Which antidepressant is the safest to give with Vyvanse?

[the5thelement]

1. Serotonin Syndrome: Both Vyvanse and sertraline can increase serotonin levels in the brain. When taken together, there may be an increased risk of developing a condition called serotonin syndrome, which is a potentially life-threatening condition that can cause symptoms like confusion, hallucination, seizure, extreme changes in blood pressure, increased heart rate, fever, excessive sweating, shivering or shaking, blurred vision, muscle spasm or stiffness, tremor, incoordination, stomach cramp, nausea, vomiting, and diarrhea.
2. Synergistic CNS Effects: Both drugs affect the central nervous system. Combining them may lead to increased side effects such as jitteriness, nervousness, anxiety, restlessness, and racing thoughts.
3. Heart and Blood Pressure: Vyvanse is a stimulant which can increase heart rate and blood pressure. If combined with sertraline, which can also have effects on heart rate, there might be an increased risk of cardiac issues.
4. Individual Response: The way drugs interact can vary from person to person. Some individuals might tolerate the combination without any noticeable side effects, while others might experience significant issues.

The problem is all the antidepressants, TCAs, SSRIs and SNRIs have "major" interactions . MAOI is out of the question. Only one i can think of is Remeron but even that shows up as a "moderate" interaction.

---

Members don't see this ad.

 

[Stagg737]

Is this a ChatGPT generated list or something?

 

[splik]

Tons of pts are on SSRIs and Vyvanse. I don't think this is an issue. Risk of serotonin toxicity is minimal. Even MAOIs are not an absolute contraindication to amphetamines - some patients do well on this combination but must be used with caution with detailed documentation of risk/benefit calculation. Expert use only. mirtazapine is perfectly fine. TCAs also combine quite well with stimulants.

 

[TexasPhysician]

you mean they don’t have major interactions right? What kind of chatgpt nonsense is this?

 

[calvnandhobbs68]

I’m guessing you’re either new or not in the United States. It takes about 2 days of outpatient to see this combo here. If you’re not in the US I bet it’s the stimulant that’s throwing you off but this is like 25% of my patients.

If you throw these into any med interaction checker it’ll come up with something similar but it’s not a major concern in real life.

 

[annoyedpsychiatrist]

its not uncommon to have comorbid anxiety with ADHD, in the same way its not uncommon to be on an SSRI+vyvanse. not even a slight concern. Ive seen serotonin syndrome 5x in my career and i can promise you it never once involved vyvanse.

 

[mistafab]

Yeah man they are all pretty safe - some more so than others.

The list you have looks like a random bunch of junk, patient-facing info.

 

[DOswag]

Yep, no concerns with most of the antidepressants with vyvanse. Have plenty of patients on various combos of AD with vyvanse. Heck, most things that pop up on my EMR as "major interaction" I barely register anymore.

 

[Merovinge]

If you walk into any child/adolescent psychiatry clinic in the country it would be impossible to go through a day and not see a patient on a combination of an amphetamine class stimulant and an SSRI. Psychostimulants have some of the best long term data of any intervention in the entire field of psychiatry from cradle to grave and there are certainly good reasons for some children and more adolescents to be on SSRIs.

 

[romanticscience]

On this topic, what are people's thoughts about bupropion + stimulant? I've given up fighting patients about the pharmacological redundancy (Wellbutrin is for my DEPRESSION and the stimulant would be for my ADHD!).

There's, of course, no good quality evidence of combo treatment. I've found old literature affirming the safety of tricyclic and methylphenidate, which would likely be more noradrenergic than bupropion. However, I've also found a case report of Wellbutrin + amphetamine = seizure.

I've heard people use low-dose bupropion and check blood pressure.

 

[Stagg737]

On this topic, what are people's thoughts about bupropion + stimulant? I've given up fighting patients about the pharmacological redundancy (Wellbutrin is for my DEPRESSION and the stimulant would be for my ADHD!).

There's, of course, no good quality evidence of combo treatment. I've found old literature affirming the safety of tricyclic and methylphenidate, which would likely be more noradrenergic than bupropion. However, I've also found a case report of Wellbutrin + amphetamine = seizure.

I've heard people use low-dose bupropion and check blood pressure.

I've had a couple patients who took bupropion for depression+ low dose stimulant (Adderall XR 20mg) for ADHD with good efficacy. I inherited them and the wellbutrin was far superior to previous SSRI trials for them but not helpful for ADHD. Were stable on those meds for years and never asked to go up on stimulants. Imo it's all about safety monitoring for those patients.

 

[Merovinge]

On this topic, what are people's thoughts about bupropion + stimulant? I've given up fighting patients about the pharmacological redundancy (Wellbutrin is for my DEPRESSION and the stimulant would be for my ADHD!).

There's, of course, no good quality evidence of combo treatment. I've found old literature affirming the safety of tricyclic and methylphenidate, which would likely be more noradrenergic than bupropion. However, I've also found a case report of Wellbutrin + amphetamine = seizure.

I've heard people use low-dose bupropion and check blood pressure.

I don't think I've ever done that combo, but I don't absolutely hate it in a patient with regular vitals monitoring and no other reason of any kind for increased seizure or cardiac risks.

Now bupropion + Strattera I absolutely have done and feel quite comfortable with.

 

[ObsequiousAplomb]

Yeah, I'm just as fine with bupropion with a stimulant as I am with fluoxetine and a stimulant. It's fine.

 

[annoyedpsychiatrist]

Yeah, I'm just as fine with bupropion with a stimulant as I am with fluoxetine and a stimulant. It's fine.

agreed. not a big deal. The seizure risk in wellbutrin ER is also overstated and not at all common. I just factor in that wellbutrin is a 2d6 inhibitor with regards to dosing of other medications. For ADHD, stimulants>wellbutrin for efficacy but a select few patients appear to respond well in terms of depression with wellbutrin so im not going to fight it.

 

[calvnandhobbs68]

I've had a couple patients who took bupropion for depression+ low dose stimulant (Adderall XR 20mg) for ADHD with good efficacy. I inherited them and the wellbutrin was far superior to previous SSRI trials for them but not helpful for ADHD. Were stable on those meds for years and never asked to go up on stimulants. Imo it's all about safety monitoring for those patients.

Yeah I've also had people show up on it who don't seem to have any issues. Maybe one time I think someone was on wellbutrin and it was the only thing that worked, so we started a low dose stimulant alongside and went up slowly but otherwise I tend not to do it myself or see if someone can come off the wellbutrin but that's probably just my own preference.

 

[Celexa]

agreed. not a big deal. The seizure risk in wellbutrin ER is also overstated and not at all common. I just factor in that wellbutrin is a 2d6 inhibitor with regards to dosing of other medications. For ADHD, stimulants>wellbutrin for efficacy but a select few patients appear to respond well in terms of depression with wellbutrin so im not going to fight it.

I'm fine with this combo but it's because there's no convincing data that at standard prescription doses stimulants increase seizure risk. I wouldn't call the seizure risk from wellbutrin overstated; yes it's uncommon for patients to have a seizure at standard doses, but the therapeutic index is narrow and the risk rapidly escalates with increase doses (toxicology folks see seizures from minor wellbutrin overdoses or accidental overingestions fairly commonly). It's like lithium and kidney damage. The risk is there, but usually the benefits outweigh the risk.

Htn would be the bupropion + stimulant side effect I'd be most concerned would be aggravated by each other, but it's easy to monitor for.

 

[Mad Jack]

A theoretical concern 99% of the time

 

[annoyedpsychiatrist]

I'm fine with this combo but it's because there's no convincing data that at standard prescription doses stimulants increase seizure risk. I wouldn't call the seizure risk from wellbutrin overstated; yes it's uncommon for patients to have a seizure at standard doses, but the therapeutic index is narrow and the risk rapidly escalates with increase doses (toxicology folks see seizures from minor wellbutrin overdoses or accidental overingestions fairly commonly). It's like lithium and kidney damage. The risk is there, but usually the benefits outweigh the risk.

Htn would be the bupropion + stimulant side effect I'd be most concerned would be aggravated by each other, but it's easy to monitor for.

from my research into this the ER formulation seizure risk is significantly lower than the IR formulation risk and ER risk is thought to be less than half a percent, comparable to placebo, at therapeutic doses.

and yeah i used to wonder about stimulants in seizure disorder but never found any convincing data that they were a significant risk increase either.

 

[Ceke2002]

If in doubt you could always try the good old 'start low, go slow'. You'll always get the odd outlier every now and then who has odd reactions, or ticks every warning label box for interactions. That doesn't necessarily mean a certain med combo is bad for everyone. My understand re Serotonin Syndrome as well is that is pretty rare (or at least the 'land you in hospital as an emergency case' type is ). I experienced S/S from a combo of Tramadol and Effexor, ED doc indicated it was the first case he'd seen in his entire career, he had to look it up to even know what he was dealing with. I don't think the risk should be hand waved all together, but I also sometimes think the actual risk can be way overstated due to CYA type issues.

 

[Ironspy]

from my research into this the ER formulation seizure risk is significantly lower than the IR formulation risk and ER risk is thought to be less than half a percent, comparable to placebo, at therapeutic doses.

and yeah i used to wonder about stimulants in seizure disorder but never found any convincing data that they were a significant risk increase either.

This is my understanding as well.

Epileptic Seizures Under Antidepressive Drug Treatment: Systematic Review - PubMed

Antidepressive treatment is rather safe in terms of risk of seizures and also can be generally recommended in the treatment of patients with epilepsy.

pubmed.ncbi.nlm.nih.gov

 

[annoyedpsychiatrist]

If in doubt you could always try the good old 'start low, go slow'. You'll always get the odd outlier every now and then who has odd reactions, or ticks every warning label box for interactions. That doesn't necessarily mean a certain med combo is bad for everyone. My understand re Serotonin Syndrome as well is that is pretty rare (or at least the 'land you in hospital as an emergency case' type is ). I experienced S/S from a combo of Tramadol and Effexor, ED doc indicated it was the first case he'd seen in his entire career, he had to look it up to even know what he was dealing with. I don't think the risk should be hand waved all together, but I also sometimes think the actual risk can be way overstated due to CYA type issues.

true serotonin syndrome is extremely rare, ive only seen 4-5 cases in roughly 6 years. Randomly half have been from effexor, and if i recall the others were just from stupid prescribing

 

[MedMan80]

CAP here, never seen serotonin syndrome. Occasional synergistic effects possible for sure, but more often I see stims causing issues in physically active kiddos re: palpitations and dehydration when it gets hot + sticky out.

 

[VA Hopeful Dr]

true serotonin syndrome is extremely rare, ive only seen 4-5 cases in roughly 6 years. Randomly half have been from effexor, and if i recall the others were just from stupid prescribing

As a non-psychiatrist, every case I've ever seen was from Zyvox plus something serotonergic.

 

[Merovinge]

from my research into this the ER formulation seizure risk is significantly lower than the IR formulation risk and ER risk is thought to be less than half a percent, comparable to placebo, at therapeutic doses.

and yeah i used to wonder about stimulants in seizure disorder but never found any convincing data that they were a significant risk increase either.

Yes always use ER and it's a good medication to have in the arsenal. That said OD on it results in a very high risk of seizure (I've seen this happen probably a dozen+ times in my career already) and there is a very real concern in patient's with active eating disorders (I've already seen seizures seen a few times taken as prescribed). It's somehow both overblown but then not fully recognized enough at the same time, like many topics in psychiatry.

 

[Ceke2002]

true serotonin syndrome is extremely rare, ive only seen 4-5 cases in roughly 6 years. Randomly half have been from effexor, and if i recall the others were just from stupid prescribing

The only legit information I could find on rates of serotonin syndrome in Australia was from self reported data given to the Therapeutic Goods Administration, specifically in regards to Bupropion and SSRI combinations. That was 6 reported cases of serotonin syndrome in a 12 month period, but the reports don't mention if it was mild to moderate cases, or more severe emergency type admissions. I would've hazarded a guess though that when an ED doctor is frantically typing 'what the heck is wrong with my patient' into a hospital search engine, that it's not a condition one comes across on a regular basis.

 

[nexus73]

The only legit information I could find on rates of serotonin syndrome in Australia was from self reported data given to the Therapeutic Goods Administration, specifically in regards to Bupropion and SSRI combinations. That was 6 reported cases of serotonin syndrome in a 12 month period, but the reports don't mention if it was mild to moderate cases, or more severe emergency type admissions. I would've hazarded a guess though that when an ED doctor is frantically typing 'what the heck is wrong with my patient' into a hospital search engine, that it's not a condition one comes across on a regular basis.

in case reports it's also challenging to know if whatever weird constellation of symptoms was actually serotonin syndrome or something else.

 

[Ceke2002]

in case reports it's also challenging to know if whatever weird constellation of symptoms was actually serotonin syndrome or something else.

There was an Australian study done back in 2016 I think, where they sent a simulated patient into a number of different pharmacies to see how well healthcare providers, like Pharmacists, could identify symptoms of potential serotonin syndrome in regards to serotonergic medications. The results were a bit of a mixed bag, with only 35.1% correctly identifying the symptoms presented. To me that makes self reports from healthcare professionals in general more unreliable, and like you said may highlight the challenges between identifying serotonin syndrome or another cluster of symptoms.

Assessment and management of serotonin syndrome in a simulated patient study of Australian community pharmacies

-----------------------------------

Btw, I have spoken about my experience with serotonin syndrome on here before, and I don't really feel like rehashing it on the forum yet again. If anyone is interested; however, you are welcome to message me (with the usual disclaimers of 'not a doctor, can't give professional/medical advice' in place of course).

 

[Stagg737]

I'm a pretty new attending but I've seen 4-5 cases of serotonin syndrome. Every case involved a minimum of 3 serotonergic meds at high doses and often involved additional meds that most PCPs/docs wouldn't even think would contribute much or at all (SGAs, tramadol, adderall, ondansetron, etc).

 

[aim-agm]

I've seen one case in a patient that was abusing dextromethorphan (from cough syrup) and took ~4500 mg of it. Interesting case, in part because they used an extended release formulation so (a) it lasted almost a week, and (b) the release mechanism behaves oddly when you have taken that much so their serotonin symptoms varied greatly even within a space of hours. It didn't help that dextromethorphan is such a complicated drug itself, so the patient remained comatose throughout basically. Poison control said it couldn't be the dextromethorphan, collateral said it happened the last ~8 times the patient took that much cough syrup, although this was the first time they brought the patient to a hospital.

 

[ObsequiousAplomb]

I've seen one case in a patient that was abusing dextromethorphan (from cough syrup) and took ~4500 mg of it. Interesting case, in part because they used an extended release formulation so (a) it lasted almost a week, and (b) the release mechanism behaves oddly when you have taken that much so their serotonin symptoms varied greatly even within a space of hours. It didn't help that dextromethorphan is such a complicated drug itself, so the patient remained comatose throughout basically. Poison control said it couldn't be the dextromethorphan, collateral said it happened the last ~8 times the patient took that much cough syrup, although this was the first time they brought the patient to a hospital.

would that even be serotonin syndrome? I would think that would be in the NMDA-related overdose arena, considering the MOA.

 

[aim-agm]

would that even be serotonin syndrome? I would think that would be in the NMDA-related overdose arena, considering the MOA.

There were likely multiple systems affected that contributed to presentation, but one of them was serotonin toxicity, e.g. hyperthermia and hyperreflexia. One clinical pearl is that you can check for ocular clonus in a comatose patient by provoking the oculocephalic reflex.

 

[milesed]

I've only seen it happen once in my 25 years of doing Child/Adol with someone taking a stimulant. It was from a big combination of meds- Vyvanse, Risperdal, and went to the ER due to vomiting and was given lots of Zofran. He was not aware he had serotonin syndrome, went back two more times to the same ER and kept getting more and more Zofran (making him MUCH worse).

 

[Ceke2002]

I've only seen it happen once in my 25 years of doing Child/Adol with someone taking a stimulant. It was from a big combination of meds- Vyvanse, Risperdal, and went to the ER due to vomiting and was given lots of Zofran. He was not aware he had serotonin syndrome, went back two more times to the same ER and kept getting more and more Zofran (making him MUCH worse).

Did he have any other symptoms? I'm just trying to understand how someone can present to the ER 3 times with what turns out to be serotonin syndrome, and neither they nor medical staff pick up that this might not be simple medication induced nausea? I take it initially presenting mild-moderate cases are a different beast in terms of recognition/diagnosis?

 

[aim-agm]

Did he have any other symptoms? I'm just trying to understand how someone can present to the ER 3 times with what turns out to be serotonin syndrome, and neither they nor medical staff pick up that this might not be simple medication induced nausea? I take it initially presenting mild-moderate cases are a different beast in terms of recognition/diagnosis?

Yes, many of the milder symptoms are non-specific (e.g. a viral gastroenteritis could also present with elevated temperature, tachycardia, N/V, etc.) especially if you don't check reflexes or for labile vitals.

 

[milesed]

Yes, he was lethargic, not talking much, confused, not eating or sleeping--don't remember other specifics. He was usually VERY talkative, hyper, animated, interactive, etc. He and his parents all have lower IQ's so may not have expressed his symptoms well to ER, but I'd known him for 8 years and could really notice the changes from baseline. He also had diarrhea, so I'm guessing they continued to think he had a GI bug.

The same ER had made some really bad mistakes with other patients as well.

 

[Ceke2002]

Yes, many of the milder symptoms are non-specific (e.g. a viral gastroenteritis could also present with elevated temperature, tachycardia, N/V, etc.) especially if you don't check reflexes or for labile vitals.

Thank you. That was very informative. Is it possibly a case of milder serotonin syndrome being more common than is thought, but patients are flying under the radar? And labile vitals, does that refer to things like sudden spikes in temperature and blood pressure? (I know labile blood pressure is when blood pressure quickly rises and then drops back to normal, just curious if labile vitals refers to the same thing).

Yes, he was lethargic, not talking much, confused, not eating or sleeping--don't remember other specifics. He was usually VERY talkative, hyper, animated, interactive, etc. He and his parents all have lower IQ's so may not have expressed his symptoms well to ER, but I'd known him for 8 years and could really notice the changes from baseline. He also had diarrhea, so I'm guessing they continued to think he had a GI bug.

The same ER had made some really bad mistakes with other patients as well.

Sounds like he was lucky to have you in his corner. I can see how seemingly non specific symptoms, perhaps not properly expressed by the patient/family, might be misinterpreted or missed in terms of serotonin syndrome, especially if you don't have a baseline to compare (which you obviously did).

The only experience with serotonin syndrome that I've had was of the full blown emergency variety, so this discussion of the more nuanced cases has been very interesting.

 

[Stagg737]

Thank you. That was very informative. Is it possibly a case of milder serotonin syndrome being more common than is thought, but patients are flying under the radar? And labile vitals, does that refer to things like sudden spikes in temperature and blood pressure? (I know labile blood pressure is when blood pressure quickly rises and then drops back to normal, just curious if labile vitals refers to the same thing).

Yes to both of your questions.

 

[shoomer]

I'm a pretty new attending but I've seen 4-5 cases of serotonin syndrome. Every case involved a minimum of 3 serotonergic meds at high doses and often involved additional meds that most PCPs/docs wouldn't even think would contribute much or at all (SGAs, tramadol, adderall, ondansetron, etc).

I've only seen it happen once in my 25 years of doing Child/Adol with someone taking a stimulant. It was from a big combination of meds- Vyvanse, Risperdal, and went to the ER due to vomiting and was given lots of Zofran. He was not aware he had serotonin syndrome, went back two more times to the same ER and kept getting more and more Zofran (making him MUCH worse).

I'm confused by the literature on this. I've heard about serotonin antagonists possibly contributing to toxicity with a sort of "spillover" effect but upon looking it up further, there are papers that dispute that notion entirely.

 

[Stagg737]

I'm confused by the literature on this. I've heard about serotonin antagonists possibly contributing to toxicity with a sort of "spillover" effect but upon looking it up further, there are papers that dispute that notion entirely.

By themselves I have not seen it, but when a patient is getting 3+ medications that interact with serotonin it can create issues. I'm assuming what you're referring to with the "spillover" effect is adding a 5-HT3 antagonist when combined with other meds can lead to greater activation of 5-HT1 and 5-HT2 receptors through increased serotonin directed there. That's how I learned some of these other meds may contribute to serotonin toxicity and it lines up pretty well with my experiences with serotonin syndrome as well.

 

[Ceke2002]

By themselves I have not seen it, but when a patient is getting 3+ medications that interact with serotonin it can create issues. I'm assuming what you're referring to with the "spillover" effect is adding a 5-HT3 antagonist when combined with other meds can lead to greater activation of 5-HT1 and 5-HT2 receptors through increased serotonin directed there. That's how I learned some of these other meds may contribute to serotonin toxicity and it lines up pretty well with my experiences with serotonin syndrome as well.

Just following on from this (I'm being a curiosity cat here, I know), if, at least according to the studies/articles I can access, MDMA effects the 5-HT receptors then why do the effects of MDMA tend to be blocked when someone is taking an SSRI, as opposed to just triggering potential serotonin syndrome? Both drugs effect serotonin release, so why does stacking them cause one to have its effects blocked, instead of just sending the person into serotonin syndrome? I would have thought something like MDMA was more serotonergic than something like Vyvanse, which as far as I know is Dexamphetamine with a different name and different release rate (?).

 

[Stagg737]

Just following on from this (I'm being a curiosity cat here, I know), if, at least according to the studies/articles I can access, MDMA effects the 5-HT receptors then why do the effects of MDMA tend to be blocked when someone is taking an SSRI, as opposed to just triggering potential serotonin syndrome? Both drugs effect serotonin release, so why does stacking them cause one to have its effects blocked, instead of just sending the person into serotonin syndrome? I would have thought something like MDMA was more serotonergic than something like Vyvanse, which as far as I know is Dexamphetamine with a different name and different release rate (?).

I'm not sure where you're reading that, but MDMA has effects as an MAOI and can absolutely contribute to serotonin syndrome to the point that mild serotonin syndrome symptoms are fairly common according to some studies, especially when combined with other serotonergic meds like SSRIs.

As to why the "high" gets blunted, the hypothesis I've seen probably has to do with the downregulation of post-synaptic receptors that comes from being on SSRI/SNRI medications. I'd guess that if someone had just started an SSRI/SNRI for the first time or was on a dose low enough to avoid down-regulation of post-synaptic receptors, then MDMA probably would still lead to a high for at least the first few days to weeks. There's been some studies with mouse/rat models which seem to support this, but there's probably also more to it on a molecular level involved. Here's a paper with a decent explanation of the theory in the discussion if you can access it:

RETRACTED ARTICLE: Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy - Psychopharmacology

Rationale MDMA-assisted psychotherapy is under investigation as a novel treatment for posttraumatic stress disorder (PTSD). The primary mechanism of action of MDMA involves the same reuptake transporters targeted by antidepressant medications commonly prescribed for PTSD. Objectives Data were...

link.springer.com

 

[Ceke2002]

I'm not sure where you're reading that, but MDMA has effects as an MAOI and can absolutely contribute to serotonin syndrome to the point that mild serotonin syndrome symptoms are fairly common according to some studies, especially when combined with other serotonergic meds like SSRIs.

As to why the "high" gets blunted, the hypothesis I've seen probably has to do with the downregulation of post-synaptic receptors that comes from being on SSRI/SNRI medications. I'd guess that if someone had just started an SSRI/SNRI for the first time or was on a dose low enough to avoid down-regulation of post-synaptic receptors, then MDMA probably would still lead to a high for at least the first few days to weeks. There's been some studies with mouse/rat models which seem to support this, but there's probably also more to it on a molecular level involved. Here's a paper with a decent explanation of the theory in the discussion if you can access it:

RETRACTED ARTICLE: Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy - Psychopharmacology

Rationale MDMA-assisted psychotherapy is under investigation as a novel treatment for posttraumatic stress disorder (PTSD). The primary mechanism of action of MDMA involves the same reuptake transporters targeted by antidepressant medications commonly prescribed for PTSD. Objectives Data were...

link.springer.com

Thank you. I feel like I should have already known this, but of course the side effects of MDMA could constitute a form of mild serotonin syndrome (nausea, vomiting, jaw shaking and grinding, shudder vision, etc). Thanks for that paper as well, I can access it and will read it a bit later on.