Time to switch?

[mct]

I am wondering whether I have given this medication a decent trial and it is time to switch.
About six months ago I developed nocturnal panic attacks and morning anxiety.This developed shortly after I retired (65M). It was accompanied by fairly mild depressive symptoms but also GI complaints (nausea, loss of appetite - negative investigations). I was on mirtazepine 15mg for 2.5 months without any effect apart from somewhat better sleep. Escitalopram was added 3 months ago and I have tapered the mirtazepine slowly to currently 3.75mg.
I started the escitalopram slowly beginning with 2.5mg. Within a few days I had marked nausea, insomnia and greatly increased anxiety/agitation.I slowly increased the dose so that in total I have been on 2.5mg 2weeks, 5mg 2 weeks, 7.5mg one week, 8.5mg 3 weeks and then 10mg for the last six weeks.
Overall I still feel worse than before I started. The insomnia has improved to some degree (with added zopiclone) but the panic attacks on waking are just the same. The increase in anxiety has reduced but I am still plagued by unfocused, unpleasant anxiety till about noon every day - this was not the case before I started.The mild feeling of depression is, if anything worse, as I am now downcast at the failure of two drugs.
Have I given escitalopram a decent shot or should I give it longer at 10mg (8weeks, 12 weeks?)? If so any suggestions for what next? Thanks for your thoughts.

[panic_down_under]

was on mirtazepine 15mg for 2.5 months without any effect apart from somewhat better sleep.

to NMP,

I'm not surprised that you failed to get a response from mirtazapine. Despite what it claims on the box, it isn't a true antidepressant (AD), but a potent sedating antihistamine, i.e. it mostly works as a sedative. Plus, 15mg is only the usual starting dose. Most need to take 30-45mg/day to get a good response. The other issue with this med is that it is very prone to stop working, sometimes within just a few weeks. All that said, it can be a useful med to stabilize a downward spiral as it works quickly as a sedative.

Escitalopram was added 3 months ago and I have tapered the mirtazepine slowly to currently 3.75mg.

Did your doctor tell you to taper off mirtazapine and onto escitalopram that slowly, or was this your idea? Have you had previous issues starting/stopping ADs?

I started the escitalopram slowly beginning with 2.5mg. Within a few days I had marked nausea, insomnia and greatly increased anxiety/agitation.I slowly increased the dose so that in total I have been on 2.5mg 2weeks, 5mg 2 weeks, 7.5mg one week, 8.5mg 3 weeks and then 10mg for the last six weeks.

Why were you on 8.5mg for 3 weeks? Side-effects?

The rule of thumb on increasing (or decreasing) AD doses is to not do so more frequently than 5 times the half-life of the med which for escitalopram is 8 days. Raising the dose sooner may significantly worsen the severity of any side-effects, however, delaying dose increases won't significantly lower their severity no matter how long the delay.

Overall I still feel worse than before I started. The insomnia has improved to some degree (with added zopiclone) but the panic attacks on waking are just the same. The increase in anxiety has reduced but I am still plagued by unfocused, unpleasant anxiety till about noon every day - this was not the case before I started.The mild feeling of depression is, if anything worse, as I am now downcast at the failure of two drugs.

So instead of using mirtazapine to aid sleep you're now taking zopiclone? How often do you take it?

Have I given escitalopram a decent shot or should I give it longer at 10mg (8weeks, 12 weeks?)? If so any suggestions for what next? Thanks for your thoughts.

I don't know. ADs typically kick-in at between 4-12 weeks on a therapeutic dose which for escitalopram is usually 10mg plus. You've only been at that dose for 6 weeks, but there is also the 3 weeks at 8.5mg which probably should count for something. It comes down to how quickly you metabolise it. Given the amount of time and effort you've put into it already, I'd probably give escitalopram another couple of weeks.

[mct]

PDU Many thanks for your thoughtful reply.
1.My GP was reluctant to prescribe mirtazepine as he was not familiar with it and he was apprehensive of the published side-effects. It was my suggestion as I had read of its effects on appetite and nausea. I don't think he would have gone above 15mg.
2.When switching to escitalopram he wanted me to simply stop the mirtazepine. I had read all the horror stories of withdrawal so it was my idea to taper slowly. I was taking 20mg paroxetine for nine months 20 years ago for a specific phobia related to performing tasks under public scrutiny. It seemed to work quickly then, although this may have been placebo effect. Apart from a few dizzy episodes I did not have any problem stopping Paxil and I think I probably only tapered it over a couple of weeks. I should mention that before starting the escitalopram he did prescribe Paxil in view of its previous success but after a few days at 5mg I was getting urinary hesitancy. I am surprised that I experienced that at such a low dose (?anxiety because I read of the side -effect) but I also wonder whether the 15mg mirtazepine might have had some additive anti-cholinergic effect?
3. I delayed upping from 8.5 to 10 because my wife and I were going on a brief trip and I did not want to suffer a new round of nausea, elevated anxiety while away. Recurrent nausea has been a problem throughout this process and I am not sure how much is the medication and how much is anxiety. Some days I have it all day, other days not at all. I was taking ondansetron periodically till about a month ago - I wonder whether this might actually delay the development of tolerance to the elevated serotonin?
4. I still take the 3.75mg mirtazepine at bedtime and have no difficulty falling asleep. I wake in the middle of the night and take just 1.25mg zopiclone, sleep till about 5am and then take another 1.25mg which may or may not give me another hour of sleep. Then the anxiety/panics kick in and eventually I get up.
5. My GP thinks that I should now switch but I think you are right to suggest another couple of weeks. If switching he is thinking of Paxil again (in case the urinary problem was imaginary) or venlafaxine. As for other medications, I am worried about the GI side-effects of sertraline in view of my nausea predisposition and the activating effects of sertraline,fluoxetine and venlafaxine.
I would certainly appreciate any thoughts you might have as I suspect that I may be overthinking all this. Thanks!

[panic_down_under]

When switching to escitalopram he wanted me to simply stop the mirtazepine. I had read all the horror stories of withdrawal

Big mistake. Relatively few people experience 'horror' withdrawal, but the many more that don't do not often post about it. Plus, there is considerable debate as to how much of the 'horror' is due to biology and how much psychology. Come to believe you will suffer greatly and an anxious mind is very capable of creating your worst nightmare even with a placebo.

I was taking 20mg paroxetine for nine months 20 years ago for a specific phobia related to performing tasks under public scrutiny. It seemed to work quickly then, although this may have been placebo effect.

Anxiety disorders (also depression) are the emotional expression of an underlying physical brain deficit, atrophy of segments of the two hippocampal regions of the brain caused by high stress hormone levels in the brain killing neurons and inhibiting the growth of new ones. It is essentially a type of autoimmune disorder (which is why these disorders often worsen during infections). Both ADs and the cognitive/behavioural (CBT, REBT, etc) and mindfulness therapies work by stimulating the growth of new brain cells in the hippocampi. It is the new cells and the connections they forge which produce the therapeutic response. It takes about 7 weeks for neurons to bud, grow and mature, however, some improvement may be noticed a little earlier.

Apart from a few dizzy episodes I did not have any problem stopping Paxil and I think I probably only tapered it over a couple of weeks.

Which was a good demonstration that withdrawal horror stories need to be taken with more than a grain of salt for paroxetine (Paxil) has quite a reputation for producing severe withdrawal symptoms due to its short half-life and lack of an active metabolite to extend its activity. Only venlafaxine (Effexor) has a worse reputation.

I should mention that before starting the escitalopram he did prescribe Paxil in view of its previous success but after a few days at 5mg I was getting urinary hesitancy. I am surprised that I experienced that at such a low dose (?anxiety because I read of the side -effect) but I also wonder whether the 15mg mirtazepine might have had some additive anti-cholinergic effect?

Most SSRIs/SNRIs and TCAs list urinary hesitancy as a potential side-effect, so it may have been the med, but reading up on side-effects can be a sure way of experiencing them all too. Mirtazapine doesn't impact muscarinic acetylcholine receptors much.

I was taking ondansetron periodically till about a month ago - I wonder whether this might actually delay the development of tolerance to the elevated serotonin?

Did you notice any reduction in anxiety when taking ondansetron? Back in the 1980s drug trials pointed to it having potent anti anxiety properties, but GlaxoSmithKline opted to target the more lucrative antiemetic instead.

I still take the 3.75mg mirtazepine at bedtime and have no difficulty falling asleep. I wake in the middle of the night and take just 1.25mg zopiclone, sleep till about 5am and then take another 1.25mg which may or may not give me another hour of sleep. Then the anxiety/panics kick in and eventually I get up.

This suggests that the insomnia is not from the escitalopram. I'd also be wary of taking zopiclone daily as tolerance tends to build quite quickly. I think you would benefit from seeing a sleep specialist.

If switching he is thinking of Paxil again (in case the urinary problem was imaginary) or venlafaxine.

Venlafaxine may be as likely to cause urinary problems as paroxetine. I'm not a venlafaxine fan (or of the other common SNRIs). Despite being classified as a SNRI, venlafaxine is really only a SSRI and has a number of potential issues such as a very short half-life and the difficulty many have with withdrawal. Imo, its active metabolite desvenlafaxine (Pristiq) would be a better option if a SNRI is preferred.

As for other medications, I am worried about the GI side-effects of sertraline in view of my nausea predisposition and the activating effects of sertraline,fluoxetine and venlafaxine.

Sertraline is more likely to affect the gut than the other SSRIs, although, as with everything about ADs your YMMV, but I'd be less concerned about the potential activating effects of the three.

as I suspect that I may be overthinking all this. Thanks!

I think you are. Everyone's response to ADs is individual to them. It all comes down to how the med meshes with their biology and there is no way of predicted this other than by sucking and seeing.

[mct]

PDU, Thank you for your insights and swift reply. I certainly appreciate, as I am sure do many others, the efforts you expend in providing information and reassurance to people (like me) who are floundering.

In answer to your points:
I did find the taking ondansetron made me drowsy so it was probably reducing my anxiety without me realising it.

I have been taking the zopiclone daily, albeit at a lowish dose, for three months so I am sure that I have developed dependency. My hope is that the early morning wakenings respond to effective anti-depressant treatment and then I can come off the zopiclone. (I never had any sleep problems before this current unpleasant illness.) If this does not work out, seeing a sleep specialist sounds a good idea. Unfortunately health care here, particularly in this province, is in such a bad state that I would probably be dead and buried before getting an appointment!

I will mention Pristiq to my GP. My hunch is that he will reluctant to prescribe it as he is obviously more familiar with venlafaxine. Looking it up, I do see that it is associated with more anxiety induction than straight venlafaxine which rather concerns me as I had such an activating reaction starting the more benign escitalopram. But as you said, you can't tell till you try it.

Lastly, I will read your attached references with great interest. After just quickly scanning them, I was surprised to learn that there is actual anatomical proof in the brain for the effect of "talking therapies". Thanks!

[panic_down_under]

I have been taking the zopiclone daily, albeit at a lowish dose, for three months so I am sure that I have developed dependency.

Possibly. Dependency isn't that big a concern, imo, but tolerance is.

I will mention Pristiq to my GP. My hunch is that he will reluctant to prescribe it as he is obviously more familiar with venlafaxine.

Desvenlafaxine is the active metabolite of venlafaxine and does much of the work so he won't be venturing far off the beaten track.

Looking it up, I do see that it is associated with more anxiety induction than straight venlafaxine which rather concerns me as I had such an activating reaction starting the more benign escitalopram. But as you said, you can't tell till you try it.

I would expect venlafaxine to give a rougher ride at the beginning as desvenlafaxine is a less potent serotonin reuptake inhibitor.

I was surprised to learn that there is actual anatomical proof in the brain for the effect of "talking therapies". Thanks!

I dislike the term 'mental disorder' as it misleads people about what they really are. They are manifestations of physical brain dysfunctions and the two ways of treating them are by either repairing the dysfunction, or by improving the efficiency of the 'broken' bits to minimise the effects. ADs and the CBT/REBT/mindfulness type therapies are in the repair category, imprecise though they may be. OTOH, meds such as the benzodiazepines (BZDs) are supports which temporarily improve the function of the affected brain parts back to something near what they should be - for example, anxious brains have fewer BZD binding sites and BZDs work by increasing the effectiveness of the ones that remain.

[mct]

PDU
Thank you for the info. I have read several of the lengthy chronicles here where people, who have already been on venlafaxine long-term, experience distressing anxiety even when modestly increasing their dose. So - if desvenlafaxine has an advantage in this area I will certainly discuss it with my GP, if things come to that.
Thanks again. For those who might be interested, I will eventually post an update here as to whether escitalopram or something else works.