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Intraocular pressure in patients receiving psychotropic medications
WILLIAM H. REID, M.D., M.P.H. STEVEN RAKES, M.D.
Intraocular pressure in patients receiving psychotropic medications This study was undertaken to confirm and refine previous work suggesting little clinically significant relationship between psychotropics and increased intraocular pressure with potential subsequent glaucoma. Schiotz tonometry in 126 psychiatric patients receiving psychotropics did not demonstrate adverse drug effects on intraocular pressure, even in persons with possible additional risk factors such as moderate or heavy smoking or who were more than 50 years old. The mean intraocular pressure was 13.7 mm Hg, and no patient displayed pressure greater than 24 mm Hg.
ABSTRACT:
The autonomic effects of many psychotropics, particularly those with significant anticholinergic activity such as anti psychotics, antidepressants, and antiparkinsonism drugs, have led to concern that increased intraocular pressure (lOP) may occur in patients receiving them. This concern primarily relates to potential for development of the anatomic changes of glaucoma, and is reflected by warnings in drug evaluations and prescribing information,l.! by caveats in psy-
chopharmacology texts,3.' and by occasional comment in the literature.6.~
Special potential for problems has been suggested for patients with preexisting vulnerability because of age, eye injury, and other factors. Insidious open-angle glaucoma is of more concern than acute narrow-angle glaucoma, because of the absence of warning signs before permanent damage occurs. Previous studies and reviews by the first author and associatesx, 1O
Dr. Reid is associate professor ofpsychiatry at the Nebraska Psychiatric Institute. At the time of this study. Dr. Rakes "'as also at the Institute. He is no\\' a fello\\' in ophthalmology at the Mayo Clinic. Reprint requests to Dr. Reid at the Institute. 602 South 45th Street, Omaha, N E 68106. JULY 1983· VOL 24' NO 7
have challenged the premise that commonly used psychiatric medications (including antiparkinsonism drugs) expose patients to any significantly increased risk of glaucoma. Reports of the comparative levels of anticholinergic activity (muscarinic binding properties) of antipsychotic drugs II and antidepressants and antiparkinsonism agents l ! reveal considerable variation but little cause for clinical alarm with regard to actions on the eye. Optimum intraocular pressure is between 13.5 and 18.5 mm Hg. Normal values vary with age, sex, blood pressure, body position, and time of day. Pressures are generally highest in the morning. Clinical attention is warranted when lOP exceeds 30 mm Hg and visual field loss or nerve damage is present. In the absence of nerve damage, treatment is recommended 13 if (I) lOP is materially greater than 30 mm Hg, (2) there is a large cup-todisc ratio in patients with high-normal lOP, or (3) a therapeutic trial of pilocarpine produces a significant drop in pressures above 30 665
Intraocular pressure
mm Hg with no side effects. In light of the continuing concern about the possibility of drug-related ocular damage, and despite fairly strong evidence to the contrary, the authors decided to measure lOP in sequential patients. Because of the number of nonpharmacologic factors that might account for much of the variance in such a study, historical information was gathered more carefully than in our 1976 stud y8 and the data were more rigorously analyzed.
means and standard deviations. More complex analysis was not done because of the obvious insignificance of group and individual differences (see Results below). The data were utilized to derive the seven groups listed in Table I. Those groups of patients who might be expected to be more or less likely to have increased lOP were analyzed separately, and as part of the entire sample, in an effort to detect any lOP increased by a specific risk factor. Subjects who had taken psychotropic or other medication
with known anticholinergic effects for at least six months qualified for the two drug groups. Results Table 2 shows the number of subjects with from zero to four possible risk factors (psychotropic or anticholinergic medication, depot fluphenazine, aged 50 years or more, and smoking one pack or more of cigarettes per day) relative to lOP at or above 20 mm Hg. As Table I shows, the mean lOP for all 252 eyes was 13.7 mm Hg
Tbe study
Subjects. The subjects were inpatients and outpatients at university and Veterans Administration psychiatric facilities. All available adults who consented to the interview and examination were accepted. One hundred and twenty-six psychiatric patients were screened for eye disease and increased lOP, for a total of252 eyes examined. No subject was taking medication to control increased lOP. Procedure. Medical (including ophthalmic), family, and psychiatric histories were elicited from each subject and verified or augmented by chart review. A data sheet with historical information and examination results was prepared for each subject. lOP was measured by Schiotz tonometry under appropriate clinical conditions. Applanation tonometry was impractical for the patients studied; Schiotz measurements are considered quite acceptable for screening. '4 All subjects were examined by the same investigator (SR), during morning hours whenever possible. There were no adverse reactions to the procedure. Data analysis. After collation and tabulation, the data were analyzed with simple computation of 666
Table 1-Mean lOP by Study Group
I
"
Subjects of ell (N) subjects
Meen lOP In mmHg (renge)
Number of eyes "of eyeswith lOP _ with lOP 2: 20 mm Hg 20 mm Hg
126
100
13.7 (5to 24)
16
6,3
103
81.7
13.7 (5 to 24)
11
5.3
Fluphenazine decanoate
31
24.6
14.4 (7 to 24)
5
8.1
No anticholinergic medication
23
18.3
13.7 (7 to 24)
5
10.9
40 years or older
26
20,6
13.6 (7 to 24)
4
7,7
50 years or older
12
9.5
13,3 (7 to 24)
Smoke one pack or more per dayt
79
62,7
13,8 (7t024)
14
8,9
Smoke two or more packs per dayt
33
26.2
14.0 (7 to 24)
7
10.6
Total Group Psychotropic or other anticholinergic medication
I
4.2
Percent calculation IS baseo on 10 al number ot ey s In eacn group smoked at least once Wltn", WO l10urs 01 t Sling
t All . mokers were assumed 10 na
PSYCHOSOMATICS
Table 2-RelaUonshlp of Possible Risk Factors to lOP
All four factors Three factors Two factors One factor Zero factors
Total
Subfecl' (N)
Number of.y.. with 10P2: 20mm Hg
the total number
3 25 60 29 9 126
1 6 5 2 2 16
16.7 12.0 4.2 3.4 11.1 6.3
(range of 5 to 24 mm Hg, SD = 3.66). The mean lOPs for all groups, with and without possible risk factors, were between 13.3 mm Hg and 14.4 mm Hg, with quite similar ranges (5 to 24 mm Hg and 7 to 24 mm Hg) and standard deviations (3.54 to 4.37). The individual and group measurements thus varied little. No subject had an lOP above 24 mm Hg or showed any sign of optic cup enlargement. Perimetry was not performed. Table 2 shows that subjects with one or two possible risk factors had the lowest percentages of eyes with lOP at or above 20 mm Hg, and approximated the result for the
JULY 1983· VOL 24· NO 7
of.y••
total sample. Subjects with three possible risk factors had a somewhat higher percentage of eyes at or above 20 mm Hg; however, this proportion was about the same as that for persons with no risk factors at all. Subjects with all four possible risk factors had a higher percentage, but this group was too small for to us assume any pattern of the results. There thus were no significant differences between any of the groups or between any group and the total sample.
Discussion In this study we attempted to refine the conclusions of our earlier
REFERENCES 1. American Medical Association: AMA Drug Evaluations, ed 4. Chicago, American Medi· cal Association, 1980. 2. Physicians Desk Relerence. Oradell. NJ, Medical Economics, 1982. 3. Ban T: Psychopharmacology. Baltimore, Wil· Iiams & Wilkins. 1969. 4. Berger PA: Antidepressant medications and the treatment of depression, in Barchas JD, Berger PA, Ciaranello RD, et al (eds): Psy· chopharmacology: From Theory to Practice. New York, Oxford University Press. 1977. pp 174-207. 5. Eichelman B: Emergency Treatment, in Bar· chas JD, Berger PA, Ciaranello RD, et al (eds): Psychopharmacology: From Theory to
A.%of
6. 7.
8. 9.
10.
Practice. New York, Oxford University Press, t977. Hollister LE: Toxicity of psychotherapeutic drugs. Practitioner 194:72-84,1965. Siddall JR: Ocular complications related to phenothiazines Dis Nerv Syst 29(suppl):10· 13,1968. Reid WH, Blouin P: Outpatient psychiatriC medications and glaucoma. Psychosomatics 17:83-85, 1976. Reid WH, Blouin p. Schermer M: A review of psychotropic medications and the glauco· mas. Int Pharmacopsychiatry 11: 163-174, 1976. Reid WH, Arkfeld DF: Psychotropic medications and glaucoma. Hillside J Clin Psychiatry 2:217-221,1980.
papers, which implied little clinically significant relationship between psychotropic drugs and increased intraocular pressure. Although the number of subjects studied is not large, the present results do not demonstrate adverse drug effects on lOP in patients taking drugs with anticholinergic properties who smoke moderately or heavily, and/or who are 50 or more years old. Our results are consistent with previous work suggesting that the danger of precipitating or exacerbating glaucoma with psychotropic drugs has been exaggerated elsewhere in the literature. Recommendations for decreasing the potential for problems even further have been outlined in our previous reports8• IO and include (I) funduscopic examination and tonometry when the patients are physically evaluated, and (2) exploration of personal and family histories for symptoms of glaucoma or intolerance of clinical dilation. If anyone of these is positive, or if the patient now has glaucoma, ophthalmologic consultation will almost always allow safe prescription of the psychotropic of choice for the psychiatric disorder. 0
11. Snyder SH, Greenberg D, Yamamura HI: An· tischizophrenic drugs and brain cholinergic receptors: Affinity for muscarinic sites pre· dicts extrapyramidal effects. Arch Gen PsyChiatry 31 :58-61, 1974. 12 Snyder SH. Yamamura HI: Antidepressants and the muscarinic acetylcholine receptor. Arch Gen Psychiatry 34:236-239, 1977. 13. Shaffer RN: Glaucoma, in Duane TD (ed): Clinical Ophthalmology. New York, Harper & Row, 1976. vol 3, pp 1-5. 14. WOr1han DM: Intraocular pressure and its diurnal variation, in Heilmann K, Richardson KT (eds): Glaucoma: Conceptions 01 a Dis· ease. Philadelphia, WB Saunders, 1978. pp 54-66.
647
Intraocular pressure in patients receiving psychotropic medications This study was undertaken to confirm and refine previous work suggesting little clinically significant relationship between psychotropics and increased intraocular pressure with potential subsequent glaucoma. Schiotz tonometry in 126 psychiatric patients receiving psychotropics did not demonstrate adverse drug effects on intraocular pressure, even in persons with possible additional risk factors such as moderate or heavy smoking or who were more than 50 years old. The mean intraocular pressure was 13.7 mm Hg, and no patient displayed pressure greater than 24 mm Hg.
ABSTRACT:
The autonomic effects of many psychotropics, particularly those with significant anticholinergic activity such as anti psychotics, antidepressants, and antiparkinsonism drugs, have led to concern that increased intraocular pressure (lOP) may occur in patients receiving them. This concern primarily relates to potential for development of the anatomic changes of glaucoma, and is reflected by warnings in drug evaluations and prescribing information,l.! by caveats in psy-
chopharmacology texts,3.' and by occasional comment in the literature.6.~
Special potential for problems has been suggested for patients with preexisting vulnerability because of age, eye injury, and other factors. Insidious open-angle glaucoma is of more concern than acute narrow-angle glaucoma, because of the absence of warning signs before permanent damage occurs. Previous studies and reviews by the first author and associatesx, 1O
Dr. Reid is associate professor ofpsychiatry at the Nebraska Psychiatric Institute. At the time of this study. Dr. Rakes "'as also at the Institute. He is no\\' a fello\\' in ophthalmology at the Mayo Clinic. Reprint requests to Dr. Reid at the Institute. 602 South 45th Street, Omaha, N E 68106. JULY 1983· VOL 24' NO 7
have challenged the premise that commonly used psychiatric medications (including antiparkinsonism drugs) expose patients to any significantly increased risk of glaucoma. Reports of the comparative levels of anticholinergic activity (muscarinic binding properties) of antipsychotic drugs II and antidepressants and antiparkinsonism agents l ! reveal considerable variation but little cause for clinical alarm with regard to actions on the eye. Optimum intraocular pressure is between 13.5 and 18.5 mm Hg. Normal values vary with age, sex, blood pressure, body position, and time of day. Pressures are generally highest in the morning. Clinical attention is warranted when lOP exceeds 30 mm Hg and visual field loss or nerve damage is present. In the absence of nerve damage, treatment is recommended 13 if (I) lOP is materially greater than 30 mm Hg, (2) there is a large cup-todisc ratio in patients with high-normal lOP, or (3) a therapeutic trial of pilocarpine produces a significant drop in pressures above 30 665
Intraocular pressure
mm Hg with no side effects. In light of the continuing concern about the possibility of drug-related ocular damage, and despite fairly strong evidence to the contrary, the authors decided to measure lOP in sequential patients. Because of the number of nonpharmacologic factors that might account for much of the variance in such a study, historical information was gathered more carefully than in our 1976 stud y8 and the data were more rigorously analyzed.
means and standard deviations. More complex analysis was not done because of the obvious insignificance of group and individual differences (see Results below). The data were utilized to derive the seven groups listed in Table I. Those groups of patients who might be expected to be more or less likely to have increased lOP were analyzed separately, and as part of the entire sample, in an effort to detect any lOP increased by a specific risk factor. Subjects who had taken psychotropic or other medication
with known anticholinergic effects for at least six months qualified for the two drug groups. Results Table 2 shows the number of subjects with from zero to four possible risk factors (psychotropic or anticholinergic medication, depot fluphenazine, aged 50 years or more, and smoking one pack or more of cigarettes per day) relative to lOP at or above 20 mm Hg. As Table I shows, the mean lOP for all 252 eyes was 13.7 mm Hg
Tbe study
Subjects. The subjects were inpatients and outpatients at university and Veterans Administration psychiatric facilities. All available adults who consented to the interview and examination were accepted. One hundred and twenty-six psychiatric patients were screened for eye disease and increased lOP, for a total of252 eyes examined. No subject was taking medication to control increased lOP. Procedure. Medical (including ophthalmic), family, and psychiatric histories were elicited from each subject and verified or augmented by chart review. A data sheet with historical information and examination results was prepared for each subject. lOP was measured by Schiotz tonometry under appropriate clinical conditions. Applanation tonometry was impractical for the patients studied; Schiotz measurements are considered quite acceptable for screening. '4 All subjects were examined by the same investigator (SR), during morning hours whenever possible. There were no adverse reactions to the procedure. Data analysis. After collation and tabulation, the data were analyzed with simple computation of 666
Table 1-Mean lOP by Study Group
I
"
Subjects of ell (N) subjects
Meen lOP In mmHg (renge)
Number of eyes "of eyeswith lOP _ with lOP 2: 20 mm Hg 20 mm Hg
126
100
13.7 (5to 24)
16
6,3
103
81.7
13.7 (5 to 24)
11
5.3
Fluphenazine decanoate
31
24.6
14.4 (7 to 24)
5
8.1
No anticholinergic medication
23
18.3
13.7 (7 to 24)
5
10.9
40 years or older
26
20,6
13.6 (7 to 24)
4
7,7
50 years or older
12
9.5
13,3 (7 to 24)
Smoke one pack or more per dayt
79
62,7
13,8 (7t024)
14
8,9
Smoke two or more packs per dayt
33
26.2
14.0 (7 to 24)
7
10.6
Total Group Psychotropic or other anticholinergic medication
I
4.2
Percent calculation IS baseo on 10 al number ot ey s In eacn group smoked at least once Wltn", WO l10urs 01 t Sling
t All . mokers were assumed 10 na
PSYCHOSOMATICS
Table 2-RelaUonshlp of Possible Risk Factors to lOP
All four factors Three factors Two factors One factor Zero factors
Total
Subfecl' (N)
Number of.y.. with 10P2: 20mm Hg
the total number
3 25 60 29 9 126
1 6 5 2 2 16
16.7 12.0 4.2 3.4 11.1 6.3
(range of 5 to 24 mm Hg, SD = 3.66). The mean lOPs for all groups, with and without possible risk factors, were between 13.3 mm Hg and 14.4 mm Hg, with quite similar ranges (5 to 24 mm Hg and 7 to 24 mm Hg) and standard deviations (3.54 to 4.37). The individual and group measurements thus varied little. No subject had an lOP above 24 mm Hg or showed any sign of optic cup enlargement. Perimetry was not performed. Table 2 shows that subjects with one or two possible risk factors had the lowest percentages of eyes with lOP at or above 20 mm Hg, and approximated the result for the
JULY 1983· VOL 24· NO 7
of.y••
total sample. Subjects with three possible risk factors had a somewhat higher percentage of eyes at or above 20 mm Hg; however, this proportion was about the same as that for persons with no risk factors at all. Subjects with all four possible risk factors had a higher percentage, but this group was too small for to us assume any pattern of the results. There thus were no significant differences between any of the groups or between any group and the total sample.
Discussion In this study we attempted to refine the conclusions of our earlier
REFERENCES 1. American Medical Association: AMA Drug Evaluations, ed 4. Chicago, American Medi· cal Association, 1980. 2. Physicians Desk Relerence. Oradell. NJ, Medical Economics, 1982. 3. Ban T: Psychopharmacology. Baltimore, Wil· Iiams & Wilkins. 1969. 4. Berger PA: Antidepressant medications and the treatment of depression, in Barchas JD, Berger PA, Ciaranello RD, et al (eds): Psy· chopharmacology: From Theory to Practice. New York, Oxford University Press. 1977. pp 174-207. 5. Eichelman B: Emergency Treatment, in Bar· chas JD, Berger PA, Ciaranello RD, et al (eds): Psychopharmacology: From Theory to
A.%of
6. 7.
8. 9.
10.
Practice. New York, Oxford University Press, t977. Hollister LE: Toxicity of psychotherapeutic drugs. Practitioner 194:72-84,1965. Siddall JR: Ocular complications related to phenothiazines Dis Nerv Syst 29(suppl):10· 13,1968. Reid WH, Blouin P: Outpatient psychiatriC medications and glaucoma. Psychosomatics 17:83-85, 1976. Reid WH, Blouin p. Schermer M: A review of psychotropic medications and the glauco· mas. Int Pharmacopsychiatry 11: 163-174, 1976. Reid WH, Arkfeld DF: Psychotropic medications and glaucoma. Hillside J Clin Psychiatry 2:217-221,1980.
papers, which implied little clinically significant relationship between psychotropic drugs and increased intraocular pressure. Although the number of subjects studied is not large, the present results do not demonstrate adverse drug effects on lOP in patients taking drugs with anticholinergic properties who smoke moderately or heavily, and/or who are 50 or more years old. Our results are consistent with previous work suggesting that the danger of precipitating or exacerbating glaucoma with psychotropic drugs has been exaggerated elsewhere in the literature. Recommendations for decreasing the potential for problems even further have been outlined in our previous reports8• IO and include (I) funduscopic examination and tonometry when the patients are physically evaluated, and (2) exploration of personal and family histories for symptoms of glaucoma or intolerance of clinical dilation. If anyone of these is positive, or if the patient now has glaucoma, ophthalmologic consultation will almost always allow safe prescription of the psychotropic of choice for the psychiatric disorder. 0
11. Snyder SH, Greenberg D, Yamamura HI: An· tischizophrenic drugs and brain cholinergic receptors: Affinity for muscarinic sites pre· dicts extrapyramidal effects. Arch Gen PsyChiatry 31 :58-61, 1974. 12 Snyder SH. Yamamura HI: Antidepressants and the muscarinic acetylcholine receptor. Arch Gen Psychiatry 34:236-239, 1977. 13. Shaffer RN: Glaucoma, in Duane TD (ed): Clinical Ophthalmology. New York, Harper & Row, 1976. vol 3, pp 1-5. 14. WOr1han DM: Intraocular pressure and its diurnal variation, in Heilmann K, Richardson KT (eds): Glaucoma: Conceptions 01 a Dis· ease. Philadelphia, WB Saunders, 1978. pp 54-66.
647