How best to manage treatment-resistant depression?
Should you augment the treatment regimen with lithium, thyroxin, or an atypical antipsychotic? This review will help you decide.
These agents don’t appear helpful in augmentation efforts
Several other agents have been studied with no effect on remission rates. These include pindolol,36 modafinil,37 buspirone, lamotrigine,38 stimulants, and estrogen replacement.
Consider side effects, cost, and patient preference
Because most studies showed that the efficacy of the tested drugs was similar, how do you decide which augmenting agent to prescribe? The usual standard is lithium, which offers rates of remission that are high, but not statistically significantly better when compared with thyroid supplementation and cognitive therapy. Quetiapine, while not more efficacious, may lower scores on depression rating scales more quickly than lithium.39 Additionally, the STAR*D trial suggests that many agents may be used in augmentation with similar results.
In the final analysis, the family physician has to consider factors other than efficacy. You also have to factor in the costs of medicines and lab testing, patient preference, and side effects. Lithium is most likely to cause side effects. Atypical antipsychotics seem to have lower short-term side effect profiles with efficacy similar to cognitive therapy. However, the potential drawbacks of antipsychotics, including aberrations in glucose metabolism, weight, and lipid profiles, are not typically seen in short-term studies. Obviously, more long-term studies are necessary before 1 agent can be deemed superior.
When should you stop therapy?
That question still doesn’t have a definitive answer. The STAR*D trial found that patients who achieved full remission were less likely to relapse/worsen than those who had only a partial response. The time to relapse ranged from 2.5 to 4.5 months and was shorter for those patients requiring 2 or more levels of treatment. As there was no control of the therapeutic interventions used during this time, we can’t be certain about what caused the relapse, but burden of disease, income levels, and ethnicity all played roles in symptom severity, decreasing remission rates, and increasing relapse rates.40,41
While we cannot identify the ideal or even preferred duration of augmentation in patients with treatment-resistant depression, it seems clear that relapse is extremely common and tends to occur relatively early after achieving remission.
CORRESPONDENCE Paul Hicks, MD, Department of Family and Community Medicine, 1450 North Cherry Avenue, Tucson, AZ 85719; phicks@uph.org
