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Weekly UpdatesThe Problem
You have a patient who suffers with depression. He does not want antidepressants and asks about transcranial magnetic stimulation.
The Question
Is transcranial magnetic stimulation an effective treatment for depression?
The Analysis
We first searched the Cochrane Database of Systematic Reviews (www.cochrane.org/reviews). We located a 2003 review but no recent reviews. We then performed a Medline search by combining "transcranial magnetic stimulation" and "depression or depressive."
The Evidence
Repetitive transcranial magnetic stimulation (rTMS) applies magnetic pulses to the cortex using a handheld coil. Early applications of TMS included replacing high-voltage transcutaneous electrical stimulation previously used in studies to measure central nervous system conduction times associated with illnesses such as multiple sclerosis.
The treatment also has application in the operating room in monitoring the integrity of motor tracts during surgery. It has been approved by the Food and Drug Administration for patients who have failed one 6-week trial of an antidepressant.
The magnetic field passes through the scalp and skull, and induces a current in the underlying tissue, which depolarizes neurons. Neuronal excitability may be altered depending on the frequency of stimulation.
In addition, an important advantage of this technique is that it is noninvasive.
PET scanning studies have shown that left: dorsolateral prefrontal cortex application of rTMS can trigger dopamine release.
Findings from other studies have also shown that transcranial magnetic stimulation may have effects on Cortisol, prolactin, and TSH (Neuropsychopharmacol. 2003;28:201-5).
Early observations that depression followed in patients who suffered a stroke in the left prefrontal cortex but not with damage in the right prefrontal cortex has led to clinical application of rTMS to the left dorsolateral prefrontal cortex. Furthermore, functional neuroimaging studies have shown left anterior hypoactivity in depressed patients.
Current dogma, however, is that restoring balance between the activity in left and right prefrontal cortices is more important than absolute activity in either side.
Some evidence has shown that inhibitory rTMS over the right dorsolateral prefrontal cortex has antidepressant activity as well (Psychol. Med. 2009;39:65-75).
For the latter article, based on a meta-analysis out of the Netherlands, only double-blind, sham-controlled studies were included.
Adults diagnosed with major depressive disorder, where the primary outcome was standardized using the Hamilton Depression Rating Scale (HAMD) or the Montgomery-Asberg Depression Rating Scale (MADRS), were included.
Patients had to complete treatment within 6 weeks. Thirty studies met inclusion criteria.
A total of 1,164 patients were included in the review, and of those, 606 patients (mean age 49.5 years) received real rTMS treatment and 558 patients (mean age 48.9 years) received sham rTMS treatment.
Most of the patients were treatment resistant to medication (451 in the real group and 399 in the sham group). Patients received between 5 and 20 treatment sessions.
The overall weighted mean effect size for treatment was 0.39. This means that the mean antidepressant effect in the treatment group is approximately at the 66th percentile of the sham group. This was considered a moderate effect by the author.
For comparison purposes, the author cited a meta-analysis examining the antidepressant effects of tricyclic and tetracyclic agents in patients with poststroke depression, where the effect size was 0.23.
To illustrate further comparison, we located a fairly recent article examining selective publication of antidepressant trials, which cited a mean weighted effect size of 0.37 for published studies (N. Engl. J. Med. 2008;358:252-60).
We also located another meta-analysis, which found the effect size of SSRIs when compared with placebo in treating panic disorder to be 0.55. Those authors suggested that early studies of small samples may have led to initial overestimations of the efficacy of SSRIs for panic disorder (Am. J. Psychiatry 2001;158:1989-92).
An analysis of variance did not find a difference in effect size between medication-resistant and non-medication-resistant depression.
One concern when interpreting a meta-analysis is the possibility of an inflated effect size because of unpublished studies showing no benefit. Using various statistical measures, the author concluded that 269 studies with null findings would have to exist to render the effect of rTMS noneffective.
The Conclusion
This most recent meta-analysis shows that transcranial magnetic stimulation is more effective than sham in the treatment of acute depression. The effect size was considered moderate. The most common side effects of the treatment were headache, dizziness, nausea, and a painful local sensation.
Of concern, however, is the potential for seizure induction. It remains to be seen how many treatments patients would need for efficacy and how long the treatment effect would be maintained.
DR. LEARD-HANSSON is a forensic psychiatrist who practices in San Diego. DR. GUTTMACHER is chief of psychiatry at the Rochester (N.Y.) Psychiatric Center. They have no financial interest in any product or service that is discussed in this column. They can be reached at cpnews@elsevier.com.
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