Possible

1. Aggravates keratitis sicca

Conditional/Unclassified

1. Upbeat nystagmus on drug withdrawal (amitriptyline)

2. Precipitate narrow-angle glaucoma

3. Induce phorias

Clinical significance

Adverse ocular reactions due to these tricyclic antidepressants are reversible, transitory and seldom of clinical significance. There are numerous reports of transitory decreased vision, decreased accommodation and slight mydriasis. While spontaneous reporting systems contain a few cases of precipitation of narrow-angle glaucoma (primarily amitriptyline), this may be difficult to sort out from emotionally induced mydriasis. These agents should have no effect on glaucoma except in very shallow anterior chamber angles. In patients with already compromised tear production, these drugs may have the potential to aggravate latent or manifested keratoconjunctivitis sicca. Drugs that cause dry mouth have the potential to aggravate ocular sicca. Drugs that have a sedative effect may exacerbate phoria, but only in overdose situations have tropias been reported. The clinician needs to be aware that tricyclic antidepressants potentiate the systemic blood pressure elevation from topical ocular epinephrine preparations. Osborne and Vivian (2004) reported a case of upbeat nystagmus occurring after stopping amitriptyline.

Recommendations

Roberts et al (1992) recommend sunblocking ocular protection for patients placed on imipramine, since it is a photosensitizer for the lens, with peak absorption above that which the cornea filters out. They recommend that when working ouside the home patients on this drug should consider wearing UV blocking glasses that protect to at least 320 nm.

Generic names: 1. Amoxapine; 2. clomipramine hydrochloride; 3. doxepin hydrochloride; 4. trimipramine.

Proprietary names: 1. Generic only; 2. Anafranil; 3. Sinequan, Zonalon; 4. Surmontil.

Primary use

These tricyclic antidepressants are used in the treatment of ­psychoneurotic anxiety or depressive reactions.

Ocular side effects

Systemic administration

Certain

1. Decreased vision

2. Mydriasis

3. Decreased accommodation

4. Suppression of rapid eye movement in sleep (clomipramine)

Possible

1.Eyelids or conjunctiva

a.Erythema

b.Edema

c.Photosensitivity

d.Urticaria

e.Pigmentation

f.Blepharospasm

g.Lyell’s syndrome

2.Extraocular muscles

a.Oculogyric crises

b.Nystagmus – horizontal or rotary – toxic states

c.Paresis or paralysis – toxic states

d.Abnormal conjugate deviations (amoxapine)

3.Visual hallucinations

4.Aggravates keratitis sicca

References and Further Reading

Beal MF. Amitriptyline ophthalmoplegia. Neurology 32: 1409, 1982. Blackwell B, et al. Anticholinergic activity of two tricyclic antidepressants.

Am J Psychiatry 135: 722, 1978.

Delaney P, Light R. Gaze paresis in amitriptyline overdose. Ann Neurol 9: 513, 1981.

Hotson JR, Sachdev HS. Amitriptyline: Another cause of internuclear ­ophthalmoplegia with coma. Ann Neurol 12: 62, 1982.

Karson CN. Oculomotor signs in a psychiatric population: a preliminary report. Am J Psychiatry 136: 1057, 1979.

Osborne SF, Vivian AJ. Primary position upbeat nystagmus associated with amitriptyline use. Eye 18: 106, 2004.

Pulst SM, Lombroso CT. External ophthalmoplegia, alpha and spindle coma in imipramine overdose: case report and review of the literature. Ann Neurol 14: 587, 1983.

Roberts JE, Reme CE, Dillon J, et al. Bright light exposure and the concurrent use of photosensitizing drugs. N Engl J Med 326(22): 1500–1501, 1992.

Spector RH, Schnapper R. Amitriptyline-induced ophthalmoplegia. Neurology 31: 1188, 1981.

Von Knorring K. Changes in saliva secretion and accommodation width during short-term administration of imipramine and zimelidine in healthy volunteers. Int Pharmacopsych 16: 69, 1981.

Vonvoigtlander PF, Kolaja GJ, Block EM. Corneal lesions induced by antidepressants: a selective effect upon young Fischer 344 rats. J Pharmacol Exp Ther 222: 282, 1982.

Walter-Ryan WG, et al. Persistent photoaggravated cutaneous eruption induced by imipramine. JAMA 254: 357, 1985.

Clinical significance

Adverse ocular reactions due to these tricyclic antidepressants are seldom of major clinical importance. Ocular anticholinergic effects are the most frequent and include blurred vision, which may require decreasing the dosage, disturbance of accommodation and mydriasis. There have been reports to the National Registry of keratoconjunctivitis sicca associated with the use of these agents, but this is not proven. Since they do cause a dry mouth, the association may be real. Since these tricyclic antidepressants may be bound to ocular melanin, there is a potential for retinal damage. A few cases of retinal pigment abnormalities have been reported to the National Registry, but no definitive relationship has been established. Kupfer et al (1994) have shown that clomipramine suppresses rapid eye movement (REM) during sleep.

References and Further Reading

Barnes FF. Precipitation of mania and visual hallucinations by amoxapine hydrochloride. Compr Psychiatry 23: 590, 1982.

Botter PA, Sunier A. The treatment of depression in geriatrics with Anafranil­ . J Int Med Res 3: 345, 1975.

D’Arcy PF. Disorders of the eye. In: Iatrogenic Diseases, 2nd edn, D’Arcy PF, Griffin JP (eds), Oxford University Press, Oxford, pp 162–168, 1983.

Donhowe SP. Bilateral internuclear ophthalmoplegia from doxepin overdose. Neurology 34: 259, 1984.

Horstl H, Pohlmann-Eden B. Amplitudes of somatosensory evoked potentials reflect cortical hyperexcitability in antidepressant-induced myoclonus. Neurology 40: 924–926, 1990.