3.2.1. OAG

A cohort-type study regarding the risk of OAG coupled with bupropion treatment, reported a reduced hazard of developing this type of glaucoma. More precisely, the percentage of bupropion users that developed OAG was 1.8% and the percentage of nonusers who developed OAG was 2.4%. Moreover, usage of this drug for 24–48 months has been associated with a 21% reduced chance of OAG [39].

#### 3.2.2. ACG

A case-control study conducted on patients under 50 years old reported bupropion treatment to be associated with an increased risk of ACG. No new prescriptions were issued afterwards, which could imply that predisposed eyes with narrow angles and pupillary dilation were not likely since iridotomy would have allowed continuation of treatment. Although the manufacturer's information references the occurrence of ACG secondary to a pharmacological pupillary dilation, there is a possibility that choroidal effusion can occur [36].

Also, 2 weeks bupropion treatment (300 mg/day) was incriminated as a cause ACG in a 40 years old woman, with complains of blurred vision. Ultrasound bio microscopy revealed bilateral choroidal effusions that caused shallow angles [65].

#### *3.3. Tricyclic Antidepressants (TCAs)*

TCAs are the first generation of antidepressants and have been used in the psychopharmacological treatment of depression since around 1950. TCAs inhibit, through action on specific transporters, the reuptake of serotonin and noradrenaline in the synapse cleft. Also, TCAs block the postsynaptic histamine, acetylcholine and alpha-adrenergic receptors. Unfortunately, due to the cardiovascular and gastrointestinal serious adverse effects and their lethality in overdose quantities, TCAs have been replaced over time by SSRIs and SNRIs in the management of depression [66].

According current literature data, tricyclic antidepressants (clomipramine, amitriptyline, imipramine, doxepin, desipramine, nortriptyline etc.) are reported to be involved only in ACG and to precipitate AACG. The pupillary block via pupil dilatation that occurs during treatment with TCAs is attributed to the significant anticholinergic and serotonergic effects of these antidepressants [67]. The most frequent anticholinergic effects on the eye are mydriasis and cycloplegia, which in turn may cause the blockage of the trabecular meshwork. These effects result in blurred vision due to loss of accommodation and in precipitation of ACG [67–70] (Figure 1).

A relative large body of case reports that linked different TCAs treatment to the raise of IOP and glaucoma occurrence is present in the literature. Schlingemann et al. (1996) described the case of a 59-year-old woman with developed monocular vision loss, increased IOP and narrowed anterior chambers supposing due to treatment with clomipramine (75 mg/day) [71]. Lowe et al. (1966) also reported the cases of 4 patients on small dosage amitriptyline therapy that developed ACG [72]. In addition, Ritch et al. (1994) documented 4 cases of narrow angled patients who developed ACG related to imipramine treatment. Ritch et al. stated that uveal tract problems could be associated with TCA, mydriasis being often transient, without major consequences. Moreover, ACG can be promoted in susceptible patients (e.g., narrow angle individuals) [73].

All things considered, current data point out the risk of using drugs with potent anticholinergics proprieties, such as TCAs. The development of the new classes of antidepressants (i.e., SSRI and SNRI) provides important alternatives. In the case that TCAs must be used, the drugs with the less anticholinergic effects, such as desipramine and nortriptyline, should be taken into consideration [74]. No doubt, further cohort studies that assess the potential risk of angle closure glaucoma associated with TCAs are necessary in order to make conclusive recommendations.
