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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.
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.
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.
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 thyroid hormone
Adding a second-generation antipsychotic
Strategies with less supporting evidence include the
Adding an anticonvulsant
Adding omega-3 fatty acids
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.,
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.