Maximizing the Initial Treatment

Patients Treated With an Antidepressant

  • Optimizing (i.e., raising) the dose is a reasonable first step if side-effect burden is tolerable, especially if the upper dosage limit has not yet been reached.

  • Some patients may require doses higher than those approved by the Food and Drug Administration.

  • In patients who have shown a partial response, particularly those who have features of personality disorders and prominent psychosocial stressors, extending the antidepressant medication trial (e.g., by 4–8 weeks, but not indefinitely) can be considered.

Patients Treated With Psychotherapy

  • As for patients treated with an antidepressant, an initial strategy is to increase the intensity of treatment (i.e., increase the frequency of psychotherapy sessions).

  • The appropriateness of the type of psychotherapy used and the quality of the therapeutic alliance should be reviewed.


Changing to Other Treatments

  • For patients treated with psychotherapy, switching to an antidepressant medication can be considered. (Another option is to combine treatments, as described in the section that follows.)

  • For patients who do not show at least a partial response to an initial antidepressant, a common strategy is to change to a different non-MAOI antidepressant in the same class (e.g., from one SSRI to another SSRI) or in a different class (e.g., from a SSRI to a TCA).

  • For patients who can adhere to dietary and medication restrictions, a nonselective MAOI after sufficient washout period (Table 4) is an option.

  • Transdermal selegiline could be considered.

  • Recent evidence supports the efficacy of quetiapine monotherapy, but potential side effects need to be taken into consideration.


Augmenting and Combining Treatments

  • Pharmacotherapy combined with psychotherapy may offer advantages over either modality alone, particularly for patients with chronic, severe, or complex illness. For patients with less severe symptoms, advantages may be modest.

  • For patients treated with an antidepressant, augmentation strategies with a modest evidence base include the following:

    • Adding another non-MAOI antidepressant, generally from a different class

    • Adding lithium

    • Adding thyroid hormone

    • Adding a second-generation antipsychotic

  • Strategies with less supporting evidence include the following:

    • Adding an anticonvulsant

    • Adding omega-3 fatty acids

    • Adding folate

    • Adding a psychostimulant medication (e.g., modafinil)

    • If anxiety or insomnia is prominent, adding an anxiolytic or sedative-hypnotic medication, including buspirone, a benzodiazepine, or a selective gamma-aminobutyric acid (GABA) agonist hypnotic (e.g., zolpidem, eszopiclone)


Treatment-Resistant Depression

  • ECT is the most effective form of therapy for patients with treatment-resistant symptoms.

  • Another option to consider, with less supporting evidence, is transcranial magnetic stimulation.

  • Vagus nerve stimulation (VNS) may be an option for patients who have not responded to at least four adequate trials of antidepressant treatment, including ECT.


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