Explains maximum dosages of which medications and what to switch to or combine with if they aren't working
Depression and the Treatment-Resistant Patient
Treatment resistance to antidepressant medication is a common problem that psychiatrists face with depressed patients.
An Agency for Health Care Policy and Research (AHCPR) Guideline review found that only 50% of patients respond positively to an initial antidepressant prescription. Moreover, only about one third of depressed
patients meet remission criteria after initial pharmacologic treatment.
Richard Shelton, MD,of Vanderbilt University, Nashville, Tennessee, reviewed the "4 Ds " to keep in mind when treating patients with treatment-resistant depression --
- Duration and
- Different Treatments
Making the correct diagnosis is, of course, essential. Physicians should carefully review the diagnosis when treatment resistance occurs to ensure the patient does not have significant drug or alcohol problems, bipolar disorder, psychotic depression, or schizoaffective disorder. These disorders require other first-line treatments and can be associated with lack of response to antidepressant agents.
It is also essential to titrate antidepressant dosages to maximum before declaring a patient treatment resistant. These maximum dosages for selective serotonin reuptake inhibitors (SSRIs) are:
- fluoxetine 40 mg, paroxetine 50-60 mg
- citalopram 50-60 mg
- sertraline 200 mg
A switch to an atypical agent, such as venlafaxine, mirtazapine, bupropion, or serzone is optimal for patients who are unresponsive to maximum dosages of SSRIs.
Tricyclic antidepressants, such as nortriptyline, may also be effective in patients not responding to SSRIs.
Another research tested modality for treatment-resistant depression is to augment an initial agent, such as an SSRI, with a second medication. The best tested agents shown to be effective in augmenting an initial antidepressant agent are lithium and liothyronine sodium. Lithium augmentation has been shown to be associated with a 50%
response rate across multiple trials.
Open trials have also suggested that bupropion augmentation of SSRIs and tricyclic augmentation of SSRIs may be effective.
The single most effective modality to approach treatment resistance with remains electroconvulsive therapy (ECT) which has about a 70% response rate. One problem with ECT is that many patients relapse over the next year, and recent studies suggest that both maintenance treatment with an antidepressant and lithium and maintenance ECT after an initial course of ECT decreases relapse rates.
Several studies have suggested that the addition of cognitive-behavioral therapy to patients showing antidepressant treatment resistance may also enhance treatment response.
In a recent study of patients with chronic major depression, nefazodone and cognitive-behavioral treatment was more effective than either of these modalities alone.
The reports suggest that most people with treatment-resistant depression can be successfully managed, but more studies are needed help optimize our treatment choices. Several ongoing studies, such as the Sequenced
Treatment Alternatives to Relieve Depression (STAR-D) study funded by National Institute of Mental Health (NIMH) should provide important new information in the near future.
154th Annual Meeting of the American Psychiatric Association
Day 1 - May 5, 2001
The Impact of Major Depression in Patients With Chronic Medical Illness
Wayne Katon, MD
May 12, 2001
Might be a consideration when medication isn't working for depression. As noted, it is expensive
- US Food and Drug Administration has agreed to an expedited review of the study. With FDA approval, the coding is already in place for reimbursement by Medicare and Medicaid.
This article suggests people putting pressure on the FDA to approved for insurance coverage.
-Approved in Canada and Europe early 2001
Vagus Nerve Stimulation Shows Promise in Treating Resistant Depression
May 9, 2001 By Carla Cantor
New Orleans - Evidence is mounting that vagus nerve stimulation (VNS), used to treat severe epileptic seizures, is effective in treating depression that has not responded to other therapies.
In the first nationwide clinical trial of its kind, presented at the annual meeting of the American Psychiatric Association in New Orleans, Louisiana, investigators from the Baylor College of Medicine in Houston, Texas, reported that nearly half of patients with treatment-resistant depression who had the VNS system implanted - dubbed by some as a pacemaker for the brain - were doing well a year later.
Of 60 patients enrolled in the study at 4 medical centers, 30% showed at least a 50% or better improvement in depression and quality of life after 10 weeks of VNS treatment. Data presented on the first 30 patients showed sustained or further improvements after a year: 46% had significantly improved or were free of depression. The patients had suffered from depression an average of 10 years; most had failed numerous treatments, from electric shock therapy to combinations of antidepressants.
"At the evaluation one year after the implant the majority of patients who had responded acutely to VNS seemed to be holding their own - even doing better," says Lauren B. Marangell, MD, lead author of the study and director of mood disorders research at Baylor. The findings took researchers by surprise. "A continuing improvement in response rates for refractory depression is highly unusual," Dr. Marangell says, suggesting that VNS may become more potent over time.
The study, which began in 1998, should offer hope to the nearly 20 million Americans 18 and older who struggle with depression in a given year. According to the National Institute of Mental Health, 2-3 of 10 people with the disorder suffer from refractory depression.
Scientists don't know exactly how VNS acts in the brain to cause an antidepressant effect. They suspect that the electrical stimulation increases the activities of some neurotransmitters, such as serotonin, while decreasing the actions of others. A generator about the size of a pacemaker is implanted in the patient's upper chest and connected via electrodes to the left vagus nerve in the neck, which communicates messages to the brain.
The device is programmed to deliver electrical current every 5 minutes, and researchers say the adverse effects of VNS are minimal. As the nerve is stimulated, some people may experience a tingling sensation, hoarseness, or the urge to cough.
In April, the VNS system, manufactured by Cyberonics, Inc., of Houston, was approved in Canada (and a few weeks before that in Europe) for treatment of resistant depression - both unipolar and bipolar. It has been approved in the United States since 1997 for epilepsy and has been used by more than 12,000 people worldwide.
Meanwhile, investigators are in the midst of the first controlled study of VNS implanted in 210 patients at 21 sites across the US and Canada. The trial began a year ago and data should be available by mid-2002. Each study participant received the device, but in half of the patients, it was turned off for 3 months to compare their responses to the VNS group. (All of the patients had been informed of the possibility that the generator could be turned off for part of the study).
Citing the importance of finding a breakthrough treatment for refractory depression, the US Food and Drug Administration has agreed to an expedited review of the study. Marangell says that this is particularly exciting because with FDA approval, the coding is already in place for reimbursement by Medicare and Medicaid.
"What a lot of patients like about VNS is that it legitimizes depression as a medical condition in a way that Prozac doesn't," she says. But VNS is expensive, and insurance coverage - even for treatment of epilepsy -varies widely. The device itself costs $12,000 and a neurosurgeon who implants it may charge another $10,000 to $15,000. The battery lasts 10 to 12 years.
James A. Halikas, MD, a professor of psychiatry at the University of Minnesota attending the APA meeting, suggests that people who feel they may be candidates for the device put pressure on the FDA to increase the probability of timely approval. "In my practice, I see a lot of patients for whom therapy hasn't worked. Many would line up for an implant if VNS was covered by insurance."