Antidepressant response should be seen at 2 weeks.
If symptoms have gotten worse, however, it's time to stop the antidepressant altogether, he said. It doesn't take 6-8 weeks for antidepressants to work; that commonly held notion is "100% wrong," he said.
Imaging studies show brain activity changes within 2 hours of a single dose, and in trials where antidepressants separate from placebo, they do so in a week or 2 (Arch. Gen. Psychiatry 2006;63:1217-23).
"Monitoring response in the first 2 weeks is essential, because it's going to tell you whether you've got the right" treatment. With any given antidepressant, about 75% of patients will respond, but about 25% will get "much, much worse. If a patient gets worse, stop. You should take that extremely seriously," he said (Arch. Gen. Psychiatry 2011;68:1227-37).
In general, anxious people and suicidal people don't do as well on antidepressants. Also, people with a history of childhood neglect, abuse, or trauma respond better to psychotherapy, so it's worth asking about such issues. It's also worth asking patients what they want to do, be it pharmaceuticals, psychotherapy, or both. Success is more likely if patients get what they want, Dr. Raison said at the annual Perspectives in Rheumatic Diseases conference held by the Global Academy for Medical Education.
"Pain is a powerful predictor of not doing well," especially with SSRIs, he said. Even so, "if you can help people with their pain, you'll probably help" relieve their depression and help their antidepressant work, he said.
When patients don't respond after a few weeks, "the first thing most of us do is increase the dose; for SSR1s, the data" indicate it doesn't work. In one study, for instance, people did just as well on a lower dose as on a higher one, he said (Br. J. Psychiatry 2006;189:309-16).
Up to a quarter of patients, however, will do better if switched to another antidepressant. Some studies suggest staying in the same class of drugs; others suggest trying a different class. For now, which one to pick "depends [mostly] on side effects. There isn't a best antidepressant; the best one is the one that works in any given patient," Dr. Raison said (Eur. Neuropsychopharmacol. 2012;22:453-68).
Augmentation is another option, with atypical antipsychotics currently the most popular choice. There's convincing evidence that they help, but they also have well-known and serious side effects, including extrapyramidal syndromes, metabolic derangements, and weight gain.
There's also strong evidence for psychotherapy as an adjunct, and good data for lithium and a range of other agents. Whole-body hyperthermia is emerging as a possible depression treatment, as well.
Dr. Raison recommended actively treating nausea, jitteriness, diarrhea, and other short-term SSRI side effects; it makes it more likely that patients will stay on their treatment. Also, anxious patients and those with somatic complaints are more likely to tolerate antidepressants if they are started on subtherapeutic doses, then are titrated slowly up to a recommended dose.
Of all the SSRIs, paroxetine (Paxil) "is the one I most highly recommend you do not use. There's no evidence it's better than any of the others," and it's the one most likely to cause weight gain, sexual dysfunction, and cardiac issues, he said.
"We don't know how long you should treat" with antidepressants; "probably at least 6-9 months," he noted.
Dr. Raison is a consultant for Pamlab, Lilly, and Lundbeck. He is on the speakers bureaus of Pam-lab and Sunovion.
Global Academy for Medical Education and this news organization are owned by Frontline Medical Communications.
Caption: It doesn't take 6-8 weeks for antidepressants to work; that commonly held notion is '100% wrong.' OR. RAISON