Doxepin

[sparky10]

I have tried many antidepressants for anxiety disorders including TcA’s, Maoi’s, Ssri’s, Snri’s. The only combination
that worked for a few years was moclobemide and pregabalin. I have tried reinstating these at different doses over
the last four years with no success.
I could not get upto therapeutic doses especially on clomipramine and imipramine unfortunately.
pdoc has give me this as a last option, starting at 25mg and working up to 75mg over time.

Is this a good medication for depression/ anxiety, I see it’s used a lot for insomnia/ hives and has a high affinity for
histamine. I’m guessing that’s where the anxiety relief may come from similiar to mirtazapine.

Any experiences with this med anyone and PDU I would appreciate your opinion?

Thanks
Mark

[panic_down_under]

I have tried many antidepressants for anxiety disorders including TcA’s, Maoi’s, Ssri’s, Snri’s.

They didn't work, or you couldn't tolerate them, Mark?


I could not get upto therapeutic doses especially on clomipramine and imipramine unfortunately.

How did you take them and what happened?


pdoc has give me this as a last option, starting at 25mg and working up to 75mg over time.

Is this a good medication for depression/ anxiety, I see it’s used a lot for insomnia/ hives and has a high affinity for
histamine. I’m guessing that’s where the anxiety relief may come from similiar to mirtazapine.

Yes, mirtazapine and doxepin are very sedating antihistamines which mostly ease anxiety through sedation. They are not really antidepressants which work by stimulating the growth of new brain cells in the hippocampal regions of the brain. That said, they can be effective enough for some.

It is probably worth a try, however, doxepin has been phased out in some countries and I note it isn't listed on the NHS Cost Comparison Chart (PDF (http://gmmmg.nhs.uk/docs/cost_comparison_charts.pdf), section 4:3, p 27) which may, or may not indicate it won't be available for much longer in the UK either so it would pay to check. Your chemist/pharmacist could know more about this than your GP.

[WiseMonkey]

Doxepin is unavailable, now it's not being produced any more. The closest alternative is Amitriptyline.

[panic_down_under]

Doxepin is unavailable, now it's not being produced any more. The closest alternative is Amitriptyline.

It is still available here, or at least it is still on the Pharmaceutical Benefits Scheme list of meds in 10mg, 25mg and 50mg tablets/capsules. There doesn't seem to be anything about it being dropped, but who knows.

[sparky10]

They didn't work, or you couldn't tolerate them, Mark?

I struggled to tolerate a lot of them but stayed on them for example, Prozac, effexor, parnate, phenelzine for a good length
of time. They never helped me though so feel stuck and therapy hasn’t done anything either. Prozac I was on for 18 months and the
others for 4 months. It was only diazepam that enabled me to stay on them.



How did you take them and what happened?

i took them at a low dose but the anxiety was too much especially clomipramine and I just felt in a daze most of the time.
it never got any better the longer I stayed on it.



Yes, mirtazapine and doxepin are very sedating antihistamines which mostly ease anxiety through sedation. They are not really antidepressants which work by stimulating the growth of new brain cells in the hippocampal regions of the brain. That said, they can be effective enough for some.

It is probably worth a try, however, doxepin has been phased out in some countries and I note it isn't listed on the NHS Cost Comparison Chart (PDF (http://gmmmg.nhs.uk/docs/cost_comparison_charts.pdf), section 4:3, p 27) which may, or may not indicate it won't be available for much longer in the UK either so it would pay to check. Your chemist/pharmacist could know more about this than your GP.

I got my prescription over here in the U.K., they have not said anything about it being discontinued.

[panic_down_under]

I struggled to tolerate a lot of them but stayed on them for example, Prozac, effexor, parnate, phenelzine for a good length of time. They never helped me though so feel stuck and therapy hasn’t done anything either. Prozac I was on for 18 months and the others for 4 months. It was only diazepam that enabled me to stay on them.

Unfortunately, while diazepam may have eased the anxiety in the short term it was likely making things worse overall. ADs don't work directly in the way diazepam does. Anxiety and depression are the emotional expressions of an underlying brain disorder, atrophy of parts of the two hippocampal regions of the brain caused by high brain stress hormone levels killing brain cells (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/) and inhibiting the growth of new ones. ADs stimulate the growth (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025168/) of new cells (neurogenesis). It is the new cells and the interconnections they forge which provide the therapeutic response. Unfortunately, diazepam and other benzodiazepines (BZDs) impair neurogenesis (Villasana LE (https://pubmed.ncbi.nlm.nih.gov/30794026/), 2019; Boldrini M (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374628/), 2014; Nochi R (https://www.ncbi.nlm.nih.gov/pubmed/23963779), 2013; Sun Y (https://www.ncbi.nlm.nih.gov/pubmed/23639432), 2013; Song J (https://www.kurzweilai.net/how-the-brains-stem-cells-find-out-when-to-make-new-neurons/comment-page-1#comment-96481), 2012; Wu X (http://www.biologicalpsychiatryjournal.com/article/S0006-3223(09)00106-1/abstract), 2009; Stefovska VG (https://www.ncbi.nlm.nih.gov/pubmed/18991352), 2008).

BTW - therapy also works by neurogenesis (https://doi.org/10.1016/j.biopsych.2013.05.017).


i took them at a low dose but the anxiety was too much especially clomipramine and I just felt in a daze most of the time. it never got any better the longer I stayed on it.

The low doses may have been the problem. To initiate and sustain neurogenesis the dose of most serotonergic ADs needs to be high enough to saturate at least 80% (https://pubmed.ncbi.nlm.nih.gov/15121647/) of the serotonin transporters (5-HTT).

Unfortunately, ADs will often make anxiety worse in the beginning. There is no way of preventing this, however, it can usually be minimized by starting at a low dose, no more than a quarter of the recommended minimum therapeutic dose and ramped up slowly by a similar amount every few weeks. Small doses of sedating antihistamines such as hydroxyzine or mirtazapine can help ease the initial anxiety spike too, as may BZDs in the short-term.

Given your experience with SSRIs and clomipramine maybe an AD that targets noradrenaline, aka norepinephrine, reuptake such as nortriptyline might be worth a shot.

[sparky10]

Unfortunately, while diazepam may have eased the anxiety in the short term it was likely making things worse overall. ADs don't work directly in the way diazepam does. Anxiety and depression are the emotional expressions of an underlying brain disorder, atrophy of parts of the two hippocampal regions of the brain caused by high brain stress hormone levels killing brain cells (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/) and inhibiting the growth of new ones. ADs stimulate the growth (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025168/) of new cells (neurogenesis). It is the new cells and the interconnections they forge which provide the therapeutic response. Unfortunately, diazepam and other benzodiazepines (BZDs) impair neurogenesis (Villasana LE (https://pubmed.ncbi.nlm.nih.gov/30794026/), 2019; Boldrini M (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374628/), 2014; Nochi R (https://www.ncbi.nlm.nih.gov/pubmed/23963779), 2013; Sun Y (https://www.ncbi.nlm.nih.gov/pubmed/23639432), 2013; Song J (https://www.kurzweilai.net/how-the-brains-stem-cells-find-out-when-to-make-new-neurons/comment-page-1#comment-96481), 2012; Wu X (http://www.biologicalpsychiatryjournal.com/article/S0006-3223(09)00106-1/abstract), 2009; Stefovska VG (https://www.ncbi.nlm.nih.gov/pubmed/18991352), 2008).

BTW - therapy also works by neurogenesis (https://doi.org/10.1016/j.biopsych.2013.05.017).



The low doses may have been the problem. To initiate and sustain neurogenesis the dose of most serotonergic ADs needs to be high enough to saturate at least 80% (https://pubmed.ncbi.nlm.nih.gov/15121647/) of the serotonin transporters (5-HTT).

Unfortunately, ADs will often make anxiety worse in the beginning. There is no way of preventing this, however, it can usually be minimized by starting at a low dose, no more than a quarter of the recommended minimum therapeutic dose and ramped up slowly by a similar amount every few weeks. Small doses of sedating antihistamines such as hydroxyzine or mirtazapine can help ease the initial anxiety spike too, as may BZDs in the short-term.

Given your experience with SSRIs and clomipramine maybe an AD that targets noradrenaline, aka norepinephrine, reuptake such as nortriptyline might be worth a shot.

Thanks pdu for your insightful reply. The amount of diazepam I was on was relatively low so not sure if this
would affect neurogenesis with the length of time I was on the antidepressants. Tops 5mg
The nortriptyline didn’t suit me at all it made me very dissociated aswell as deer in the headlights syndrome. I definetely
dont think norepinephrine is the answer as Cymbalta had similiar effects.

[panic_down_under]

Thanks pdu for your insightful reply. The amount of diazepam I was on was relatively low so not sure if this would affect neurogenesis with the length of time I was on the antidepressants. Tops 5mg

If taken daily that 5mg mounts up especially given the long diazepam half-life.


The nortriptyline didn’t suit me at all it made me very dissociated aswell as deer in the headlights syndrome. I definetely dont think norepinephrine is the answer as Cymbalta had similiar effects.

How long were you on nortriptyline and at what dose? Disassociation and the 'deer in headlight' feeling are not uncommon when first taking ADs, but it usually passes.

You've been on a lot of different ADs and it is unusual for all to produce completely negative results given the array of different receptor, transporter and neurotransmitter system effected. I wonder how much of the issues were created by the meds and how much by anxiety. An anxious mind is more than capable of producing the most unpleasant side-effects imaginable.

[sparky10]

[QUOTE=panic_down_under;1971566]If taken daily that 5mg mounts up especially given the long diazepam half-life.



How long were you on nortriptyline and at what dose? Disassociation and the 'deer in headlight' feeling are not uncommon when first taking ADs, but it usually passes.

You've been on a lot of different ADs and it is unusual for all to produce completely negative results given the array of different receptor, transporter and neurotransmitter system effected. I wonder how much of the issues were created by the meds and how much by anxiety. An anxious mind is more than capable of producing the most unpleasant side-effects imaginable.[/QUOTE

would 5mg stop the anti-depressant/ anxiety effects being produced though given the time I was on them?

From memory as it’s been a while since I tried nortriptyline it was 10mg/20mg , I know this is a low dose aswell
but I just cannot tolerate higher doses of tricyclics. I would say I tried it for around a month or two. Norephenerine reuptake
medications definetely do not help my conditions.
I do have essential tremor aswell so a lot of meds affect it badly.
i know when I first went on pregabalin it worked a charm and that lowers norephenerine but felt too doped up
after a while so added moclobemide which felt stimulating and they combined well. Unfortunately that’s not the
case now.
like you say with hitting all the the different receptors and neurotransmitters something should have helped, I am
at a loss what to try. Day 3 on doxepin, insomnia/ nightmares and all round spaced out /flat feeling.

[panic_down_under]

From memory as it’s been a while since I tried nortriptyline it was 10mg/20mg , I know this is a low dose as well but I just cannot tolerate higher doses of tricyclics. I would say I tried it for around a month or two.

Unfortunately, the dose never got near the therapeutic minimum. I suspect beyond the initial side-effects most of the problems were driven by anxiety rather than chemical.


Norephenerine reuptake medications definetely do not help my conditions.

You also found clomipramine and imipramine, which have only modest impact on norepinephrine/noradrenaline (NA) pathways, difficult.

What side-effects were there with SSRIs and phenelzine?


Day 3 on doxepin, insomnia/ nightmares and all round spaced out /flat feeling.

Which are common initial side-effects. Unfortunately, there are no side-effects free ADs. While they can be awful meds at the beginning when they work they can almost magically transform lives and worth all the trauma. The trick is to keep focussing on the goal, not the here and now and to keep increasing the dose up to therapeutic levels.

It takes about 10 days for doxepin plasma levels to stabilize to a steady-state. Increasing the dose sooner than 10 days may increase side-effects severity, but delaying increases won't significantly reduce the subsequent intensity no matter how long the delay.

[sparky10]

Unfortunately, the dose never got near the therapeutic minimum. I suspect beyond the initial side-effects most of the problems were driven by anxiety rather than chemical.


You also found clomipramine and imipramine, which have only modest impact on norepinephrine/noradrenaline (NA) pathways, difficult.

What side-effects were there with SSRIs and phenelzine?

The side effects I had with ssri’s is an increase in anxiety and no relief from depression. The anxiety never went down along with
feeling flat on them all the time. Phenelzine gave me no relief from anxiety despite it affecting GABA and also a bad head tremor and shuddering when doing anything physical so I had to discontinue. I wonder if selegeline would be an option?



Which are common initial side-effects. Unfortunately, there are no side-effects free ADs. While they can be awful meds at the beginning when they work they can almost magically transform lives and worth all the trauma. The trick is to keep focussing on the goal, not the here and now and to keep increasing the dose up to therapeutic levels.

This is problem none have ever worked for me so I’m stuck on the medigoround with few options left and a very low quality/ functioning life
unfortunately.

It takes about 10 days for doxepin plasma levels to stabilize to a steady-state. Increasing the dose sooner than 10 days may increase side-effects severity, but delaying increases won't significantly reduce the subsequent intensity no matter how long the delay.

interesting so at the ten day mark is when I should be upping the dosage? I believe 75mg is the therapeutic dose for depression/ anxiety.

[panic_down_under]

interesting so at the ten day mark is when I should be upping the dosage? I believe 75mg is the therapeutic dose for depression/ anxiety.

You should increase the dose as directed by your GP. Biologically, ten days is the earliest the dose should be increased, but taking an extra few days won't matter. However, in terms of side-effects severity there is no advantage in delaying increases. Any subsequent side-effects spike will be about as severe when upping the dose at 10 days as at 100 days.

The usual doxepin dose range for healthy adults is 75-150mg with a maximum of 300mg for severe cases in an inpatient setting. So the first step should be to get to 75mg. Only time will tell if you will need to take a higher dose.

[karenp]

I am 150mg of Doxepin but I read they no longer prescribe it to new patients. Never have a problem getting my prescription. It's been so easy to tolerate compared to Ssri's. It helps me a lot but I still.take Lorazepam 2mg too and now hrt..

[panic_down_under]

I am 150mg of Doxepin but I read they no longer prescribe it to new patients.

Doxepin is now regarded as a sedating antihistamine instead of an antidepressant (AD). Which doesn't mean it doesn't work, but it relies on sedation rather than stimulating neurogenesis which is the mechanism of true ADs (and also cognitive/behavioural/mindfulness therapies).


It's been so easy to tolerate compared to Ssri's.

The tricyclic class ADs (TCAs) tend to have less initial side-effects than SSRIs/SNRIs, but that is often at the expense of more ongoing issues such as constipation and dry mouth. They are also less prone to poop-out.

I can't tolerate SSRIs either, but TCAs have kept my PD under control for 37 years.


It helps me a lot but I still.take Lorazepam 2mg too and now hrt..

Do you take the lorazepam daily, or only as needed?

[karenp]

I take 150mg of Doxepin. It's still available in the UK. It has really helped me the last 6 years but now I am perimenopausal, my anxiety is sky high and I'm not sleeping at all. I need a change of antidepressant I think, and I am on my 5th week of hrt.

[panic_down_under]

I need a change of antidepressant I think, and I am on my 5th week of hrt.

The heightened anxiety might be being driven by the hrt and may settle down, but as doxepin isn't really an antidepressant and may have an uncertain future now might be a good time to switch to another TCA such as amitriptyline, or imipramine.

Once stabilized on an effective AD please talk to your GP about weaning off the lorazepam if you're taking it regularly as benzodiazepines block the mechanism by which AD work.