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Hi Everyone! A friend of my recommended this site where l hope to get some support. For 2years ago around the covid l collapsed mentaly and the Anafranil l used to take did not worked anymore. After that my doc tried 10different antidepressants (ssri ssrn etc) none of those seemd to work. I feltbso bad that l spent 4week in a mental clinic where they described my Parnassan (10mg in the evening) Agomelatin (50mg in the evening) Lamolep (100mg in the evening), but somehow l dont feel better. At the moment my anxiety is that strong that l had to take Frontin (benzo) 0,25mg to calm down. I am so fed up this meds those are poisoning me l am sure. I dont know what to do, how to start getting off them. l take also some supplements like magnesium, omega3, copper, zinc, b complex, probiotics l would appreciate some support! thank you

Posting on behalf of my partner who I am caring for through withdrawal and tapering. He is not in a good place to be on the internet much currently but we have questions and still need support, so I am posting for him (hope that's okay). Anytime I say "we", I am referring to my partner and I as we've discussed and strategized together. Longer-form version of his drug history: 2008-2012: Fluoxetine for 4 years during high school Doesn't remember exact dose but likely 10mg Had a really easy time discontinuing in 2012 when he wanted to stop taking it. Doesn't remember if he stopped cold turkey or did any kind of taper at the time 2016: Fluoxetine 20mg for a few months, around age 21 Remember it being easy to start without bad symptoms from updosing Was experiencing sexual side effects and stopped cold turkey Remembers it being "medium" difficult to stop. Mostly some increased depression for a period after stopping, but nothing close to what he is going through right now with citalopram 2018-2020: Began citalopram 20mg for depression and anxiety after difficult life events. Wanted to avoid fluoxetine due to sexual side effects Severe depression as side effect from updosing when originally starting. Remembers it being about a month of the worst depression he had ever felt up to that point, worse than the depression that led him to take it in the first place. Then was at 20mg for a few years after stabilizing Jan - Mar 2020: Was feeling happy, wanted to discontinue citalopram. Psychiatrist said the 20mg dose was so low that he could just stop cold turkey, but that he could do a few cut and holds if he wanted to be extra cautious. After cutting to 15mg, was feeling agitated for months Mar 2020 - Jul 2023: Decided to reinstate the 20mg citalopram and micro-taper Got liquid form of citalopram and tapered from 20mg -> 5mg over a few years, with some holds along the way Mar 2023: Began feeling regularly agitated. This was around the time of an injury and some other difficult life circumstances that challenged his mental health routine, so he thought maybe he needed a higher dose. Bumped up to citalopram 7mg all at once Jul 2023: Was still feeling regularly agitated. (In retrospect, we're pretty confident the agitation beginning in mar 2023 was poop-out) Bumped up to citalopram 10mg all at once This bump up was severely destabilizing. Began experiencing panic attacks, chest pain, and higher anxiety (had never had panic attacks or chest pain from anxiety before in his life, so these were brand new as a result of the updose). Started taking hydroxyzine 25mg or 12.5mg regularly as needed to manage the heightened anxiety, and propranolol 10mg or 5mg very occasionally as needed to prevent/manage panic attacks Determined the citalopram had probably been pooping out before bumping up. Made a plan with psychiatrist to switch to fluoxetine in the short-term to get off the citalopram, and then eventually taper off the fluoxetine since he had gentler reactions to fluoxetine in the past when starting & stopping Plan was to make the switch in January 2024 - this was due to some planned life events that made it inconvenient to switch sooner, and because the poop-out symptoms seemed somewhat manageable in the short term Around November-December, the poop-out symptoms were worsening again and we determined he needed to make the switch sooner Psychiatrist was concerned about serotonin syndrome and did not want him to take fluoxetine and citalopram simultaneously. Instead they wanted him to do a clean switch, taking 10mg citalopram one day and then fully switching over to 10mg fluoxetine the next day (with 0 citalopram from that point on) Dec 21 - 25 2023: Began the "clean switch" Began feeling some moderate withdrawal symptoms after a couple of days By Dec 25 the withdrawal became severe, both physically and mentally. During a peak wave of uncontrollable shivers, headache, nausea, chest pain, insomnia, severe anxiety and depression we decided to reinstate 2mg citalopram. Within an hour of reinstating the worst of the physical symptoms had significantly lessened - especially the shivers, headache, and nausea. The anxiety and depression also lessened. Dec 26 2023 - present: Have been taking 2mg citalopram (1mg morning and 1mg nighttime), 10mg fluoxetine Taking 25mg or 12.5mg hydroxyzine as needed, generally totaling about 37.5-75mg daily depending on the day Also taking 0.125-0.5mg lorazepam occasionally as needed, not every day. Has been about a few days per week. From Dec 26-Jan 2, it seemed like things were improving. We starting tracking FINISH a few times a day and he was doing better than he had been at the peak waves before we reinstated the citalopram. But since January, most of the withdrawal symptoms have plateaued. The physical symptoms have improved a lot: headache and nausea are almost nonexistant now, and dizziness has steadied at a low-medium level. But ever since those lessened, he has been having more insomnia, and constant and severe anxiety daily, accompanied with chest pain and stomach pain, and occasionally a more severe bout of panic. This has also begun being accompanied with increasing depression, often at the same time as waves of panic or severe anxiety. The depression is increasing day by day from the despair and exhaustion from the prolonged physical and mental pain with no improvement on any of the withdrawal over the last two weeks. For the first time in his life, this has brought on questions of his will to keep on trying during his worst waves. He is running out of steam and feeling very scared and demoralized. Our immediate goal: We want to try to get him stable on 2mg citalopram in the short-to-medium term (from there, we will begin a very slow micro-taper from the citalopram, but for now we are just struggling to stabilize). This is complicated by the fact that the citalopram has been pooping out since Mar 2023, which may also be contributing to the plateau in any improvement on the withdrawal symptoms. We're trying to use strategies other than drugs as much as we can. We are both taking medical leave. We're being strict about our bedtime routine, eating extremely healthy with tons of fruits and veggies daily and little-to-no processed foods, getting out for two walks outside daily, meditating 1-2 times daily, doing yoga at home, avoiding stressful or over-stimulating activities. We are visiting his family until things improve, for extra help with care and morale. These things are making a difference, but even with them we are in the current state. We don't want to increase the citalopram any more, (a) because he seems to have a severe kindling effect from any dose changes to citalopram and (b) because it's pooping out so updosing may not do much to help anyways, even in the short-term He would like to increase his fluoxetine dose to 20mg to help stabilize, provide some relief on the sooner side for the anxiety and depression, and hopefully continue to help with some symptom relief when he eventually tapers off of citalopram. We know that he's had a gentler reaction to fluoxetine starting & stopping in the past, which we feel makes it an okay strategy for him to use as an intermediate step. We're also hoping increasing the fluoxetine can allow us to eliminate the lorazepam sooner - although he isn't taking it daily, we know it is highly habit-forming and would like to remove it before anything else. But in his current state, it's the only thing that has been able to get him through his worst waves. Our primary question-area for now (we'll probably have more later): We're trying to figure out how to updose the fluoxetine, assuming that we do. What we're considering: All-at-once updose to 20mg pros: get it over with; less time spent going through any updosing effects after getting past updosing effects, will get to any relief it provides sooner cons: could be very destabilizing updose very slowly, basically a micro-increase pros: likely less destabilizing if it ends up providing some therapeutic effect at a dose lower than 20, he could stop there at a lower dose cons: if there are still some negative effects to updosing, those would be drawn out over a long period of time likely will take longer to get a therapeutic effect from the drug to get relief from the citalopram withdrawal/poop-out. in the meantime, his anxiety and depression is already severe and worsening day by day rather than improving middle ground?? target 20mg, but updose over a few weeks by 0.5mg/day or similar pros: maybe still less destabilizing than the all at once updose? still get to some therapeutic effect sooner than the micro-increase version cons: could still end up being destabilizing, and then just prolong the destabilized period Questions: In your experience, does kindling tend to be specific per drug, or have you tended to find that when somebody develops a kindling reaction to one drug, they also begin to have kindling reactions to other psychiatric drugs including those that they haven't had severe reactions to in the past? We have read the reinstatement advice which says that increasing a dose after reinstatement should be extremely cautious and slow due to the likely kindling effect. But are there any general patterns or learnings around how best to increase dosage of a medicine in general, when not referring to a drug that you're already hypersensitive to? Any other advice on stabilizing for his particular situation?

Pharmacol Res. 2018 Oct 29. pii: S1043-6618(18)31201-5. doi: 10.1016/j.phrs.2018.10.025. [Epub ahead of print] The Emergence of loss of efficacy during Antidepressant Drug Treatment for Major Depressive Disorder: An Integrative Review of Evidence, Mechanisms, and Clinical Implications. Fornaro M1, Anastasia A2, Novello S3, Fusco A4, Pariano R5, De Berardis D6, Solmi M7, Veronese N8, Stubbs B9, Vieta E10, Berk M11, de Bartolomeis A12, Carvalho AF13. Abstract at https://www.ncbi.nlm.nih.gov/pubmed/30385364 The re-emergence (i.e. 'breakthrough') of depressive symptoms despite maintenance treatment of depression with antidepressant drugs is a complex clinical phenomenon referred to as tolerance. Herein we critically appraise evidence from both pre-clinical and clinical studies, focusing on putative mechanisms as well as clinical correlates and implications of the emergence tolerance during antidepressant treatment for major depressive disorder (MDD). It is firstly unclear to what extent this phenotype reflects a pharmacological effect of an antidepressant, is driven by non-adherence, is a marker of latent bipolarity or another comorbidity, a marker of neuroprogression of the underlying disorder or the intrusion of the impact of psychosocial variables into the clinical course. The operational definitions of tolerance and its related phenomena have also been largely inconsistent. Several protective clinical indicators have been proposed, including a rapid-cycling course and comorbid chronic anxiety, whilst poor treatment adherence, proneness to emotional blunting and sub-threshold bipolarity have been identified as possible correlates of tolerance to antidepressant treatment in MDD. Putative neurobiological underpinnings include adaptations in the hypothalamic-pituitary-adrenal (HPA) axis and the serotonergic system. Due to the clinical and diagnostic challenges imposed by the emergence of tolerance to antidepressants, there is an urgent need for upcoming international guidelines to reach a consensus on operational definitions for this complex clinical phenomenon, thus enabling a more precise appreciation of the incidence and correlates of tolerance to antidepressants. Taken together, the present review underscores the need to cautiously weight benefits and risks prior to considering long-term antidepressant treatment for patients with MDD as tolerance may emerge in a subset of patients.