Antidepressants

[marianco]

Originally Posted by T Man

In your opinion what medications/substances can safely raise Dopamine levels? I want to talk to my Doctors about this option. I am on Remeron 7.5mg nightly and Klonopin as needed as I mentioned before (.25 or .5mg twice a week usually). I think I am getting symptoms of Akastitia when we try to raise my Testosterone levels. I am not certain of this, but the symptoms seem to be as you described. Anxiety, ants in the pants, burning or tingling skin feeling. Maybe it is estrogen related as someone mentioned in another thread. Also I do get restless legs for a short time after taking the Remeron. It goes away within an hour or so and doesn't affect my sleep.

I also have a low sense of well being or contentment. I always felt content when on testosterone replacement therapy in the past. I know that I must raise my Testosterone levels back up to high normal again to feel good. I just can't seem to get this through my Doctors head. I have been on TRT since 1989.

Once again my problem is that I can't seem to tolerate Testosterone levels above 400 ng/dl. I never had this problem before I went moronic and did a few cycles of high Testosterone (400-500mg weekly for 10 weeks) and a few other Anabloic/androgenic agents. I am tired of this anxiety and depression that comes and goes. Could higher levels of Dopamine possibly help with my situation. The Doctors at a very good reasearch University don't seem to know what to do or what medications I should take. They suggested Buspar or Nardil. Or just stay on the Remeron and take Klonopin. Any suggestions?

As far as I know, akathisia is difficult to create with testosterone alone. Akathisia (I speculate) is a state created by lowered dopamine activity. But testosterone does the opposite - raising dopamine activity.

Estradiol (or estrone) created from testosterone (via the aromatase enzyme) can cause akathisia, agitation, anxiety. Estrogens raise serotonin levels. One mechanism by which this occurs is that estrogens work in the brain as monoamine oxidase inhibitors (which primarily raise serotonin). Raising serotonin reduces the production of dopamine - thus akathisia as a side effect.

Estrogen is extremely potent compared to testosterone. I estimated that in regard to their roles, estrogen is about 10,000 times more potent than testosterone. A small change in estrogen level can make a huge difference.

If I was faced with akathisia as a side effect of testosterone treatment from the creation of estrogen, I would first focus on reducing estrogen activity given how potent estrogen is. In general, I prefer reducing the offending agent that is causing akathisia.

There are various ways to reduce estrogen activity including aromatase inhibitors, Diindoylmethane, and Indole-3-carbinol. With any of them, care must be taken since excessive reductions in estrogen has its own consequences (e.g. memory impairment, osteoporosis, high cholesterol levels, no sex drive, etc.)

Treatments for akathisia - which can also manifest as restless legs syndrome - include medications which raise dopamine or act like dopamine, and medications which reduce the manifestations of akathisia - often primarily by sedation.

Medications used to reduce the manifestations of akathisia include norepinephrine beta-receptor blockers (such as propranolol, atenolol), sedative/antianxiety GABA-enhancers (such as Klonopin), histamine receptor blockers (antihistamines) which calm akathisia down primarily by sedation (such as diphenhydramine, Remeron). Remeron often reduces akathisia. I often use it as a treatment. But occasionally the increase in serotonin it causes can also cause akathisia.

Buspar is worth a try for the treatment of anxiety. However, in clinical use, it rarely helps - though it is worth a try because of its relative safety.

Monoamine oxidase inhibitors (MAOIs - such as Nardil) is an interesting call in regard to reducing akathisia - apparently with the thought of increasing dopamine levels. However, Monoamine oxidase inhibitors primarily increase serotonin, which may negate the increase in dopamine if a person already is starting from a lowere dopamine state - such as of akathisia. I haven't heard or read of its use in the treatment of akathisia. MAOIs are good antidepressant medications - though are highly limited by the dangerous interactions they have with numerous medications and foods and the life-style change they require as a result. MAOIs are good, however in treating anxiety and depression.

Medications which act to raise dopamine or act like dopamine include essentially all the medications used to treat Parkinson's Disease (an illness due to the lack of production of dopamine). These medications are tricky to use since excessive doses can cause psychotic symptoms and anxiety among other serious side effects. However they are useful when used carefully. Mirapex, for example, is often used in psychiatry when a dopamine agonist is desired.

Another class of medications which raise dopamine levels are the stimulants such as methylphenidate, dexedrine. The limitation they have is stress and anxiety from increasing norepinephrine, besides the taboo of abuse-potential in some patients. Theoretically they can treat akathisia, but I have not used them so - preferring reducing the causative agent (e.g. estrogen, antipsychotic, serotonergic medication) or by using one of the medications to reduce manifestations of akathisia or a more pure dopamine agonist since akathisia at night cannot usually be treated with a stimulant. Stimulants, however, are valuable adjuncts in treating depression.

Aside from problems with estrogen or excessive dihydrotestosterone (which can be addressed), the cleanest way to raise dopamine levels to improve one's sense of well-being is by raising testosterone level. I have yet to see something cleaner or safer treatment than by using testosterone. If it takes a high normal level to accomplish this for an individual, that is what I would aim for. I would not advocate supraphysiologic doses, however. That would be asking for health problems not wellness.

Unless I run out of options - which is difficult to do with the hundreds of medications available in my toolkit - I usually would not settle for a partial response to treatment. I usually try for remission of symptoms - something patients want and - ideally - doctors should strive for.

I am not familiar with the molecular pharmacology or neuroendocrinology of former steroid abusers - and their post-abuse testosterone replacement problems. SWALE would be more familiar of how to treat such patients, being part of his specialty. I would bow to his expertise on this issue.

[Novick]

While estrogen can be anxiogenic, many of the dopaminergic effects of testosterone are aromatization dependent. Estrogen is also important in maintaining dopamine receptor density. Not only will this effect one's baseline sense of well being, but also affect the efficacy of antidepressant drugs.

Just another of the many good reasons to regulate estrogen to normal levels rather than suppressing it too much.

[GEARMASTER]

i heard 5htp helps.

[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 of 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.

[T Man]

Which of the SSRI's is the least activating? I am told that Prozac will hype you up the most. I know that it was activating to me. Is Prozac known to be the biggest activator? Which one is known to have the least activating effect? Prozac, Zoloft, Paxil, Luvox, celexa, lexapro? I tried Paxil for a few days about 5 years ago and it seemed to make me feel slightly sedated. But a Doc told me it is just as activating as all the rest. Not from what I felt.

I have talked with many people that have used Zoloft without any side effects at all. They said none at all. Men and women. They took anywhere from 25 to 150 mgs. Only one women told me that it made her a bit sleepless and dry mouth for 8 weeks than went away. Everyone said it was a godsend to them in term of how it helped them.

Also is Buspar an alternative to SSRI's? Does it have the same clinical effects on depression/anxiety/panic/OCD that the main SSRI group has??? Someone told me that it won't activate you or make you anxious as the SSRI's because it only raises certain serotonin levels and not all. Whatever that means. Docs please.

[marianco]

Originally Posted by T Man

Which of the SSRI's is the least activating? I am told that Prozac will hype you up the most. I know that it was activating to me. Is Prozac known to be the biggest activator? Which one is known to have the least activating effect? Prozac, Zoloft, Paxil, Luvox, celexa, lexapro? I tried Paxil for a few days about 5 years ago and it seemed to make me feel slightly sedated. But a Doc told me it is just as activating as all the rest. Not from what I felt.

Also is Buspar an alternative to SSRI's? Does it have the same clinical effects on depression/anxiety/panic/OCD that the main SSRI group has??? Someone told me that it won't activate you or make you anxious as the SSRI's because it only raises certain serotonin levels and not all. Whatever that means. Docs please.

The "activating" phenomenon of SSRIs may occur as a result of:
1. the increase in serotonin (which over time helps improve adrenal function - and energy), or
2. an increase in norepinephrine and dopamine (from norepinephrine reuptake inhibition and dopamine reupatke inhibition), or
3. a reduction in dopamine (resulting from the increase in serotonin, which inhibits dopamine production).
4. etc.

The reduction in dopamine may result in a condition called "akathisia". This is a psychomotor disorder with varied symptoms including: agitation, anxiety, restlessness, fidgetiness, insomnia, irritability, a feeling of ants in one's pants, a feeling of wanting to jump out of one's skin, etc. Akathisia may contribute to behaviors including suicides that have resulted from treatment with antidepressants.

The sum effect of any SSRI depends on the mechanisms of action of the SSRI, the person's genetic predisposition to response to any and all of the SSRI's actions, the dose of the SSRI, etc.

What will happen to any given individual cannot be fully determined until that person tries the medication.

For example, for some people, Paxil causes "activation" or "akathisia" because it is the most potent serotonin reuptake inhibitor. In others, Paxil's antihistamine action outweighs the other effects and causes sedation.

Prozac may have the reputation as the most "activating" SSRI. But that cannot be applied to the individual person. Some people would be sleepy on Prozac.

"Activation" depends highly on the dose used. Since Zoloft is the least potent SSRI (since a higher dose is needed for the same effect as the other SSRIs), one can make a case that Zoloft is the least activating when used at the same dose as the other SSRIs. Of course, that dose of Zoloft may not be in its effective range. Zoloft is also usually not taken over 200 mg a day since side effects may rapidly occur.

In clinical use, in regard to potency as a serotonin reuptake inhibitor (outside of the other multiple mechanisms of action, and outside of the dose used), I would rank the SSRIs as follows: Paxil > Lexapro > Prozac > Celexa > Zoloft > Luvox. Clinically, when treating an individual, this ranking does not mean much since there are so many other variables to take into consideration. These include: the person's prior experience with SSRIs, side effects, interactions with other medications, etc.

In general, each person has to try each SSRI to find out which is more activating than the others. The "activating" effect occurs very rapidly, depending on the dose. Thus one can tell quickly whether or not they like a particular medication. One does not have to wait weeks to find out.

Akathisia, as a side effect, usually does not go away. I use it as "the glass ceiling" - the dose limit of an SSRI - meaning the dose is too high if it occurs. And I tell patients to automatically reduce the dose if it occurs.

Buspar is usually not an effective antidepressant when used alone. It can help reduce anxiety in some people. It is also used as an additive - help help an antidepressant work better. Buspar's effects have been highly variable - often not working at all. But it is worthwhile to keep in mind since some people respond to it well.

[MrT]

Since you've been on antidepressants for a while it might be a shock to consider this but... When I first saw my doctor about some symptoms that I had. Low sex drive, Anxiety, lack of energy, Mood problems etc. She quizzed me at length and told me "You fit the profile for mental depression. However I KNOW you. And I'm pretty sure your not depressed. Lets check your hormones." This all came like a bolt out of the blue. I knew NOTHING about male hormones. I thought she must have been talking to the Nurse since women are the ones with hormone problems. Anyway, I've been on Androgel and am free of all my depression issues. I can't tell you that you don't have both mental depression and testosterone problems at the same time. Thats possible. But... If I were in your shoes I would speak to my doctor about slowly weening me off the depression mens and seeing if hormones are the source of the issues you had. At least it will be cheaper!

Good luck!

And remember. I'm not a doctor I don't even play one on TV. My comments are just joe six packs 2 cents worth and probably not worth the 2 cents!

Originally Posted by earthdog

I have been on 300mg Wellbutrin and 75mg of Effexor (down from 225mg since starting TRT about one year ago under Swale's care) per day, and I don't feel that combo is doing its job. About 9 years ago I was on Prozac and I feel I did better on that. I was taken off if it because of sexual side effects - which were more likely due to low T than the Prozac - and put on Celexa and Wellbutrin. Then I was taken off Celexa and put on Effexor because of weight gain and general lethargy (also probably due in part to low T).

One problem I have that I think is due to the Effexor is faulty memory.

What are your feelings on this combo I'm on (300mg Wellbutrin and 75mg Effexor)?

While I solicit everyone's response, I'm really hoping Marianco will see this and take a shot at it.

[r100proof]

Originally Posted by marianco

The "activating" phenomenon of SSRIs may occur as a result of:
1. the increase in serotonin (which over time helps improve adrenal function - and energy), or
2. an increase in norepinephrine and dopamine (from norepinephrine reuptake inhibition and dopamine reupatke inhibition), or
3. a reduction in dopamine (resulting from the increase in serotonin, which inhibits dopamine production).
4. etc.

The reduction in dopamine may result in a condition called "akathisia". This is a psychomotor disorder with varied symptoms including: agitation, anxiety, restlessness, fidgetiness, insomnia, irritability, a feeling of ants in one's pants, a feeling of wanting to jump out of one's skin, etc. Akathisia may contribute to behaviors including suicides that have resulted from treatment with antidepressants.

The sum effect of any SSRI depends on the mechanisms of action of the SSRI, the person's genetic predisposition to response to any and all of the SSRI's actions, the dose of the SSRI, etc.

What will happen to any given individual cannot be fully determined until that person tries the medication.

For example, for some people, Paxil causes "activation" or "akathisia" because it is the most potent serotonin reuptake inhibitor. In others, Paxil's antihistamine action outweighs the other effects and causes sedation.

Prozac may have the reputation as the most "activating" SSRI. But that cannot be applied to the individual person. Some people would be sleepy on Prozac.

"Activation" depends highly on the dose used. Since Zoloft is the least potent SSRI (since a higher dose is needed for the same effect as the other SSRIs), one can make a case that Zoloft is the least activating when used at the same dose as the other SSRIs. Of course, that dose of Zoloft may not be in its effective range. Zoloft is also usually not taken over 200 mg a day since side effects may rapidly occur.

In clinical use, in regard to potency as a serotonin reuptake inhibitor (outside of the other multiple mechanisms of action, and outside of the dose used), I would rank the SSRIs as follows: Paxil > Lexapro > Prozac > Celexa > Zoloft > Luvox. Clinically, when treating an individual, this ranking does not mean much since there are so many other variables to take into consideration. These include: the person's prior experience with SSRIs, side effects, interactions with other medications, etc.

In general, each person has to try each SSRI to find out which is more activating than the others. The "activating" effect occurs very rapidly, depending on the dose. Thus one can tell quickly whether or not they like a particular medication. One does not have to wait weeks to find out.

Akathisia, as a side effect, usually does not go away. I use it as "the glass ceiling" - the dose limit of an SSRI - meaning the dose is too high if it occurs. And I tell patients to automatically reduce the dose if it occurs.

Buspar is usually not an effective antidepressant when used alone. It can help reduce anxiety in some people. It is also used as an additive - help help an antidepressant work better. Buspar's effects have been highly variable - often not working at all. But it is worthwhile to keep in mind since some people respond to it well.

Where would Effexor XR fall in the SSRI effect per dose of drug when compared to the other SSRI's. I am making the change from 20mg's of Lexapro to 75mg of Effexor XR. It was one week at 10mg Lexapro with 37.5mg's of Effexor to 2nd week 75mg Effexor with no Lexapro. When the Lexapro was totally dropped 2 days ago....I am noticing less energy and a lower mood. Does the dose just still have to be adjusted higher in your experience?

[marianco]

Originally Posted by r100proof

Where would Effexor XR fall in the SSRI effect per dose of drug when compared to the other SSRI's. I am making the change from 20mg's of Lexapro to 75mg of Effexor XR. It was one week at 10mg Lexapro with 37.5mg's of Effexor to 2nd week 75mg Effexor with no Lexapro. When the Lexapro was totally dropped 2 days ago....I am noticing less energy and a lower mood. Does the dose just still have to be adjusted higher in your experience?

It is difficult to compare Effexor with the SSRIs because individual response varies greatly.

However, as a ballpark approximation, 10 mg of Lexapro and 150 mg of Effexor are approximately equivalent. At about 150 mg, Effexor is mostly an SSRI, with a mild increase in norepinephrine reuptake (again depending a lot on individual response).

[glg]

What is your impression of Cymbalta. My Dr. prescribed this for what she feels is mild depression (primarily anxiety oriented due to chronic back pain) and as an adjunct to my pain medication (Vicodin). I am going to be reviewing this with her in a few weeks becuase I am definitely experiencing low libido, erectile/ejaculatory issues as well as an increase in my RLS.

She has not been exposed to Male Andropause and is not sure how to address any issues in the area. She feels that my levels are within acceptable limits. Serum Test 490 (range 241 - 827) and free test 9.8 (range 7.2 - 24).

I am planning to cease the Cymbalta unless there are other factors I need to consider.

I had an angioplasty and stent placement 7 mo. ago and am currently on Plavix and Vytorin.

My sleep Dr. has me on Requip for the RLS and was very concerned regarding the Cymbalta and a recent lab that has my Serum Ferritin at 18 (range 22 - 322). I am pursuing more tests on the Ferritin issue.

Would the Cymbalta have that significant of an effect on sexuality and RLS.