Successful NHS Trial of Ketamine for Depression

[Marco]

Ketamine treatment of depression isn't news but to be trialed within the normally ultra-conservative NHS strikes me as unusual :

We've seen remarkable changes in people who've had severe depression for many years that no other treatment has touched. It's very moving to witness. Patients often comment that that the flow of their thinking seems suddenly freer. For some, even a brief experience of response helps them to realise that they can get better and this gives hope.

http://www.ox.ac.uk/media/news_stories/2014/140403.html

 

[aimossy]

Some of these trials are happening here in my own home town. Horse tranquilisers.

 

[Esther12]

Doesn't look worthy of the hype to me (after a very, very quick look):

http://jop.sagepub.com/content/early/2014/03/17/0269881114527361.full

No control group.

29% reported a positive result while 25% stopped treatment because of serious adverse reaction or increased anxiety.

Sounded like the positive effects didn't really last and would require ongoing treatment.

If people are seriously ill and want to try some ketamine, that should be up to them. Seems dodgy to promote it as a medical treatment though.

 

[Marco]

Doesn't look worthy of the hype to me (after a very, very quick look):

http://jop.sagepub.com/content/early/2014/03/17/0269881114527361.full

No control group.

29% reported a positive result while 25% stopped treatment because of serious adverse reaction or increased anxiety.

Sounded like the positive effects didn't really last and would require ongoing treatment.

If people are seriously ill and want to try some ketamine, that should be up to them. Seems dodgy to promote it as a medical treatment though.

To be fair Esther (outside of its horse tranquiliser and street drug of abuse rep) Ketamine is a well established drug in medical treatment including chronic pain.

Additionally there really isn't anything else for treatment resistant depression (hence the name) with a very high risk of suicide. In this context a relatively safe treatment that can often have very quick results (sometimes instantaneous c/w several weeks for conventional anti-depressants that don't work for these folks anyway) and appears to help almost 30% doesn't sound too bad to me.

I don't see a need for a control group in a condition that isn't known for either spontaneous recovery or placebo effects (again its treatment resistant). Also isn't ongoing treatment the norm with severe depression?

 

[Esther12]

To be fair Esther (outside of its horse tranquiliser and street drug of abuse rep) Ketamine is a well established drug in medical treatment including chronic pain.

Additionally there really isn't anything else for treatment resistant depression (hence the name) with a very high risk of suicide. In this context a relatively safe treatment that can often have very quick results (sometimes instantaneous c/w several weeks for conventional anti-depressants that don't work for these folks anyway) and appears to help almost 30% doesn't sound too bad to me.

I don't see a need for a control group in a condition that isn't known for either spontaneous recovery or placebo effects (again its treatment resistant). Also isn't ongoing treatment the norm with severe depression?

The problems around CFS have made me pretty wary of claims about effective treatments!

re need for a control group: Different groups of patients can end up responding to things in different ways, so it's always important to have a control group when assessing an intervention imo. Admittedly, I don't know much about treatment resistant depression, but even so the results here didn't seem so great that we could be confident ketamine is useful without a control group.

Again, given the problems around CFS, I'm not keen on the suggestion that a lack of effective treatments is legitimate reason for medical staff to be less cautious about their assessment or promotion of interventions. I think that patients should be free to decide for themselves whether to try things like this, but I don't think that trials like this should be presented as good evidence for efficacy.

Some of the headlines I saw seemed really over-excited, eg: http://metro.co.uk/2014/04/03/horse-drug-ketamine-is-remarkable-treatment-for-depression-4687036/

At the same time though, I don't mean to really slate this and maybe I did come across as too harsh in my first response - I just think it's best to be cautious about this sort of stuff.

 

[peggy-sue]

I don't really know what I feel about this.

Just the very idea of Ketamine scares me silly, it's not on my list of illegal drugs I'd like to try, or any legal list either.
But I also know what the true depths of depression can be, and having to wait, while climbing the walls and bouncing off the ceiling with increased anxiety for 6 weeks before an SSRI kicks in, as I had to last time, might be enough to get me to try it.

I'd really rather science got to the root of things though. It's HORMONES, not neurotransmitters.

I've had more than enough of the serotonin myth that's been promulgated for decades by the makers of SSRIs.

 

[Marco]

The problems around CFS have made me pretty wary of claims about effective treatments!

re need for a control group: Different groups of patients can end up responding to things in different ways, so it's always important to have a control group when assessing an intervention imo. Admittedly, I don't know much about treatment resistant depression, but even so the results here didn't seem so great that we could be confident ketamine is useful without a control group.

In an ideal world perhaps. One of the serious adverse effects noted (and I'm paraphrasing cos I'm just passing through at the mo) was increased suicidal ideation in one individual who claimed that this was due to disillusionment that the Ketamine intervention didn't appear to be working for them. In this context there could be genuine ethical concerns with randomising 50% of the cohort to placebo.

That's why I believe that research protocols should be tailored to the problem/cohort rather than carried out in cookie cutter fashion just because the methodology is considered to be 'gold standard'.

At the same time though, I don't mean to really slate this and maybe I did come across as too harsh in my first response - I just think it's best to be cautious about this sort of stuff.

Quite right too. I think we've all had a boot camp in questioning apparently 'clear cut' science in recent years.

 

[Marco]

I've had more than enough of the serotonin myth that's been promulgated for decades by the makers of SSRIs.

The Ketamine results do kind of blow the serotonin hypothesis out of the water since (a) Ketamine doesn't work directly on serotonin (production, transport or receptors) and (b) serotonin reaches physiological levels within hours following SSRI's but the therapeutic effects take weeks. Current thinking is that their beneficial effects are via anti-inflammatory pathways.

 

[peggy-sue]

My current thinking is hormones. My thinking has been hormones for a very, very long time, before SSRIs came out.

PMT is hormones.
"Instant Mother-love" is hormones.
"Roid rage" is hormones.
"Post-natal depression" is hormones.

Hormones are at the root of our moods and feelings.

 

[A.B.]

The Ketamine results do kind of blow the serotonin hypothesis out of the water since (a) Ketamine doesn't work directly on serotonin (production, transport or receptors) and (b) serotonin reaches physiological levels within hours following SSRI's but the therapeutic effects take weeks. Current thinking is that their beneficial effects are via anti-inflammatory pathways.

I think they are due to counteracting excessive glutamate levels (overexcitation) in the brain caused by environmental toxins.

 

[Esther12]

In an ideal world perhaps. One of the serious adverse effects noted (and I'm paraphrasing cos I'm just passing through at the mo) was increased suicidal ideation in one individual who claimed that this was due to disillusionment that the Ketamine intervention didn't appear to be working for them. In this context there could be genuine ethical concerns with randomising 50% of the cohort to placebo.

Just a brief point: a control group with just therapist time could be used instead of placebo. With something like ketamine, a sugar pill probably wouldn't cut it as a control anyway, but I agree that there are also particulars that need to be accounted for in assessing different treatments/interventions.

 

[barbc56]

I absolutely agree about some kind of control group with these type of trials but we also have to keep in mind the ethical issues involved in some trials. For example, it would be unethical to have a control group only getting a placebo for a group of cancer patients.

Maybe this study needs to be considered a pilot study, unless it already is, but it does not sound like it's being touted in this way. It might lead to further studies but IMO, it's too early to say this is the answer. When I see such things being said, for me, it raises red flags.

If we want to find out what is causing or helping us with this DD, I feel it is imperative to have good solid evidence about what is going on. Otherwise it's just detritus and takes up valuable time that could be put to better use.

Think of how long the XMRV debacle lasted and if that research had been unproven sooner than it was, buy politics intervened as it often is. That time could have been put to better use. Of course this is all in hindsight and we can't always predict the future.

Is the answer only in clinical trials? Not necessarily, but we need to get as close as possible with rigorous information to get answers.

For some things medically, there may never be a cure or answers but damn we need to try get as close as possible to this goal.

Barb

ETA Brain fart here. I may have posted on the wrong thread. Whichever, my comments were specifically about me/cfs but I think many of the points still relate to us as far as quality of research for any condition.

 

[heapsreal]

Ketamine is an nmda antagonist, too much nmda is inflammatory. Ketamine was what dr goldstein stated was one of the best drugs he used for cfs. From what i have read on this before the doses used to treat depression were very low and not enough to zonk one out on it??? I think i read recently that goldstein also use to use a paste of ketamine for some patients, i guess now it would be in a patch like other pain meds??

 

[aimossy]

Its an interesting thing in general.
Some sleeping tablets helped people with brain injury get physical and cognitive improvements like it relaxed something in the system enough for things to flow better..
This may be working in some similar strange way for this level of depression, Intractable depression is extremely hard to treat so I don't fully know how I feel about it either...Would side effects be anymore scary than most psych drugs.
What scares me is the process about which the use will be applied and consent given and all the context of this...
Its such a difficult area and people can be powerless.
I just wish mental health conditions had a bigger range of research done into possible causes so better treatments can be developed.