Treatment-Resistant Depression Can Be Treated

Depressed Patients Told They Are Refractory Should Not Lose Hope

Feb 20, 2009 Maija Haavisto

The term "treatment-refractory depression" refers to major depression that hasn't responded to at least two antidepressants, but other therapies may still help.

There are many different types of antidepressants and trying two (or even three, four or five) different antidepressants does not mean that drugs are going to be useless. Trying a different class of antidepressant, but even switching to a different drug in the same class, often works.

Monoamine oxidase inhibitor (MAOI) antidepressants may be particularly useful in refractory depression. The most effective MAOIs require rather drastic dietary restrictions, but may be worth it in severe cases.

Psychotherapy can benefit patients who are not helped by antidepressants. Cognitive psychotherapy is the most commonly used form of therapy, but there are others. The personality of the therapist is an important factor and change of therapist may result in improvement.

Other Drug Therapies

Antidepressants are not the only drugs used in the treatment of major depression. Antipsychotic drugs are sometimes useful, even if the person does not have psychosis, but they tend to have quite unpleasant side effects.

Anticonvulsants (epilepsy drugs) like gabapentin (Neurontin), pregabalin (Lyrica) and lamotrigine (Lamictal) are used in the treatment of bipolar disorder and increasingly also in unipolar depression. The mood stabilizer lithium is sometimes used to augment the efficacy of antidepressants. Sometimes bipolar disorder is misdiagnosed as ordinary depression.

NMDA receptor antagonists like riluzole (Rilutek) and memantine have been successfully tried in the treatment of major depression. Of these drugs ketamine has been shown effective in refractory depression, though this treatment is rarely used, as ketamine is also a drug of abuse.

Narcotic painkillers (opiates) like buprenorphine have been successfully tried in refractory depression, but due to their potential for addiction this treatment is highly controversial. The same goes for stimulant drugs like methylphenidate (Ritalin) and modafinil (Provigil), sometimes used in the treatment of depression.

In one study a 7.5 mg dose of the corticosteroid prednisone helped patients with refractory depression and fatigue, but long-term use of corticosteroids has significant risks.

Alternative Therapies

Some supplements like L-tryptophan, 5-HTP (both precursors to serotonin) and S-adenosylmethionine (SAM-e) may alleviate depression. St. John's wort is a herb commonly used as an antidepressant, but there is only good evidence of its efficacy in mild to moderate clinical depression.

Acupuncture may be helpful in depression, but there have been few high-quality studies and the evidence is somewhat conflicting. It has not been specifically tried in treatment-resistant depression.

Organic Causes of Depression

Some illnesses and conditions, especially hormonal deficiencies, may manifest as depression, which may not respond to treatment unless the underlying illness is properly treated. One common cause of depression is hypothyroidism, which is luckily well-treatable.

Everyone with depression should be tested for hypothyroidism, but what many doctors don't understand is that some people suffer from hypothyroidism, even though their thyroid hormone values are supposedly in the normal range (usually low normal, with an elevated TSH).

Patients should be evaluated as a whole, taking into account their symptoms, not just numbers on a chart. Studies have shown that adding thyroid medication to antidepressants can be helpful in seemingly "euthyroid" patients with treatment-resistant depression.

Doctors often confuse fatiguing conditions like CFS/ME and vitamin B12 deficiency with depression, assuming that since the patient is "tired" they must be depressed. Some cases of treatment-resistant "depression" may thus not be depression at all.

Electrical Stimulation of Brain

Traditionally severe, intractable cases of depression were treated with electroconvulsive therapy (ECT, also known as electroshock therapy). It is a highly effective treatment, but due to side effects like permanent memory loss it has been mostly abandoned.

There are now several methods of safely and conveniently treating refractory depression by electrical stimulation of the brain. Vagus nerve stimulation (VNS) is the one with most research supporting its efficacy. It is FDA-approved for treatment-resistant depression.

Other possible treatments include deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS). VNS and DBS require surgical installation, but TMS is non-invasive. TMS is approved for treatment-resistant depression in Canada, but not in the U.S. DBS was recently approved in the U.S., but only for severe OCD (obsessive-compulsive disorder).

All of these stimulation techniques have potential side effects, just like medication, and do not help everyone, but they can produce a prolonged remission.

References

Bodkin JA, Zornberg GL, Lukas SE, et al. Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995 Feb;15(1):49-57.

Bouwer C, Claassen J, Dinan TG, et al. Prednisone augmentation in treatment-resistant depression with fatigue and hypocortisolaemia: a case series. Depress Anxiety. 2000;12(1):44-50

Cooper-Kazaz R, Lerer B. Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors. Int J Neuropsychopharmacol. 2007 Nov 30;:1-15.

Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64.

The copyright of the article Treatment-Resistant Depression Can Be Treated in General Medicine is owned by Maija Haavisto. Permission to republish Treatment-Resistant Depression Can Be Treated in print or online must be granted by the author in writing.

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Mar 24, 2009 4:45 AM

Maija Haavisto :

As an addendum it should be noted, that the FDA has now approved the first medication, called SYmbyax, for treatment-resistant depression. Symbyax combines the antidepressant fluoxetine (better known as Prozac) and the antipsychotic drug olanzapine (Zyprexa). Fluoxetine and olanzapine can also be used as two separate pills for the same purpose.

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