If you read my earlier post about Venlafaxine (Effexor), you’ll know that it genuinely changed my life. The panic attacks stopped. The anxiety went away. My old, happy self came back. I started singing again, a lot!

What I didn’t mention is what it did to my sleep.

The Unexpected Side Effect

I started Venlafaxine in January of this year, building up slowly from 37.5mg to the target dose of 150mg. By the time I arrived at the full dose, something had shifted. I was falling asleep without any problem, but I was waking constantly throughout the night. Fragmented, unrestorative sleep that left me exhausted regardless of how many hours I spent in bed.

Over eight months, I also gained 10 kilos. For a medication that is actually known to cause weight loss in many people, this was baffling.

More on that in a moment, because what my psychiatrist told me this week turned out to be one of the most fascinating pieces of pharmacological information I’ve come across in my entire medication journey.

The Medication Parade

First, let me walk you through what the past few months have looked like, because I think it’s important for people to know that finding the right sleep solution is rarely straightforward, and that trying and failing medications is not failure. It’s information.

I had been taking Lunivia for about three years. It worked well, until Venlafaxine entered the picture. After starting Venlafaxine, Lunivia stopped doing its job properly. It would knock me out, but it couldn’t keep me asleep. I would wake constantly throughout the night, unable to get the restorative sleep I needed. So my GP and I began the search for something that would work alongside Venlafaxine.

Quviviq (Daridorexant) – a newer sleep medication that works by blocking orexin, the chemical that keeps you awake. It is supposed to restore the natural sleep cycle. The plan was to cross-taper: take Quviviq alongside Lunivia while gradually reducing the Lunivia dose. The first week I took the full 3mg of Lunivia with Quviviq, then dropped to 2mg, then 1mg. Here’s what I noticed: the further I tapered down from Lunivia, the less the Quviviq seemed to be doing. By the time I was completely off Lunivia, Quviviq stopped working altogether. It turned out Quviviq hadn’t really been carrying the sleep on its own, Lunivia had been doing most of the heavy lifting underneath it the whole time.

There was also one alarming episode during this period: I was fully awake, about to get up to go to bed, and when I tried to say something to my husband, nothing came out but gibberish. I tried three times. No coherent sentence. It only happened once, but it was unsettling enough to report to my GP immediately. He attributed it to the complex interaction of multiple medications during the taper period.

Promethazin – this was the worst. Promethazin is an antihistamine with strong sedative properties, and antihistamines and I simply do not get along. I cannot take NyQuil or any medication like it. Medical marijuana affects me badly because of the combination of THC and antihistamine properties – both give me a deeply unpleasant “speediness,” an uncomfortable restless uneasiness that borders on anxiety. Promethazin did exactly the same thing, amplified. I took it for five nights at various doses. Every single night, the same result: hours of an unpleasant twilight state where I was neither properly awake nor asleep. I couldn’t fall asleep, and in the morning I woke up with a horrible headache and a hangover so heavy I literally could not open my eyes properly or drag myself into consciousness. Exhausted despite having been in bed all night. Five nights of this was enough. I went back to my previous medication while we figured out the next step.

In hindsight, if someone had asked me about antihistamine sensitivity before prescribing it, we could have skipped this chapter entirely. Which brings me to something worth mentioning: always tell your doctor about reactions to over-the-counter medications and supplements, not just prescription ones. Those reactions are data.

Amitriptyline – a tricyclic antidepressant sometimes prescribed at low doses for sleep. I tried it one night. My sleep tracker told me everything I needed to know: REM sleep of just 16 minutes, core sleep of 3 hours 36 minutes. Amitriptyline and I were not going to work together.

The Psychiatrist Appointment – The Plot Twist

Yesterday I saw my psychiatrist and discussed both the sleep problems and the weight gain. She said something that stopped me in my tracks.

She raised my Venlafaxine dose from 150mg to 187.5mg, and explained why in terms I hadn’t heard before.

Venlafaxine below 150mg works primarily on serotonin. Above 150mg, it shifts mechanism, what she described as going onto “two tracks” – producing mainly noradrenaline and dopamine instead. This shift does two important things: it makes the medication work more in alignment with how it helps ADHD brains, and it significantly reduces the risk of serotonin-related side effects.

Including, potentially, weight gain.

Here is where it gets interesting: Venlafaxine is actually known to cause weight loss in many patients. But at lower, serotonin-dominant doses, some people experience the opposite, increased appetite and weight gain, because serotonin affects hunger regulation. I may have been sitting at exactly the dose where serotonin dominates, experiencing the serotonin side effects, without getting the full noradrenaline and dopamine benefits.

Raising the dose slightly may shift that balance entirely.

She also prescribed Trimipramin in drop form, a tricyclic antidepressant with sedative properties that she has had good results with in patients also taking Venlafaxine, partly because the reduced serotonin interaction risk at the higher dose makes the combination safer.

Last night was my first night on Trimipramin. 8 drops at 9pm.

Sleep score: 76. REM sleep: 1 hour 44 minutes. Core sleep: 6 hours 11 minutes.

Compare that to Amitriptyline’s 16 minutes of REM.

This morning I woke up slightly tired, but after months of genuinely poor sleep, that’s hardly surprising. The moment I got out of bed, something felt different. I was happy. Full of energy. I did a full hour of yoga without any issues, no pain, no fatigue, no dragging myself through it. The contrast with the Promethazin mornings, where I couldn’t open my eyes and felt like I’d been hit by a bus, could not have been more stark.

It’s one night. I never draw conclusions from one night. But it’s a very promising start.

What I Want You to Take Away

This is the third medication post I’ve written, and I keep coming back to the same theme: the medication landscape for neurodivergent people is complex, under-researched, and deeply individual. What works brilliantly for one person does nothing for another. What causes weight loss in most people caused weight gain in me, because of a dose-dependent mechanism shift that most people are never told about.

The questions worth asking your doctor:

• At what dose does your antidepressant shift its primary mechanism?
• What are the serotonin-specific side effects vs. the noradrenaline/dopamine ones?
• Are your sleep problems potentially related to the serotonin dominance of your current dose?

I am not a doctor and none of this is medical advice. I am someone with a complicated brain and a complicated medication history, sharing what I’ve learned in the hope that someone else’s journey becomes slightly less bewildering.

The sleep chapter isn’t over yet. But for the first time in eight months, last night I got nearly two hours of REM sleep.

I’ll take it. 😊