Stagg737

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So I've had a few VA patients lately who have been a bit unique in terms of medications and was hoping to get some input on people's experience with Cyproheptadine, as I have some questions about it that my supervising attending hasn't been able to answer (overall he's great, but just doesn't use Cyproheptadine and admits he doesn't really know a lot about it).

First patient is more straightforward, 30-something yo m with PTSD and insomnia 2/2 severe nightmares. Prazosin did nothing and Trazodone made nightmares worse. Started him on 4mg cypro and nightmares decreased from multiple per night to 2-3 nights per week. Have increased the dose to 8mg and patient reports sleep is far better, but still only getting 4-5 hours and then he's wide awake and having some ongoing daytime symptoms (mostly sleepiness in the afternoon). I'm curious if increasing the dose a bit to 12-16mg may be helpful with maintaining sleep a bit longer and if there's dose-dependent sedative effects.

Second patient is much more interesting, 25 yo m with MDD and PTSD with primary symptom of irritability/lability who is super sensitive to medications. Had trialed him on 3-4 different antidepressants all of which were discontinued d/t side effects and finally landed on Duloxetine 60mg which has been his miracle drug (per patient and wife). Problem is patient has had unusual sexual side effect of anorgasmia and anejaculation without any impact on his erection (able to achieve and maintain easily without problems).
Decreased dose to 40mg which is still effective for mood, but no difference in sexual side effects. Trialed him on Wellbutrin to mitigate side effects and had extreme agitation. Had previously tried Trazodone and Mirtazapine for sleep both of which he could not tolerate (Traz made him feel hungover until noon and Mirt. knocked him out until noon and made him totally non-functional the rest of the day). Consulted Urology who suggested stopping Duloxetine or psycho-sexual therapy (not available in this area). I've done some research and apparently there's some evidence for Cyproheptadine to mitigate anorgasmia as well as Buspar, but is pretty weak. Also talked to one attending who has used sildenafil for anorgasmia even with no erectile problems and was effective for some.

I've inherited a few other patients who are on Cyproheptadine for nightmares and swear by it, but I hadn't really encountered it in the past other than the one or two SS patients I saw on consults. I'm interested in hearing if anyone has used Cyproheptadine or would have other recommendations before this for the second patient. Also interested on hearing general thoughts on Cyproheptadine for nightmares or other psychiatric uses.
 

nexus73

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I’ve tried it on a few patients for sexual side effects without benefit. But it’s a simple intervention to try and if it works, great!
 
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clausewitz2

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I have only used cypro for a) children who need their stimulant like some people need Jesus but who also were losing weight, at the direction of CAP attendings and b) for someone with a history of AN who had developed a very poor appetite and was terrified of slipping back into restricting. It was...fine, I guess for the kiddos and semi-miraculous for the later.

Sildenafil usually works pretty well for SRI related sexual dysfunction in men and women actually.
 
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cj03

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How about buspirone for the sexual dysfunction? Some lower level evidence, but worth a shot since it's pretty well-tolerated as long as you titrate it slowly.
 

SourceOfDenial

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I have only used cypro for a) children who need their stimulant like some people need Jesus but who also were losing weight, at the direction of CAP attendings and b) for someone with a history of AN who had developed a very poor appetite and was terrified of slipping back into restricting. It was...fine, I guess for the kiddos and semi-miraculous for the later.

Sildenafil usually works pretty well for SRI related sexual dysfunction in men and women actually.
Sometimes I run into psychiatrists who seem terrified/refuse to rx sildenafil. What gives?
 

clozareal

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Make sure you get a prolactin level because most SSRI/SNRIs can cause elevated prolactin levels. If it's elevated, can try to use a low dose of aripiprazole to normalize prolactin and improve sexual function. Of course, you can wait for spontaneous remission to occur for up to 6 months.

For appetite, I prefer mirtazapine over cyproheptadine because cyproheptadine is antiserotonergic and can counter the effects of the SSRI that I'm prescribing. I've had a patient who went from doing not that great to worse in terms of depression after the PCP started cyproheptadine for low appetite. From what I've read in the literature, there is no dose-related effect of antihistamine for insomnia (which mainly treats middle insomnia) but rather the efficacy of antihistamines on sleep goes away with time from continued use.

I haven't used cyproheptadine for nightmares. I've had moderately good success with prazosin and clonidine for nightmares and was told by an attending in a PTSD clinic at the VA never to use trazodone for nightmares because it worsens nightmares in 1 out of 10 people. If he's still waking up in the middle of the night, I would try a brisk course of CBT-I including sleep restriction before increasing the dose of cyproheptadine any more.

All of the recommendations for treatment of SSRI induced sexual dysfunction are going to have low quality evidence because there's just not enough studies on this. I've heard of using methylphenidate (30-60 minutes before sexual activity), amantadine (for at least 2 days continuously before sexual activity), and nefazodone (≥60 mins before sexual activity or as a standing adjunct) for treating SSRI-induced sexual dysfunction (anorgasmia) when the other options for anorgasmia (trazodone, mirtazapine, bupropion) fail, but haven't tried any of those. If you are really adventurous, you can also consider bromocriptine. I've heard of loratadine and yohimbine as well and even though the evidence is poor, the risk is pretty low, so why not. Selegiline was negative in an RCT to treat sexual dysfunction so I wouldn't bother.
 
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SourceOfDenial

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We give people diabetes all the time, and we refuse to use something well tolerated by many millions of people because of an extremely rare potential side effect?
I thought they were referencing going blind from masturbating...and deaf from sex?
 
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We give people diabetes all the time, and we refuse to use something well tolerated by many millions of people because of an extremely rare potential side effect?
I thought they were referencing going blind from masturbating...and deaf from sex?

when you have this unfortunate complication with one of your patients and you significantly damage a patients eyesight in order to help him increase his sex life, you too might reconsider the risk/benefits. At the end of the day it’s up to the patient but for many patients sex is not worth their eye sight. I do not support a blanket refusal on any medication but a thorough discussion of the risks and benefits. Giving patients diabetes from antipsychotics when they are psychotic or extremely depressed is a different set of calculations in my opinion but you should also not be cavalier with any medication.
 

Merovinge

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I have only used cypro for a) children who need their stimulant like some people need Jesus but who also were losing weight, at the direction of CAP attendings

I never learned this is fellowship, but have a few patients on it as an attending and have been moderately impressed as well. Has the added benefit of helping with sleep and headaches, creating a holy trinity type treatment for children who need to gain weight, sleep better, and have recurrent headaches (not atypical of some ADHD kids). Reminds me of imipramine in children with bed wetting, ADHD, and OCD where a single treatment can make you look divine.
 
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SourceOfDenial

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when you have this unfortunate complication with one of your patients and you significantly damage a patients eyesight in order to help him increase his sex life, you too might reconsider the risk/benefits. At the end of the day it’s up to the patient but for many patients sex is not worth their eye sight. I do not support a blanket refusal on any medication but a thorough discussion of the risks and benefits. Giving patients diabetes from antipsychotics when they are psychotic or extremely depressed is a different set of calculations in my opinion but you should also not be cavalier with any medication.
I’m sorry this patient has this complication and sorry you have been so impacted by it—I hope you were able to get the support needed to help process what happened.
 

Stagg737

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Sildenafil usually works pretty well for SRI related sexual dysfunction in men and women actually.

An attending I talked to yesterday said he's had some success in men with it. Interesting that it has positive outcomes in women though. Any idea of the proposed MOA for this?

How about buspirone for the sexual dysfunction? Some lower level evidence, but worth a shot since it's pretty well-tolerated as long as you titrate it slowly.

Patient prefers not to add another scheduled med, but certainly something I'm considering.

There are a bunch of options for SSRI induced anorgasmia, including amantadine, loratadine, and yohimbine. I don't think evidence for any of them is fantastic but if one doesn't work, try another.


I've seen those as well as a few others in reading (midodrine, pseudo/ephedrine, and apomorphine) but haven't seen that article yet. Will have to read that later.

Make sure you get a prolactin level because most SSRI/SNRIs can cause elevated prolactin levels. If it's elevated, can try to use a low dose of aripiprazole to normalize prolactin and improve sexual function. Of course, you can wait for spontaneous remission to occur for up to 6 months.

Interesting thought, was trying to avoid abilify because of his reaction with other dopaminergic meds (mainly wellbutrin), but will definitely talk to him about getting a prolactin level at the next appointment.

For appetite, I prefer mirtazapine over cyproheptadine because cyproheptadine is antiserotonergic and can counter the effects of the SSRI that I'm prescribing.

Fair, but I'm not overly concerned about potentially trying 1-2mg of Cypro to see if it does anything for his sexual side effects. This does make me wonder if Atomoxetine or Reboxetine may be a replacement or augmentation option for him though, as he did pretty poorly on antidepressants until a noradrenergic med was started. I also saw some interesting case reports suggesting Reboxetine caused spontaneous ejaculation as well as suggestions that NRIs may not have sexual side effects. Anyone have any experience with Reboxetine?

I've had moderately good success with prazosin and clonidine for nightmares and was told by an attending in a PTSD clinic at the VA never to use trazodone for nightmares because it worsens nightmares in 1 out of 10 people. If he's still waking up in the middle of the night, I would try a brisk course of CBT-I including sleep restriction before increasing the dose of cyproheptadine any more.

First patient is currently on a waitlist for CBT-I, as he does not want to go outside the VA. I disagree with the Trazodone (as do most of my attendings), I know it can worsen nightmares, but for some it is significantly helpful and largely benign. Also has the added benefit of antidepressant effects if you titrate up. So worth at least a brief trial for patients with sleep issues and nightmares imo. Was wondering about the sedative effects because it has been his miracle drug for nightmares, so was wondering if I could get a 2-for-1 deal by increasing it.

nefazodone (≥60 mins before sexual activity or as a standing adjunct)

Recently got an e-mail that the sole producer in the US is no longer making Nefazodone, from what I understand it will be unavailable in the US in the near future which is really unfortunate imo.
 

clausewitz2

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when you have this unfortunate complication with one of your patients and you significantly damage a patients eyesight in order to help him increase his sex life, you too might reconsider the risk/benefits. At the end of the day it’s up to the patient but for many patients sex is not worth their eye sight. I do not support a blanket refusal on any medication but a thorough discussion of the risks and benefits. Giving patients diabetes from antipsychotics when they are psychotic or extremely depressed is a different set of calculations in my opinion but you should also not be cavalier with any medication.

It actually has not been very well established that PDE-2 inhibitors directly cause vision loss/decrement in color discrimination to date. The risk mainly seems to exist in folks who probably have underlying microvasculature issues to begin with (older men, HLD, diabetes, etc). So sure reason to be cautious and not cavalier about it, since being cavalier about any medication is bad. I think though that sexual health is actually tremendously important to the quality of life of many people and not presenting it as an option or framing these hearing/vision AEs as if they were not vanishingly rare does a disservice.
 
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jettavr6

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Tadalafil 10mg (1 tab) or Sildenafil 20mg (1-2) tabs. The risk of any adverse event, is extremely low in comparison to many of the medications that we prescribe.
 
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