Friday, May 10th, 2013
By Sabrina Bachai | May 03, 2013
Minor studies have shown that a mix of ketamine drug therapy and electroconvulsive therapy (ECT) can give faster results for severe depression treatments.
Researchers at the University of Manchester are coordinating a study to prove these effects on a larger scale in hopes of having these treatments used in clinical practices. While proven effective in treating depression, ECT treatments have also had cases of severe side effects such as long-term memory loss, confusion, and impaired cognitive function.
“ECT is the most effective treatment we have for severe and Treatment Resistant Depression – but it can cause cognitive and memory difficulties as a side-effect,” said Ian Anderson, head of biological research on mood disorders at the University of Manchester.
ECT, formerly known as electroshock therapy, has been a practice used to treat various psychiatric illnesses since the 16th century. Speculatively, if combined with ketamine, the adverse side effects could potentially decrease or even disappear.
Ketamine is used in common medical practice to induce general anesthesia. Also known by its street name “Special K,” it is often time used as a recreational drug. When improperly used, it produces as dissociative state with hallucinatory effects and feelings of euphoria. According to the National Institute on Drug Abuse (NIDA), ketamine can have addictive effects and eventually be lethal.
Researchers are hopeful that these trials will prove the therapeutic benefits that have been found in their studies.
“It’s a great opportunity to really study ECT and see how we can improve it,” said Anderson.
Jo Lowe, project manager for this study, has started recruitment for 160 participants for the clinical trials. The project is being funded by Medical Research Council (MRC).
Friday, May 10th, 2013
Medscape: Fran Lowry(May 2, 2013)— Bilateral prefrontal repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for the negative symptoms of schizophrenia, new research shows.
Preliminary results from a double-blind, randomized controlled trial showed that patients with schizophrenia or schizoaffective disorder who were treated with rTMS had a significant improvement in their negative symptoms, as assessed on the Scale for the Assessment of Negative Symptoms (SANS), that lasted for 4 weeks post treatment.
However, after 4 weeks, this beneficial effect diminished.
The findings were presented here at the 14th International Congress on Schizophrenia Research (ICOSR).
Effective Treatment Urgently Needed
Effective treatment options for the negative symptoms of schizophrenia are urgently needed, said study investigator Jozarni Dlabac-de Lange, MD, from the University of Groningen, the Netherlands.
“The outcome for patients who are suffering from negative symptoms is much worse, and there has not been a lot of research in this subgroup of patients because they are very difficult to include in studies,” she told Medscape Medical News.
In addition, the few studies that have reported on the efficacy of rTMS treatment for negative schizophrenia symptoms have shown inconsistent results, Dr. Dlabac-de Lange said.
Each treatment lasted 20 minutes and was given in the morning and again in the afternoon. Patients were stimulated at 90% of the motor threshold.In the current study, the investigators randomly assigned 32 patients with schizophrenia or schizoaffective disorder and moderate to severe negative symptoms (Positive and Negative Syndrome Scale [PANSS] negative subscale ≥ 15) to receive either real (n = 16 patients) or sham (n = 16 patients) rTMS of the bilateral dorsolateral prefrontal cortex.
The researchers found that there was a significant improvement in the SANS measure of negative symptoms in the rTMS group compared with the sham group 4 weeks after the treatment sessions stopped (P = .04); however, the effects diminished by 3 months (P = .14).
Additionally, there was no significant difference between the 2 groups on the PANSS negative symptom score at 4 weeks (P = .38) and at 3 months (P = .32).
“Results were good at first, so the next step is to try and see how we can enhance these treatment effects, perhaps by combining rTMS with psychosocial interventions, discovering the optimal treatment parameters and learning which of the negative symptoms show a better response to rTMS,” Dr. Dlabac-de Lange said.
Tags: depression, depression treatment, major depression, MDD, negative symptoms, neuropsychiatry, neurotransmitters, psychiatrist, psychiatry, schizophrenia, tms, transcranial magnetic stimulation
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Wednesday, April 24th, 2013
By Andrea Petersen
The hunt is on for a faster-acting, more effective antidepressant.
Current treatments for depression, including drugs like Prozac and Celexa, often take a month or more to give patients relief—and they don’t work for everyone. Now, researchers and several pharmaceutical companies are testing medications that early studies are showing can lift mood in just a few days or even within a couple of hours.
“You can control seizures and control hypertension within minutes and hours,” says Carlos A. Zarate, chief of the experimental therapeutics and pathophysiology branch in the intramural research program at the National Institute of Mental Health and a leading researcher in the search for new antidepressant medications. “That is what we should aim for [with depression],” he says.
Some of the fast-acting treatments being studied, such as ketamine and scopolamine, use existing medications in a new way. Ketamine has been used in higher doses as an anesthetic for decades. Small doses of scopolamine delivered via skin patch are used to treat motion sickness. AstraZeneca PLC, the London-based drug company, Naurex Inc., a pharmaceutical firm in Evanston, Ill., and Cerecor Inc., a Baltimore-based biotechnology company, are all developing new drugs for depression that act similarly to ketamine.
It will likely be at least a couple of years before any of the new drugs come to market, since they first need further clinical trials and Food and Drug Administration approval. Some doctors are already using ketamine off label with depressed patients.
Ann Wroth has struggled with depression for more than 30 years and has tried eight different medications. Each time she has a relapse and tries a new medication, she says, it takes at least three to four weeks before she sees any benefit. “The waiting period is very difficult. You’re still in pain. [You think] ‘I’m taking this pill, ‘why isn’t it helping,’ ” says the 53-year-old who trains volunteers at the National Alliance on Mental Illness, an Arlington, Va.-based mental health education and advocacy group.
In a study published in the American Journal of Psychiatry in 2006 of nearly 3,000 patients taking the popular antidepressant citalopram (brand name Celexa) for up to 14 weeks, only about one-third achieved remission from their depression. (About half of the participants responded to the drug, meaning their scores on a survey assessing depression improved by at least 50% during the trial.) For those who did achieve remission or had a response, it generally took about eight weeks of being on the medication.
The new fast-acting drugs act on the brain in an entirely different way than the current popular antidepressants. Ketamine and the new compounds from AstraZeneca and Naurex all act on the brain’s N-methyl-D-aspartate (NMDA) receptors, which are involved in learning and memory. These receptors interact with the neurotransmitter glutamate, the levels of which seem to be out of balance in depression.
Scientists believe glutamate is a much more direct target for depression than serotonin, a neurotransmitter affected by selective serotonin reuptake inhibitor (SSRI) drugs like Prozac and Paxil. The SSRIs’ more indirect method of action is likely the reason why there is a lag time before patients feel relief from depressive symptoms, says Ronald S. Duman, professor of psychiatry and neurobiology at the Yale University School of Medicine in New Haven, Conn.
In a small but groundbreaking study published in 2006 in the Archives of General Psychiatry, 17 people with major depression who had failed to get adequate relief from at least two other antidepressants were given a single injection of ketamine. About one-third of patients went into remission and 71% had a response. Patients began to feel better within two hours and the beneficial effects lasted about a week.
But ketamine has side effects including hallucinations and other “dissociative” feelings during and for a bit after an intravenous infusion. “People may see trails of light, they may feel a bit foggy,” says Dr. Zarate, lead author of the study. Indeed, Ketamine is sometimes abused as a street drug called “special K.” There is also concern that repeated doses of ketamine could be harmful to the brain.
AstraZeneca and Naurex say their new compounds deliver the rapid benefits of ketamine without the disturbing side effects because they act differently on the NMDA receptor. Naurex said the main side effects in a Phase IIa study of its GLYX-13 compound with 116 people with depression were headache and sleepiness, similar to the effects of a placebo saline injection. Patients began feeling relief of their depression symptoms within two hours and the effects lasted at least one week.
Naurex is in the middle of another study with 400 patients. It expects to apply to the FDA for approval of GLYX-13 in early 2016, says Ronald M. Burch, the company’s chief medical officer. While GLYX-13 will likely be indicated for patients who failed to benefit from conventional antidepressants first, the company is also beginning to study an oral version of the drug. That formulation could be used as a first treatment option for depression, Dr. Burch says.
AstraZeneca is in the middle of a second Phase IIb trial of its AZD6765 compound, testing it in 282 people.
Pierre Blier, a professor of psychiatry at the University of Ottawa in Canada has given ketamine to about 25 patients in the last 18 months. “I use it in my severely ill patients who are on medications already,” he says. He only uses it with patients who don’t have a history of addiction, he says, and who he knows well. “When it works it is so striking,” he says.
Some psychiatrists believe ketamine or drugs like it will be helpful in emergency rooms with patients who are actively suicidal. Richard Shelton, a professor in the department of psychiatry and behavioral neurobiology at the University of Alabama at Birmingham has been conducting a small study and has used ketamine this way in 16 people.
“People come in urgently wanting to kill themselves,” he says. After a low-dose ketamine infusion, “the sense of urgency goes away.”
Tags: AstraZeneca, depression, depression treatment, ketamine, major depression, MDD, neuropsychiatry, neurotransmitters, pharmaceutical companies, psychiatrist, psychiatry
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Wednesday, April 24th, 2013
Overview: The standard of care for clinical depression has significant limitations: traditional drugs that focus on monoamine neurotransmitters can take several weeks to be effective, and many patients never respond to any form of treatment. Several clinical trials have demonstrated strikingly better outcomes using the anesthetic ketamine to treat depression. Notably, a single application can have rapid and lasting antidepressant effects in patients who do not respond to other treatments. Because ketamine is an antagonist of NMDA-type glutamate receptors, research is focused on the role of glutamate neurotransmission in depression and on drug development that targets the glutamatergic system. The March 25, 2013, meeting of the Academy’s Biochemical Pharmacology Discussion Group, Treatment-resistant Depression: Glutamate, Stress Hormones, and their Role in the Regeneration of Neurons, presented this new research and the avenues it is opening for the treatment of depression.
Tags: antidepressants, Anxiety, depression, depression treatment, major depression, MDD, neuropsychiatry, neurotransmitters, psychiatrist, psychiatry, tms, transcranial magnetic stimulation
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Wednesday, April 24th, 2013
WEDNESDAY, April 3 (HealthDay News) — Rats addicted to cocaine lost the craving when researchers used laser light to stimulate a specific part of their brains.
The same team of scientists also used the laser technique to trigger new cocaine addictions in rats. They say the therapy — which targets the prefrontal cortex of the rat brain — could point the way to a new method of treating the addiction in humans.
“When we turn on a laser light in the prelimbic region of the prefrontal cortex, the compulsive cocaine seeking is gone,” study co-researcher Dr. Antonello Bonci, adjunct professor of neurology at the University of California, San Francisco, said in a university news release.
As the researchers explained, the mammalian prefrontal cortex plays an important role in impulse control, decision-making and behavioral flexibility.
In this study, the researchers used genetic engineering to insert light-sensitive proteins called rhodopsins into nerve cells (neurons) in the rats’ prefrontal cortex. Activating this brain region with a laser tuned to the rhodopsins turned the neurons on and off.
Turning on the neurons eliminated cocaine addiction while turning them off triggered addiction in the rats, according to the study published online April 3 in the journal Nature.
The findings highlight the central role the prefrontal cortex plays in cocaine addiction and also suggest a new therapy that could be immediately tested in humans, said the team of researchers from UCSF and the U.S. National Institute of Drug Abuse (NIDA).
However, human therapy would not use lasers. Instead, it would most likely rely on electromagnetic stimulation outside the scalp — in particular, a technique called transcranial magnetic stimulation (TMS) — to trigger a similar activation in the prefrontal cortex. TMS has been used to treat depression.
Research in animals often does not pan out in humans, experts note. However, clinical trials are now being designed to test the use of TMS in people, said Bonci, who is also scientific director of the intramural research program at NIDA and an adjunct professor at Johns Hopkins University in Baltimore.
In the clinical trials, TMS will be used a few sessions a week to stimulate the prefrontal cortex in cocaine addicts. The researchers will see if they can restore activity to the prefrontal cortex and help reduce the addicts’ desire for cocaine.
An estimated 1.4 million Americans are addicted to cocaine, which was the reason for more than 482,000 emergency department visits in 2008 and is a leading cause of heart attack and stroke among people younger than 35.
Along with the health toll, cocaine has a major impact on crime, imprisonment, treatment and prevention programs, lost job productivity and lost earnings, the researchers pointed out.
The U.S. National Institute on Drug Abuse has more about cocaine.
Wednesday, March 27th, 2013
Tuesday, March 26, 2013-Bob Shepard
University of Alabama at Birmingham (UAB) researchers think ketamine, an anesthesia medication in use since the 1970s, might be a valuable tool in treating severe depression and reducing suicidal urges; they have launched two studies to explore the possibility. One of the studies, ketamine is administered to suicidal patients in the UAB Hospital emergency department (ED), is the only such trial actually being conducted in an ED in the nation.
“There is a growing body of evidence that indicates that lower doses of ketamine can reduce suicidal feelings and relieve symptoms of severe depression in a very short period of time, as little as a few hours, which makes it an extremely attractive candidate for treating acute depression,” said Richard Shelton, M.D., professor in the Department of Psychiatry and Behavioral Neurobiology and lead investigator on the studies.
Shelton said ketamine appears to work on depression by blocking a neurotransmitter called glutamate from binding to the NMDA receptor on neurons. Too much glutamate on an NMDA receptor leads to the opening of a calcium ion channel, releasing too much calcium downstream. This then affects a brain chemical, brain derived neurotrophic factor (BDNF), which increases connections between neurons in the brain. These connections help the brain regulate emotions better.
In the trial, patients presenting to the ED with suicidal thoughts can be enrolled in the ketamine trial. The drug is administered via infusion, which takes about five minutes.
“We have seen a decrease in depression scores and suicide scores, sometimes within 15 minutes after giving ketamine,” said Cheryl McCullumsmith, M.D., Ph.D., assistant professor and director of hospital psychiatry. “The antidepressants commonly used to treat depression and suicidal thoughts take weeks or months to begin to show positive effects. When a patient is actively suicidal, we don’t have that much time.”
McCullumsmith said patients entered in the ketamine trial at the ED are admitted to the psychiatric inpatient unit for observation.
“We are attempting to determine just how quickly the drug produces a beneficial result, as well as how long that result lasts,” McCullumsmith said.
Shelton said a second trial, sponsored by Janssen Research & Development, LLC., is a multi-site trial of patients with severe depression and possible suicidal thoughts who are seen in an outpatient setting. Patients receive two or three infusions of ketamine or placebo each week for four-to-six weeks. Patients who do not benefit from study treatment after the first two weeks are offered two weeks of treatment with ketamine without the chance of placebo.
“We’re interested in knowing how long each infusion will sustain the beneficial effect,” said Shelton. “Ketamine does not appear to be curative, and we have a lot of work to do to see if it might be a useful drug for depression and suicide prevention on a long-term, regular-use basis.”
A third trial underway at UAB is testing a compound called Glyx-13, produced by Naurex, Inc. Glyx-13 may produce similar results as ketamine by blocking an amino acid called glycine, which works in tandem with glutamate. Glycine regulates glutamate signaling, so it is like an added layer of fine-tuning. When glycine and glutamate bind to NMDA together, the calcium ion channel opens widely. Blocking glutamate with ketamine can reduce the release of calcium. Blocking glycine with Glyx-13 may achieve the same result, but more subtly and with fewer side effects.
“Glyx-13 may prove to be a more promising candidate than ketamine in terms of potential side effects,” said Shelton. “Glyx-13 is being evaluated with just one infusion per week.”
Ketamine, when used in anesthesia, has some side effects, including hallucinations and psychotic symptoms. It has also been a drug of abuse, known on the street as Special K. Shelton said the dose used in the depression trials is much lower, and given over a longer period. Side effects observed thus far in the ketamine trials have been minimal, he said.
UAB is enrolling patients in the outpatient trials of ketamine and Glyx-13. Male and female patients ages 19-64 with a diagnosis of depression, who have failed two drug regimens for depression, are candidates for the trials. Total time involved in the studies, with treatment and follow-up, is about 13 weeks.
Thursday, March 21st, 2013
NEW YORK (WABC) – Imagine finding a new, life changing use for a dangerous street drug, one that has been known for destroying lives.
Now, an experimental treatment could hold life changing promises.
What’s exciting about this drug is that it works fast.
But the studies so far show this one starts to work the very same day.
You may know it as the club drug, Special K, but now researchers say ketamine is a promising new treatment option for depression.
About half the patients get about 50% better with one dose of ketamine,” said Dr. John Mann with NYS Psychiatric Institute.
And that one dose works in just a few hours. Ketamine targets a chemical in the brain called glutamate and unlike most antidepressants which target serotonin. Dr. John Mann is overseeing three ketamine studies at the Columbia Psychiatric Institute.
“This may be a medication that works faster and 2 it may work in some patients who have not had much success in getting better with regular treatments,” he adds.
Todd Landua is one of those patients, he’s battled depression for 4 years.
“Basically I felt fear, sadness or nothing- that was it,” he said.
He took part in the new clinical trial, and says after he got ketamine, he felt an immediate difference.
“I was recovering memories that had been very painful for me but the pain was completely gone,” adds Todd.
But although it’s fast acting, it’s not necessarily long lasting. So far they found the benefits of one dose last about a week.
That could mean needing frequent IV infusions of ketamine, until there’s a better way like a pill. And in large doses, ketamine can cause dangerous symptoms of psychosis, but Dr. Mann says they are working to find the lowest dose possible that works, but with the fewest side effects.
The studies at Columbia are scheduled to go until 2017.
Thursday, March 21st, 2013
By RICK NAUERT PHD Senior News Editor
Reviewed by John M. Grohol, Psy.D. on March 13, 2013
Those with schizophrenia are often functionally limited by mental or cognitive impairments.
Memory, attention, IQ, and verbal and motor skills are often disrupted, and these deficits tend to compromise the ability to perform normal day-to-day activities.
Scientists have been exploring a variety of strategies to reduce these impairments, including “exercising the brain” with specially designed computer games and medications that might improve the function of brain circuits.
In a new study, Mera Barr, Ph.D., and her colleagues at University of Toronto provide evidence that stimulating the brain using repetitive transcranial magnetic stimulation (rTMS) may be an effective strategy to improve cognitive function.
“In a randomized controlled trial, we evaluated whether rTMS can improve working memory in schizophrenia,” said Barr and senior author Zafiris Daskalakis, M.D.
“Our results showed that rTMS resulted in a significant improvement in working memory performance relative to baseline.”
Transcranial magnetic stimulation is a non-invasive procedure that uses magnetic fields to stimulate nerve cells. It does not require sedation or anesthesia and so patients remain awake, reclined in a chair, while treatment is administered through coils placed near the forehead.
In 2008, rTMS was FDA-approved to treat depression for individuals who don’t respond to pharmacotherapy.
The study is presented in the journal Biological Psychiatry.
“TMS can have lasting effects on brain circuit function because this approach not only changes the activity of the circuit that is being stimulated, but it also may change the plasticity of that circuit, i.e., the capacity of the circuit to remodel itself functionally and structurally to support cognitive functions,” said Dr. John Krystal, editor of the journal.
Experts say that previous studies have shown that rTMS improves working memory in healthy individuals, and a recent open-label trial showed promising findings for verbal memory in schizophrenia patients.
These findings informed the current study to determine if high frequency rTMS could improve memory in individuals with schizophrenia.
Researchers recruited medicated schizophrenia patients who completed a working memory task before and after 4 weeks of treatment.
Research methodology involved a double-blind study, where neither the patients nor the researchers knew who was receiving real rTMS or a sham treatment that was designed to entirely mimic the procedure without actually delivering brain stimulation.
Investigators discovered TMS not only improved working memory in patients after 4 weeks, but the improvement was to a level comparable to healthy subjects.
These findings suggest that rTMS may be a novel, efficacious, and safe treatment for working memory deficits in schizophrenia.
While the current findings are preliminary, researchers hope additional investigations will replicate the findings and provide an approved treatment for cognitive impairments in schizophrenia.
The authors concluded: “Working memory is an important predictor of functional outcome. Developing novel treatments aimed at improving these deficits may ultimately translate into meaningful changes in the lives of patients suffering from this debilitating disorder.”
Tags: Anxiety, dementia, depression, major depression, memories, memory, neuropsychiatry, neurotransmitters, psychiatrist, psychiatry, therapy, tms, transcranial magnetic stimulation
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Thursday, March 21st, 2013
Working memory represents a core cognitive domain that is impaired in schizophrenia for which there are currently no satisfactory treatments. Repetitive transcranial magnetic stimulation (rTMS) targeted over the dorsolateral prefrontal cortex has been shown to modulate neurophysiological mechanisms linked to working memory in schizophrenia and improves working memory performance in healthy subjects and might therefore represent a treatment modality for schizophrenia patients. The objectives were to evaluate the effects of rTMS on working memory performance in schizophrenia patients and evaluate whether rTMS normalizes performance to healthy subject levels.
In a 4-week randomized double-blind sham-controlled pilot study design, 27 medicated schizophrenia patients were tested at the Centre for Addiction and Mental Health (a university teaching hospital that provides psychiatric care to a large urban catchment area and serves as a tertiary referral center for the province of Ontario). Patients performed the verbal working memory n-back task before and after rTMS magnetic resonance image targeted bilaterally sequentially to left and right dorsolateral prefrontal cortex 750 pulses/side at 20 Hz for 20 treatments. The main outcome measure was mean magnitude of change in the n-back accuracy for target responses with active (n=13) or sham (n=12) rTMS treatment course.
The rTMS significantly improved 3-back accuracy for targets compared with placebo sham (Cohen’s d=.92). The improvement in 3-back accuracy was also found to be at a level comparable to healthy subjects.
These pilot data suggest that bilateral rTMS might be a novel, efficacious, and safe treatment for working memory deficits in patients with schizophrenia.
Tags: major depression, memories, memory, neuropsychiatric, neuropsychiatry, neurotransmitters, psychiatrist, psychiatry, schizophrenia, tms, transcranial magnetic stimulation
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Thursday, March 21st, 2013
Harborough Mail- Published on 04/03/2010 16:48
A handheld device could ‘zap away’ headaches according to several newspapers. They say that the device, which delivers a magnetic pulse to the back of the head, could be an alternative to drug treatments for sufferers.
The news is based on a well-conducted randomised controlled trial and has found promising results when using a ‘single-pulse transcranial magnetic stimulation’ device to treat people who frequently suffer from migraine with visual distortions (aura). Within two hours of the onset of symptoms more people were pain-free when using the handheld device than those who had used an identical dummy device.
Although the study has reliable results, there are some points to consider when putting these findings into context. Importantly, the results will need to be verified in larger trials that directly compare the technology to other active treatments for migraine, principally medication. Therefore, the news reports are premature in announcing this treatment as an ‘alternative’ to pain medications. Further issues of optimal use, effectiveness and safety also need to be explored when further researching this promising technology.
Where did the story come from?
This research was conducted by Dr Richard Lipton and colleagues from Einstein College of Medicine, New York and other institutions across the US. The study was funded by Neuralieve, the medical technology company that makes the prototype device being tested. The study was published in the peer-reviewed medical journal The Lancet.
What kind of research was this?
This was a phase 2 randomised, ‘sham’-controlled trial testing the use of a prototype ‘single-pulse transcranial magnetic stimulation’ (sTMS) device using magnetic fields to treat certain types of migraine. The study was termed a ‘sham trial’ as it compared a real device against an identical mock device that actually performed no function.
A randomised controlled trial is the best way of examining the safety and efficacy of a treatment. However, results of this trial will need follow-up in larger phase 3 trials that compare sTMS use to other active treatments for migraine (eg replace the sham sTMS device with suitable drugs) and in larger groups of people.
News coverage has generally reflected the findings of this well-conducted trial, although most reports have jumped too far ahead in hailing this as a new treatment for migraine ‘at the press of a button’. The current stage of this research, plus the fact that it hasn’t been compared to any active treatment, mean that questions still remain over its safety and efficacy.
What did the research involve?
This research was carried out at 18 different locations across the US and studied people who experienced migraines accompanied by aura – visual distortions that precede the pain of migraines. Aura symptoms usually last less than an hour and can include visual disturbances (such as flashing/flickering spots of lights, zigzag lines or even temporary blindness), numbness, tingling sensations and slurred speech.
All eligible adults met diagnostic criteria of having at least 30% of their migraines accompanied by aura. Their migraines also had to occur at least once a month and to be associated with moderate or severe headache in 90% of those attacks. People were excluded if their migraine was suspected to be caused by, or associated with, overuse of painkillers, use of other medications, or underlying disease or trauma.
Before the treatment phase began, the recruited participants were trained in the use of an electronic headache diary, which they used for one month to verify that they had a suitable diagnosis of migraine for the trial. Sixty-six people dropped out in this phase, after which the remaining 201 individuals were randomly allocated by computer to either sham stimulation (99 people) or sTMS (102 people). Training was given in the use of the devices before the trail.
The sTMS machine tested was a handheld device that could be positioned against bone at the base of the skull. It delivers two magnetic pulses, 30 seconds apart, when the ‘treat’ button is pressed. The ‘sham’ stimulator device was identical to the real device, even buzzing and vibrating in the same manner. Neither researchers nor participants knew which device each person was using.
Participants were instructed to treat up to three attacks over a three-month period at the onset of aura. The main outcome was being pain-free within two hours of the attack, and with secondary outcomes being no difference between the sTMS device and sham device in terms of reports of symptoms of nausea, oversensitivity to light, and oversensitivity to sound within two hours of the attack. All participants were allowed to use their usual migraine medication throughout the trial.
What were the basic results?
The researchers excluded the results on 37 people who did not treat a single migraine attack during the trial. This left 164 patients (82 sTMS and 82 sham). Significantly more people treated with sTMS were pain-free within two hours (39% v 22%; 17% difference, 95% CI 3 to 31%).
At 24 and 48 hours after using the device, sustained pain-free response rates were also better in the treatment group.
There were also no differences between the sTMS and sham groups in rates of associated nausea, sensitivity to light, or sensitivity to sound. No device-related serious adverse effects were observed.
How did the researchers interpret the results?
The researchers conclude that early treatment of migraine with aura using sTMS resulted in increased freedom from pain at two hours compared with sham stimulation, and sustained absence of pain at 24 and 48 hours. They say that sTMS this could be a promising new treatment for migraine with aura.
This well-conducted, double-blind, randomised controlled trial has found promising results when using single-pulse transcranial magnetic stimulation (sTMS) to treat people who frequently suffer from migraine with visual aura. Within two hours of the onset of symptoms, more people were pain-free when using the handheld device than those who had used an identical ‘sham’ device.
Although the study has reliable results, there are a couple of things to consider when putting these findings into context:
This was a phase 2 trial, which has so far compared sTMS only with no treatment in a relatively small number of people (164 completed the study). Results will need follow-up in larger phase 3 trials that compare sTMS to other active treatments for migraine (eg actual drugs rather than sham sTMS) and in larger groups of people.
People in this trial were allowed to use medications to treat their migraine as normal, so at this stage it is difficult to extract the extent of the effect that sTMS alone is having, for example how people would feel if they used sTMS as their sole treatment for migraine. Therefore, the news reports are premature in announcing this treatment as an ‘alternative to pain medications’.
Although no significant adverse effects of this device were observed, a greater number of people who had used this device for much longer than three months (the period of this study) would need to be observed in order to see whether there were any longer-term adverse effects or health risks of sTMS.
As the researchers say, they have not yet explored the possible range of sTMS doses that could be given, or the optimum timing of treatment (at what stage in the headache, for example). The device at the current time would only be suitable for people who experience migraine with visual aura.
Overall, the findings of this study are promising, and further trials are awaited.