Abstract
To the Editor:
R
To the best of our knowledge, although reboxetine was reported to be effective in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and anxiety disorder (AD), there is no study in the literature about its effect on weight loss in pediatric patients. Here, we present three adolescent patients who experienced weight loss with the use of reboxetine.
Case Reports
Case 1
A 15-year-old girl with bipolar disorder was referred to our clinic by her psychiatrist because of her family's immigration to our residence. She had no history of any neurologic disorder and had mild mental retardation with an intelligence quotient (IQ) of 61 on Stanford– Binet intelligence test. She had been on valproic acid 1250 mg/day, aripiprazole 20 mg/day, and biperiden 4 mg/day for 3 years, and her family had no complaint except weight gain resulting from medication use. She gained 30 kg (from 58 kg to 88 kg) during this period. According to her parents, dietary interventions failed, because she refused to comply with the instructions. We decided to add a pharmacologic agent for weight loss. Metformin and topiramate were used, but the former was discontinued because it provided no benefit, and the latter was discontinued because of severe apathy. Reboxetine, 4 mg/day, was initiated and increased to 8 mg/day a week later. The patient's weight decreased dramatically from 88 kg to 70 kg after 12 weeks. She experienced no side effects other than loss of appetite, and had also not used any herbal drug for weight loss. She was still on reboxetine treatment and her weight remained the same even after 6 months.
Case 2
An overweight 16-year-old girl was referred to our clinic by her pediatrician for psychiatric examination. She was diagnosed with ADHD (predominantly inattentive type) with comorbid AD after clinical evaluation. She had history of methylphenidate and atomoxetine use with no benefit, and also side effects that caused her to discontinue the medications. Therefore, we decided to start reboxetine for both ADHD and AD. Reboxetine, 4 mg/day, was initiated and increased to 8 mg/day a week later. She benefited some from reboxetine for her ADHD, and anxiety symptoms decreased after use of reboxetine for 8 weeks. However she lost 15 kg weight and her BMI decreased, surprisingly, from 29 kg/m2 to 23 kg/m2 after reboxetine treatment. She felt very satisfied with this situation and her mood ameliorated during this period. She had also not used any herbal drug or dietary intervention for weight loss, and experienced loss of appetite and mild headache with reboxetine. Her BMI was still 23 kg/m2 in spite of withdrawal of the drug after 6 months.
Case 3
An obese 13-year-old girl was referred to our outpatient unit by her pediatrician because of unexpected panic attacks. She was diagnosed with AD-not otherwise specified after clinical evaluation. She had a history of sertraline and fluoxetine use, but discontinued the drugs because of experiencing weight gain with the former and skin rash with the latter. Therefore, we decided to start reboxetine for her anxiety symptoms. Reboxetine, 4 mg/day, was initiated and increased to 8 mg/day a week later. Symptoms gradually diminished with the use of reboxetine for 12 weeks. Meanwhile, she surprisingly lost 14 kg weight without any diet or antiobesity drug use after reboxetine treatment. Her pediatrician was also pleased with the weight loss, because the patient had difficulties complying with dietary interventions suggested to her. Loss of appetite and nausea were observed as side effects. Withdrawal of the drug after 6 months led to 2 kg weight gain in 3 months, but this increase rate was lower than her rate of weight gain before reboxetine treatment.
Discussion
We reported three adolescent patients with different psychiatric problems, who experienced weight loss with the use of reboxetine. To us, this is the first report of weight loss associated with reboxetine in adolescents. Weight loss was most likely the result of reboxetine use in all cases, as none of the patients were given dietary interventions or any other antiobesity drugs.
Reboxetine was believed to have diminished psychotropic drug-induced weight gain in case 1. Both valproic acid and aripiprazole have been reported to cause weight gain. However, in the literature, reboxetine was mostly related to be effective in patients with antipsychotic-induced weight gain, particularly with olanzapine and clozapine (Yun-Jung Choi 2015). Therefore, case 1 is also important for its supporting reboxetine use to reverse weight gain caused by valproic acid, a mood stabilizer, and also for being, most probably, the first case report of this.
We used reboxetine not because of weight gain, but to treat psychiatric comorbidities in cases 2 and 3. Surprisingly, however, both patients experienced weight loss with reboxetine.
Effectiveness of reboxetine has been detected in the treatment of binge eating disorder in obese patients in an open trial study by Silveira et al. (2005). They also emphasized that weight loss in obese patients may be related to the decrease in binge eating disorder or even to a direct effect of reboxetine in reducing weight. Cases 2 and 3 with overweight and obesity, respectively, probably benefited from the direct effect of reboxetine, because they had no binge eating disorder.
Moreover, in the literature, the efficacy of reboxetine was also determined in children and adolescents with ADHD and AD (Toren et al. 2007; Riahi et al. 2013). Loss of appetite was among the most common side effects in these studies. This might contribute to weight loss in the cases in our study. Association between certain psychiatric disorders (e.g., ADHD and AD) and obesity has been shown in the literature (Cortese et al. 2015). Because both cases 2 and 3 benefited from reboxetine for their psychiatric symptoms, amelioration of these symptoms may also be considered another contributing factor to weight loss.
The mechanism of reboxetine's weight-attenuating effect is unknown. It is conceivable that reboxetine acts as an appetite suppressant by facilitating NE neurotransmission by a selective blockade of the NE transporter (Poyurovsky et al. 2007). The evaluation of energy expenditure and energy intake during reboxetine treatment may clarify its effect on energy homeostasis. The pharmacogenetic aspects of NE neurotransmission in weight regulation may play a role. Another possible mechanism is the drug's ability to partially inhibit serotonin reuptake in the central nervous system. Serotonin has been implicated in the regulation of eating behavior and appetite control (Halford et al. 2004). Disruption of this system might lead to clinical symptoms of anorexia and subsequent weight loss.
These adolescent cases provide some support for reboxetine's anorexigenic effect in different psychiatric conditions. Surprisingly, weight loss in these cases was effected by reboxetine in a short period. However, randomized, double-blind controlled trials of this effect in children and adolescents are needed for further investigation.
Footnotes
Disclosures
No competing financial interests exist.