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Akosua
30-12-15, 01:04
Hi guys,
I've struggled with anxiety for many years, but until now I've resisted taking medication. I've tried CBT and exercise which have both benefitted me greatly, but I'm having pretty severe anxiety at the moment and I feel like I can't manage with just that anymore. Yesterday I starting taking Lexapro (10mg).

However, I was reading up on it last night and I'm concerned about some of the long term effects - specifically tardive dysphoria - where long-term SSRI use may actually induce depression, even in people who are taking it for anxiety and do not have a history of depression. Most of the evidence for it seems to come from a single meta-study (attached).

Since the evidence implicates long-term use and high doses, I decided to cut my dosage to 5mg and see how that goes, and to stop taking it after a couple of months (one of the major factors in my current anxiety level is an upcoming external event and some other short-term life stuff). I just need the medication to get me through this period. I also feel like my anxious thoughts and negative self-talk are now so routine and habitual, that I just need to break the habit a little through medication and weaken the neural pathways that access those negative thoughts.

However, I am concerned about doing this as it goes directly against the instructions of both my doctor and pharmacist when I was given the drug - that I should not stop taking it when I am feeling better. Does anybody have any advice, thoughts, experience?

Thanks in advance,
Heather

MyNameIsTerry
30-12-15, 05:01
Hi and welcome to NMP :welcome:

At the start of this document we have:

Results:Depressed patients who ultimately become treatment resistant frequently have had a positive
initial response to antidepressants and invariably have received these agents for prolonged time periods
at high doses. Parallels between this course and tardive dyskinesia are noted. It is proposed that neuroplastic processes related to dendritic arborization may underlie the treatment resistant depression that
occurs in the setting of chronic antidepressant use. Since the prodepressant effect is seen after prolonged
antidepressant use, the term tardive dysphoria is proposed.
Conclusions:Tardive dysphoria, needs to be considered in studies of treatment resistant depression, and
should be examined in blinded, randomized antidepressant discontinuation trials.
2011 Published b

So, this appears to be a study of people diagnosed with depression, not anxiety. This seems to further be backed up throughout the document in statements such as:

It is proposed that tardive dysphoria (TDp) is an abnormal dysphoric state that develops in some predisposed individuals with
prolonged antidepressant treatment. Patients with this syndrome
may comprise a significant fraction of TRD subjects. TDp is defined
as a chronic, frequently treatment resistant, depressive state with
onset in the setting of ongoing, persistent antidepressant treatment. Antidepressants may be initially administered for any reason
(e.g., anxiety or depression), but afflicted subjects with a history of
a recurrent major depressive disorder would have historically
experienced an initial positive response to antidepressant medication (generally with their first exposure). The depressive state is
perpetuated (and possibly worsened) by continuing the antidepressant. It is believed that SRI antidepressants might be selectively associated with the development of TDp

It seems to say that a significant number of TDp sufferers, what you fear, come from the TRD group. But you are not in the TRD group as you have an anxiety disorder. So, if they comprise a significant fraction, who are the rest?

Looking on here:

https://www.psychologytoday.com/blog/mad-in-america/201106/now-antidepressant-induced-chronic-depression-has-name-tardive-dysphoria

This is an article about this study and there are comments that talk about this:

In his discussion, El-Mallakh notes that people without any history of depression who are prescribed an antidepressant for other reasons—anxiety, panic disorder, or because they are serving as “normal controls” in a study—may become depressed, with that depression at times persisting for a fairly long period of time after the antidepressant is withdrawn. The reason that antidepressants may have a “prodepressant effect,” El-Mallakh writes, is that “continued drug treatment may induce processes that are the opposite of what the medication originally produced.” This is the “oppositional tolerance” that Fava has written about, and this process may “cause a worsening of the illness, continue for a period of time after discontinuation of the medication, and may not be reversible.”

From what I can tell the could be a potential for someone with an anxiety/panic disorder to enter this TDp group because they have experienced depression from their meds. That's what that appears to be saying. So, does that mean people who experience none at all are ok? Also, what about low mood/depression from side effects on start up? Is this the same as a prolonger period of depression brought on by the opposite effect the drug brings? It sounds to me like this depression would be more constant and diagnosable in it's own right, although the link to TDp would be unknown at this time.

And this:

With antidepressants, the problem may be that patients, because of the “oppositional tolerance” process, end up with a depleted serotonergic system. The postsynaptic neurons end up with a reduced density of receptors for serotonin; in rat studies(link is external), long-term treatment with an SSRI led to markedly reduced levels of serotonin in "nine areas of the brain." El-Mallakh, in his paper, details several other ways that exposure to an SSRI may deplete serotonergic function, and notes that in experiments with young animals, such impairments are "associated with increased depressive and anxious behaviors."

In conclusion, El-Mallakh writes that "a chronic and treatment-resistant depressive state is proposed to occur in individuals who are exposed to potent antagonists of serotonin reuptake pumps [i.e. SSRIs] for prolonged periods. Due to the delay in the onset of this chronic depressive state, it is labeled tardive dysphoria. Tardive dysphoria manifests as a chronic dysphoric state that is initially transiently relieved by -- but ultimately becomes unresponsive -- to antidepressant medication. Serotonergic antidepressants may be of particular importance in the development of tardive dysphoria."


The trouble is, this could cover everybody because no one will ever know until it happens to them. You would know when it happens given it's about reduction of Serotonin, which will be evident. That's only based on a rat study though and these are the same rat studies that show these drugs working...but they fail many people. I think a bit more is needed than a rat study and a statistical study.

I've only scan read the doc to look for some of this so is there anything else in there about anxiety/panic disorders or antidepressant treatment use outside of depression treatment? Many people use these meds for pain management or urinary issues so it would be relevant to all of them as well.

What is the definition of long term and high doses? I can't see specific doses mentioned unless you have looked at the studies they are quoting. There are some times quoted in here but they seem more about showing a med made no improvement over time or subsequently developed depressive symptoms lasted over a year after cessations in some studies.

I have to say though it would surprise me that a load of drugs they can't actually explain the method of action for have such fallouts. Citalopram worked well for me but I sunk 6 months after coming off it (a lot of that was environmental and lack of education given to me about it by my GP) but my latest one, Duloxetine, caused me mood swings which I had never had before (now largely resolved by high strength Omega 3).