A case of melancholic depression induced by β‐blocker antiglaucoma agents

he most common medical treatments for glaucoma in Australia are prostaglandin analogues. However, β-blockers still comprise a substantial proportion of all prescriptions, either alone or in combination. Despite their topical administration, β-blockers are absorbed from the eye through the conjunctival epithelium, lacrimal channels, nasal mucosa and gastrointestinal tract into the systemic circulation. Although only small amounts are absorbed, concentrations may be sufficient to cause systemic β-adrenergic receptor-mediated effects, including slowing of heart rate, lowering of blood pressure and non-response to bronchodilators. Central effects such as depression have also been reported. The literature investigating a causal relationship between βblockers and depression is controversial. An evidence-based review concluded that depression was an uncommon side effect of treatment with β-blockers and usually occurred only in the presence of a pre-existing condition. 2 Randomised controlled studies of β-blockers in cardiovascular disease found the incidence of depressive symptoms was similar in β-blocker- and placebotreated groups. 3 However, a review of 24 case reports 4 showed a temporal relationship between the use of β-blockers and depression in more than half the cases. If there is a close temporal relationship between the commencement of a new treatment and the development of symptoms, the symptoms are considered likely to have been caused by the medication. In the initial case that we reported on this patient, 1 depressive symptoms began within days after the diagnosis of glaucoma and commencement of betaxolol treatment. The patient’s symptoms only fully remitted when the drug was stopped, providing further evidence of a causative relationship. The case we report here describes recurrence of depression after the introduction of another β-blocker, timolol, and again cessation of symptoms when treatment was stopped. The recurrence of the syndrome following a re-challenge further strengthens the argument for a causal relationship. (The travoprost component of the medication was unlikely to have been the cause of the depression.) It is possible that the onset of the disorder occurred coincidentally with the introduction of the medication (though such an event is unlikely to have occurred twice) or was caused by the underlying illness for which the new medication was prescribed. In the only study we could find of ophthalmological patients with depression with and without glaucoma, no association was shown between depression and glaucoma. 5 Glaucoma is mostly a disease of older people, a group prone to developing depressive illness. Depression is often dismissed in older people as a normal reaction to ageing, loss or chronic illness. However, it is treatable, with a very good prognosis. Older patients are frequently taking multiple medicines and may develop depressive symptoms as a side effect. The purpose of this case presentation is to emphasise that even a drug that is administered topically, such as antiglaucoma eye drops, is absorbed systemically and can potentially cause adverse effects elsewhere, including centrally. There are credible theoretical reasons why β-blockers may cause depression: the number of β 1 receptors is increased in the brains of suicide victims and chronically stressed animals, and antidepressants cause down-regulation of β 1 receptors. The fact that only a few patients develop depression after taking β-blockers may be due to genetic differences. It is possible that poor metabolisers of the enzyme cytochrome P450 2D6 will be exposed to higher systemic concentrations of β-blockers than those who are normal or fast metabolisers. 6,7 To our knowledge, there have been no