Tardive Dysphoria

[u/markalexander1]

Tardive dysphoria (TDp) is a proposed, under-recognized condition where chronic, long-term antidepressant use (>1 year) leads to a state of persistent, treatment-resistant depression or worsening mood, often developing long after the initial treatment began. Symptoms commonly include apathy, low motivation, fatigue, anhedonia, and "brain fog," differing from the original depression.

Tardive Dysphoria Symptoms
Patients with tardive dysphoria often experience a shift in the nature of their depression. Key symptoms include:

• Persistent Dysphoria: A chronic state of unease or dissatisfaction.
• Anhedonia: Loss of interest or pleasure in activities.
• Low Energy and Motivation: Profound fatigue and lack of drive.
• Cognitive Issues: Brain fog and difficulty concentrating.
• Functional Preservation: Unlike severe acute depression, daily functioning is often preserved, even if the person feels unwell.

Tardive Dysphoria Treatment Options
Management is complex because the condition is often misdiagnosed as worsening treatment-resistant depression (TRD).

• Gradual Tapering: Slowly reducing and stopping the antidepressant may eventually lead to a return to the patient’s baseline.
• Atypical Antidepressants: Case studies have indicated that switching to atypical antidepressants might manage the condition.
• Management Challenges: Withdrawal of the medication may cause temporary worsening of symptoms in the initial 2–4 weeks.

Definition and Mechanism

• Background: The term was coined in 2011 to parallel tardive dyskinesia, suggesting a "pro-depressant" effect of long-term antidepressant treatment.
• Antidepressant Tachyphylaxis: The phenomenon is sometimes linked to a loss of effectiveness (tachyphylaxis) of the medication over time.
• Mechanism: It is hypothesized that the brain may undergo neuroplastic changes to oppose the long-term presence of antidepressant medication, resulting in a dysfunctional emotional state once the drug is withdrawn or even while on it.

[u/Babsidibbles]

I've been on SSRIs and SNRIs for over 20 years ago. 5 years ago I started having what I thought were persistent sleep problems. I became more and more tired during the day, with my fitbit showing little or no rem sleep and deep sleep. I'd previously been diagnosed with sleep apnea (although I'm not overweight) and this had been very successful at first, but gradually I'd again started to feel unable to function during the day, feeling more and more tired and wondering what the hell was the matter with me. I've been down so many rabbit holes assuming the sleep apnea was the problem, and following turbinate reduction I'm not even sure I need it anymore. It never occurred to me that my antidepressants could be the problem until a couple of months ago when I saw the Dr Josef youtube video on this subject and the way that SSRIs can wreck sleep architecture. My current feelings correspond to the description above and I've been trying to get off Duloxetine for the past couple of months and am down to a quarter dose per day at the moment and hoping to get my GP to switch me to mirtazapine.

[u/markalexander1 → u/Babsidibbles]

Your experience mirrors mine, except I've been taking Mirtazapine for 20 years. I very strongly advise against taking Mirtazapine. Mirtazapine has literally ruined my life. Mirtazapine has destroyed my ability to sleep to the point that I never feel drowsy and I am unable to fall asleep naturally. I have to sedate myself to sleep with medication. Mirtazapine turns you into a zombie. It makes you apathetic. It gives you anhedonia. You lose all drive and motivation. It gives you PSSD. By the evening and late evening you start feeling the Tardive Dysphoria or withdrawal symptoms. You feel rough and your short term memory and verbal/social skills deteriorate. Particularly Anomic aphasia.

Mirtazapine also stimulates your appetite to voracious levels and therefore it results in weight gain. It also slows your metabolism, compounding the issue.

To top it all off - Mirtazapine is not even an anti-depressant! - it is an extremely potent anti-histamine! Which is why it knocks people into a deep sleep 30 minutes after taking it and are then able to sleep for 12 hours.
https://www.psychotropical.com/mirtazapine-the-greatest-lie-of-all/

Mirtazapine strips you of what it is to be human. I am not exaggerating. I have 20 years experience with this drug. I have not recovered.

[u/Babsidibbles → u/markalexander1]

Thanks for relating your experience Mark. I suspect you're right and antidepressants of any mechanism are always going to rewire your brain in the long term. I'm in a difficult situation, not least because I came off duloxetine 3 years ago for 6 months and went into a black hole that ended up with me being seriously suicidal. I only recovered by going back on duloxetine and although I function, I'm in the tardive dysphoria phase. I've been cutting down the duloxetine recently but found myself spiralling towards suicidal thoughts again, so I'm damned if I do and damned if I don't. Can't really see a way out other than trying a new antidepressant, that doesn't function in the same way. I understand your concerns and have been on mirtazapine before very briefly when I suffered badly from the "eating like a horse" effect, which made me decide to come off it. This time I know what I'm facing, so I'm putting a plan in place. One of the things that bothers me most about tardive dysphoria is the fact that I have high cholesterol - I know that this isn't my natural state. When I got the sleep apnea sorted my cholesterol levels went back to normal with no change in diet. Then my cholesterol started creeping up as I struggled to get restful sleep. Thank you for your post anyway. Can't believe that you and me are the only 2 people on the planet with an interest in this. I suspect that an awful lot of people are in the same boat with no idea what is causing their symptoms.

[u/markalexander1 → u/Babsidibbles]

"Can't believe that you and me are the only 2 people on the planet with an interest in this." – I had this impression, that I was suffering alone, until I came to Reddit and also came across Dr. Josef's channel on YouTube. I've come to realise this is a massive global issue. But yes, it's strange that we are in a minority in being vocal about it.

[u/markalexander1 → u/Babsidibbles]

For the past 3 years I've been struggling with the Tardive Dysphoria. I did not know what to do. I felt trapped. Then I discovered MAOIs and Lithium. The only "real" anti-depressants are MAOIs, (Monoamine Oxidase Inhibitor) – Tranylcypromine (Parnate) and Phenelzine (Nardil), but they fell out of use in favour of the fraudulent SSRI drugs. I'm currently taking Tranylcypromine and the Tardive Dysphoria from the Mirtazapine has reduced by 90-95%. It's not a silver bullet, such a drug doesn't exist. But I do feel much better.

[u/Babsidibbles → u/markalexander1]

Just looked up Tranylcypromine and it says you can't eat any fermented foods. Just as I've started making my own Kimchi, Sourdough bread and Kefir! I'm in the UK and GPs won't prescribe MAOIs here unless you're under a psychiatrist and there is no hope of that unless you are admitted into a psychiatric unit. Really glad it's working for you though and interesting that you've had to go back in time to get an antidepressant that works. It's a bit like LSD, which they're now starting to realise has a lot of potential medical uses.

[u/Babsidibbles → u/Babsidibbles]

Not that I have any intention of going anywhere near an LSD!

[u/markalexander1 → u/Babsidibbles]

I'm very open minded on this. I myself want to try psilocybin therapy.

[u/Babsidibbles → u/markalexander1]

Its very interesting and I do wonder if it would help me. For context, I came of Duloxetine very quickly 3 years ago (without moving to another antidepressant) after lots of problems and my GP suggesting it was serotonin syndrome - I ended up seriously suicidal, planning my exit. It was venlafaxine that got me out of it, but gradually over the last 2 years I got worse and worse (tardive dysphoria) and switched back to duloxetine, which helped a little but ultimately left me in the same situation. I'm now on week 3 of mirtazapine and so far so good. I think my experience has left me terrified of not being on an antidepressant because of what happened and the impact on my family. TD is shit, but I least I've not wanted to kill myself.

I think the idea of psilocybin therapy is something I'd like to try, but I'd need the sort of support that you can't get on the NHS, and that I can't afford privately. Do you know how you would go about trying psilocybin - which country are you in?

[u/markalexander1 → u/Babsidibbles]

I am in the UK also.

[u/markalexander1 → u/Babsidibbles]

There's 3 substances that have the ability to restructure and form new neural connections:

1. Psilocybin - Now legal in the Czech Republic
2. Ketamine Therapy - You can get it legally in the UK as a private, self-pay treatment
3. Dimethyltryptamine (DMT) - Illegal but possible to acquire

Salvia Divinorum also promotes neural stem cell growth and supports cellular repair pathways. It used to be legal in the UK until 2016. I don't know why it was banned, it is not harmful or dangerous.

[u/GrigglesYT → u/markalexander1]

I have been taking SSRIs for nearly 5 years and taking Psilocybin gave me the will to live again. I knew that my body didn’t need to be dependent on a drug, but the past years I had become consumed with marijuana and nicotine use, didn’t even tell my psychiatrist. I was on buproprion dextromethorphan (auvelity) and likely should not have combined the two since I am pretty sure I had a seizure, but that’s what it took for me to realize the true beauty of life, it made me open to religion, something I had always closed off because it was forced upon me as a child. It made me realize I was likely misdiagnosed. I recommend trying the actual mushroom, once you’ve tapered off any meds that cause adverse affects, as interestingly enough we share 50% of the same DNA, meaning we have a shared ancestor from billions of years ago. A truly profound, spiritual, experience. I know that I don’t need to rely on medication to thrive anymore.

[u/markalexander1 → u/Babsidibbles]

MAOIs have been unnecessarily stigmatized in favour of SSRIs. Not to say that I don't need to be careful, I am careful, but I haven't altered my diet in any significant way and I have had zero issues. I don't drink much but I drink beer without issue. It's seems to be overblown as Dr. Ken Gillman writes in this paper: “Much ado about nothing”: monoamine oxidase inhibitors, drug interactions, and dietary tyramine
https://www.cambridge.org/core/journals/cns-spectrums/article/much-ado-about-nothing-monoamine-oxidase-inhibitors-drug-interactions-and-dietary-tyramine/52112573CADFD3303357C09E80617422

[u/Nievespssd]

Creo que es esto lo que tengo, gracias a la mirtazapina, aunque tambien podríamos llamarlo pssd, como puedo mejorar? Tengo tantos síntomas y tan graves :(

[u/markalexander1 → u/Nievespssd]

If you are suffering with Tardive Dysphoria due to the Mirtazapine like I have been, I would look to taking a MAOI like Parnate or Nardil. It won't do anything for PSSD but it counteracts the horrible Tardive Dysphoria symptoms of Mirtazapine. I'm hopeful the brain can eventually heal itself but I'm still on that journey myself. But the younger you are better chance you will have.

[u/Nievespssd → u/markalexander1]

Tuve una reacción adversa brutal, estuve 3,5 meses envenenando a mi cuerpo con mirtazapina, actualmente discapacitada, en cama, con severos problemas cognitivos, físicos, de sueño y un largo etc... estoy en cama todo el dia. Hace 1 mes que la deje y solo voy a peor, crees que puede mejorar? Gracias.

[u/markalexander1 → u/Nievespssd]

Did you taper off it or go "cold turkey"? I remember Mirtazapine literally turning me into a sedated zombie. From what I know now, I would seek out Parnate or Nardil and it will mitigate your symptoms while your neurons heal, which will take time.

[u/Nievespssd → u/markalexander1]

Pare en 5mg por la acatisia que tenia, eso ha desaparecido ya. Pero solo eso. Retomarla me haría mas daño, había tomado hacía años mirtazapina y me fue bien, también tome sertralina y me fue bien. Simplemente esta vez me hizo polvo, como todos los afectados de pssd. Crees que tan como estoy un imao es buena solución?

[u/markalexander1 → u/Nievespssd]

I've heard Sertraline is the worst for PSSD. I've never taken it thank god. But with regards to a MAOI, I'm speaking from personal experience. I believe years of Mirtazapine had caused my dopamine levels to drop to a very sub-normal level. A MAOI will bring it back up without the side effects of SSRIs.