Antidepressants

[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.

[marianco]

"I don't feel that combo is doing its job": What are the expectations of treatment? What symptoms are suppose to be addressed by treatment?

I think any combination of antidepressants (and/or other medications) is fine so long as it achieves the intended purpose, the benefits outweigh the risks of treatment, and the side effects are tolerable and don't impair functioning.

Medications which increase serotonin (such as Celexa, Prozac, Effexor) can also reduce dopamine. If the reduction in dopamine is too low, it may manifest as impaired memory, increased weight, agitationed/restlessness, lethargy, anxiety, sexual dysfunction, among other side effects. Serotonin, itself, can directly impair sexual function in excessively high doses for the person.

Wellbutrin works by increasing norepinephrine. If the dose is too high, increased norepinephrine can increase a person's stress level. The appropriate dose depends on the person. The range of doses I use is between 37.5 mg to 500 mg a day. The risk of seizure at 600 mg a day is about 1 in 20. Wellbutrin can significantly inhibit cytochrome P450 2D6 - an enzyme in the liver which metabolizes many medications, and is needed to convert thyroid hormone T4 to the active version T3.

In general (which needs to be interpreted for every individual patient) Effexor works primarily by increasing serotonin at doses from 1 to 150 mg a day. Above 150 mg a day, it also increases norepinephrine significantly. Around 300 mg a day, it also increases dopamine significantly. Thus its pharmacological effect will depend on the dose. My own maximum dose is 575 mg a day - rarely needed, or tolerated (due to side effects).

When a patient does well on an antidepressant or combination of medications then the medication or combination seems to stop working, it is the patient's illness or condition that has changed, not the medication. The medications always work the same way - their mechanisms of action do not change. But other factors in the patient's condition or health may change the patient's response to treatment. These factors may include other neurotransmitter-hormone changes and health related changes (hypothyroidism, further decreases in testosterone, obesity, diabetes, stress and othe psychological factors, etc.) as well as the addition of other medications with interactions.

Some practitioners believe in "SSRI Poop-out" - where it is thought that "tolerance" develops to an SSRI (serotonin reuptake inhibitor - such as Prozac), which is why it will stop working. I do not believe this generally happens. I think the patient's illness either changes in characteristics or the diagnosis needs to be reassessed (e.g. bipolar disorder rather than major depressive disorder may be present) or other complicating health factors contribute to worsening of their symptoms.

The patient will have to continue working with his/her doctor to determine what factors have changed.

[HeadDoc]

thanks Marianco for clarifying that last point. I never understood the "poop out". Regarding the sexual s/e's of SSRI's, it would appear that you are less confident in augmenting the SSRI with Wellbutrin. I have never seen it used, but would a small amount of stimulant be a better choice.

Also have you used any secondary messengers for depression or anxiety, like inositol?

This is a reference that I have relied upon in the past. Any comments?

http://www.fpnotebook.com/PSY184.htm

[marianco]

Originally Posted by HeadDoc

thanks Marianco for clarifying that last point. I never understood the "poop out". Regarding the sexual s/e's of SSRI's, it would appear that you are less confident in augmenting the SSRI with Wellbutrin. I have never seen it used, but would a small amount of stimulant be a better choice.

Also have you used any secondary messengers for depression or anxiety, like inositol?

This is a reference that I have relied upon in the past. Any comments?

http://www.fpnotebook.com/PSY184.htm

The reference is good.

Like most psychiatric medications, your mileage will vary. In my experience, dating back to when Wellbutrin was first introduced (1985), I have not seen it work often in improving sexual function (but then I usually treat very severely ill people, thus the population itself may not respond well because they have numerous physical and other co-morbid problems). Yes, it may in some patients - thus making it worthwhile to prescribe first, given its relative safety. But improvement in sexual function has been a rare occurrence. Realizing that Wellbutrin primarily increases norepinephrine, this is then understandable. Dopamine has the much larger role in sexual function. What is good about Wellbutrin as an antidepressant - when not used primarily to improve sex drive - is that it does not interfere, by and large, with sexual function, unless the dose gets too high.

The cleanest (i.e. with fewer side effect and other mechanisms of action) and best way I've seen to improve Dopamine level is by optimizing testosterone activity for the individual, while maintaining physiologic levels. I like this method because sex can then be spontaneous, in the here-and-now. This is as opposed to having to prepare for it by taking Viagra or some other medication, which removes spontaneity from sex. If you have to focus on a medication prior to sex, sex isn't as fun. There tends to be too much anxiety about performance, whether the medication will work or not. Being in the here-and-now and being spontaneous during sex is very important to the pleasure of and loving experience for the woman/wife/girlfriend/partner.

A small amount of a stimulant (including pseudoephedrine, Dexedrine, Ritalin) is an option when optimizing testosterone is not enough (given the multiple other factors that can affect sex drive, arousal, the nervous system, physical illness etc.). I have prescribed Dexedrine or Ritalin for patients in this regard. They tend to not prefer it over time, however. Stimulants increase both norepinephrine and dopamine. The norepinephrine side tends to cause anxiety and insomnia. They end up preferring a phosphodiesterase inhibitor such as Viagra. (As an aside, cocaine, which I would not recommend using, is a strong multiple re-uptake inhibitor - increasing dopamine, norepinephrine, and serotonin - not just a dopamine reuptake inhibitor as is commonly thought.)

I like Cialis over the other phosphodiesterase inhibitors because its long half-life allows more spontaneity in sex, and multiple sexual episodes - which is why it is called a "weekend" drug. However some people are very sensitive to the flush reaction, headache, reddened eyes, and nasal drip as side effects.

If possible, reducing the offending sexually-inhibiting drug to restore sexual function is preferable to using another medication to address a side effect.

With the usual severe depressive and anxiety problems in patients I see, psychotherapy and actual medications and hormones have the strongest effect. Supplements (like SAMe, Inositol, etc.) are useful as adjuncts, but do not have a strong enough effect on depression and anxiety to be used on their own. Some (like SAMe) would cost more than prescribed medications at the doses useful to treat depression and anxiety.

In milder cases of depression and anxiety - such as would be treated by a primary care provider, the supplements may be more useful since a small effect is all that may be needed, when coupled with psychosocial interventions.

Supplements are much more useful in the patients I see, for the co-morbid conditions accompanying, possibly contributing to depression and anxiety, and possibly caused by depression and anxiety themselves - i.e. the psychosomatic illnesses. For example, if anxiety and depression has a large component due to adrenal fatigue/insufficiency, then there is a large contingent of supplements (including vitamins, minerals, etc.) which can be very useful to help improve function and reduce symptoms of illness. If there is insulin resistance and diabetes as a component of depression and anxiety, then there are supplements which can be highly useful. If vascular insufficiency or neuropathy is a component of the illness, then there are supplements which can be highly useful.

[HeadDoc]

these issues surrounding depression come up so often, I decided to sticky the thread for others. Thanks for the responce.

[pmgamer18]

Thanks for the dam good post this tells me my Dr. is doing a dam good job. He put me on Concerta 36 mgs. a slow release Ritlain when it came out to help me with fatigue. I ran out of it 5 days a go and started having with draw I get my meds in the mail from MedcoHealth and hate this if I send a scrip in to soon they reject it now I had to go to the drug store and get 14 pills to last me until MedcoHealth sends them in the mail. They said they are behind because of the Holidays. I feel much better today now that I am taking them again. I don't have ADD but this med makes me feel dam good the brain fog is much better. My Dr. also has me doing Cialis 20 mgs. every 72 hrs. doing this I can have sex anytime and it is keeping my BP down.

[chap]

Just noticed this topical thread: would a single 8mg dose of ephedrine be a possible sexual stimulant then? or is that dose too high or low? Is the effect of the stimulant short lived, and therefore timing needs to be critical?

[marianco]

Originally Posted by chap

Just noticed this topical thread: would a single 8mg dose of ephedrine be a possible sexual stimulant then? or is that dose too high or low? Is the effect of the stimulant short lived, and therefore timing needs to be critical?

I do not know the answer.

The dose of stimulant that is effective will vary with the individual.

Timing is critical, particularly with shorter duration of action medications, since improvement in function may occur only while the medication is active, not eliminated. Further, withdrawal may occur after the effects end - possibly themselves impairing functioning.

[earthdog]

Thank you, Doctor.

[marianco]

Paxil Alternatives
That was quite a read on Testosterone and Neurotransmitters, Doc. My wife and I take Paxil, 20 mg per day. I wonder if it causes akathisia because I toss and turn a lot, have restless leg syndrome, and irritibility. Can I suggest an alternative to my M.D.? Like what? The wife has tried alternatives because of increased appetite but they make her feel awful. Any suggestions? Thanks

Akathisia is a motor movement disorder I hypothesize occurs when dopamine levels in the brain become too low. Manifestations include fidgetiness, restlessness, tossing and turning in bed, restless legs, irritability, anxiety, insomnia, agitation, anger outbursts, a feeling of wanting to jump out of one's skin, a feeling of ants in one's pants. It can cause worsening of the illness being treated. At the extreme, it can increase violent behavior, raise the likelihood of a suicide attempt - as a way to escape extreme discomfort due to akathisia.

Akathisia is an important side effect to watch for with medications that raise serotonin levels because raising serotonin will simultaneously reduce dopamine levels. I use it as the sign that the serotonergic medication is at an excessively high dose. I instruct patients to automatically reduce the dose of their medication if they think akathisia is occurring.

Reducing the dose often relieves the person of Akathisia. The lower dose is the optimal dose, then, for that particular medication. If depression or whatever target symptoms still persists - though reduced by the original medication - I will consider additional medications - which use different mechanisms of action - to add to the treatment to try and achieve a fuller response - such as a lower severity of depression.

When a partial response to an antidepressant occurs, I also consider if there are other, undiagnosed underlying conditions which can be targetted in treatment, which contribute to the development of the mental illness.

Paxil works by increasing serotonin levels in the brain.
Alternative medications that primarily raise serotonin levels include Prozac, Zoloft, Luvox, Celexa, Lexapro, Effexor (at doses < 150 mg/day). Medications that increase serotonin and norepinephrine include the tricyclic antidepressants (e.g. Elavil, Nortriptyline), Cymbalta, Remeron.

[androjello]

I'm guessing Effexor at doses >150 mg's could be added to the list of drugs that raise seratonin and norepinephrine?

[Cryptochid]

Ive been on every anti dep for over a 25 year period. The worse side effect is lack of sexual arrousal and erectile dysfunction. I found the sustanon shots left me with the equivelant of "that time of the month" issues amongst women.

The adroderm for me was useless - depression was constant and my GP suggested anti deps while on androderm, but when I started pallets, the depression completely resolved itself. Have touched anti deps since last August, probably due the the "constant" secretion of T.

I did notice when my free T dropped of after 4 months with pallets, depression started to kick in. I only had the depression return for one week as another "insert" was done.

Would like to know what SWALE thinks about the link of free T and depression

[Albert]

Thank YOU marianco,

The more I read about these drug and there use, the more I think our GP's and Primary Care Physicians should not be handing these out like kids candy.

Every time I see my doctor and we end up not doing anything about my problems, the more they pushed anti-depressants on me.

The drug companies must be making a killing from the drugs.

In the past when I have tried these drugs they have knocked me around and all I want to do is sleep, 24/7.

No thanks, my brain is already stuffed from the other drugs they said would help.

Later,
Albert.

[marianco]

Originally Posted by Cryptochid

Ive been on every anti dep for over a 25 year period. The worse side effect is lack of sexual arrousal and erectile dysfunction.

I found the sustanon shots left me with the equivelant of "that time of the month" issues amongst women.

The adroderm for me was useless - depression was constant and my GP suggested anti deps while on androderm, but when I started pallets, the depression completely resolved itself. Have touched anti deps since last August, probably due the the "constant" secretion of T.

I did notice when my free T dropped of after 4 months with pallets, depression started to kick in. I only had the depression return for one week as another "insert" was done.

Testosterone Pellets generally would be third in line behind Depot-Testosterone injections and Transdermal Testosterone because of the additional risks of a surgical procedure, and (for myself) dependence on the physician (whereas with the other options, one can administer testosterone to oneself).

However, when the first two options fail for various reason, the testosterone pellets may be a good idea.

The improved level of Free Testosterone is an interesting finding - and possible benefit of the pellets versus injections and transdermal route.

I wonder if an attempt to increase Free Testosterone when using injections or testosterone cream/gel by using substances that reduce estrogen levels - which then reduces sex hormone binding globulin - which is what binds testosterone, reducing free testosterone.

I wonder if a high enough dose of depo-testosterone or transdermal testosterone was used to help increase Free Testosterone levels. Testosterone can be compounded at higher concentrations (such as 10% Testoscreme) using absorption accelerants other than alcohol to improve absorption and possibly effectiveness.

I wonder how depression correlates with dihydrotestosterone levels (DHT) in addition to Free testosterone. If depression improves with higher DHT levels, then a testosterone cream can be placed on scrotal skin to achieve higher DHT levels than at other locations.

[marianco]

Originally Posted by Albert

The more I read about these drug and there use, the more I think our GP's and Primary Care Physicians should not be handing these out like kids candy. Every time I see my doctor and we end up not doing anything about my problems, the more they pushed anti-depressants on me.

Antidepressants are highly useful. However, they do not solve every problem. They have a difficult time treating depression when a different neuroendocrine imbalance not addressed by the antidepressant is the cause (e.g. testosterone, estrogen, progesterone, cortisol insufficiency). And, if the physician is not aware of all the profound effects antidepressants can have, problems can arise.

[earthdog]

Doctor, a few more questions if you will.

Out of the SSRIs you mention, do you have a particuar favorite? Maybe one you start with?

In your experience, do any of the SSRIs mentioned above cause memory loss? How about Wellbutrin (not an SSRI, I know)?

Are you aware of any memory loss problems related to Effexor?

Thanks again.

[marianco]

Serotonin Reuptake Inhibitors (SSRIs) are very complex medications. The primary mechanism of action is to block serotonin reuptake (causing an increase in serotonin). However, they also block norepinephrine reuptake, block dopamine reuptake (increasing dopamine), reduce dopamine production, act directly on serotonin 2C receptors, block acetylcholine receptors, inhibit nitric oxide synthetase, block liver enzymes including 2D6, 3A4 or 1A2, etc. Each SSRI does these things to a varying extent. However, even if weak on one mechanism, I do not discount it because I may and have met patient who were sensitive to a mechanism of action, causing side effects, when the textbooks would say it should not.

Reducing dopamine levels or blocking acetylcholine can lead to memory problems. Each SSRI has the potential to impair memory depending on the genetic response of the person taking it.

In general, I prefer SSRIs which tend to have less weight gain as a problem. Obesity causes so many neuroendocrine problems that impair treatment (e.g. excess estrogen activity, insulin resistance, impaired self-esteem, etc.), that I prefer minimizing weight gain as a side effect. Cosmetically, women and men prefer to avoid weight gain strongly. I use to have patient who would gain 20-30 pounds while on an SSRI, and losing weight would be difficult. The ones which are less likely to cause weight gain are Lexapro and it's "mother", Celexa. However, I keep the other ones in mind, because depending on the person, he or she may respond better to the other ones (Prozac, Paxil CR, Paxil, Zoloft, Luvox) for the intended purpose of treatment.

Wellbutrin (regular, SR, XR), works primarily as a norepinephrine reuptake inhibitor (not dopamine reuptake inhibitor). It is almost a pro-drug in that its metabolite is a much more potent norepinephrine reuptake inhibitor than Wellbutrin itself, and is concentrated more in the brain than Wellbutrin itself. Memory impairment, in my experience, is much less frequent with Wellbutrin than the SSRIs. It may help improve attention - thus help improve memory - in people with attentional problems. "Your mileage may vary" as the statement goes.

I have not heard of memory loss as a problem with Effexor. It is more potent than the SSRIs at increasing dopamine levels, thus possibly compensating for the reduction in dopamine from blocking serotonin reuptake. However, at about 150 mg a day and below, it primarily acts as a serotonin reuptake inhibitor, and thus may have similar risks for memory problems - depending on individual response to the treatment.

There is no perfect antidepressant. Depending on the severity of life stresses, a response to any individual antidepressant can vary from 17-70 percent. Response means a 50% reduction in symptoms of depression. Patients with severe stress respond most poorly to antidepressants because the stress can overwhelm treatment. Often a multiple-medication treatment is needed to adequately reduce the severity of symptoms.

Treatment has to be customized for the person - taking into account genetics, symptoms, the nature of the illness, previous response to treatment, health problems, side effects and interactions to avoid, etc. It is an art since we do not yet have specific testing for brain status and function which partain specifically to mental illness. Since there is no perfect antidepressant, I have to maintain an open mind about what may help a patient.

[chap]

Is there hope (or reason) to get a person off of ssri treatment, after they have been on for years and are convinced they need it? Is it just wishful thinking on behalf of a loved one to think there must be a better way?