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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 18 of 18. This is the beginning of the thread.
Posted by PeterJ on May 17, 2000, at 17:49:43
For those of you who have taken several SSRIs, did you find they were mostly similar in their effects or did you find them different?
I am taking Celexa (citalopram) and I find it initially is rather different from Prozac (fluoxetine). Prozac was a nightmare for me. Horrible anxiety. Celexa is tolerable, although it hasn't helped yet.
I would like to hear others' experience comparing SSRIs, including Prozac (fluoxetine), Celexa (citalopram), Zoloft (sertraline), Paxil (paroxetine), and Luvox (fluvoxamine).
Peter
Posted by stjames on May 17, 2000, at 18:06:16
In reply to SSRIs: Same or Different?, posted by PeterJ on May 17, 2000, at 17:49:43
> For those of you who have taken several SSRIs, did you find they were mostly similar in their effects or did you find them different?
>
> I am taking Celexa (citalopram) and I find it initially is rather different from Prozac (fluoxetine). Prozac was a nightmare for me. Horrible anxiety. Celexa is tolerable, although it hasn't helped yet.
>
> I would like to hear others' experience comparing SSRIs, including Prozac (fluoxetine), Celexa (citalopram), Zoloft (sertraline), Paxil (paroxetine), and Luvox (fluvoxamine).
>
> PeterJames here...
SSRI's are not chemically related, just their action is somewhat the same. So it follows that
they will have different side-effects.james
Posted by Rebecca on May 17, 2000, at 18:15:18
In reply to SSRIs: Same or Different?, posted by PeterJ on May 17, 2000, at 17:49:43
Peter--
SSRIs definitely differ in their effects upon me. I hear about people switching SSRIs, and I can't believe that some people do it so easily.
prozac gave me insomnia and horrible anxiety, too (it felt like a constant adrenaline rush); only stayed on it for 2 weeks. zoloft helped the depression but left me dizzy and zonked. celexa seems to be doing the right thing for me (I think...I hope...). It causes insomnia if I don't take anything to counteract that. I have a friend who had a similar (perhaps stronger) reaction to prozac. he ended up on paxil, which he found helpful but somewhat sedating.
maybe if we had similar reactions to prozac, we'll have similar ones to celexa; how long have you been on it? it took a couple weeks before I started feeling better. good luck!
Rebecca
Posted by CarolAnn on May 17, 2000, at 18:17:54
In reply to SSRIs: Same or Different?, posted by PeterJ on May 17, 2000, at 17:49:43
Hi Peter, I've never had any dramatic improvement with any drug(I get so mad when I read about people get completely well as soon as they start Prozac or Zoloft). Anyway, I've been on both of those, as well as Effexor, which isn't classed as an SSRI, but is supposed to have some serotonin effect. Currently I'm on Celexa(40mgs) and Wellbutrin.
Prozac did nothing for me at all, even at the highest dose(80mgs.). Zoloft helped initially, but after only a few months, it stopped working and even moving the dose up from 50 to 100mgs. did not make any difference. Effexor did nothing except increase my fatigue.
I was taking the Wellbutrin first, then the doctor added Celexa, so I don't know if my experience is just from the Celexa or from the combo. As far as I could tell, the Wellbutrin was not doing anything. When I started 20mgs. of Celexa, I began to feel less bad, but no where near good. Now that I am on 40mgs., I have frequently had times when I felt so much better, that it borders on feeling good(and now and then, a moment or two of actually feeling good).
It had taken me almost six months to reach this point, where I feel comfortable telling the doctor that I don't want to change the medications for a while(I also take 10mgs. Adderall 3xper day), since I am feeling better then I have in a couple years. Hopefully, I will either keep seeing improvement or at least, not slide back down again. For now, it's so nice to feel stable, that I'm not even going to worry about trying to get to feeling completely well.
Sorry this is so long, hope my experience helps. CarolAnn
Posted by Cam W. on May 17, 2000, at 19:21:46
In reply to SSRIs: Same or Different?, posted by PeterJ on May 17, 2000, at 17:49:43
Peter - The reason why SSRIs are act differently in different people is that they attach to receptors other than serotonin. Everyone has a different body make up and will react differently to SSRI attachment. This is partially what causes the different effects (eg anti-anxiety effect with Paxil). What the SSRIs all have in common is that they bind (and block) to the serotonin reuptake site on the presynaptic neuron. Although they are called "Selective" Serotonin Reuptake Inhibitors (SSRI), they do not bind 'only' to serotonin reuptake receptors (with the possible exception of Celexa).Here is a partial breakdown of other main receptors that different SSRIs affect:
Prozac - norepinephrine reuptake receptors, serotonin type 2C receptors.
Zoloft - dopamine reuptake receptors, sigma receptors.
Paxil - muscarinic/cholinergic, norepinephrine reuptake receptors, nitric oxide receptors.
Fluvoxamine - sigma receptors.
Attaching to these, and possibly other receptors can cause differences. Also, some of the SSRIs are metabolized selectively by different liver enzymes and in different ways, which can also affect their action.
Hope this helps - Cam
Posted by Tom on May 17, 2000, at 21:51:47
In reply to SSRIs: Same or Different?, posted by PeterJ on May 17, 2000, at 17:49:43
> For those of you who have taken several SSRIs, did you find they were mostly similar in their effects or did you find them different?
>
> I am taking Celexa (citalopram) and I find it initially is rather different from Prozac (fluoxetine). Prozac was a nightmare for me. Horrible anxiety. Celexa is tolerable, although it hasn't helped yet.
>
> I would like to hear others' experience comparing SSRIs, including Prozac (fluoxetine), Celexa (citalopram), Zoloft (sertraline), Paxil (paroxetine), and Luvox (fluvoxamine).
>
> PeterPeter,
Here's my pro's and con's of SSRIs (&others) :
Paxil - very little positive effect, extremely nervous, some insomnia
Serzone - no positive effect, very dizzy and a little anxiety
Prozac - almost deadly to me... anxiety almost sent me over the edge
Zoloft - a little gun shy at this point... quit one week into therapy when nervousness started getting worse
Wellbutrin - 1 week positive, then poof, gone. 3 weeks in nervousness made me quit
Effexor - nice effect for 10 days, then once again, gone. Side effects were agitation and constant yawning (but not sleepy, go figure).
Desipramine - minimal positive attributes, very restless sleep
Nortryptiline - After 2 days had a bizarre side effect and quit immediately
Buspar - nothing to speak of, just diziness
There you have it. I haven't tried Celexa yet. Probably won't. I'm thinking about the stimulant route next.
Tom
Posted by Cindy W on May 17, 2000, at 21:59:19
In reply to Re: SSRIs: - Different, posted by Cam W. on May 17, 2000, at 19:21:46
>
> Peter - The reason why SSRIs are act differently in different people is that they attach to receptors other than serotonin. Everyone has a different body make up and will react differently to SSRI attachment. This is partially what causes the different effects (eg anti-anxiety effect with Paxil). What the SSRIs all have in common is that they bind (and block) to the serotonin reuptake site on the presynaptic neuron. Although they are called "Selective" Serotonin Reuptake Inhibitors (SSRI), they do not bind 'only' to serotonin reuptake receptors (with the possible exception of Celexa).
>
> Here is a partial breakdown of other main receptors that different SSRIs affect:
>
> Prozac - norepinephrine reuptake receptors, serotonin type 2C receptors.
>
> Zoloft - dopamine reuptake receptors, sigma receptors.
>
> Paxil - muscarinic/cholinergic, norepinephrine reuptake receptors, nitric oxide receptors.
>
> Fluvoxamine - sigma receptors.
>
> Attaching to these, and possibly other receptors can cause differences. Also, some of the SSRIs are metabolized selectively by different liver enzymes and in different ways, which can also affect their action.
>
> Hope this helps - Cam
PeterJ, I've tried Prozac (worked for a while for depression, but didn't help OCD even at 80 mg/day...plus made me anorgasmic). Next tried Luvox (great for OCD, OK for depression, but not even any sexual desire and a lot of thirst). Then Zoloft (sexual desire, but inability to climax again...otherwise OK for depression but not much good for OCD). Serzone was great for social anxiety and depression, and for good sleep and good sex, but didn't impact OCD. Effexor-XR has been great for depression and OCD at a higher dose (375 mg/day) but makes me feel like I'm too energized sometimes (have trouble sleeping at night) and interferes a bit with sexual arousal. The only side effects I've ever experienced on SSRI's besides the sexual side effects were thirst, initial fatigue (went away after a while with each medication), dizziness (esp on Effexor-XR;again went away), and mood swings (on Serzone; went away after a few weeks). Maybe I'm lucky, but only the sexual side effects really bother me (just indicates what my priorities are, huh?) ;)
--Cindy W
Posted by PeterJ on May 17, 2000, at 23:05:42
In reply to Re: SSRIs: - Different, posted by Cam W. on May 17, 2000, at 19:21:46
>
> Peter - The reason why SSRIs are act differently in different people is that they attach to receptors other than serotonin. Everyone has a different body make up and will react differently to SSRI attachment. This is partially what causes the different effects (eg anti-anxiety effect with Paxil). What the SSRIs all have in common is that they bind (and block) to the serotonin reuptake site on the presynaptic neuron. Although they are called "Selective" Serotonin Reuptake Inhibitors (SSRI), they do not bind 'only' to serotonin reuptake receptors (with the possible exception of Celexa).Thanks, Cam.
I was aware of the differences in binding to non-serotonergic sites. In fact that's the reason I'm trying Celexa, as it is the "purest" SSRI.
The thing is, if you look at the IC50 or Ki values for the SSRIs at various receptors, there is, in most cases, a 10 to 1000-fold separation in the concentrations needed to block serotonin uptake versus that needed to affect other receptors. For example Zoloft is about 16 times more potent at blocking serotonin uptake than at blocking dopamine uptake. One could take a dose of Zoloft that saturates serotonin uptake and still have mimimal effect on dopamine uptake, if--and it's a big "if"--in vivo and in vitro values correlate.
If you go by the binding values one might expect the differences between SSRIs to be fairly subtle. They are all primarilly SSRIs with some other mild affects. But some people do report pretty dramatic effects between SSRIs.
Differences in metabolism probably account for some of it. And perhaps the slight differences in receptor binding make more difference than one might expect on purely quantitative grounds.
Drug company reps tend to emphasize the differences to differentiate their own products. But many doctors are sceptical of the reality of these differences.
What I am trying to get a handle on is how different these drugs are clinically. If you had 100 people on Prozac and switched them all to Celexa or to Paxil, how many could tell the difference? Would some notice a big difference?
Or to put it another way, if you have tried one or two or three SSRIs can you conclude that you know how you respond to SSRIs in general or are they different enough that you would want to try them all. If you did not respond to some of them, might you respond to others.
There has been some work on this question, but not much. I appreciate your comments and those of the other babblers who have posted in this thread. All the comments have been helpful and I encourage others to respond with their SSRI experiences.
Peter
Posted by PeterJ on May 17, 2000, at 23:23:39
In reply to Re: SSRIs: Different!, posted by Rebecca on May 17, 2000, at 18:15:18
> Peter--
>
> SSRIs definitely differ in their effects upon me. I hear about people switching SSRIs, and I can't believe that some people do it so easily.
>
> prozac gave me insomnia and horrible anxiety, too (it felt like a constant adrenaline rush); only stayed on it for 2 weeks. zoloft helped the depression but left me dizzy and zonked. celexa seems to be doing the right thing for me (I think...I hope...). It causes insomnia if I don't take anything to counteract that. I have a friend who had a similar (perhaps stronger) reaction to prozac. he ended up on paxil, which he found helpful but somewhat sedating.
>
> maybe if we had similar reactions to prozac, we'll have similar ones to celexa; how long have you been on it? it took a couple weeks before I started feeling better. good luck!
I hope you are right! I am on day 16 of Celexa ,but I'm still on a small dose (10mg). We are working up the dose slowly because of my bad responses to other meds, especially Prozac. Even 1mg a day of Prozac was too much for me. So far the Celexa has caused a little tension and some insomnia (treatable with Halcion), but it's not too bad. My family is actually surprised at the absence of any horrible side effects, having seen the way other meds affect me.Hopefully I'll see some therapeutic effect as we increase the dose. Wish me luck. Oh, wait, you already did. Thank you!
Peter
Posted by Cam W. on May 18, 2000, at 2:13:48
In reply to Re: SSRIs: - Different, posted by PeterJ on May 17, 2000, at 23:05:42
Peter - Clinically, predicting how an AD will work is still very much a crap shoot. You see many side effects that the companies report as minimal (eg mentrual irregularities, weird rashes) every now and then.I have found that you can be burned by in vitro receptor binding information. If it were entirely accurate, then Effexor would bs strictly an SSRI, with mild norepinephrine side effects (at least a 1000-fold difference in k-values). This is not the case, as many people experience significant norepinephrine efficacy with Effexor.
Clinically, for depression though, I believe that if one has no to minimal response on a first antidepressant (eg SSRI), then the next step should be to use another AD from a different class (eg SNRI, NRI, TCA), as experience dictates. Other SSRIs can be tried upon subsequent failures (a second SSRI should probably be tried for OCD and/or panic disorder if the first SSRI doesn't work).
Interesting thread here. Good luck with the Celexa - Cam
Posted by PeterJ on May 18, 2000, at 3:53:39
In reply to Re: SSRIs: - Different (Peter), posted by Cam W. on May 18, 2000, at 2:13:48
> I have found that you can be burned by in vitro receptor binding information. If it were entirely accurate, then Effexor would bs strictly an SSRI, with mild norepinephrine side effects (at least a 1000-fold difference in k-values). This is not the case, as many people experience significant norepinephrine efficacy with Effexor.
Actually, Venlafaxine is one case in which the Ki values match the clinical effects pretty well. The Ki values for serotonin reuptake versus norepineprhine differ by a factor of 5.4 (more potent at serotonin sites) according to Richelson. A study just out by Preskorn's group in the Archives of General Pyschiatry shows that effects on human subjects are primarily serotonergic at 75mg/day, with pronounced noradrenergic effects occuring at 375mg/day.
Blier and DeMontigny's group (up your way at McGill) do claim some discrepencies in rat studies of raphe vs locus ceruleus effects compared to receptor binding, but even they find ratio of 3, which isn't too far from the clinically observed effects.
1. Richelson, Elliott. Synaptic Effect of Antidepressants. J Clin Psychopharm. Vol 16, No. 3, Suppl. 2. June 1996 1S-9S.
2. Harvey, Ann; Rudolph, Richard; Preskorn, Sheldon. Evidence of the Dual Mechanisms of Action of Venlafaxine. Arch Gen Psychiatry. Vol 57, May 2000, 503-509
3. Beique JC; de Montigny C; Blier P; Debonnel G. Venlafaxine: discrepancy between in vivo 5-HT and NE reuptake blockade and affinity for reuptake sites. Synapse 1999 Jun 1;32(3):198-211
Nonetheless I agree with your point that receptor binding information has to be taken with a grain of salt. That's why I am looking for people's clinical reactions as a guide to what really goes on.
> Interesting thread here. Good luck with the Celexa - CamThanks, I appreciate your interest, and I'm keeping my fingers crossed on the Celexa.
Peter
Posted by SLS on May 18, 2000, at 7:44:41
In reply to Re: SSRIs: - Different (Cam), posted by PeterJ on May 18, 2000, at 3:53:39
Hi guys.
I just wanted to jump in with a few observations.1. It seems that a great percentage of people fail to respond at all to one SSRI (and perhaps do worse), and go on to respond fantastically when switched to another. At least, that's what I see here. I would find it hard to justify abandoning SSRIs after failing to respond to the very first one tried. It would be nice if there were statistics providing correlations between the non-response to a particular SSRI and response to another. Anyway, if I were a doctor and treating a patient with a de novo trial of an antidepressant using an SSRI, I would try a second SSRI before opting to switch to a different "class" of drug. Of course, the specific symptom profile of a patient must be taken into consideration, knowing that there are some statistical correlations between profile and drug response.
2. I rarely see anyone attribute the clinical differences that may exist between antidepressants within the same class to pharmacokinetic differences. Do these drugs accumulate differentially in different brain structures?
- Scott
Posted by Rockets on May 18, 2000, at 10:14:59
In reply to Re: SSRIs: - Different, posted by SLS on May 18, 2000, at 7:44:41
and now for the layperson's perspective.. heh.
I have been on 20mg of Celexa for five weeks, since my first anxiety attack. I took Ativan for 2 1/2 weeks .05mg per day but stopped taking the Ativan with my pdocs permission 2 1/2 weeks ago.
The first two weeks were spent learning about anxiety disorder and getting used to the Celexa. The Ativan had its own side effects so I can't comment on Celexa by itself except for the past 2 1/2 weeks and here is what I have found.
The Celexa has helped whatever depression I had. Depression wasn't my diagnosis.. anxiety was, however, I do believe I had that low grade irritable depression for the past year and the Celexa minimized any depressive symptoms I had. It flattened them out so to speak. I have found though that treating the anxiety has required me to go to bed earlier than normal, practice relaxation and breathing techniques every night for 30 minutes to 45 minutes, seek emotional support from my family and friends, counsel with a qualified Christian therapist each week, and never ever wake up fast in the morning. I wake up slow and pat myself on the back for a job well done as I prepare for work (yes it is an office job). I also believe Xanax would help me if I have another anxiety attack, say at work for example, but my pdoc hasn't perscribed any yet. I have a call into her about that.
Now the stats I have seen say 6 months to a year for full recovery. That is my hope. Peace to all you anxiety and depression sufferers :).
-Rockets
Posted by Cam W. on May 18, 2000, at 16:00:23
In reply to Re: SSRIs: - Different (Cam), posted by PeterJ on May 18, 2000, at 3:53:39
Peter - Thanks for keeping me honest. My memory isn't what it used to be. I checked my files at work and the 1000 figure came from Tatsumi, et al (Richelson's group, 1997) study, but was the 5HT/DA transporter selectivity factor rather than the 5HT/NE transporter selectivity factor of 120. The Kd's of 5HT & NE transporters in vitro were 8.9nM and 1060nM, respectively.Tatsumi, et al, Pharmacological profile of antidepressants and related compounds at human monoamine transporters, Eur J Psychopharmacology, 340(1997): 249-258.
Inhibition constants (Ki) from an Owens, et al (Nemeroff's group, 1997) study gave a similiar 100:1 ratio in cultured human cells (5HT - 102nmol/L; NE - 1644nmol/L).
Owens, MJ, et al, Neurotransmitter receptor and transporter binding profiles of antidepressants and their metabolites, J Pharmacol and Exp Ther, 283(1997): 1305-1322.
So, since I do not have access to the Richelson study you mention, I decided to check in Preskorn's book and look at the charts for Ki's. His charts, while not giving exact values, seem closer to your value of 5.4 than the value of 100 (for the selectivity factor) in Richelson's 1997 Kd study. Since comparing dissociation constants (Kd) and inhibition constants (Ki) may be different (are they?), it may be we are comparing apples and oranges. (I've been out of school too long to remember the difference).
Preskorn S, Outpatient management of depression: aguide for the primary care practioner, Chapter 6: The rational basis for the development and use of newer antidepressants, PCS, 1999.
The Harvey study you mention is in vivo, but the are measuring transporter levels outside of the CNS. Even that the pressor (NE) response at day 15 was not statistically significant in low and high dose venlafaxine groups (p 505-506). This is surprizing, as clinical experience shows that venlafaxine does have NE action at higher doses, as seen with the escalating dose/response curve.
Thanks again for finding my mistake. I am really not able to dig this deep into these subjects, anymore. This was fun and shows that I still make mistakes. Keep on Babbling, your presence here is needed to keep us honest. Also, good luck with your Celexa.
Fellow Babbler - Cam
Posted by Cam W. on May 18, 2000, at 19:03:26
In reply to Re: SSRIs: - Different, posted by SLS on May 18, 2000, at 7:44:41
Scott - I totally agree with you that it depends on the presentation of the depression as to which AD to try second. Many times one SSRI will work when another hasn't. To bad no systematic evalutions or guidelines have been done or are available. Any grad students looking for a project?Scott, the Johns, Elizabeth, bob, Dr.Bob and any other techno-pharmageek (like me) that I may have missed.
You people might be interested in an article I downloaded from Neuroscion (http:neuroscion.com). They give you six months or 30 articles to download. It is really a technical "geek" site; very in depth articles (the kind we like - COMT inhibitors, CRH antagonists, etc.).
Articles with names like, "On the design of neural networks in the brain by genetic evolution" or "Cannabinoids inhibit excitatory neurotransmissions in the substantia nigra pars reticulata" or "Serotonergic neurons and serotonergic receptors: gains from cytochemical approaches" or "Novel brain function: biosynthesis and actions of neurosteroids in neurons" or "Multiple substrates for seotonergic modulation of rat locus coeruleus neurons and relationships with kainite receptors" or "In vivo NMDA/dopamine interaction resulting in Fos productin in the limbic system and the basal ganglia of the mouse brain." I think you get the picture.
An article that you MUST read is in a journal called Brain Research Bulletin entitled:
"The specificity of stress responses to different nocuous stimuli: neurosteroids and depression" by someone out of McGill University by the name of B.Dubrovsky. It is an excellent article on man's thoughts on stress and depression from Plato through the existentialists to present day. A fantastic article (easy to read, too).
Posted by PeterJ on May 19, 2000, at 0:29:29
In reply to Re: SSRIs: - Different (Peter), posted by Cam W. on May 18, 2000, at 16:00:23
Cam,
Thank you for the additional data and analysis. I think were are in the same ballpark on the binding constants now.
You clearly know your stuff and your posts are always informative. It's fascinating how these abstract numbers somehow translate into human thoughts and emotions.
I just hope we haven't scared everyone away from this thread with our biochemistry geek talk! As as scientist I am always interested in the science behind these drugs. But as someone struggling with illness I am also interested in hearing the first hand experiences other people have had with these medications. I may be able to toss around some numbers and big words but when I am starting a new medication and I'm standing there with one of those colorful little pill in my hand I'm just as scared as anyone else.
Peter
Posted by Cam W. on May 19, 2000, at 7:14:57
In reply to Re: SSRIs: - Different (Cam and others), posted by PeterJ on May 19, 2000, at 0:29:29
Peter - Hang in there, I have found that this wonderful collection of people make up a huge brain mass of experience and knowledge. If you have a question, someone in this room will have already exprienced the problem.
The good thing is, is that many depressions can be resolved through pharmacotherapy, but more importantly, cognitive-behavioral therapy. This room is my psychotherapy. I actually find reading and posting in Babbleland therapeutic.
Also, the people here allow us to "geek-out" every now and then, so let's keep it coming when you come across interesting new "stuff". We also check and double check each other's figures and data. It keeps us honest.
Nice to hear from you - Cam
Posted by SLS on May 19, 2000, at 22:49:05
In reply to Re: SSRIs: - Different, posted by Cindy W on May 17, 2000, at 21:59:19
> PeterJ, I've tried Prozac (worked for a while for depression, but didn't help OCD even at 80 mg/day...plus made me anorgasmic). Next tried Luvox (great for OCD, OK for depression, but not even any sexual desire and a lot of thirst). Then Zoloft (sexual desire, but inability to climax again...otherwise OK for depression but not much good for OCD). Serzone was great for social anxiety and depression, and for good sleep and good sex, but didn't impact OCD. Effexor-XR has been great for depression and OCD at a higher dose (375 mg/day) but makes me feel like I'm too energized sometimes (have trouble sleeping at night) and interferes a bit with sexual arousal. The only side effects I've ever experienced on SSRI's besides the sexual side effects were thirst, initial fatigue (went away after a while with each medication), dizziness (esp on Effexor-XR;again went away), and mood swings (on Serzone; went away after a few weeks). Maybe I'm lucky, but only the sexual side effects really bother me (just indicates what my priorities are, huh?) ;)
> --Cindy W
Dear Cindy,How are you?
That's one hell of a compendium of serotonergic drug profiles you gave here. It's the best I've ever seen. I am struck by how well your descriptions match the reputations these drugs have. Thanks.
I was just wondering how you are doing, and whether you have managed to find the right drug regimen.
If you aren't doing well, I thought I might mention that I see three combination alternatives staring me in the face.
1. Serzone + Luvox
2. Effexor + Serzone (I believe Noa is currently having success with this).
3. Effexor + Remeron
See ya'
- Scott
This is the end of the thread.
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