaning that there is a need to consider randomized controlled trials.
The majority of the randomized controlled trials have shown disappointing but important results concerning the use of fluoxetine in anorexia nervosa. Sebaaly et al., (2013) carried out randomized control trial to find out if fluoxetine can promote recovery, as well as prolong the time relapse among patients diagnosed with anorexia nervosa after weight restoration. The findings of the study failed to indicate any benefit from fluoxetine in the management of patients having anorexia nervosa. Similar findings were reported by Attia et al. (1998) in a randomized, placebo-controlled, double-blind among women taking part in an inpatient program for anorexia nervosa. There were no significant differences in terms of clinical outcome between the patients that were taking a placebo and those that received fluoxetine. Walsh et al. (2006b) offer similar study findings in their random double-blind controlled trial to find out the effectiveness of fluoxetine in patients in prolonging time-to-relapse among the patients with anorexia nervosa after weight restoration. The study failed to support any benefit from the use of fluoxetine in the treatment of patients with anorexia nervosa.
However, Kaye et al. (2001) carried a study to find out if SSRIs can improve outcomes and lower relapse following weight restoration among anorexics. In the study, a double-blind placebo-controlled trial of fluoxetine was administered to 35 patients. Anorexics were randomly assigned to fluoxetine(n=16) or a placebo (n=19) following in-patient weight gain and observed as outpatients for 12 months. Even though only 3 out of 19 continued to take a placebo for the whole period, the subjects that remained on fluoxetine for a year had lower relapse rates as evidenced by a significant increase in weight and lowering of the symptoms. The study provides light at the end of the tunnel about the use of fluoxetine in preventing relapses in patients after weight restoration.
A significant number of methodological limitations reduce the power of the studies conducted so far to show differences between medication and placebo. The trials for the use of fluoxetine among anorexics used small sample sizes. For example, in the study by Kaye et al. (2001) only 16 participants were in the medicated group. It should also be noted that the trials of fluoxetine in anorexia nervosa have been provided with an adjuvant to an established treatment program. Therefore, few studies have been conducted to find out if antidepressant medication is better than placebo as monotherapy. A randomized naturalistic trial comparing a routine clinical practice for example psychotherapy and nutritional advice, and routine clinical practice without medication in the outpatient setting could deal with the methodological shortcomings raised. Therefore, the use of fluoxetine in the local population should be based on the clinical experience of effectiveness. Since there is no evidence for use as monotherapy, fluoxetine should only be used with other treatment programs.
