Augment. Evidence from a meta-analysis with aggregate data from 3 studies representing a total of 110 patients showed that augmentation of various antidepressants with lithium leads to improved outcomes (number needed to treat [NNT]=3.7).8 A cohort study of augmentation with an atypical antipsychotic agent such as aripiprazole (Abilify) suggest improved outcomes, but similar studies found no benefit.9 A small (23-patient) randomized trial of lamotrigine (Lamictal) suggests that it may augment the effect of fluoxetine.10
Psychotherapy. A systematic review of psychological therapies in treatment-resistant depression found 2 controlled studies (of cognitive therapy and cognitive behavioral therapy) out of 12 total studies meeting their inclusion criteria that demonstrated improved scores on the Hamilton Rating Scale for Depression. Further study of these therapies was recommended.11
ECT. The evidence supporting use of ECT for treatment-resistant depression comes from studies following failure of treatment with tricyclic antidepressants and monoamine oxidase (MAO) inhibitors. Methodological problems in these older studies do not permit an estimate of response rate.12
Recommendations by others
The American Psychiatric Association treatment guideline recommends changing antidepressant, adding or changing to psychotherapy, or ECT if no response to 4 to 8 weeks of the initial therapy in depression.13 A guideline from the University of Michigan recommends referral to a psychiatrist if patients have treatment refractory depression (defined in their guideline as failure of 2 successive trials of antidepressants).14 The Institute for Clinical Systems Improvement guideline recommends considering switch, augmentation, or other therapies (including adding or modifying psychotherapy).15