Abstract
Pharmacotherapy in anorexia nervosa (AN) deserves further exploration. In this case report of AN with depression, the use of mirtazapine is discussed regarding its weight gain propensity via serotonin (5-HT) 5HT2C/histamine (H) H1 receptor antagonisms besides its proven efficacy in depression and good safety profile.
Case report
A 16-year-old Malay girl presented with a body mass index (BMI) of 13.4 after 2 years of dietary restriction followed by binge-eating with compensatory behaviour (e.g. vomiting and excessive exercise). She developed generalized weakness, hyperventilation, cold intolerance, dental hypersensitivities and secondary amenorrhea (reduced midcycle peak luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels, i.e. 7.8 IU L−1 and 6.5 IU L−1, respectively). She also had major depression characterized by persistent depressed mood associated with anhedonia, insomnia, poor concentration with recurrent death wishes 6 months prior to presentation. A diagnosis of anorexia nervosa, binge-eating type, comorbid major depressive disorder [1] was made. Her severe weight loss (<75% of expected bodyweight) and suicidal risk warranted inpatient treatment. However, following the patient's reluctance for admission, weekly outpatient appointments were agreed upon to maintain a strong therapeutic alliance. A multidisciplinary approach involving medical, dental, nutritional and psychological interventions was taken. At no time during follow up did she present with any medical or psychiatric emergencies. Mirtazapine was started primarily to treat the depression at an initial dose of 15 mg, then titrated to 30 mg over a 2 week period. Her weight gain fluctuated in the first 3 months with overall increase of 2.5 kg. Over the subsequent 2 months, however, she started to gain weight more steadily to reach 37 kg (BMI = 15). At this point, she binge-ate much less frequently. Her depression achieved full remission at 6 weeks of treatment, thus motivating her to continue treatment. Cognitive behavioural therapy and family counselling were started as the weight gain stabilized.
Discussion
Mirtazapine is the choice medication in this case after deliberating over common considerations in the treatment of the multifaceted disorder of AN. Weight restoration is a primary goal of treatment; most sensibly attained by administering food [2]. However, the challenge lies in the resistance of the patients. Psychotherapy may be valuable only after some weight gain has occurred due to the cognitive deficits associated with undernourishment [3]. During the acute refeeding stage, we considered mirtazapine's role in weight gain via 5HT2C and H1 antagonisms [4]. Olanzapine has also been used either singly or combined with mirtazapine to aid weight gain [5]. Besides improving appetite, both drugs may increase weight by restricting energy use as sleep improves due to the sedating effect [2]. The combination treatment, however, poses the risk of drug interaction and complicates compliance, while olanzapine alone may not address depression adequately [5]. The depressive features commonly seen in AN may resolve with weight gain alone [6]. However, depression may also interfere with the treatment process (e.g. the patient's lack of motivation and poor appetite). Moreover, such comorbidity is found to have a lasting effect on the psychosocial functioning even when the acute episode of the eating disorder has remitted [7]. Treating depression requires caution, given AN patients’ physical vulnerability; particularly considering the cardiac effects of tricyclics and antipsychotics [6] and the gastrointestinal disturbance of selective serotonin re-uptake inhibitors (SSRIs). We feel that these considerations made mirtazapine, a non-SSRI antidepressant, theoretically suitable in treating depression in AN. Nevertheless, severe depletion of central 5-HT levels reported in AN resulting from starvation and weight loss [8–10] may compromise the effectiveness of antidepressants including mirtazapine. Therefore, controlled trials of mirtazapine for AN are needed for more conclusive evidence regarding its use in clinical practice.