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.
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
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
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
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
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.
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.
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.
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
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).
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."