Benzodiazepines

The benzodiazepine class of medications is often the first-line therapy for patients with GAD. They are also beneficial as an adjunct to anesthesia or for management of alcohol withdrawal, treatment of seizures, alleviation of muscle spasm, treatment of insomnia, and treatment of nocturnal myoclonus. Table 11-2 lists the common antianxiety and hypnotic medications as well as the older class of barbiturates. The use of barbiturate drugs has declined due to their high potential for addiction and abuse. Although effective in treating these disorders, benzodiazepine use has also diminished over concerns related to dependency. Benzodiazepines are often prescribed to patients to manage the acute stage of chronic anxiety to allow time for prescribed serotonin–norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs), which may be safer for prolonged use, to take effect.

Table 11-2 Antianxiety and Hypnotic Medications

The mechanism of action for benzodiazepines is centered around their effect on gamma-aminobutyric acid (GABA) receptors in the central nervous system. Although these agents are similar in their effects, there is variation in the time of onset, half-life, and how they are metabolized. Withdrawal symptoms, including anxiety, tremors, psychosis, and even seizures, are more likely if intake is abruptly stopped after long-term use. All of the benzodiazepine drugs have the potential to cause retrograde amnesia, and respiratory depression is possible, especially if combined with alcohol. Benzodiazepines are involved in overdose suicide attempts in about 5% of cases.

Ophthalmic considerations The abuse potential of benzodiazepines is mild compared with other drugs such as hydromorphone and cocaine. Nevertheless, long-term administration of these agents can cause physical dependence. Ocular adverse effects can occur, although they tend to be dose-related and transient. Decreased accommodation, induced phorias, and nystagmus are sometimes associated with benzodiazepine use.

Antidepressants

A growing number of patients with major depression are being managed with medication alone, despite reports that demonstrate the benefits of combining pharmacologic treatment with psychotherapy. Nevertheless, this group of drugs is effective in managing the symptoms associated with depression, improving the rate of recovery, reducing the risk of suicide, and aiding in social and occupational rehabilitation.

In general, antidepressants can take up to 6 weeks to show significant effect; treatment is generally continued for up to 12 weeks, although long-term management may be needed in select cases. Antidepressants are associated with a 50%–60% response rate among patients with major depression in the primary care setting. These drugs can result in mood elevation, improved appetite, better sleep, and increased mental and physical activity.

Table 11-3 lists the various classes of antidepressants. The first-generation tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) are generally no longer prescribed as first-line treatment due to safety concerns (in particular, overdose) and adverse effects. Second-generation options include SSRIs, SNRIs, atypical antidepressants, and serotonin modulators. Of these, SSRIs are the most widely prescribed; they are very effective and tend to be better tolerated. Occasional adverse effects associated with SSRIs include sexual dysfunction, drowsiness, insomnia, weight gain, dizziness, headache, and blurred vision (likely related to dry eye and, to a lesser extent, mydriasis). Rare cases of angle-closure glaucoma have been reported. SSRIs may also cause inhibition of platelet function, and some studies suggest a possible increase in risk of bleeding, especially involving the upper gastrointestinal system.

Because major depression is now thought to affect 5% of children and adolescents, the use of SSRIs has steadily increased in this population as well. There have been some reports of antidepressants leading to increased suicidal ideation in a small percentage of children and adolescents. Close monitoring for abnormal behavior, agitation, and suicidal thoughts is advised, especially within the first 4 weeks after the individual begins antidepressant therapy.

Table 11-3 Antidepressant Medications

Mood stabilizers

Mood stabilizers are a heterogeneous group of medications that do not clearly share a common mechanism of action. They are the drugs of choice for the treatment of bipolar disorder. Lithium carbonate was the first drug to be developed in this class and has been the most widely studied. Other mood stabilizers include the antiepileptic agents valproic acid, carbamazepine, and lamotrigine. Potential ocular adverse effects of lithium use include blurred vision, nystagmus (usually downbeat), and exophthalmos associated with lithium-induced changes in thyroid function.

Ophthalmic considerations Although behavioral disorders do not directly affect the eye, several related issues are important for ophthalmologists to be aware of. Patient education and reassurance may be required because the underlying mental disorder may mean that anticholinergic side effects, such as dry eye and accommodative changes, are more concerning to patients. Poor adherence to treatment is another common problem among patients with mental health issues. Malingering and functional vision loss require a high index of suspicion and special diagnostic skills on the part of the clinician. Some medications used to treat eye disease, including carbonic anhydrase inhibitors, brimonidine, and oral corticosteroids, may induce or exacerbate depression. Although β-blockers were thought to increase the risk of depression, recent studies suggest this correlation is not as strong as was previously believed.

• Richa S, Yazbek JC. Ocular adverse effects of common psychotropic agents: a review. CNS Drugs. 2010;24(6):501–526.

Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.