Tricyclic Antidepressants Tricyclic antidepressants are the oldest antidepressants still in use and are available in generic preparations (118–122). They all have significant anticholinergic side effects that may be problematic in medically ill and elderly patients. They are associated with some slowing of intracardiac conduction; this side effect can be tolerated and managed in all but a few patients, and it can be therapeutic for those with hyperconductibility. Tricyclic antidepressants should be taken in divided doses through the day, although bedtime dosing may help patients who have difficulty sleeping. Some tricyclic agents, such as nortriptyline, have “therapeutic windows”—blood levels above or below which they are not effective—that must be monitored. The average dose for tricyclic agents is 225 mg per day in divided doses (122). The most important drawback of tricyclic medications is their lethality in overdose, which is especially important because they are used with depressed patients who are already at risk for suicide. In the rare event that they must be used by a potentially suicidal patient, the patient must be given only a few pills at a time (121). Some medication plans, private or public, require that treatment begin with the least expensive generic medication, and that the patient first fail with that medication before a newer compound will be provided. The clinician may have to serve as advocate for the patient when this is not a clinically acceptable approach.
Monoamine Oxidase Monoamine oxidase (MAO) inhibitors are especially effective for atypical depression, which is
Inhibitors associated with abnormally increased, rather than decreased, sleep and appetite. They require dietary restrictions and can be used only in patients who are able to understand and comply with those restrictions to avoid hypertensive crises (117).
SSRIs pose few risks of medical complications. Side effects include anxiety, tremor, headache, and gastrointestinal upset (either diarrhea or constipation), and usually abate within a few days of the onset of treatment. A more serious side effect is loss of libido and interference with orgasm (119). Patients may be reluctant to report sexual side effects, but they may discontinue treatment because of them. Some women are willing to accept the sexual side effects of SSRIs as an acceptable price to pay for recovery, especially considering that depression already interferes with their sexual functioning. Female patients are frequently concerned about weight gain. In one study, it appeared that a weight gain of 5 to 7 pounds might be attributed to an SSRI; the return of normal appetite may lead to weight gain. Concerned patients should be advised to watch their diets carefully while taking the medication. There is some evidence that bupropion causes less weight gain than SSRIs. SSRIs appear to interfere with the efficacy of tamoxifen, resulting in excess mortality from breast cancer (120).
SSRIs are administered in a once-a-day regimen, with little need for dosage adjustments in most cases. SSRIs have long half-lives, so occasional late or missed doses do not constitute a problem. Withdrawal, especially sudden withdrawal, from SSRIs causes ﬂulike symptoms and sleep problems in a small proportion of patients (121). Patients should be cautioned not to discontinue their medications without consulting the physician, and only then by gradually decreasing the dose. As with most medications, antidepressants were not initially tested in older women, but several are under consideration by the U.S. Food and Drug Administration (FDA) for use in this age group (122). The FDA mandated so-called black box warnings on SSRIs when used in adolescents and young adults. This decision is highly controversial. The studies upon which the decision was based included no subject who had committed suicide. Suicidal thoughts, which are extremely common, were conﬂated with serious attempts, all lumped together as suicidality. SSRI prescriptions decreased after the warning was imposed, and there is some evidence that suicides have gone up as a result (123–125).