effects side ocular induced-Drug • 7 t Pa r

Kinoshita A, Kitaoka T, Oba K, Amemiya T. Bilateral drug-induced cataract in patient receiving anticonvulsant therapy. Jpn J Ophthalmol 48: 81–82, 2004.

Kurian MA, King MD. Antibody positive myasthenia gravis following treatment with carbamazepine – a chance association? Neuropediatrics 34: 276–277, 2003.

Mullally WJ. Carbamazepine-induced ophthalmoplegia. Arch Neurol 39: 64, 1982.

Neilsen N, Syversen K. Possible retinotoxic effect of carbamazepine. Acta Ophthalmol 64: 287, 1986.

Noda S, Umezaki H. Carbamazepine-induced ophthalmoplegia. Neurology 32: l320, 1982.

Ponte CD. Carbamazepin-induced thrombocytopenia, rash and hepatic dysfunction. Drug Intell Clin Pharm 17: 642–644, 1983.

Rasmussen M. Carbamazepine and myasthenia gravis. Neuropediatrics 35: 259, 2004.

Silverstein FS, Parrish MA, Johnston MV. Adverse behavioral reactions in children treated with carbamazepine (Tegretol). J Pediatr 101: 785, 1982.

Smith H, Newton R. Adverse reactions to carbamazepine managed by desensitization. Lancet 1: 785, 1985.

Sullivan JB, Rumack BH, Peterson RG. Acute carbamazepine toxicity resulting from overdose. Neurology 31: 621, 1981.

Sutcliffe AG, Jones RB, Woodruff G. Eye malformations associated with treatment with carbamazepine during pregnancy. Ophthalmic Genet 19: 59–62, 1998.

Tedeschi G, Gasucci G, Allocca S, et al. Neuro-ocular side effects of carbamazepine and phenobarbital in epileptic patients as measured by saccadic eye movements analysis. Epilepsia 30(1): 62–66, 1989.

West J, Burke JP, Stachan I. Carbamazepine, epilepsy, and optic nerve hypoplasia. Br J Ophthalmol 74: 511, 1990.

Wheller SD, Ramsey RE, Weiss J. Drug-induced downbeat nystagmus. Ann Neurol 12: 227, 1982.

Generic names: 1. Citalopram hydrobromide; 2. fluoxetine hydrochloride; 3. fluvoxamine maleate; 4. paroxetine hydrochloride; 5. sertaline.

Proprietary names: 1. Celexa; 2. Prozac, Sarafem; 3. Generic only; 4. Paxil, Paxil CR; 5. Zoloft.

Primary use

These selective inhibitors of serotonin re-uptake are used as antidepressants. They are chemically unrelated to tricyclic, tetracyclic or other available antidepressant agents, and are reported to cause fewer antimuscarinic side effects than tricyclic antidepressants.

Ocular side effects

Systemic administration

Certain

1. Blurred vision

2. Photophobia

3. Increased eye movement during sleep (NREM) (fluoxetine)

4. Abnormal ocular sensations (paroxetine)

Probable

1. Keratitis sicca

2. Pupil

a.Mydrasis

b.Anisocoria

3. Increased intraocular pressure (minimal)

Possible 

1. Conjunctivitis – non-specific

2. Diplopia

3. Eyelids

a.Tics

b.Rash

c.Urticaria

d.Angioneurotic edema

Conditional/Unclassified

1. Activation of ocular herpes (fluoxetine)

Clinical significance

This group of selective serotonin reuptake inhibitors (SSRI) is one of the most commonly prescribed antidepressant drugs in the world because of its favorable safety profile. While ocular side effects are few and rare, they may be of clinical importance. Costagliola et al (1996, 2004) in a 20-patient double-blind crossover study showed that all 20 patients had subclinical intraocular­ pressure elevations within 2 hours of oral ingestion. Some eyes remained elevated for up to 8 hours. This was also found with other SSRI drugs such as citalopram, fluvoxamine (Jiménez-Jiménez et al 2001), paroxetine (Eke and Carr 1998) and sertraline. While the authors cannot prove an association, they strongly implied causation. Further studies are indicated, but very rare precipitation of narrow-angle glaucoma might occur­ (Ahmad 1991). Clinical trials against placebo shows that blurred vision and dry mouth are significant. It is probable that all drugs that cause dry mouth can aggravate or possibly cause ocular sicca.

There are a number of positive rechallenge cases of photophobia in the National Registry. Schenck et al (1992) have shown that fluoxetine can cause extensive, prominent eye movements during non-rapid eye movement sleep (NREM). In one case, this continued for 19 months after the drug was discontinued. While diplopia, ptosis and nystagmus have been seen, it is hard to prove a direct cause-and-effect relationship since these patients are often on multiple drugs. Armitage et al (1995) reported that fluoxetine could cause these findings since it causes increased availability of serotonin with secondary dopaminergic effects. Wakeno et al (2006) described three patients who, after discontinuing paroxetine, developed abnormal ocular sensations with eye movement. This occurred within 3–6 days after the drug was stopped and disappeared as soon as the drug was restarted. There are two cases in the National Registry of possible druginduced myopia of up to 3 diopters. A series of three cases of reactivation of genital herpes has been attributed to fluoxetine; however, no cases of reactivation of ocular herpes have been reported. The SSRIs probably have a weak mydriatic effect. For some unknown reason, this may be unilateral, as Barrett (1994) reports, and we confirm this with three additional cases in the National Registry.

References and Further Reading

Ahmad S. Fluoxetine and glaucoma. DICP Ann Pharmacother 25: 436, 1991. Anonymous. SSRIs and increased intraocular pressure. Aust Adverse Drug

React Bull 20: 3, 2001.

Armitage R, Trivedi M, Rush AJ. Fluoxetine and oculomotor activity during sleep in depressed patients. Neuropsychopharmacology 12(2): 159–165, 1995.

Barrett J. Anisocoria associated with selective serotonin reuptake inhibitors. BMJ 309: 1620, 1994.

Beasley CM, Koke SC, Nilsson ME, Gonzales JS. Adverse events and treatment discontinuations in clinical trials of fluoxetine in major depressive disorder: an updated meta-analysis. Clin Ther 22: 1319–1330, 2000.

Costagliola C, et al. Fluoxetine oral administration increases intraocular pressure. Br J Ophthalmol 80: 678, 1996.

Costagliola C, Parmeggiani F, Sebastiani A. SSRIs and intraocular pressure modifications: evidence, therapeutic implications and possible mechanisms. CNS Drugs 18: 475–484, 2004.