Treatment Resistant Depression

Treatment-Resistant Depression

In one third to two thirds of cases of depression, patients fail to remit with first-line therapy.[106, 119] No factors have been identified for reliably predicting whether an individual patient will respond.[119]

Assessment of patients with treatment-resistant depression should include consideration of the following:

    Accuracy of diagnosis and possible comorbid medical conditions
    Adequacy of medication dose and duration of treatment, as well as adherence to treatment regimen
    Possible comorbid psychiatric conditions (eg, substance abuse, anxiety disorders, personality disorders)

Assuming that the assessment of the diagnosis is correct, there are no significant complicating diagnoses, and the current treatment has been at a therapeutic dose for a sufficient amount of time, possible interventions for persistent symptoms can include the following[6] :

    Increasing the medication dose to the maximum tolerated
    Augmenting the current medication with another antidepressant
    Changing to a different antidepressant
    Adding psychotherapy or more intensive care if not already completed
    Considering the use of ECT

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, the largest open-label trial to date, examined various strategies for treatment-resistant depression. The STAR*D trial showed that in patients who did not respond to an initial SSRI (citalopram), switching to another SSRI antidepressant, changing medication class, and switching to CBT were all equally effective treatments. Achieving remission, rather than partial response, was the best predictor of a better long-term prognosis.[119, 120]

The AHRQ found conflicting evidence regarding the differences between second-generation antidepressants for treatment-resistant depression. A good-quality study revealed no substantial differences in the effectiveness of sustained-release bupropion, sertraline, and sustained-release venlafaxine; however, fair-quality studies indicated a trend toward greater effectiveness with venlafaxine than with citalopram, fluoxetine, or paroxetine.[119]

Augmentation combinations can include the following:

    Bright-light therapy plus any antidepressant
    Buspirone (BuSpar) plus a TCA or SSRI
    Lithium (Eskalith, Lithane, Lithobid) plus any antidepressant
    Methylphenidate (Ritalin) or dextroamphetamine (Dexedrine) plus any antidepressant other than an MAOI
    TCA plus an SSRI
    Triiodothyronine (Cytomel) plus any antidepressant

The STAR*D trial found that augmentation of an SSRI with bupropion and augmentation with buspirone were equally effective after a lack of response to the SSRI.[119]

Aripiprazole (Abilify) is the first drug approved by the FDA for adjunctive treatment in major depressive disorder and the first drug to receive FDA approval for use in treatment-resistant depression.[121, 122, 123]

Conway et al studied 13 patients with treatment-resistant major depression (TRMD) who received 12 months of treatment with vagus nerve stimulation (VNS).[124, 125] Positron emission tomography (PET) brain imaging was performed before the initiation of stimulation and again 3 and 12 months after stimulation had begun.

Of the 13 patients in the study, 9 experienced improvement in depression with the VNS treatment.[125] Among those who responded, the PET scans showed changes in brain metabolism after 3 months of stimulation, but this occurred several months before any improvements in their symptoms of depression were noted.

Transcranial magnetic stimulation (TMS) has also been studied in treatment-resistant patients. In one trial of 307 patients with a primary diagnosis of unipolar, nonpsychotic major depressive disorder who had failed to receive benefit from previous antidepressant therapy, acute treatment with TMS resulted in symptomatic improvement in 62% of patients and complete remission in 41%.[126]

Of the 257 patients who entered a 12-month follow-up phase of the study, 68% achieved symptomatic improvement at 12 months and 45% reported complete remission.[126] Long-term maintenance therapy consisted of continuation of antidepressant medication and access to TMS reintroduction for symptom recurrence.