Psychosomatics 46:91-93, February 2005
© 2005 The Academy of Psychosomatic Medicine
Citalopram-Induced Diplopia
Karin Dorell, M.D.,
Mary Ann Cohen, M.D.,
Shirish S. Huprikar, M.D.,
Jack M. Gorman, M.D., and
Makeda Jones, M.D., New York, N.Y.
TO THE EDITOR: We present the case of a person with HIV and hepatitis C co-infection who developed diplopia while being treated with citalopram.
Since citalopram was developed in 1989, it has been used in more than 65 countries, with a total estimated worldwide exposure of 8 million persons. Its use is extensive, and its safety is well established.1–4 Citalopram is a selective serotonin reuptake inhibitor (SSRI) that is N-demethylated partially by cytochrome P450 2C19 and partially by cytochrome P450 3A4. The fact that citalopram is metabolized by more than one cytochrome P450 isoenzyme suggests that inhibition of its biotransformation by other drugs is less likely.2 In addition, citalopram has little or no affinity for acetylcholine, histamine, norepinephrine, dopamine,  -aminobutyric acid (GABA), or opiate receptors. Citalopram has a favorable pharmacokinetic profile, exhibiting high bioavailability, linear pharmacokinetics, and low protein binding. Citalopram’s minimal effect on the cytochrome P450 isoenzyme system has made it tolerable for patients with comorbid medical illnesses who are taking a variety of other medications.
We searched MEDLINE (1966–2003), OVID, PsychInfo, Psycharticles, and EBM Cochrane. We found no reports on citalopram and diplopia. Information on citalopram’s side effect profile is available from controlled and uncontrolled studies as well as postmarketing surveillance reports. Several meta-analyses have also been conducted.3,4 The most common side effects reported with citalopram are nausea and vomiting (20%), increased sweating (18%), headache (18%), dry mouth (17%), tremor (16%), sedation (15%), and insomnia (15%). Most side effects decrease over time, except dyspepsia and sweating. The rate of reported sexual side effects is 10%, although it was found to be higher in studies making use of direct questioning. Hepatic, renal, and hematological adverse events; seizures; and extrapyramidal side effects are rare.5,6 To date, we know of no double-blind, placebo-controlled studies on citalopram in HIV patients. A small open-label prospective study of citalopram in HIV patients revealed that it was effective and well tolerated, with few adverse events, including insomnia, nausea, and dry mouth.7 Persons with HIV constitute a special population that is exquisitely sensitive to the side effects of psychotropic medications.
To date, the only ocular side effects reported with citalopram are disturbances of accommodation due to anticholinergic effects. Rare reports of xerophthalmia, diplopia, photophobia, anterior chamber eye hemorrhage, accommodation changes, anisocoria, and conjunctivitis have been noted with sertraline therapy.8–10 In a postmarketing evaluation, optic neuritis and cataracts have been temporally associated with the use of sertraline. One case of paresis of the sixth cranial nerve after use of 3,4-methylenedioxymethamphetamine (ecstasy) was also reported, implicating a relation between diplopia and serotoninergic interneuronal fibers.11,12 We report what we believe to be the first case of citalopram-associated diplopia.
Case Report
Ms. A was a 47-year-old woman with HIV and hepatitis C infections, a history of cervical cancer, and a history of opioid and cocaine dependence that was in full, sustained remission. Ms. A was diagnosed with HIV in 1996; she had been cared for at our HIV clinic since 2001. Her nadir CD4 cell count had remained well above 200/µl, and she has no history of opportunistic infections. Although she had previously received highly active antiretroviral therapy, she has remained virologically and immunologically stable without it since her referral to our clinic. She was referred for psychiatric evaluation because of depression that developed at the time that her second husband was dying of late-stage AIDS.
Ms. A has a history of multiple losses and traumas, including the loss of her first husband, who was murdered, and the deaths of her mother, grandmother, and uncle. She was found to have a mood disorder with depressive features, posttraumatic stress disorder, and anticipatory bereavement. Treatment with psychotherapy and psychotropic medication was recommended. Her husband died shortly after she was referred for psychiatric care. Despite her depression and loss, Ms. A was able to hold a full-time job as an office manager.
Ms. A was given citalopram, 10 mg at bedtime. Her dose was increased to 20 mg and then 30 mg over the course of 1 month. Shortly after her dose was increased to 30 mg at bedtime, Ms. A began to have paranoid ideation, and olanzapine, 2.5 mg at bedtime, was added to her drug regimen. When her husband’s condition was deteriorating, her dose of citalopram was increased to 40 mg at bedtime, and over the course of 1 week, Ms. A developed urinary retention with abdominal pain and difficulty starting her stream. The results of a urinalysis and urine culture were negative. Citalopram was discontinued for 2 days, and the urinary retention resolved. Citalopram was then restarted at 10 mg at bedtime. Eight weeks after the initiation of psychiatric care, Ms. A’s husband died. During the mourning period, in the first 2 months after the death of her husband, she was unable to keep her weekly appointments with her psychiatrist (M.A.C.), and attempts to increase her citalopram dose were unsuccessful. Citalopram was then increased gradually from 10 mg to 20 mg at bedtime, and olanzapine was continued at 2.5 mg at bedtime. Two weeks after her citalopram dose was increased to 30 mg at bedtime, she came to the clinic with an acute onset of diplopia: "My right eye is not straight. When I woke up this morning, I was dizzy and started seeing double."
Ms. A was evaluated that day by a neurologist and an ophthalmologist and was diagnosed with diplopia secondary to decompensated exotropia. Citalopram was discontinued because of a report in the Physicians’ Desk Reference of a case of sertraline-induced diplopia.9 Three days after discontinuation of citalopram, the diplopia resolved. At the time of this event, her CD4 cell count was 254/µl, and her viral load was unavailable. One month before her development of diplopia, her CD4 cell count was 329/µl, and her viral load was 9400 copies/ml. Her medications included olanzapine, 2.5 mg at bedtime, and citalopram, 30 mg at bedtime. Ms. A had no other acute medical conditions, medication changes, or stressors at the time she developed diplopia. For 1 year after discontinuation of citalopram, she improved clinically with weekly psychotherapy and was able to maintain her full-time job. She remained on olanzapine, 2.5 mg at bedtime, throughout the year. She was given nortriptyline, 75 mg at bedtime, about 1 month after citalopram was discontinued, but after a month it had to be discontinued because she was unable to tolerate the anticholinergic side effects. She was taking no antidepressants for about 2 months but became more depressed 5 months after discontinuation of citalopram, when she was given pegylated interferon and ribavirin treatment for hepatitis C. At that time, bupropion, 75 mg b.i.d., was added, and olanzapine, 2.5 mg at bedtime, was continued. She was able to complete a 12-month course of interferon-ribavirin and to continue her job, despite interferon-induced fatigue. She has had no recurrence of diplopia in the year and a half since citalopram was discontinued.
Discussion
We report a unique case of a woman who developed diplopia that was presumed to result from treatment with citalopram, an SSRI. The rapid resolution of the diplopia after discontinuation of citalopram suggests a correlation between the adverse effect and the drug. Although diplopia is listed in the Physicians’ Desk Reference as a possible rare side effect of sertraline therapy, we did not find any case reports in the literature. As far as citalopram is concerned, this is the first report of any ocular side effect. The underlying etiology of this event remains unclear but might involve ocular serotonergic interneuronal fibers. Our patient had no family history of diplopia but did have some weakness in her eye muscles before starting citalopram. It is important to mention that diplopia is one of the neuro-ophthalmic manifestations that can be observed during HIV infection. The etiological agents of diplopia in HIV-positive patients can be identified with HIV itself, opportunistic pathogens, or other related conditions.13 The rapid resolution of the diplopia after discontinuation of citalopram in this case makes underlying CNS pathology unlikely. Diplopia was also reported following interferon treatment.14 Although the patient was on interferon treatment for 1 year, she has had no diplopia since citalopram was discontinued. The diagnosis of citalopram-induced diplopia will certainly remain controversial until further evidence of a cause-and-effect relationship emerges in a greater number of patients. However, we believe that patients and physicians should be aware of the potential for the induction of diplopia by citalopram and other SSRIs.
REFERENCES
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- May PJ, Baker H, Vidal PP, Spencer RF, Baker R: Morphology and distribution of serotoninergic and oculomotor internuclear neurons in the cat. J Comp Neurol 1987; 266:150–170[Medline]
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