Hughes IW. Adverse reactions in perspective, with special reference to gastrointestinal side-effects of clomipramine (Anafranil). J Int Med Res 1: 440, 1973.

Hunt-Fugate AK, et al. Adverse reactions due to dopamine blockade by amoxapine. Pharmacotherapy 4: 35–39, 1984.

Kupfer DJ, Pollock BG, Perel JM, et al. Effect of pulse loading with clomipramide on EEG sleep. Psychiatry Res 54(2): 161–175, 1994.

LeWitt PA. Transient ophthalmoparesis with doxepin overdosage. Ann Neurol 9: 618, 1981.

Litovitz TL, Troutman WG. Amoxapine overdose. Seizures and fatalities. JAMA 250: 1069, 1983.

Micev V, Marshall WK. Undesired effects in slow intravenous infusion of clomipramine (Anafranil). J Int Med Res 1: 451, 1973.

Schenck CH, Mahowald MW, Kim SW, et al. Prominent eye movements during NREM sleep and REM sleep behavior disorder associated with fluoxetine treatment of depression and obsessive-compulsive disorder. Sleep 15(3): 226–235, 1992.

Steele TE. Adverse reactions suggesting amoxapine-induced dopamine blockade. Am J Psychiatry 139: 1500, 1982.

3. Eyelids or conjunctiva

a.Erythema multiforme

b.Stevens-Johnson syndrome

c.Exfoliative dermatitis

d.Lyell’s syndrome

e.Lupoid syndrome

Conditional/Unclassified

1. Cataracts

a.Punctate cortical

b.Anterior and posterior sub-capsular 2. Retinal pigmentary change

Ocular teratogenic effects

Certain

1. Anophthalmos

2. Microphthalmos

3. Optic disc coloboma

4. Optic nerve hypoplasia

Generic name: Carbamazepine.

Proprietary names: Carbatrol, Epitol, Equetro, Tegretol, Tegretol-XR, Teril.

Primary use

This iminostilbene derivative is used in the treatment of pain associated with trigeminal neuralgia.

Ocular side effects

Systemic administration

Certain

1.Extraocular muscles

a.Diplopia

b.Downbeat or horizontal nystagmus

c.Oculogyric crises – toxic states

d.Decreased spontaneous movements

e.Paralysis – toxic states

f.Ophthalmoplegia

2. Decreased vision

3. Visual hallucinations

4. Eyelids or conjunctiva

a.Photosensitivity, increased glare

b.Allergic reactions

c.Conjunctivitis – non-specific

d.Edema

e.Urticaria

f.Blepharoclonus

g.Purpura

5. Color vision – decreased blue perception

6. Decreased accommodation

7. Decreased convergence

Possible

1. Subconjunctival or retinal hemorrhages secondary to drug-induced anemia

2. Myasthenia gravis

a.Diplopia

b.Ptosis

c.Paresis of extraocular muscles

Clinical significance

The most common side effects due to carbamazepine are ocular, with transitory diplopia being the most frequent, followed by blurred vision and a ‘heavy feeling in the eyes.’ Ocular adverse reactions are reversible, usually disappear as the dosage is decreased and may spontaneously clear even without reduction of the drug dosage. A toxic syndrome may occur as an acute phenomenon with downbeat nystagmus, confusion, drowsiness and ataxia. Bayer et al (1995a) pointed out that patients complain of increased glare and have a blue color deficiency. This drug can also cause the ocular effects of lupus erythematosus. Carbamazepine can be recovered in the tears, and this method has been advocated to test for blood levels as a non-invasive technique in the pediatric age group.

The cataractogenic potential of this agent is still open to debate. While Neilsen and Syversen (1986) first postulated this association, this has not been proven. The National Registry, however, has 30+ possible cases. Neilsen and Syversen (1986) reported two patients with retinotoxicity attributed to long-term therapeutic use of carbamazepine and while a few cases have been reported to the National Registry, there is no proven association. This drug ­interacts with multiple other drugs causing visual side effects. Toxic reactions in overdosage situations possibly cause dilated sluggish or non-reactive pupils and papilledema. There are a number of reports of a fetal carbamazepine syndrome, which may include ocular abnormalities (Glover et al 2002; Sutcliffe et al 1998).

References and Further Reading

Bayer A, Thiel HJ, Zrenner E, et al. Sensitive physiologic perceptual tests for ocular side effects of drugs exemplified by various anticonvulsants. [German] ophthalmologe 92: 182–190, 1995a.

Bayer A, Thiel HJ, Zrenner E, et al. Disorders of color perception and increased glare sensitivity in phenytoin and carbamazepine therapy. Ocular side effects of anticonvulsants. [German] Nervenarzt 66: 89–96, 1995b.

Breathnach SM, et al. Carbamazepine (‘Tegretol’) and toxic epidermal necrolysis: report of three cases with histopathological observations. Clin Exp Dermatol 7: 585, 1982.

Chrousos GA, et al. Two cases of downbeat nystagmus and oscillopsia associated with carbamazepine. Am J Ophthalmol 103: 221, 1987.

Delafuente JC. Drug-induced erythema multiforme: a possible immunologic pathogenesis. Drug Intell Clin Pharm 19: 114, 1985.

Glover SJ, Quinn AG, Barter P, et al. Ophthalmic findings in fetal anticonvulsant syndrome(s). Ophthalmology 109: 942–947, 2002.

Goldman MJ, Shultz-Ross RA. Adverse ocular effects of anticonvulsants. Psychosomatics 34: 154–158, 1993.

Gualtieri CT, Evans RW. Carbamazepine-induced tics. Dev Med Child Neurol 26: 546, 1984.