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Focus on compliance in refractory depression: patients need to be told repeatedly to continue taking their medication even when they feel better.

SAN FRANCISCO -- A large number of patients with major depression seem to be resistant to treatment. But a focus on compliance, proper dosing, and when to switch or augment medications can increase the probability of an initial response or convert a nonresponse to a response, Dr. Mantosh J. Dewan said at the annual meeting of the American Academy of Clinical Psychiatrists.

Dr. Dewan said patients should be questioned about their compliance at every visit. Patients' significant others should be enlisted to help as well.

"Noncompliance is probably the biggest factor that we need to worry about," said Dr. Dewan of the State University of New York, Syracuse. "People who take their medicines essentially do well."

He referred to one 3-year study of maintenance antidepressants that showed that only 1.5% of patients who were well were clearly noncompliant, compared with 58% of patients who had a recurrence.

Compliance requires repeated education. For example, patients should be told to continue taking their medications even after they feel better, he said.

One strategy that might be used to improve adherence would be to adopt the disease-management model used in diabetes, Dr. Dewan said. For example, diabetes patients are sent frequent reminders in the mail about the importance of checking their blood glucose levels. Perhaps reminders about the importance of adherence would benefit psychiatric patients.

It is also important to make sure that the patient is getting proper doses of medication. "It's become very clear that you need as much of the medicine as you can get into people," Dr. Dewan said. An old rule of thumb--that the dose should be escalated until just before side effects start--appears to be coming back into vogue.

In the STAR*D trial, for example, doses of citalopram (Celexa) were raised aggressively, and the mean dose ended up being 42 mg.

An adequate trial at a maximum dose also is essential. The treatment should not be regarded as a failure until the patient has been taking the medication for 12-14 weeks.

Many psychiatrists are moving back to the tricyclic antidepressants after realizing that selective serotonin reuptake inhibitors are not a magic bullet. But with tricyclics, patients' blood levels are critical. One study with imipramine, for example, demonstrated that among patients whose blood levels were less than 150 ng/mL, the response rate was only 30%. Patients with blood levels of 150-225 ng/mL had a 60% response rate, and those with blood levels above 225 ng/mL had a 93% response rate.

If the patient is compliant, and he or she is getting the proper dose of medication, the question becomes whether to augment or to switch. Dr. Dewan said the general consensus is that if one is getting a partial response, that should be preserved, so it is best to augment. On the other hand, if there's no response at all, it is probably best to switch.

Augmenting tends to yield a faster response, partly because switching often requires a cross-taper. On the other hand, switching is less expensive, because two medications cost more than one. Likewise, adherence may be better with one medication than two.

In the second phase of the large STAR*D trial, patients who either failed to remit or were intolerant to citalopram were permitted a choice of switching to bupropion (Wellbutrin SR), sertraline (Zoloft), or venlafaxine (Effexor XR) or augmenting with bupropion or buspirone (BuSpar).

Overall, augmenting resulted in a 30% response, and switching to another antidepressant resulted in a 25% response.

Among the group that switched, those who moved to bupropion and sertraline appeared to do somewhat better than those who moved to venlafaxine. Among the group that augmented, those who chose bupropion did significantly better than those who chose buspirone. Examples of other common augmenting strategies involve the use of lithium, the thyroid hormone [T.sub.3], or an atypical antipsychotic such as olanzapine. However, lithium, thyroid hormone, and olanzapine were not tested in this trial.

Still other possible augmenting strategies include bromocriptine (2.5-20 mg/day for 1 week), pindolol (7.5-15 mg/day for 1 week), modafinil (200-400 mg/day for 1 week), estrogen (0.125-0.375 mg/day for 2 weeks), or testosterone (10 g of 1% gel for 8 weeks).

If augmentation is the choice, Dr. Dewan recommended the approach called "rational polypharmacy," which is often associated with Dr. Stephen M. Stahl, who is a psychiatrist in San Diego with subspecialty expertise in psychopharmacology.

In this scheme, the "classic combo" is an antidepressant plus lithium; the "hormone combo" is an antidepressant plus thyroid hormone; the "norepinephrine combo" is an SSRI plus a tricyclic; the "adrenergic combo" is a tricyclic plus bupropion or a stimulant; the "cautious combo" is a tricyclic plus a monoamine oxidase inhibitor (in that order); and the "serotonin combo" is an SSRI plus buspirone, mirtazapine (Remeron), or trazodone.

Finally, the "heroic combo" involves using three or four antidepressants simultaneously. But Dr. Dewan said when patients get to this point, it's probably time to consider electroconvulsive therapy.


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Title Annotation:Adult Psychiatry
Author:Finn, Robert
Publication:Clinical Psychiatry News
Geographic Code:1USA
Date:Aug 1, 2006
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