Maria has been increasingly depressed for the past few years. She has tried at least four newer antidepressants but so far, she doesn’t seem to respond. Unable to work, she’s now feeling helpless and hopeless. Likewise, her family is discouraged. Frustrated and baffled by Maria’s lack of progress, the family doctor refers her to a psychiatrist.

What can the psychiatrist do to help Maria?

The psychiatrist has several options in dealing with a treatment-resistant or refractory depression. First, Maria’s psychiatrist can optimize the dose of her antidepressant. Maria has been taking low doses of antidepressants. In spite of her lack of response, the medication dosage has not been increased. To obtain a clinical response, her psychiatrist should increase the dose every two to three weeks. The antidepressant can be adjusted up to the maximum allowable dose if no or only partial response is observed.

Second, her psychiatrist can choose to augment the effect of her antidepressant with another medication such as lithium, triiodothyronine (T3), or buspirone. Among augmenters, lithium and triiodothyronine have the best support from the literature. Despite lithium’s efficacy, some doctors avoid this drug because it requires regular blood monitoring and has unfavorable side effect profile such as acne, tremors, and thyroid and renal dysfunction.

Recently, studies have shown atypical neuroleptics such as olanzapine and risperidone to be good augmenters. In my opinion, further studies are necessary to establish these two drugs as standard augmenter. Indeed, research studies and clinical experience have found augmentation strategy to be effective.

Third, combination strategy is worthwhile to try. Maria’s psychiatrist can add another antidepressant to boost the effect of her current antidepressant. For instance, trazodone can be added to an SSRI (serotonin reuptake inhibitor e.g. citalopram). Literature suggests that combining two drugs with different mechanisms of action and drugs that involve several brain chemicals has resulted in clinical improvement. In this scenario, one antidepressant plus another antidepressant is equal to three, or four or even ten, not two.

Fourth, the psychiatrist can switch from one antidepressant to another. Previous studies have shown that when making a switch, a drug should be replaced by a drug from a different class e.g. from SSRI to SNRI (serotonin and norepinephrine reuptake inhibitor e.g. venlafaxine), or from TCA (tricyclic agent e.g. nortriptyline) to SSRI. But recent studies show that switching drugs within the same class (e.g. SSRI to another SSRI) is just as effective.

Fifth, Maria’s psychiatrist can also treat other ongoing symptoms or drug-related problems that further complicate her depression. If she is anxious and agitated, then her psychiatrist should prescribe antianxiety drug (e.g. lorazepam) or if Maria is psychotic then adding an antipsychotic drug should help. Moreover, medication side effects (such as insomnia, dryness of mouth, constipation, etc.) that negatively affect Maria’s compliance to the drug should be addressed promptly.

Lastly, if despite above measures Maria doesn’t respond to antidepressants, then electroconvulsive therapy should be entertained. Of course, this procedure should be done with her consent.

In summary, Maria’s psychiatrist can optimize the dose, augment or combine treatment, switch the medication, treat side effects and ongoing symptoms, or use electroconvulsive therapy for treatment-resistant or refractory depression.