Is glaucoma a known side effect of sertraline?/nA female patient who has been taking sertraline for

Fråga: Is glaucoma a known side effect of sertraline? A female patient who has been taking sertraline for several years suffers from open angle glaucoma since 4 years. Is it probable that the glaucoma is caused by sertraline? If yes, what is the mechanism? Is continued treatment with sertraline contraindicated, given the risk of elevated intraocular pressure?

Sammanfattning: Sertraline like the other SSRIs can raise IOP mainly via passive mydriasis, which can trigger/exacerbate closed angle glaucoma. Noradrenergic, anticholinergic and serotonergic effects can play role in this circumstance. Then again, since SSRI can raise IOP even in absence of closed angle, risk of aggravation of open angle glaucoma by these agents cannot be ruled out.

However, SSRIs are not contraindicated in glaucoma.

Svar: Glaucoma refers to damage to the optic nerve, usually associated an increased intra-ocular pressure (IOP). However, some may have high IOP for years and never develop damage, while others can develop nerve damage at a relatively low pressure. Untreated glaucoma can lead to permanent damage of the optic nerve and resultant visual field loss, which over time can progress to blindness. Glaucoma is the second leading cause of blindness after cataracts.

Glaucoma can be divided into two categories, "open angle" and "closed angle" glaucoma. The angle refers to the irido-corneal area. In case of narrow irido-corneal angle (closed angle) a dilation of the pupil can block the outflow of aqueous humor, which leads to an increase in pressure.

Many antidepressants, particularly tricyclics may cause papillary dilation both via directly anticholinergic receptor activity and by inhibiting the reuptake of norepinephrine. Studies in both animals and humans suggest that serotonergic mechanisms are also involved in the control of pupil diameter (1).

In addition there is some evidence suggesting that SSRIs may raise IOP even in absence of closed angle. In a randomised crossover double blinded study on 20 depressed outpatients oral administration of fluoxetine raised IOP by over 4 mm Hg, lasting 6-8 hours (2). However, the manufacturers own data suggest that chronic dosage of fluoxetine does not seem to lead to a sustained elevation of IOP, and IOP change after treatment can be detected in less than 1% (3). In the case of SSRIs, the sympathomimetic noradrenergic or anticholinergic action, stimulating the iris dilator muscle, produces an active mydriasis. In addition stimulation of serotonin receptors within the iris musculature causes passive mydriasis via papillary sphincter relaxation (4, 5). These mechanisms together are able to reinforce the crowding at the level of the iridocorneal angle (6). A relatively large number of closed angle glaucoma attacks are reported with paroxetine treatment (6 case reports) compared to the other SSRIs (maximum 2 case reports for each other SSRI). This may be due to its relatively high noradrenergic effect (6).

According to the manufacturer glaucoma is listed as a rare side effect of sertraline. A search in the company´s marketing database showed that since introduction of sertraline to the market a few spontaneous reports of glaucoma and increased IOP has been registered (7).

Among a total of 112 reported ophthalmic-adverse events in association to SSRI treatment, one report on glaucoma associated with fluoxetine treatment, one associated with zimelidine treatment and two associated with paroxetine treatment recurs in the Swedish adverse drug reaction database (8).

Sertraline treatment is neither contraindicated in glaucoma nor in elevated IOP. However, since the patient has taken the drug for several years tapering of sertraline should be considered if the patinet´s clinical situation allows it.

We recommend this case to be reported to the "Pharmacovigilance unit of the Swedish Medical Products Agency".