Dry Eye Related to Commonly Used New Antidepressants
Emel Koçer, MD,* Abdulkadir Koçer, MD,† Mustafa Özsütçü, MD,‡ Ali Emre Dursun, MD,* and İsmet Kırpınar, MD*
addition, we determined the correlation between clinical variables
Abstract: Antidepressants may have an impact on the course of eye dry- and DE. ness. The aim of this study was to investigate the effects of commonly used new antidepressants on eye wetting. Fifty-four patients using new antide- MATERIALS AND METHODS pressants and 57 controls were recruited. The Beck Depression Scale and The patients followed-up by a diagnosis of depression based Beck Anxiety Scale questionnaires were completed by the patients, and drug on the criteria of the Diagnostic and Statistical Manual of Mental use time and dosages were recorded. The Schirmer test was performed Disorders, Fourth Edition, and a history of escitalopram (selec- without prior instillation of topical anesthesia to the ocular surface, and tive serotonin reuptake inhibitor [SSRI]), duloxetine (serotonin- the wetting result was recorded for each eye. Escitalopram, duloxetine, and norepinephrine reuptake inhibitor [SNRI]), or venlafaxine (SNRI) venlafaxine were used by 27, 13, and 14 patients, respectively. The Schirmer usage at least for 4 weeks in psychiatry outpatient clinics of our test results in the patients were significantly lower than in the controls medical faculty were examined in this study. The patients using (P < 0.001). The patients using selective serotonin reuptake inhibitors (SSRIs) only high doses of venlafaxine were included in the study because displayed lower wetting measurements (≤5 mm) compared with those using high-dose venlafaxine had effect on noradrenergic and cholinergic serotonin-norepinephrine reuptake inhibitors, which was independent of system. The patients were excluded if they were aged younger than the duration of antidepressant usage (P < 0.05). Although SSRIs do not 16 years or older than 60 years, currently using xerogenic drugs that have anticholinergic adverse effects except paroxetine, we found that both causes the oral cavity to be unusually dry (Table 1). Those with un- SSRIs and serotonin-norepinephrine reuptake inhibitors increased the risk derlying human immunodeficiency virus infection, graft versus for eye dryness. The lower Schirmer test results of the SSRIs may be associ- host disease, thyroid disease untreated with hormone, amyloidosis, ated with a mechanism other than the anticholinergic system. An awareness lymphoma, prior head and neck radiation, sarcoidosis, chronic ac- of the drugs that contribute to dry eye will allow ophthalmologists, optome- tive hepatitis, renal insufficiency, and vasculitis were also excluded. trists, and other physicians to better manage patients who have this problem. In addition, those who used or who were using a tear substitute or Key Words: antidepressant, depression, dry eye, Schirmer test those who were long-term contact lens wearers were excluded from the study. Cigarette smoking was another exclusion criterion. (J Clin Psychopharmacol 2015;35: 411–413) First, sociodemographic variables and the drugs that were used by the patients included in the study were recorded. Second,
D ry eye (DE) is a disorder resulting from tear deficiency or ex-
cessive evaporation, causing irritation to the interpalpebral ocular surface, and is associated with symptoms of ocular dis- all patients completed the Beck Depression Scale and Beck Anx- iety Scale.11,12 Third, all patients and age- and sex-matched con- trols were examined for tear volume by Schirmer test. Research comfort.1–4 Dry eye is a multifactorial disease, and one of the most in this study adhered to the tenets of the Declaration of Helsinki. prevalent eye diseases, and requires eye care, particularly among Informed consent was obtained from each participant before any the elderly.1–6 A strong association between the use of antidepres- related procedure was performed, and the study was approved sant medications and DE risk was reported in several studies, in- by the local ethics committee. cluding epidemiological studies.5–9 However, the presence of DE is normally underdiagnosed in clinical practice. This may be a Schirmer Test Measurement methodological issue because the adverse effects in drug trials are Schirmer test determines whether the eye produces enough often assessed via spontaneous reporting by patients or by closed- tears to keep it moist. Schirmer test measure change in tear by ended lists of symptoms not including DE. Therefore, DE is un- the observed wetting of a standardized paper strip placed over common in clinical trial reports on antidepressant drugs, whereas the inferior eyelid over a given period.13 The patients sat with their dry mouth is prevalent. For example, the only ocular symptom on eyes closed for 5 minutes before the strips were removed. The the list of 17 common adverse effects reported by patients taking length of wet area starting from the notch corresponding to the antidepressants from a specific study was blurred vision, as re- lower eyelid margin was measured. Schirmer test was performed ported by 85% of the patients.10 without prior instillation of topical anesthesia to the ocular sur- Moreover, the presence of DE has, to our knowledge, never face, and the test result was recorded in millimeter for each eye. been studied systematically in patients using new and widely pre- After that, wet areas were classified as greater than 5 mm and scribed antidepressants. Therefore, we investigated the prevalence 5 mm or less at 1 or both eyes.13,14 The patients with 5 mm or less of DE in patients with depression who were using antidepressants result were recorded as the patients having DE. All tests were per- and compared the findings with those of age-matched controls. In formed on both eyes by the same researcher.
Koçer et al Journal of Clinical Psychopharmacology • Volume 35, Number 4, August 2015
wettings (P = 0.00). The right eye and left eye wettings were similar TABLE 1. Well-Known Causes Related to DE with results of 10.44 (5.84) mm and 10.50 (5.42) mm, respectively, in the patients. After classification of wettings as greater than 5 mm Xerogenic drugs associated with an increased risk for DE or 5 mm or less in the Schirmer test, we have found that there was •β-Blockers a strong correlation between antidepressant use and DE (P < 0.000, •Diuretics Table 2). In the comparison of 3 drugs evaluated in the study, wet- •Antihistamines ting measures were similar (P > 0.05, Table 3). On the other hand, •Anxiolytics the patients using SSRIs revealed lower wetting measurements •Neuroleptics (≤5 mm) in comparison to the patients using SNRIs. Ten patients •Anticholinergics (18.8% of 54 eyes of the patients) had DE in the SNRI group and •Parasympatholytics 19 patients (35% of 54 eyes of the patients) had DE in the SSRI group. The relationships between drug dosages and wetting mea- •Steroids surements were not statistically significant in the evaluation of •Oral contraceptives each group. There was not a relationship between the time duration •Antiparkinsonian drugs of drug use and wetting measurement either (P = 0.57). In the eval- •Clonidine uation of each drug, only venlafaxine use duration negatively cor- •Drugs including pseudoephedrine related to wetting, which was 5 mm or less (r = −0.76, P = 0.002). Diseases associated with an increased risk for DE In addition, the correlations between DE and other parameters • Arthritis such as age, sex, anxiety, and depression scales were not significant. • Sjögren syndrome DISCUSSION • Lupus erythematous Dry eye patients experience tear film instability with potential • Ocular rosacea damage accompanied by inflammation of the ocular surface.1,3,13,14 • Allergy This condition is a frequently underrecognized clinical condition • Thyroid disease and poses strong etiological and management challenges.1,3,7,10 • Depression Many studies reported that the DE incidence increased signifi- • Poorer self-rated health cantly with age and female sex; in subjects with arthritis, Sjögren • Hypertension syndrome, lupus erythematous, ocular rosacea, allergy, and thyroid • Benign prostatic hypertension disease not treated with hormone; in subjects using antihistamines, antianxiety medications, antidepressants, oral steroids, vitamins, Pearson test were used for other variables. The level of statistical β-blockers, and diuretics; and in subjects with poorer self-rated significance was set at P < 0.05. health.7,9,15–17 Depression, hypertension, and benign prostatic hy- pertension were also associated with an increased risk for DE.2,6,7 RESULTS Dry eye–related diseases were shown in Table 1. We assessed the frequency of DE among 54 patients with An association between antidepressant use, particularly tricy- antidepressant use in comparison to 57 healthy controls. The socio- clic antidepressants and SSRIs, and DE, with decreased lacrimal demographic variables and Schirmer test results were shown in secretion being the likely mechanism, has been reported in several Table 2. Twenty-seven patients were using escitalopram (mean studies.5–8,16,18 Experimental rat studies suggested that parasym- [SD] dosage, 17.78 [4.24] mg/d); 13 patients were using duloxe- pathetic denervation of the human lacrimal gland may induce DE tine (mean [SD] dosage, 48.46 [15.19] mg/d), and 14 patients through reduced tear flow and lacrimal protein secretion as well were using venlafaxine (mean [SD] dosage, 166.07 [31.94] mg/d). as the activation of inflammatory changes in the gland.19,20 Chronic Comparison of drug-related results was shown in Table 3. exposure to histamine and 5-hydroxytryptamine altered the functions The observed wetting measurements in patients were lower thought to be involved in the secretory process, and neuronal re- than controls in both eyes (P < 0.000, Table 2). There was also a sig- lease of 5-hydroxytryptamine may be involved in the acute regu- nificant positive correlation between the right and left eyes for lation of lacrimal secretion in a broad range of species.19,20
TABLE 2. Sociodemographic and Schirmer Test Findings of Subjects in Comparison
Variable Patients (n = 54) Controls (n = 57) F t Z P
Age, mean (SD), y 34.7 (7.9) 34.6 (6.2) 5.93 0.07 0.95 Sex Male 12 15 0.62 Female 42 42 Right eye wetting, mean (SD), median, mm* 10.4 (5.8), 9 12.3 (0.7), 12 −3.95 0.00 Left eye wetting, mean (SD), median, mm 10.5 (5.4), 10 12.2 (0.6), 12 −3.76 0.00 No. subjects with wetting Right eye >5 mm 39 57 0.00 Right eye ≤5 mm 15 0 0.00 Left eye >5 mm 40 57 Left eye ≤5 mm 14 0 Italic data indicates all values are <0.001. *Time of exposure is 5 minutes.
Journal of Clinical Psychopharmacology • Volume 35, Number 4, August 2015 Dry Eye and Antidepressants
TABLE 3. Assessment of DE in Comparison Among 3 Antidepressants
Patients Using Patients Using Patients Using
Variable Escitalopram (n = 27) Duloxetine (n = 13) Venlafaxine (n = 14) P Age, mean (SD), y 33.1 (8.8) 36.6 (6.3) 36.0 (7.3) 0.34 Sex Male 5 3 4 0.76 Female 22 10 10 Right eye wetting, mean (SD), mm 9.6 (5.9) 11.9 (6.9) 10.6 (4.6) 0.51 Left eye wetting, mean (SD), mm 9.6 (5.7) 11.9 (6.5) 11.0 (3.7) 0.44 No. subjects with wetting Right eye >5 mm 17 9 13 0.17 Right eye ≤5 mm 10 4 1 0.42 Left eye >5 mm 18 9 13 Left eye ≤5 mm 9 4 1 Beck Depression Scale score, mean (SD) 17.11 (9.21) 15.92 (9.17) 15.43 (8.95) 0.83 Beck Anxiety Scale score, mean (SD) 22.66 (14.59) 12.30 (8.39) 17.00 (9.66) 0.043 Duration of drug, mean (SD), wk 20.81 (18.57) 17.23 (15.78) 46.85 (32.01) 0.001
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Intraocular Pressure-Lowering Efficacy and Safety of Bimatoprost 0.03% Therapy For Primary Open-Angle Glaucoma and Ocular Hypertension Patients in China
