Current Drug Therapy

A practical approach to prescribing antidepressants

Author and Disclosure Information

ABSTRACTAlthough antidepressant drugs do not differ much in their efficacy rates, the particular characteristics of one drug may make it a better choice in a given patient. This article provides insight into the art of prescribing antidepressants in primary care, with recommendations for prescribing for patients with chronic pain, sexual dysfunction, anxiety, chronic fatigue syndrome, fibromyalgia, severe insomnia, old age, diabetes, and heart problems.


  • We suggest that clinicians become familiar with one drug from each class of antidepressants.
  • Many antidepressants are also approved for conditions other than depression, and for patients who have both depression and one or more of these comcomitant conditions, these drugs can have a “two-for-one” benefit.
  • Adverse effects of an antidepressant are usually predictable on the basis of the drug’s mechanism of action.



With the variety of drugs available for treating depression, choosing one can be daunting. Different agents have characteristics that may make them a better choice for different types of patients, but even so, treating any kind of mental illness often requires an element of trial and error.

Primary care providers are on the frontline of treating mental illness, often evaluating patients before they are seen by a psychiatrist. The purpose of this article is to provide insight into the art of prescribing antidepressants in the primary care setting. We will discuss common patient presentations, including depressed patients without other medical comorbidities as well as those with common comorbidities, with our recommendations for first-line treatment.

We hope our recommendations will help you to navigate the uncertainty more confidently, resulting in more efficient and tailored treatment for your patients.


When starting a patient on antidepressant drug therapy, we recommend obtaining a set of baseline laboratory tests to rule out underlying medical conditions that may be contributing to the patient’s depression or that may preclude the use of a given drug. (For example, elevation of liver enzymes may preclude the use of duloxetine.) Tests should include:

  • A complete blood cell count
  • A complete metabolic panel
  • A thyroid-stimulating hormone level.

Electrocardiography may also be useful, as some antidepressants can prolong the QT interval or elevate the blood levels of other drugs with this effect.


There are several classes of antidepressants, and each class has a number of agents. Research has found little difference in efficacy among agents. So to simplify choosing which one to use, we recommend becoming comfortable with an agent from each class, ie:

  • A selective serotonin reuptake inhibitor (SSRI)
  • A selective serotonin-norepinephrine reuptake inhibitor (SNRI)
  • A tricyclic antidepressant (TCA)
  • A monoamine oxidase (MAO) inhibitor.

Each class includes generic agents, many of which are on the discount lists of retail pharmacies. Table 1 shows representative drugs from each class, with their relative costs.

Start low and go slow. In general, when starting an antidepressant, consider starting at half the normal dose, titrating upward as tolerated about every 14 days. This approach can minimize side effects. For example, if prescribing fluoxetine, start with 10 mg and titrate every 2 weeks based on tolerance and patient response. That said, each patient may respond differently, requiring perhaps a lower starting dose or a longer titration schedule.

Anticipate side effects. Most of the side effects of an antidepressant drug can be explained by its mechanism of action. Although side effects should certainly be considered when choosing an agent, patients can be reassured that most are transient and benign. A detailed discussion of side effects of antidepressant drugs is beyond the scope of this article, but a review by Khawam et al1 was published earlier in this journal.

Reassess. If after 4 to 6 weeks the patient has had little or no response, it is reasonable to switch agents. For a patient who was on an SSRI, the change can be to another SSRI or to an SNRI. However, if two SSRIs have already failed, then choose an SNRI. Agents are commonly cross-tapered during the switch to avoid abrupt cessation of one drug or the increased risk of adverse events such as cytochrome P450 interactions, serotonin syndrome, or hypertensive crisis (when switching to an MAO inhibitor).

Beware of interactions. All SSRIs and SNRIs are metabolized through the P450 system in the liver and therefore have the potential for drug-drug interactions. Care must be taken when giving these agents together with drugs whose metabolism can be altered by P450 inhibition. For TCAs, blood levels can be checked if there is concern about toxicity; however, dosing is not strictly based on this level. Great care should be taken if a TCA is given together with an SNRI or an SSRI, as the TCA blood level can become significantly elevated. This may result in QT interval prolongation, as mentioned earlier.

Refer. Referral to a psychiatrist is appropriate for patients for whom multiple classes have failed, for patients who have another psychiatric comorbidity (such as psychosis, hypomania, or mania), or for patients who may need hospitalization. Referral is also appropriate if the physician is concerned about suicide risk.

Next Article: