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Objective: The aim of this paper is to alert the medical community to the potential risk of
clinical depression following the use of antiglaucoma medication.
Method: The available literature concerning systemic side-effects of topical antiglaucoma
medication and the association of these agents with clinical depression were reviewed. In
addition, two cases are reported of the occurrence of clinical depression following use of
topical betaxolol which only resolved completely after switching glaucoma medication.
Results/Conclusions: The case reports presented here add to the increasing body of
literature linking topical ophthalmic -adrenoceptor antagonists with depression. While these
cases are uncommon, this phenomenon continues to be poorly recognized by the medical
profession, psychiatrists, ophthalmologists and general practitioners alike.
Key words: beta-blockers, betaxolol, depression, topical.
newly prescribed beta-blockers to cause depression was While these cases are uncommon, this phenomenon
not evaluated and thus not ruled out in this study as only continues to be poorly recognized by the medical profes-
on-going beta-blocker use was investigated [6]. sion, psychiatrists, ophthalmologists and general prac-
Theoretically, there are plausible pathophysiological titioners alike. Patients can be educated in techniques to
mechanisms by which beta-blockers could cause depres- limit systemic absorption of topical agents and newer
sion. Down-regulation of 1-adrenoceptors in the CNS formulations such as Beptoptic-S (Alcon Laboratories,
has been associated with the mechanism of action of Frenchs Forest, NSW, Australia) have been designed to
antidepressants, -adrenoceptors are increased in the limit drug exposure. Both will reduce the risk of adverse
brains of suicide victims and in most valid animal model effects, however, potentially dangerous side-effects
of depression [7]. Interestingly, augmentation of antide- warrant careful monitoring by the prescribing physician.
pressant treatment with another beta-blocker pindolol
has recently received much attention. Many studies sug- References
gest that this combination treatment leads to improve-
ment of otherwise refractory patients or a faster onset 1. Rait LL. Systemic effects of topical ophthalmic -adrenoceptor
of antidepressant action. The mechanism of action of antagonists. Australian and New Zealand Journal of
Ophthalmology 1999; 27:5764.
pindolol in this case has been attributed to its affinity for 2. McMahon CD, Shaffer RN, Hoskins HD, Hetherington J.
5-HT receptors as it has been shown by positron emis- Adverse effects experienced by patients taking timolol.
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tors [8]. Betaxolol however, has negligible affinity for 3. Shore JH, Fraunfelder FT, Meyer SM. Psychiatric side-effects
from topical ocular timolol, a beta-adrenergic blocker. Journal of
5-HT receptors and has different effects to pindolol on Clinical Psychopharmacology 1987; 7:264267.
the actions of fluoxetine [9]. Thus although both drugs 4. Bourgeois JA. Depression and topical ophthalmic beta
are beta-blockers, one has the propensity to induce depres- adrenergic blockade. Journal of the American Optometry
sion whereas the other may help to alleviate it. Association 1991; 62:403406.
5. Orlando RG. Clinical depression associated with betaxolol.
The number of cases involved is small and points to American Journal of Ophthalmology 1986; 102:275.
some patients being more susceptible than others. One 6. Bright RA, Everitt DE. -blockers and depression. Journal of
explanation may lie in the way individual patients metab- the American Medical Association 1992; 267:17831787.
olize particular beta-blockers. Timolol is metabolized by 7. Vetulani J. Current concepts of mechanisms of action of
antidepressant treatments based on preclinical studies.
the cytochrome P450 enzyme CYP2D6. Approximately In: Judd, LL, Saletu, B, Filip, V, eds. Basic and clinical science
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greater systemic effects and higher plasma concentrations
to 5HT1A receptors in human brain confirmed with positron
of timolol following topical administration of timolol. In emission tomography. Psychopharmacology 1999;
the case of betaxolol, this may also be the explanation. 144:303305.
A minor metabolite of betaxolol, -hydroxylated betax- 9. Gobert A, Millan MJ. Modulation of dialysate levels of
dopamine, noradrenaline, and serotonin (5HT) in the frontal
olol, can be catalysed by CYP2D6. Further evidence for cortex of freely-moving rats by (-) -pindolol alone and in
this explanation comes from the observation that CNS association with 5HT reuptake inhibitors: comparative roles of
complaints were more common in those patients with beta-adrenergic, 5-HT1A, and 5-HT1B receptors.
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10. Edeki TI, He H, Wood AJJ. Pharmacogenetic explanation for
sibly to higher drug concentrations [2]. excessive beta-blockade following timolol eye drops: potential
These case reports add to the literature linking topical for oralophthalmic drug interaction. Journal of the American
ophthalmic -adrenoceptor antagonists with depression. Medical Association 1995; 274:16111613.