The potential CNS adverse effects of OBBs are discussed in section3.6.3. In patients with subtle changes in mental status, OBBs may contribute to symptoms. This effect is reversible with discontinuation of OBBs. Depression, a common condition, is also commonly listed as a CNS adverse effect of beta blockers. Most of the data propagating the notion that beta blockers cause depression emanate from individual case reports or short case series in the late 1960s and 1970s. In contrast, there are at least 10 published studies that used standardized rating assessments for depression, such as the Hamilton Rating Scale for Depression, Profile of Mood States, and Zung Self-Rating Depression Scale, rather than less rigorous methods of assessment, such as using the isolated symptom "depression" or providing simple checklist responses. Eight of these 10 studies were prospective studies. Four were double-masked, randomized, placebo-controlled trials, and another had a placebo arm but used a crossover design. Nine of these 10 studies did not demonstrate an association between beta-adrenergic blockers and depression. Three of these were relatively large and had between 312 and 487 subjects. The only one that reported a positive association had only 20 patients randomized, and the agents were administered for only 4 days. This detailed illustration shows how case reports may not be supported by appropriately designed studies. This is summarized in reviews.95,96
Use of OBBs is contraindicated in the presence of several cardiovascular diseases as mentioned in section 3.6.4. In a patient with uncompensated heart failure, sick sinus syndrome, or undetected bradycardia, OBBs may cause adverse symptoms or even be life-threatening. They can also lower blood pressure, potentially worsening symptoms in patients with orthostatic hypotension, cerebrovascular insufficiency, or peripheral vascular disease.
The OBBs should be avoided in patients with known reactive airway disease. As discussed in section 3.6.5, pulmonary function can be affected even in healthy asymptomatic individuals. While betaxolol formerly was considered relatively safe for use in those individuals, now newer classes of drugs offer safer alternatives.
Oral beta blockers can mask symptoms of thyrotoxicosis. Similarly, abrupt withdrawal of OBBs can exacerbate symptoms of hyperthyroidism. In a labile diabetic patient with known history of hypoglycemic unawareness, OBBs could theoretically mask the symptoms of hypoglycemia, which are mediated by catechol-amines. Patients with non-insulin-dependent diabetes mellitus receiving systemic beta blockers do not appear to be at increased risk of hypoglycemic unawareness, nor have beta blockers been shown to be associated with prolonged hypoglyce-mia due to blockade of catecholamine-mediated recovery. However, patients with insulin-dependent diabetes or labile diabetes may be potentially at greater risk for prolonged hypoglycemia when receiving systemic doses of beta blockers.97-99
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