Choosing an Antidepressant - Clinical Pharmacology of Antidepressants

Choosing an Antidepressant

The choice of an antidepressant depends first on the indication. Not all conditions are equally responsive to all antidepressants. However, in the treatment of MDD, it is difficult to demonstrate that one antidepressant is consistently more effective than anotherThus, the choice of an antidepressant for the treatment of depres-sion rests primarily on practical considerations such as cost, avail-ability, adverse effects, potential drug interactions, the patient’s history of response or lack thereof, and patient preference. Other factors such as the patient’s age, gender, and medical status may also guide antidepressant selection. For example, older patients are particularly sensitive to the anticholinergic effects of the TCAs. On the other hand, the CYP3A4-inhibiting effects of the SSRI fluvoxamine may make this a problematic choice in some older patients because fluvoxamine may interact with many other medications that an older patient may require. There is some sug-gestion that female patients may respond to and tolerate seroton-ergic better than noradrenergic or TCA antidepressants, but the data supporting this gender difference have not been consistent. Patients with narrow-angle glaucoma may have an exacerbation with noradrenergic antidepressants, whereas bupropion and other antidepressants are known to lower the seizure threshold in epi-lepsy patients.

At present, SSRIs are the most commonly prescribed first-line agents in the treatment of both MDD and anxiety disorders. Their popularity comes from their ease of use, tolerability, and safety in overdose. The starting dose of the SSRIs is usually the same as the therapeutic dose for most patients, and so titration may not be required. In addition, most SSRIs are now generically available and inexpensive. Other agents, including the SNRIs, bupropion, and mirtazapine, are also reasonable first-line agents for the treat-ment of MDD. Bupropion, mirtazapine, and nefazodone are the antidepressants with the least association with sexual side effects and are often prescribed for this reason. However, bupropion is not thought to be effective in the treatment of the anxiety disor-ders and may be poorly tolerated in anxious patients. The primary indication for bupropion is in the treatment of major depression, including seasonal (winter) depression. Off-label uses of bupro-pion include the treatment of attention deficit hyperkinetic disor-der (ADHD), and bupropion is commonly combined with other antidepressants to augment therapeutic response. The primary indication for mirtazapine is in the treatment of major depression. However, its strong antihistamine properties have contributed to its occasional use as a hypnotic and as an adjunctive treatment to more activating antidepressants.

The TCAs and MAOIs are now relegated to second- or third-line treatments for MDD. Both the TCAs and the MAOIs are potentially lethal in overdose, require titration to achieve a thera-peutic dose, have serious drug interactions, and have many trou-blesome adverse effects. As a consequence, their use in the treatment of MDD or anxiety is now reserved for patients who have been unresponsive to other agents. Clearly, there are patients whose depression responds only to MAOIs or TCAs. Thus, TCAs and MAOIs are probably underused in treatment-resistant depressed patients. 

The use of antidepressants outside the treatment of MDD tends to require specific agents. For example, the TCAs and SNRIs appear to be useful in the treatment of pain conditions, but other antidepressant classes appear to be far less effective. SSRIs and the highly serotonergic TCA, clomipramine, are effective in thetreatment of OCD, but noradrenergic antidepressants have not proved to be as helpful for this condition. Bupropion and nortrip-tyline have usefulness in the treatment of smoking cessation, but SSRIs have not been proven useful. Thus, outside the treatment of depression, the choice of antidepressant is primarily dependent on the known benefit of a particular antidepressant or class for a particular indication.