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, 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 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.