Certain side effects such as loss of libido and erectile dysfunction occur in a proportion of patients and are difficult to differentiate from the signs of depression. Other side effects occur in a proportion of patients, including gastrointestinal upset, increased anxiety as discussed in Chap. 47, blurred vision, dizziness, among many others (see Chap. 41).
The contentious issues of (1) inducing mania, (2) precipitating suicide soon after the institution of these medications, and (3) the use of these drugs in children are important ones that can only be addressed here cursorily. Ryan summarizes these problems and points out that the overall rates of suicide among adolescents are decreasing at the time of increasing use of SSRI agents. The precipitation of a manic episode by serotonergic antidepressants in some patients with bipolar disorder seems a regular enough occurrence that this risk is no longer a point in question. Also to be emphasized is an increased risk of pulmonary hypertension in the babies of mothers exposed to SSRI during the pregnancy.
The tricyclic antidepressants comprise amitriptyline, imipramine, desipramine, doxepin, clomipramine, and trimipramine, and the closely related drugs nortriptyline and protriptyline. Among this group, most psychiatrists start with imipramine or amitriptyline because of their relative safety. In general, all of these drugs are equally effective, although an individual patient may have a better response or tolerance to one than to another. The starting dose for amitriptyline or imipramine is 25 mg/d, which is then raised by 25 mg q3–4d as needed up to 150 mg/d. These drugs, taken at bedtime, are also very helpful in alleviating the insomnia that accompanies depression. The therapeutic effect of tricyclic medication is generally not evident for 2 to 4 weeks after treatment has been initiated, and it is important that this be explained to the patient and family. Common side effects are orthostatic hypotension, dry mouth, constipation, tachycardia, urinary hesitancy or retention (especially in patients with prostatic hypertrophy), tremor, and drowsiness. Closed-angle glaucoma may decompensate. Caution should be exercised in elderly patients with cardiac disorders of all types because of the possibility of causing heart block or arrhythmia. For such patients, the serotonin drugs or one of a group of nontricyclic antidepressant drugs—bupropion and trazodone—may be preferable, but the latter causes orthostatic hypotension and sedation in doses required for consistent antidepression effects. The non-trycyclic drugs appear to be as effective as the tricyclic agents in the treatment of depression without the adverse anticholinergic and cardiotoxic effects.