TMS for negative symptoms

Sometimes psychotic · May 19, 2014, 07:37 PM

Double-blind, randomized sham controlled s... [J Psychopharmacol. 2014] - PubMed - NCBI

TMS is magnetic stimulation of brain...non invasive no memory loss or anything but effective in treating negative symptoms where every other treatment fails...it's being more widely offered...we actually have it at my hospital and we don't even have inpatient psych...

nbritton · May 20, 2014, 12:21 PM

Quote:

Originally Posted by Sometimes psychotic

Double-blind, randomized sham controlled s... [J Psychopharmacol. 2014] - PubMed - NCBI

TMS is magnetic stimulation of brain...non invasive no memory loss or anything but effective in treating negative symptoms where every other treatment fails...it's being more widely offered...we actually have it at my hospital and we don't even have inpatient psych...

How significant is a 7.7 point reduction in Scale for the Assessment of Negative Symptoms (SANS)?

Sometimes psychotic · May 20, 2014, 01:12 PM

SANS score started around 55 and dropped roughly 10 points---so I posted this based on the abstract but looking at the actual paper there is a weird thing where the sham treated control started with much lower symptoms like 40 and they drop even with sham treatment down to 30 although it was not significant due to more variation in outcome. Not sure why there was so much variation in the control but either "treament' results in the same 10 point drop in SANS score could just be time or placebo effect....

May 20, 2014, 01:22 PM

I'm not convinced both groups were the same if their SANS scores differed by 15 points to begin with. Then they both drop the same, so it's ?placebo. I'm interested in TMS from a depression POV, but I get the impression that it's not done in the UK outside of any research trials. Also, I worry about the side effect profile as it's not been studied long term I don't think and problems may only appear 10 or 20 or whatever years down the line :/ It definitely sounds less invasive than ECT though, which is good.

*Willow*

nbritton · May 20, 2014, 01:23 PM

I added a TMS section to the wikipedia article on the Management of Schizophrenia... https://en.wikipedia.org/wiki/Manage...ophrenia#Other

I found several other TMS schizphrenia studies on pubmed, so I add their citations into wikipedia as well. I only had time to skim through them, but from what I read the results look promising. Someone should read through those studies and expand on the wikipedia TMS section.

I've always wanted to try TMS, is it widely available now? Does Medicare, in Illinois, cover the procedure?

May 20, 2014, 01:33 PM

The only place in the UK is in London and it costs £2000 a week and they say you need 3-6 weeks!

It also says that TMS increases serotonin and dopamine - if it increases dopamine, couldn't that increase the risk of psychosis?! But I don't really think that it's as simple as too much dopamine = psychosis, because aripirazole/Abilify works to increase dopamine in some areas and reduce it in others, so I've been thinking that too much dopamine in some brain areas causes positive symptoms, and too little dopamine in other areas causes the negative symptoms, but I don't have any evidence for that idea or know which brain areas correlate with which dopamine concentration (I'm still struggling to understand scientific journals, which is a pain given I can skim-read fiction/autobiographies with no problems now) Sorry, rambling!

*Willow*

nbritton · 02:03 PM

Quote:

Originally Posted by WeepingWillow23

I'm not convinced both groups were the same if their SANS scores differed by 15 points to begin with. Then they both drop the same, so it's ?placebo. I'm interested in TMS from a depression POV, but I get the impression that it's not done in the UK outside of any research trials. Also, I worry about the side effect profile as it's not been studied long term I don't think and problems may only appear 10 or 20 or whatever years down the line :/ It definitely sounds less invasive than ECT though, which is good.

*Willow*

One of the studies for minocycline (an antibiotic typically used to treat acne) noted a 9 point SANS reduction. I've been on it before, to treat acne, and did notice an improvement with my psychiatric symptoms, in general my mind felt less cluttered, I was able to think better. At the time I didn't know minocycline had this effect, so I didn't attribute the improvements to the drug. Now that I know, I'm going to ask if my psychiatrist will prescribe it...

Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment.
Chaudhry IB, Hallak J, Husain N, Minhas F, Stirling J, Richardson P, Dursun S, Dunn G, Deakin B.
J Psychopharmacol. 2012 Sep;26(9):1185-93. doi: 10.1177/0269881112444941

A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia.
Levkovitz Y, Mendlovich S, Riwkes S, Braw Y, Levkovitch-Verbin H, Gal G, Fennig S, Treves I, Kron S.
J Clin Psychiatry. 2010 Feb;71(2):138-49. doi: 10.4088/JCP.08m04666yel

Sometimes psychotic · May 20, 2014, 02:24 PM

Quote:

Originally Posted by nbritton

I added a TMS section to the wikipedia article on the Management of Schizophrenia... https://en.wikipedia.org/wiki/Manage...ophrenia#Other

I found several other TMS schizphrenia studies on pubmed, so I add their citations into wikipedia as well. I only had time to skim through them, but from what I read the results look promising. Someone should read through those studies and expand on the wikipedia TMS section.

I've always wanted to try TMS, is it widely available now? Does Medicare, in Illinois, cover the procedure?

Not sure if medicare covers it or not but we offer it through psych outpatient at a teaching/university hospital. I don't think its widely available though a few years ago I think it was mostly out of the East coast...

Sometimes psychotic · May 20, 2014, 02:25 PM

Quote:

Originally Posted by WeepingWillow23

The only place in the UK is in London and it costs £2000 a week and they say you need 3-6 weeks!

It also says that TMS increases serotonin and dopamine - if it increases dopamine, couldn't that increase the risk of psychosis?! But I don't really think that it's as simple as too much dopamine = psychosis, because aripirazole/Abilify works to increase dopamine in some areas and reduce it in others, so I've been thinking that too much dopamine in some brain areas causes positive symptoms, and too little dopamine in other areas causes the negative symptoms, but I don't have any evidence for that idea or know which brain areas correlate with which dopamine concentration (I'm still struggling to understand scientific journals, which is a pain given I can skim-read fiction/autobiographies with no problems now) Sorry, rambling!

*Willow*

Still cheaper than an inpatient stay here in the states....and if it can potentially change your ability to work that's kind of huge..

Sometimes psychotic · May 20, 2014, 02:27 PM

Quote:

Originally Posted by WeepingWillow23

Also, I worry about the side effect profile as it's not been studied long term I don't think and problems may only appear 10 or 20 or whatever years down the line :/ It definitely sounds less invasive than ECT though, which is good.

*Willow*

We'll find out soon enough there are people called mind hackers that are setting up rigs to do it themselves at home---I'm not really sure that its any more dangerous than an MRI given that the magnetic field is a lot weaker than one of those...

nbritton · May 20, 2014, 03:13 PM

Quote:

Originally Posted by Sometimes psychotic

SANS score started around 55 and dropped roughly 10 points---so I posted this based on the abstract but looking at the actual paper there is a weird thing where the sham treated control started with much lower symptoms like 40 and they drop even with sham treatment down to 30 although it was not significant due to more variation in outcome. Not sure why there was so much variation in the control but either "treament' results in the same 10 point drop in SANS score could just be time or placebo effect....

Do you know of any reviews that compare the SANS scores of various treatment options to determine relative effectiveness?

Sometimes psychotic · May 20, 2014, 03:39 PM

Quote:

Originally Posted by nbritton

Do you know of any reviews that compare the SANS scores of various treatment options to determine relative effectiveness?

No there really aren't even a lot of meta-analysis studies for negative symptoms in general---

nbritton · May 20, 2014, 05:33 PM

Psychiatry Res. 2014 Mar 30;215(3):505-13. doi: 10.1016/j.psychres.2013.12.019. Epub 2013 Dec 21.
Revisiting the therapeutic effect of rTMS on negative symptoms in schizophrenia: a meta-analysis.
Shi C1, Yu X2, Cheung EF3, Shum DH4, Chan RC5.

Abstract:
This study sought to determine the moderators in the treatment effect of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms in schizophrenia. We performed a meta-analysis of prospective studies on the therapeutic application of rTMS in schizophrenia assessing the effects of both low-frequency and high-frequency rTMS on negative symptoms. Results indicate that rTMS is effective in alleviating negative symptoms in schizophrenia. The effect size was moderate (0.63 and 0.53, respectively). The effect size of rTMS on negative symptoms in sham-controlled trials was 0.80 as measured by the SANS and 0.41 as measured by the PANSS. A longer duration of illness was associated with poorer efficacy of rTMS on negative symptoms. A 10 Hz setting, at least 3 consecutive weeks of treatment, treatment site at the left dorsolateral prefrontal cortex (DLPFC) and a 110% motor threshold (MT) were found to be the best rTMS parameters for the treatment of negative symptoms. The results of our meta-analysis suggest that rTMS is an effective treatment option for negative symptoms in schizophrenia. The moderators of rTMS on negative symptoms included duration of illness, stimulus frequency, duration of illness, position and intensity of treatment as well as the type of outcome measures used.

nbritton · 06:54 PM

Quote:

Originally Posted by Sometimes psychotic

No there really aren't even a lot of meta-analysis studies for negative symptoms in general---

I was searching through pubmed and actually found one meta review...

Rev Psiquiatr Salud Ment. 2011 Jul;4(3):126-43. doi: 10.1016/j.rpsm.2011.02.005. Epub 2011 Jun 14.
Efficacy of second-generation-antipsychotics in the treatment of negative symptoms of schizophrenia: A meta-analysis of randomized clinical trials.
Darbà J1, Minoves A, Rojo E, Jimenez F, Rejas J.

Abstract:

OBJECTIVES:
To determine whether second-generation-antipsychotics (SGAs) are effective for negative symptoms treatment in schizophrenia.

METHODS:
Two meta-analyses were carried out using placebo or haloperidol as comparators. The search included the following databases: Pubmed, The Cochrane Central Register of Controlled Trials, Proquest Health and Medical Complete, Science Citation Index Expanded, and Current Contents Connect. The outcome measure used was the change in negative symptoms, choosing a standardized statistic (Cohen's d) to synthesize the data.

RESULTS:
In the placebo-controlled meta-analysis, the effect sizes (Cohen's d) obtained for amisulpride, haloperidol, olanzapine, quetiapine, risperidone and ziprasidone were 0.52, 0.34, 0.43, 0.36, 0.40 and 0.46, respectively, favoring active treatment against placebo (P<0.001 in all cases). The haloperidol-controlled meta-analysis only showed a statistically significant trend favoring antipsychotics over haloperidol (Cohen's d=0.15).

CONCLUSIONS:
Most antipsychotics (amisulpride, haloperidol, olanzapine, quetiapine, risperidone and ziprasidone) are effective in the treatment of negative symptoms. Amisulpride and ziprasidone showed higher effect sizes.

Update: I think it is important to point out that this study was funded by Pfizer, the makers of ziprasidone (geodon). It's disheartening to know that the only reason amisulpride isn't approved for use in the US is simply due to it's expired patent status.

May 22, 2014, 08:48 PM

I get an email from the British Psychological Society about some of the latest research, and this week's one had a study on TMS:

Quote:

Antidepressant brain stimulation: Promising signs or continuing doubts?
----------------------------------------

Depression is a growing public health concern, affecting 1 in 9 people [http://www.ncbi.nlm.nih.gov/pubmed/23514317] at some point in their lives, and with a third of sufferers experiencing little or no benefit from medication. The World Health Organization predicts that by 2020 depression will become the second leading cause of disability worldwide. By 2026 it is expected to afflict nearly 1.5 million people in the UK, costing the economy more than £12bn every year.

Faced with this crisis, scientists have looked for alternative solutions to medication. Since the mid 1990s [http://www.ncbi.nlm.nih.gov/pubmed/8684201] there has been a steady interest in developing brain stimulation methods as antidepressants, particularly for patients who are resistant to drug therapy. The general logic of this approach is that because depression is associated with abnormally low activity in the left prefrontal cortex, methods that increase prefrontal activity, such as transcranial magnetic stimulation (TMS - see Transcranial magnetic stimulation - Wikipedia, the free encyclopedia), might help promote recovery.

A new Taiwanese study now reports that a particularly potent form of transcranial magnetic stimulation called theta burst stimulation [http://www.ncbi.nlm.nih.gov/pubmed/15664172] could lead to benefits in treatment-resistant depression. Cheng-Ta Li and colleagues compared the efficacy of three different types of theta burst stimulation: a protocol believed to increase activity in the left prefrontal cortex, one that reduces activity in the right prefrontal cortex, and a combined protocol that seeks to achieve both in the same treatment session. Compared with sham (placebo) stimulation, the team found that two weeks of daily treatment using the combined protocol was most effective, reducing self-ratings of depression by about 35 per cent.

These results are promising but preliminary. The sample size was small, including just 15 patients per group, and the trial was not preregistered. Such limitations are common in a literature that is dominated by controversy and small exploratory reports. A major 2007 study [http://www.ncbi.nlm.nih.gov/pubmed/17573044], which concluded that TMS is clinically effective (and which led to the treatment becoming approved by the FDA) was later criticised [http://www.ncbi.nlm.nih.gov/pubmed/19793580] for selectively reporting positive outcomes, deviating []Nature Publishing Group : science journals, jobs, and information from its registered analysis protocol, and being contaminated by uncontrolled placebo effects. The most recent review of evidence [http://www.ncbi.nlm.nih.gov/pubmed/24724996] to date concluded that the benefits of TMS, while measurable statistically, are so small as to be clinically insignificant. And as to how these benefits of TMS arise in the first place – well, the truth is we have almost no idea. Our best guess is 'because dopamine' [http://www.ncbi.nlm.nih.gov/pubmed/16259998].

These uncertainties, in turn, raise concerns about ethics and regulation. With a growing number of companies offering TMS as a private healthcare intervention, and with standard treatments running into thousands of pounds, the fact that its efficacy remains unproven and unexplained is especially pertinent.

Notwithstanding these issues, this latest study by Li and colleagues is a helpful addition to the literature and suggests that more potent neurological interventions, such as theta burst stimulation, have potential. But realising that potential will require a commitment to rigorous and unbiased research practices. We need meticulously preregistered studies [http://orca.cf.ac.uk/59475/1/AN2.pdf] to prevent negative findings being censored [http://en.wikipedia.org/wiki/Publication_bias] and to ensure that authors don’t cherry pick analyses that 'work' or engage in other questionable research practices [http://www.cmu.edu/dietrich/sds/docs...thTelling.pdf]. We need studies with larger samples [http://www.montefiore.ulg.ac.be/~lwh...roscience.pdf] to determine which individual differences determine the efficacy of TMS and to generate reproducible effects. And we need a renewed focus on understanding the neurobiology underlying any benefits of TMS.

Once these challenges are met, brain stimulation may well provide a complementary treatment for depression. For now, though, the jury is out.
_________________________________

Li CT, Chen MH, Juan CH, Huang HH, Chen LF, Hsieh JC, Tu PC, Bai YM, Tsai SJ, Lee YC, & Su TP (2014). Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. Brain : a journal of neurology PMID: 24817188

Post written for the BPS Research Digest by guest host Chris Chambers, senior research fellow in cognitive neuroscience at the School of Psychology, Cardiff University, and contributor to the Guardian psychology blog, Headquarters [http://www.theguardian.com/science/head-quarters].

*Willow*

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