Weighing the Risks and Benefits of Antidepressants in Idiopathic Intracranial Hypertension

Letters to the Editor In Dr. Horton's comments about our article, he stated that conventional visual field testing may not be sensitive enough to detect functional changes associated with ganglion cell damage (3). We agree, but we also have been impressed with the possibility that, despite what seems to be significant GCC loss, there are enough ganglion cells remaining, especially in the macula, for patients to retain excellent visual function. In other words, the GCC loss may not have reached a "tipping point" as suggested by Dr. Costello, who also commented on our study (4). This seems to occur in other conditions, including Leber hereditary optic neuropathy in which, despite what seems to be almost complete loss of macular ganglion cells, some patients, over time, may regain excellent visual acuity and visual fields. Marisa Gobuty, MD Thomas R. Hedges, III, MD Joseph Ho, MD Natalie Erlich-Malona, MD Laurel N. Vuong, MD Geetha K. Athappilly, MD New England Eye Center, Tufts University School of Medicine, Weighing the Risks and Benefits of Antidepressants in Idiopathic Intracranial Hypertension W e read with interest the recent State of the Art Review on "Obesity and weight loss in idiopathic intracranial hypertension" by Subramaniam and Fletcher (1) and would like to share our thoughts on a related topic. Obesity, especially in young women, can provoke a negative body image and increase the risk of depression (2). As patients with idiopathic intracranial hypertension (IIH) not only have to tackle their weight but also the debilitating effects of chronic headaches and the fear of potential vision loss, it is not surprising that mood disorders and functional overlay often coexist (3). As a result, many patients with IIH are prescribed antidepressants. Increased antidepressant exposure has been identified as a contributory factor to the obesity pandemic (4). In fact, multiple studies have shown that the tricyclics such as amitriptyline (Elavil, Vanatrip), nortriptyline (Aventyl, Pamelor), and imipramine (Tofranil) and the noradrenergic and specific serotonergic antidepressant mirtazapine (Remeron) are associated with weight gain (5-7). Mirtazapine, in particular, has been shown to induce carbohydrate craving and often leads to significant weight gain in a short period of time (8,9). This is especially relevant in the context of patients with comorbid IIH, intractable headache, and low mood, where tricyclics and mirtazapine, at least in the United Kingdom, are commonly prescribed (10,11). In addition, 128 Tufts Medical Center, Boston, MA Carlos E. Mendoza-Santiesteban, MD New England Eye Center, Tufts University School of Medicine, Tufts Medical Center, Boston, MA Bascom Palmer Eye Institute, Miami, FL The authors report no conflict of interest. REFERENCES 1. Tieger MG, Hedges TR, Ho J, Erlich-Malona NK, Vuong LN, Athappilly GK, Mendoza-Santiesteban CE. Ganglion cell complex loss in chiasmal compression by brain tumors. J Neuroophthalmol. 2017;37:7-12. 2. Ochoa J, Danta G, Fowler T, Gilliati R. Nature of nerve lesion caused by pneumatic tourniquet. Nature. 1971;233:265-266. 3. Horton JC. Ganglion cell complex measurement in compressive optic neuropathy. J Neuroophthalmol. 2017;37:13-14. 4. Costello F. Form versus function: a state of disunion? J Neuroophthalmol. 2017;37:15-16. use of selective serotonin reuptake inhibitors, with the exception of fluoxetine (Prozac), also has been associated with weight gain of 7% or more in 40% of patients (12). Indeed, most psychotropic medications are associated with weight gain, with the notable exception of topiramate (Topamax), an anticonvulsant and mood stabilizer, also used in the treatment of IIH (13). There is no doubt that acetazolamide (Diamox), cerebrospinal fluid diversion procedures such as lumboperitoneal shunting, and optic nerve sheath fenestration are invaluable in the management of IIH (14). However, it must be emphasized that although they alter physiology, they do not address the underlying pathophysiology of the disease. In other words, these interventions can only provide symptomatic relief, rather than a cure. In addition, all medical and surgical treatment options have the potential for adverse effects. Although the exact mechanism remains unclear, the only cure for IIH is weight loss (15). Intentional weight loss in any setting can be difficult, which is why bariatric surgery has become increasingly popular as one of the treatment strategies in IIH (16). Bariatric surgery is by no means without risks and may be complicated by various long-term health problems such as malabsorption and nutrient deficiencies (17). Therefore, except in fulminant cases, natural weight loss remains the best treatment strategy for IIH. Furthermore, although reversal of papilledema and prevention of visual loss should always be the main treatment goal in IIH, the importance of weight loss to improve our patients' general health should not be underestimated. Antidepressants are an important group of medications, several of which have multiple applications other than treating Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 122-133 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor depression; a key one being in the treatment of chronic headaches. Antidepressants may inadvertently undermine a patient's attempts at losing weight. By no means do we suggest withholding or suddenly withdrawing antidepressants from patients who truly need them. However, when faced with a patient who struggles to lose weight, we would encourage a careful review of the patient's medications. In addition, in treating chronic intractable headaches, clinicians should weigh the risks and benefits before prescribing a tricyclic, as in the long-term management of patients with IIH, these drugs may cause more of a headache than you bargained for. Anna M. Gruener, BMedSci(Hons), BMBS, MSc, FRCOphth Department of Ophthalmology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom Neuro-Ophthalmology Division, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland Alexander D. Jolly, BMBS, MRCPsych Urgent Medical Mental Health Line, Nottinghamshire Healthcare NHS Foundation Trust, Nottingham, United Kingdom James M. A. Ellison, BMedSci(Hons), BMBS, PGDip, MRCPsych Department of Examinations and Assessments, University of Nottingham School of Medicine, Nottingham, United Kingdom Michael A. Burdon, MBBS, FRCP, FRCOphth Department of Ophthalmology, University of Birmingham Hospitals NHS Foundation Trust, Birmingham, United Kingdom The authors report no conflicts of interest. REFERENCES 1. Subramaniam S, Fletcher WA. Obesity and weight loss in idiopathic intracranial hypertension: a narrative review. J Neuroophthalmol. 2017;37:197-205. Leber Hereditary Optic Neuropathy Caused by a Mitochondrial DNA 10663T.C Point Mutation and Its Response to Idebenone Treatment W e read with interest the consensus report by Carelli et al (1) describing the value of idebenone in the treatment of patients with Leber hereditary optic neuropathy Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 122-133 2. Jung SJ, Woo HT, Cho S, Park K, Jeong S, Lee YJ, Kang D, Shin A. Association between body size, weight change and depression: systematic review and meta-analysis. Br J Psychiatry. 2017;211:14-21. 3. Kesler A, Mosek A, Fithlicher N, Gidron Y. Psychological correlates of idiopathic intracranial hypertension. Isr Med Assoc J. 2005;7:627-630. 4. Lee SH, Paz-Filho G, Mastronardi C, Licinio J, Wong ML. Is increased antidepressant exposure a contributory factor to the obesity pandemic? Transl Psychiatry. 2016;6:e759. 5. Himmerich H, Minkwitz J, Kirkby KC. Weight gain and metabolic changes during treatment with antipsychotics and antidepressants. Endocr Metab Immune Disord Drug Targets. 2015;15:252-260. 6. Carbone F, Vanuytsel T, Tack J. The effect of mirtazapine on gastric accommodation, gastric sensitivity to distention, and nutrient tolerance in healthy subjects. Neurogastroenterol Motil. [published online ahead of print July 11, 2017] doi: 10.1111/nmo.13146. 7. Salvi V, Mencacci C, Barone-Adesi F. H1-histamine receptor affinity predicts weight gain with antidepressants. Eur Neuropsychopharmacol J. 2016;26:1673-1677. 8. Badowski M, Pandit NS. Pharmacologic management of human immunodeficiency virus wasting syndrome. Pharmacotherapy. 2014;34:868-881. 9. Hilas O, Avena-Woods C. Potential role of mirtazapine in underweight older adults. Consult Pharm J Am Soc Consult Pharm. 2014;29:124-130. 10. Xu XM, Liu Y, Dong MX, Zou DZ, Wei YD. Tricyclic antidepressants for preventing migraine in adults. Medicine (Baltimore). 2017;96:e6989. 11. Krishnan A, Silver N. Headache (chronic tension-type). BMJ Clin Evid. 2009;2009:1205. 12. Uguz F, Sahingoz M, Gungor B, Aksoy F, Askin R. Weight gain and associated factors in patients using newer antidepressant drugs. Gen Hosp Psychiatry. 2015;37:46-48. 13. Mahmood S, Booker I, Huang J, Coleman CI. Effect of topiramate on weight gain in patients receiving atypical antipsychotic agents. J Clin Psychopharmacol. 2013;33:90-94. 14. Chan JW. Current concepts and strategies in the diagnosis and management of idiopathic intracranial hypertension in adults. J Neurol. 2017;264: 1622-1633. 15. Sinclair AJ, Burdon MA, Nightingale PG, Ball AK, Good P, Matthews TD, Jacks A, Lawden M, Clarke CE, Stewart PM, Walker EA, Tomlinson JW, Rauz S. Low energy diet and intracranial pressure in women with idiopathic intracranial hypertension: prospective cohort study. BMJ. 2010;341:c2701. 16. Manfield JH, Yu KKH, Efthimiou E, Darzi A, Athanasiou T, Ashrafian H. Bariatric surgery or non-surgical weight loss for idiopathic intracranial hypertension? A systematic review and comparison of meta-analyses. Obes Surg. 2017;27:513-521. 17. Moss HE. Bariatric surgery and the neuro-ophthalmologist. J Neuroophthalmol. 2016;36:78-84. (LHON). In addition, the Expanded Access Program (EAP) of patients with LHON with disease duration ,1 year found that the number of patients who recovered clinically relevant visual acuity (VA) increased with idebenone treatment duration, reaching almost 50% by 16 months (2). We describe a patient with LHON caused by an uncommon mitochondrial DNA 10663T.C point mutation and his response to idebenone. A 16-year-old boy developed acute and painless visual loss in both eyes 2 weeks apart. He was an only child with 129 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.