A question about ssris antidepressants

[bullmastiff]

It seems that ssris raise prolactin, reduce dopamine and ultimately reduce
testosterone. Is there any way of combining ssris with other medications to
negate the side effects?Also are there certain ssris that have less sexual side
effects than others? I guess the higher the dosage the greater the sexual side effects. So at low dosages do these medications not have sexual side effects?

[mxim]

did you ever try wellbutrin? no sexual side effects at all,i took it for a year.

[marianco]

Originally Posted by bullmastiff

It seems that ssris raise prolactin, reduce dopamine and ultimately reduce testosterone. Is there any way of combining ssris with other medications to negate the side effects?Also are there certain ssris that have less sexual side effects than others? I guess the higher the dosage the greater the sexual side effects. So at low dosages do these medications not have sexual side effects?

Serotonin-Reuptake Inhibitors (e.g. Paxil, Zoloft, Prozac, Celexa, Lexapro, Luvox, etc.) primarily increase serotonin. But they also mildly increase norepinephrine, dopamine, stimulate serotonin 2C receptors, block muscarinic acetylcholine receptors, interact with sigma receptors, inhibit nitric oxide synthetase, block the enzymes cytochrome450 2D6, 3A4 or 1A2.

The overall effect of largely increasing serotonin can lead to a reduction in dopamine. This in turn can lead to reduction in testosterone production and an increase in prolactin.

Actions of SSRIs which may lead to the sexual side effects (e.g. decreased sex drive, decreased arousal, and/or impaired orgasms) include: the reduction in dopamine, the increase in prolactin, the reduction in norepinephrine, the reduction in testosterone, the blockade of muscarinic acetylcholine receptors, the inhibition of nitric oxide synthetase, and the increase in serotonin.

The sexual side effects will depend factors including:
1. The individual's genetic susceptibility to each action
2. The dose used (the lower the dose, the less of an antidepressant effect a person may have, however).
3. The particular SSRI used.

All the SSRIs can have sexual side effects - I don't have a preference for one or the other when it comes to sexual side effects. One's mileage may vary a lot. It may be useful to try several to see which one can reduce depression or anxiety best, at the lowest dose, with the fewest side effects.

Counteracting the sexual side effects with other substances may or may not work because there are multiple actions of SSRIs which lead to sexual side effects. Covering one or some with one medication thus may or may not work - but is usually worth a try if one wants to keep the SSRI.

1. Wellbutrin (Bupropion, Zyban) can be tried to reduce sexual side effects. Wellbutrin acts primarily by increasing norepinephrine. The increase in norepinephrine may be enough to recover sexual function. (Some believe it also may significantly increase dopamine).

If the dose of Wellbutrin is too high, however, then adrenal fatigue may occur (since norepinephrine is also a signal for stress). Adrenal fatigue, itself, can lead to other neuroendocrine changes which will impair sexual function. Wellbutrin, with its simpler mechanism of action, tends to usually not result in sexual dysfunction. However, it can cause sexual dysfunction in some people (I think primarily by worsening or causing adrenal fatigue). From the prescribing information, as far as I recall, sexual dysfunction occurs in about 3-percent of patients.

I tend to prefer low doses of Wellbutrin regular-release (e.g. 37.5 to 75 mg a day) when trying to counteract SSRI sexual side effects, because adrenal fatigue often is present. SSRIs, themselves, by increasing serotonin, work to reduce depression and anxiety by reducing perceived stress which is causing adrenal fatigue.

2. Another alternative to reduce SSRI sexual side effects is to use Viagra (Silfenadil), Cialis (Tadalafil), or Levitra (Vardenafil). These inhibit the enzyme Phosphodiesterase type V.

Signals from the brain, through peripheral nerves to smooth muscle cells in the blood vessels of the penis, trigger the production of nitric oxide. Nitric oxide then triggers the creation of cycle GMP. Cyclic GMP then triggers and maintains an erection. Blocking Phosphodiesterase type V with Viagra/Cialis/Levitra then prevents the destruction of cyclic GMP - allowing erections to occur and be maintained.

In women, Viagra, Cialis, or Levitra, may help reduce anorgasmia from SSRIs through the same mechanism that causes erections in men.

3. Another alternative to reduce SSRI sexual side effects is to use a low dose of a stimulant (e.g. Ritalin, Dexedrine). Stimulants act by increasing dopamine and norepinephrine. Increasing dopamine can reduce prolactin level. These stimulant actions directly counteract three of the SSRI mechanisms of action.

Other alternatives to reduce SSRI sexual side effects (usually by counteracting some of the SSRI actions) include:
4. Buspirone (Buspar)
5. Amantidine (which increases dopamine release)
6. Dopamine-like medications (dopamine receptor agonists such as Requip/Ropinirole, Bromocriptine, Mirapex/Pramiprexole)
7. Ginkgo Biloba (which, by speculation, may work by increasing circulation in the genital area - though there is a small risk for stroke)
8. Cyproheptidine (Periactin - an antihistamine which can block serotonin - which if dosed high enough can cause sedation, and block the antidepressant effect of SSRIs)
9. Trazodone (though I would stay way from using this in men with normal to high testosterone levels given the potential to kill the penis via priapism)
10. Yohimbe
11. Serotonin 3 Receptor blockers (antinausea agents such as Kytril/Granisetron, Zofran/Ondansetron - though at too high of a dose can reduce the antidepressant effect of SSRIs. They are extremely expensive too - Zofran can run $2000 for a month's supply. Kytril can cost $50 a pill. These, however, can also be used as smart drugs/nootropics, albeit for the very rich).
12. Testosterone (which also increases dopamine - particularly if it is not at a high enough blood level - though estrogen levels need to be monitored and controlled).
13. Progesterone (which can lead to increased serotonin, norepinephrine, dopamine, GABA levels, and may improve adrenal function since progesterone can be turned into cortisol by the adrenals - particularly if the blood level is low - though if the dose is too high (e.g. men produce about 10 mg a day, as far as I recall, thus replacement doses need to be less than that), may cause gynecomastia by increasing sensitivity to estrogen through increased estrogen receptor production).
14. DHEA (which is a mild androgen, which can lead to higher testosterone levels - 7-Keto-DHEA may be an alternative (though untested) - since DHEA can lead to hair loss and acne).

Note that increasing norepinephrine can increase adrenal fatigue or precipitate mania. Increasing dopamine excessively can cause mania or psychotic episodes. A doctor's supervision is necessary in these treatments since serious adverse effects may occur.

(This reply was also posted to the antidepressant thread).

[HeadDoc]

thanks for another one your thorough responses Marianco. Have you found any value from adding acetylcarnitine or phosphatydalserine to SSRI's for enhancing sexual reponse? How about l'arginine?

[pmgamer18]

Originally Posted by HeadDoc

thanks for another one your thorough responses Marianco. Have you found any value from adding acetylcarnitine or phosphatydalserine to SSRI's for enhancing sexual reponse? How about l'arginine?

Dr. Alan J. Cohen, M.D. had a artticle over 15 yrs. ago that taking High does of Ginko Biloba gave relief of Sexual Dysfunction do to SSRI meds. I can't find it but this is a take off of it.
http://www.mhsanctuary.com/rx/testos.htm

[marianco]

Originally Posted by HeadDoc

thanks for another one your thorough responses Marianco. Have you found any value from adding acetylcarnitine or phosphatydalserine to SSRI's for enhancing sexual reponse? How about l'arginine?

Acetyl-L-Carnitine: A combination of Acetyl-L-Carnitine and Alpha Lipoic Acid many in some people reduce erectile dysfunction. The problem is that the doses used are relatively high. The acetyl- part of Acetyl-L-Carnitine is essentially vinegar, is acidic, and may not be pleasant for many people to take in large doses. I have to do some research on this, but high alpha lipoic acid doses may cause problems - are not as safe as I thought it would be.

Phosphatidylserine: The available phosphatidylserine is made from soy, not extracted from brain (due to risk of mad-cow-like disease). Unfortunately, the studies on brain function by-and-large use brain phosphatidylserine - which is totally different from plant-derived phosphatidylserine. Phosphatidylserine (plant derived) does reduce cortisol production from the adrenals. The problem I have with lowered cortisol and sexual response is that reducing cortisol may blunt sexual response since a person then would not be able to generate enough energy to maintain sexual response. Lowering cortisol with phosphatidylserine may make sense only if the person has tonically high cortisol levels in the first place, not normal or low levels.

L-Arginine - L-Arginine can increase Nitric Oxide levels - which then increases cyclic-GMP, which then causes an erection. The problem is that L-Arginine may not be able to persistently increase Nitric Oxide levels enough to improve sexual response. I haven't seen yet if it is effective in improving sexual response. Body builders have attempted to use L-Arginine to increase Nitric Oxide, to improve muscle blood flow, to increase muscle growth in response to exercise. But I have yet to see good data indicating that this is effective. Note that persistent high nitric oxide levels can be dangerous. It is a strong oxidant. L-Arginine does not localize the increase in nitric oxide to only the penis - it does so everywhere in the body. As an aside, Nitric Oxide is a retrograde neurotransmitter given out by the receiving neurons to reinforce neurotransmitter signaling from the originating neuron - e.g. to reinforce learning and memory. Increasing total nitric oxide levels would not be useful since the increase needs to be localized to the specific neurons for the specific desired function.

[bullmastiff]

I'm currently using ritalin LA 30 mg in addition to luvox 50 mg. It seems as if the ritalin is negating the action of the luvox. Usually I feel the effects of luvox at 50 mg however with the addition of the ritalin I just seem to feel the stimulation of the ritalin and the luvox is not doing anything that I can feel.