Introduction

Orthorexia nervosa (ON) is a recently proposed eating-disordered behaviour characterized by an obsessional or exaggerated fixation on healthy eating that leads to malnutrition and daily functioning disability [1,2,3]. It may also be associated with several medical conditions related to dietary restriction and malnutrition, affective instability, social isolation and also to higher depressive symptoms [1,2,3,4]. Although ON is not officially recognized by classifications of mental disorders as an autonomous entity, it is an area of increasing interest at both clinical and research settings. However, the published literature regarding its aetiology, epidemiology, clinical course, psychiatric comorbidity and clinical management (including evidence-based therapeutic strategies) remains scarce [5]. Further, its relation or distinction amongst other eating disorders such as anorexia nervosa (AN) warrants more investigation [5].

Importantly, due to few ON published case reports and to the lack of evidence-based strategies for the management of this disorder, the current approach of ON is challenging. In particular, there is a lack of evidence regarding the best psychopharmacological options for the management of ON. Mirtazapine is a noradrenergic and specific serotonergic antidepressant with a unique pharmacological profile, which may determine several advantages over other antidepressants [6, 7]. Besides its relative rapid-onset of action and good tolerability, mirtazapine is effective in the treatment of major depressive disorder (MDD) (including the subgroups of anxious, agitated, melancholic, geriatric and treatment-resistant depression), obsessive–compulsive disorder (OCD) and a range of anxiety disorders [6, 7]. Further, because of its anxiolytic, sleep-improving, appetite and weight gain enhancer, antiemetic and pain-management properties, it may offer particular therapeutic benefits in depression with insomnia or weight loss; depression comorbid with medical illness such as post-myocardial infarction, post-stroke; depression associated with temporal lobe epilepsy; and in the treatment of other medical (weight loss in cystic fibrosis or cancer-related cachexia) and neurologic conditions (progressive multifocal leukoencephalopathy or movement disorders) [6, 7].

In the current report, and to the best of our knowledge, we present the first case of ON comorbid with depression successfully treated with mirtazapine. We also review the published literature regarding the approach of ON, as an attempt to face the clinical challenges in the recognition, management and long-term follow-up of this eating disorder.

Case presentation

A 18-year-old woman, living with his mother, presented to our ambulatory treatment unit accompanied by her parents with a 1-month history of depressed mood, anxiety, irritability and emotional lability, anhedonia, social isolation and withdrawal, insomnia with early morning wakening, fatigue and diminished ability to think or concentrate. She also reported substantial decrease in academic performance and absenteeism (to the high school).

Further, in the prior 12 months, patient also began to be “more concerned and obsessional” about her diet, spending several hours a day on the internet, studying food elements (namely nutrients, vitamins and amount of calories and what she called “incompatibilities between foods”), becoming obsessional for selective healthy eating habits (“what should I and should I not be eating”) and to eat what she assumed to be “healthy food” (as she called “clean food”, without preservatives or additives), which led her to a substantial modification of her food habits. Accordingly, she progressively suppressed all foods with sugar including sodas and soft drinks, fried and processed foods (including fried chips, popcorns, “fast food”). She gave preference to vegetables, fruits, fish, dry fruits (nuts, almonds and hazelnuts), berries and white meat (only sporadically). She banned red meat and certain complex carbohydrates from her diet. As she stressed, the food needed to be consumed “in certain amounts and specific combinations, with no preservatives or additives” to be considered “healthy”. She also began to buy the ingredients and cook her meals (therefore she “knew what I was eating and did not wanted to eat other foods”), spending more hours in the kitchen. She began to walk with her own food stored in plastic containers, eating alone and reporting that “everywhere I go I always have to go with my food”. Further, when she went to a restaurant accompanied by her friends or family, she had to verify the cuisine and the food served. If the restaurant did not have the type of food that she judged as appropriate, she invented excuses to go away even if “no one understood my concerns and behaviour”. She also had personal conflicts with family, friends and boyfriend that led her to become more socially isolated. Two weeks previously to the first psychiatric consultation, she broke up with her mother due to easy irritability and issues related to academic absenteeism and moved to the father’s house. Due to this obsessional behaviour, the patient lost approximately 15 kilograms (kg) in 12 months.

She had no relevant medical history, no allergies nor toxicological habits. There was a positive family history for MDD in her mother and grandmother and also for bipolar disorder in a paternal uncle and a paternal aunt. She was the only daughter and her parents are divorced since she was 8-year-old.

At the mental state of examination, the patient was alert and orientated in all references. Speech was fluent and coherent. Her mood was depressed with mild psychomotor retardation. She also presented easily irritability in some instances of the interview (when contradicted by her parents regarding the difficulty to assume the “exaggerated preoccupations, thoughts and behaviour regarding food and obsession with healthy food”). No suicidal ideation was perceived. She presented obsessional thoughts related with eating healthy food. No hallucinatory and delusional activity or thought formal abnormalities were detected. Insight and critical appraisal were preserved. She also referred mild subjective complaints and difficulties in concentration and attention. She denied fear of being fat or a disturbed body image and assumed her low weight and recognized that “if it progresses it may become into a putative medical problem”. She denied episodes of compulsive eating, purgative/compensatory behaviours (such as vomiting, laxative or diuretic misuse) or history of hypomanic or manic symptoms. She also denied amenorrhea or irregular menstrual cycles.

On physical examination, the patient had an overall good appearance despite her thinness. Apparent age was coincident with the chronological age. A slim appearance, mild proximal muscle wasting and lanugo over the face and upper limbs were noted. She also had dry skin, brittle hair and nails. On vital signals she presented bradycardia (56 beats per minute) and normal blood pressure. She had 42 kg, a body mass index (BMI) of 16.2 kg/m2 and 78.8% of ideal body weight (IBW). The remaining physical examination was unremarkable.

In the initial assessment, she performed the ORTO-15 test (a 15 item, multiple choice questionnaire) with a score of 19-points [8]. This result corresponds to the presence of, or a trend to ON behaviours including obsessive attitudes regarding time spent on thinking, choosing, buying, preparing and consuming food that the patient considers healthy.

Her analytical evaluation, including complete blood count, glucose, electrolytes, renal, hepatic and thyroid functions, lipid profile and basic urinalysis, was within the normal limits. The electrocardiogram revealed sinus bradycardia, without other alterations.

Our presumptive diagnosis was ON, comorbid with moderate to severe MDD, with significant impairment of occupational and social functioning. The patient started a structured individual treatment with regular appointments settled initially fortnightly, then monthly and finally every 2 months. Pharmacologic treatment was initiated in the first appointment and consisted in mirtazapine 7.5 mg everyday at bedtime (increased to 15 mg after 3 days), alprazolam 0.25 mg (when required) and multivitamin-mineral supplements once a day—containing fish-derived omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], folic acid, vitamin B12, vitamin E, and magnesium. Psychoeducation regarding medical consequences of malnutrition, nutritional counselling on healthy amount and variety of food and monitoring of weight, mental and physical health were also provided during psychiatric follow-up.

After 1 month, although the sleep-wake cycle normalized, mirtazapine was raised to 30 mg qhs due to a partial remission of mood and anxious symptoms (sadness, frustration, mild irritability and anxiety) and maintenance of some degree of absenteeism to the high school. After 6 weeks of the initial mirtazapine dose titration, a progressive amelioration of her mood and anxious states was noticed, as was a parallel improvement in her academic performance. A progressive reduction of obsessional fixation for healthy eating and food-related ideas was evident, with progressive recovery of her previous eating habits with diversification of her eating food. The patient also started regular physical activity (daily walks) of moderate-intensity. Further, a gradual improvement in her weight/BMI was documented, and after 5 months of treatment she gained 3 kg (weight 45 kg, BMI 17.36 kg/m2 and IBW 84.43%) (Fig. 1). After 6 months of therapy, she stopped the multivitamin-mineral supplements and maintained mirtazapine 30 mg qhs. Due to remission of depressive and anxiety symptoms, with maintenance of euthymia, the dose of mirtazapine was decreased to 15 mg and then suspended after 9 and 10 months of treatment, respectively. Additionally, she scored 31 and 41 points on a repeated ORTO-15 [8] at 5 and 11 months of therapy, respectively (Fig. 1).

Fig. 1
figure 1

Evolution of scores of ORTO-15 scale, weight and body mass index during the follow-up period between March 2017 and January 2018, and temporal relation with mirtazapine treatment. BMI body mass index, qhs every bedtime

Full size image

At the time of the writing of this case report (11 months of follow-up), the patient maintains remission of depression and anxiety symptoms and a sustained increase in her weight, reaching 50 kg (BMI 19.29 kg/m2 and IBW 93.81%) (Fig. 1) or a 19.1% increase in weight. Despite maintaining “some care regarding healthy eating”, the patient remains without ON obsessional fixation or behaviour (buying, choosing, preparing or eating “healthy food”) and has a normal occupational, psychosocial and personal functioning. As she stated “now my preference for a healthy diet is an option, not an obsession”. She is currently in the first year of college, with good academic performance and social integration.

Discussion

To our knowledge, this is the first case report of ON comorbid with MDD successfully treated with mirtazapine. Comorbid moderate to severe MDD was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria [9], but ON tendencies and behaviours preceded the onset of depressive symptomatology. The utility and validity of considering ON a specific entity within the well-established classification of eating disorders is currently a matter of discussion [5]. Notwithstanding, our patient met the current ON diagnostic criteria proposed by Moroze et al. and by Dunn and Bratman [2, 3]: obsessional preoccupation with eating self-defined “healthy foods” and with the composition of meals that are believed to promote optimum health; unbalanced diet that results in malnutrition and weight loss (which is not a primary goal); preoccupation and worries with, and rigid avoidance of foods believed to be “unhealthy” by the patient (foods that are processed or contain fat, preservatives or sugar); excessive amount of time reading about, acquiring, and preparing a specific type of food (quality and composition); progressive restriction of food rules, including elimination of food group elements, more frequent “cleanses” and partial fasts assumed to be purifying and detoxifying; guilty feelings about “transgression” with eating “unhealthy” or “impure” foods; and exaggerated fear of disease, emotional response, anxiety or shame when failing to accomplish self-imposed dietary rules; intolerance to beliefs and opinions of other people regarding nutrition. The symptoms of ON also result in malnutrition, severe weight loss or other medical complications; severe personal, social and academic impairment or distress; are not merely an exacerbation of other mental disorders (e.g., OCD, schizophrenia or another psychotic disorder); and do not result from religious beliefs regarding food, or medical conditions requiring specific diets or restrictions (such as food allergies).

In the initial assessment, the patient scored 19-points on ORTO-15 test, a tool that may aid in supporting the diagnosis of ON [8]. According to Donini and colleagues, values below a 40-point cut-off indicate ON behaviours or tendencies with a sensitivity, specificity, positive predictive value and negative predictive value of 100, 73.6, 17.6, and 100%, respectively [8]. During the follow-up, our patient performed progressively better on ORTO-15 test (31- and 41-points after 5 and 11 months, respectively) (Fig. 1), with a parallel weight gain and maintenance, reflecting improvement on orthorexic tendencies and behaviours [8]. Although ORTO-15 is one of the most used tools to assess symptoms suggestive of ON, some limitations of this test, namely its psychometric properties, have been recently stressed [2]. Accordingly, limitations regarding the validation of the existing psychometric tools or scales (such as ORTO-15 or its available shorter versions, and Bratman Orthorexia test) represent a current major issue that needs to be addressed in future research. Thus, the results of ORTO-15 (as a diagnostic and monitoring tool) reported in our case should be interpreted with caution [2].

The differences and similarities between ON and other eating or feeding disorders (such as low body weight or the avoidance of “fattening” foods) need to be better investigated, as a clear differential diagnosis is warranted for a proper clinical management and treatment. ON patients seem to be more concerned about the “quality” rather the “quantity” of food demonstrated by patients with AN and bulimia nervosa (BN); these two disorders also seem to be characterized by a higher obsession with the physical appearance [3]. In our patient, AN was excluded since there was no desire for thinness or fear to become fatness, no dysmorphophobia, endocrine disorders (such as amenorrhea) or other self-induced weight loss behaviours (e.g., purging, vomiting, excessive exercise or drug misuse). In addition, the patient recognized that loosing additional weight could lead to medical complications. BN was also excluded due to the absence of recurrent episodes of binge eating or overvalued ideas about ideal body shape or weight.

The concern about aversive consequences of food (rigid choices for food considered “healthy” and avoidance of that considered “unhealthy”), the significant weight loss, nutritional deficiency and persistent failure to meet nutritional needs, are putative criteria that possibly better fits ON in the DSM-5 diagnostic category of avoidant/restrictive food intake disorder (ARFID). However, this broader group of diseases may comprise (but is not limited to) other clinical settings such as ‘‘sensory food aversions’’ (avoidance of food based on its sensory characteristics), lack of interest in food or eating, dependence on enteral feeding or oral nutritional supplements, or previous aversive experience with food that may occur in choking phobia [10]. As stated by Dunn and Bratman, contrarily to ARFID, the pathologic drive for the eating behaviour that characterizes ON is to be as healthy as possible [2].

There is also an ongoing discussion regarding whether obsessional ideas related to healthy food or ritualized eating behaviour suffice to include ON in the spectrum of OCD [2, 3]. Although ON may be accompanied by anxiety and depression symptoms, such as those reported in our patient, in OCD the obsessions/compulsions are typically accompanied by marked anxiety symptoms and are not the result of another mental disorder. Further, OCD also differs from ON in that OCD is experienced as dystonic, while orthorexic behaviour is syntonic.

Despite the recent increase in research on this field, there is limited evidence regarding psychopharmacological or psychotherapeutic treatment approaches to ON. Accordingly, the currently available data are derived from single cases published in the literature [2, 3, 11]. A recent case report suggested the utility of olanzapine and brief supportive psychotherapy in an ON patient that resulted in weight gain and maintenance and remission of obsessional ideas related to healthy eating [3]. Another case report of ON that presented with a prodrome of schizophrenia, was also treated with an atypical antipsychotic [11].

To our knowledge, there are no published reports regarding the use of mirtazapine in ON (comorbid with depression). Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) with a dual mode of action—serotonin type 2A, 2C and 3 receptors (5-HT2A/2C/3) antagonism and alpha2 adrenergic receptors antagonism [7]. Common side-effects include sedation and weight gain [histaminergic type 1 receptors (H1) antagonism], orthostatic hypotension (alpha1 adrenergic receptors antagonism) and anticholinergic effects [muscarinic acetylcholine type 1 receptors (M1) antagonism] [7]. Due to mirtazapine side-effects of increased appetite and weight gain, its use in eating disorders may be considered controversial. However, the decision to choose this therapy in our patient (with her informed consent) was related to its well-established efficacy on depression and anxiety symptoms, its utility on insomnia due to the sedative action and also its weak impact on sexual function. Additionally, there are published data (case reports), suggesting the efficacy of mirtazapine in the treatment of AN comorbid with depression [12] that supported its use in our patient. Notwithstanding, mirtazapine should normally not be used for children and adolescents under 18 years due to the lack of demonstrated efficacy [13, 14], therefore the results of this research should not be generalized to these age populations. The use of an oral multivitamin-mineral with fish-derived omega-3 fatty acids supplement was related to its utility in weight restoration and as a co-adjuvant treatment of depression [15].

Conclusion

Herein we have presented a case of ON comorbid with MDD that was successfully treated with mirtazapine. This approach resulted in an improvement and maintenance of weight gain and remission of orthorexic tendencies and behaviours, as well as resolution of depressive symptoms after an 11-month follow-up period. Future research may thus consider the usefulness of mirtazapine in the management of ON on well-designed randomized trials. Considering ON as a specific entity along with the clarification of its position amongst other eating disorders warrants additional research, which may shed light on the appropriate diagnosis and management of this clinical context. Furthermore, the timely implementation of evidence-based strategies to approach ON may prevent the development of other medical complications, and may also avoid the progression to other eating disorders.