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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by turalizz on July 31, 2002, at 10:19:19
Hi Shawn,
Do you have any interesting information about trazodone? Where does its sedation come from? What affinities does it have for receptors (as agonist or antagonist)? What is its half-life and clearance time?
It is the best sleep aid I've ever tired, and very interestingly I am not developing a tolerance against it. I am very curious why.
thanks,
cem
Posted by Stan on August 1, 2002, at 1:17:19
In reply to Shawn -- info on trazodone needed!, posted by turalizz on July 31, 2002, at 10:19:19
> Hi Shawn,
>
> Do you have any interesting information about trazodone? Where does its sedation come from? What affinities does it have for receptors (as agonist or antagonist)? What is its half-life and clearance time?
>
> It is the best sleep aid I've ever tired, and very interestingly I am not developing a tolerance against it. I am very curious why.
>
> thanks,
>
> cemhi cem -- i'm not shawn (obviously) but if you don't mind i'll take a shot at partially answering a couple of your queries -- perhaps shawn'll follow up with more detail and in a more technical fashion (i've come across a few of his posts since i starting checking out this board a week ago and they are very comprehensive!).
i took trazodone for about a year, up until such time that serzone became available in the usa (i think this was about 1995?). i had tried a couple of SSRIs (zoloft, paxil) for short trials before i started the trazodone (i suffer from "anxious depression") but they didn't improve my symptoms of restlessness and anxiety......in fact they made me feel a little "speedy" and "wired" -- so i discontinued them and decided that SSRIs in general weren't my bag. once i started the trazodone i noticed an almost immediate improvement in my symptoms of anxiety and restlessness -- but it was highly sedating, even at fairly low doses. trazodone is a weak reuptake inhibitor of serotonin and norepinephrine, but these mild effects are not its main mechanism of action. rather, the drug acts as a relatively potent antagonist at the group of 5HT2 serotonin receptors, and this activity is viewed as a major factor in relieving anxiety and helping to supress negative, intrusive thoughts. in addition, trazodone antagonizes alpha1-adrenergic receptors in similarly potent fashion, and therein lies the major reason for its prominent sedative qualities. by antagonizing this group of adrenoreceptors (i think that's a word), it acts a bit like certain blood pressure medications which work on the same receptor group in the same way -- the result can be drowsiness, fatigue, weakness,dry mouth, hypotension, etc.
however, on the plus side, trazodone can have additive anti-anxiety effects for certain individuals by antagonizing this receptor group, because the "activating" effects that the alpha1 group produces can heighten anxious feelings when left unchecked in a person sensitive to excess norepinephrine coursing through the body.i had difficulty tolerating trazodone because of the sedation and when serzone came out i made the switch and i still take serzone today (although i feel like it's "pooping-out" on me). serzone and trazodone are strikingly similar in many respects and it's been said that bristol-myers (manufacturer of both branded drugs) developed serzone as a response to complaints about trazodone's extreme sedation and occasional reports of priapism -- the main difference is that while serzone is also an antagonist at "alpha1," its effects there are so weak as to be nearly inconsequential, thus clearing up the two potential problems mentioned just above. the two drugs have a very similar chemical structure and serzone can almost be considered an "update" on desyrel (brand name for trazodone). for a time i combined them -- serzone in the morning, trazodone at night, but now i'm combining serzone with some other meds.
well, that was quite a ramble and i get the feeling that you're simply taking it as a sleep aid, cem, and one of your questions had to do with developing a tolerance to its effects - you may have to increase the dosage somewhat as time goes by -- if you keep antagonizing "alpha1," the receptor group may "fight back" and "up-regulate" for awhile.....the same phenomenon can be observed with some blood pressure meds that target this receptor group. you asked about half-life; i think it's about 7-8 hours.....if you take a decent dose you may have a bit of trouble dragging yourself out of bed in the morning. i'm guessing that you're taking about 50 mg before retiring. when used as an AD the range is more like 150-300 mg for most people, i believe.
hope that info helped a bit -- i think most of my statements are relatively accurate but i'm just an amateur :)
good luck,
Stan
Posted by turalizz on August 1, 2002, at 9:18:56
In reply to Re: Shawn -- info on trazodone needed! » turalizz, posted by Stan on August 1, 2002, at 1:17:19
Posted by Anyuser on August 1, 2002, at 10:39:18
In reply to Re: Shawn -- info on trazodone needed! » turalizz, posted by Stan on August 1, 2002, at 1:17:19
I am considering trying Serzone and I would like to ask you a couple of questions.
Do you have any problems with dizziness or somnolence on Serzone?
When do you take Serzone? There is one Bristol-Meyer study that says Serzone can be taken in one dose at night. Ever tried that? I wonder if taking a therapeutic dose at night would minimize daytime side effects.
What other drugs do you take with Serzone? I am considering Serzone with Wellbutrin.
Thanks.
Posted by Stan on August 2, 2002, at 2:27:41
In reply to Serzone » Stan, posted by Anyuser on August 1, 2002, at 10:39:18
> I am considering trying Serzone and I would like to ask you a couple of questions.
>
> Do you have any problems with dizziness or somnolence on Serzone?
>
> When do you take Serzone? There is one Bristol-Meyer study that says Serzone can be taken in one dose at night. Ever tried that? I wonder if taking a therapeutic dose at night would minimize daytime side effects.
>
> What other drugs do you take with Serzone? I am considering Serzone with Wellbutrin.
>
> Thanks.________________________
hey anyuser -- i wasn't aware that B-M had conducted a study which suggested that serzone might work just as well with a once-daily dosing regimen. for my part, i take a 200 mg pill at noon and another at midnight. after an initial "break-in" period of about a week while your body adjusts to the medication, you probably won't experience any bothersome side effects to speak of during the day. if there's some mild drowsiness, dizziness, or postural hypotension at first, it should fade fairly soon. it's not like trazodone which delivers a "knock-out punch" of sleepiness with each dose. but if B-M says it's ok to take the whole daily dose before bed, then you could always try it if your doc gives you the green light. i think it has a relatively short half-life (about 4 hrs) but some of its metabolites have much longer half-lives.....
.....which brings me to your questions about combining serzone with other meds. unfortunately, serzone interacts with a lot of other psych-meds because it is processed by a liver enzyme which i believe is known as P450 CYP3A4. i found out the hard way that when you take serzone concurrently with certain other drugs, the metabolism of serzone and these other drugs can be altered and often slowed down, and you end up with higher blood levels of some in your system.....and the half-lives are extended. i took xanax with serzone for awhile but the combo causes xanax blood levels to double what they normally would be and the half-life is doubled as well. so now i combo w/ativan.
but that's not all on the interaction front....i combine it with buspar as well....for years i took 15 mg a day -- it made me lightheaded and dizzy at first but after awhile i got used to it.....but a few months ago i found that coadministration of these two causes plasma buspirone levels to rise up to 20 to 50-fold times normal! (this info is in the package insert, but i'd never gotten one from the pharmacy until last winter) i've probably fried every serotonin receptor in my brain by now! it's the liver enzyme issue again....if you're going to try a combo, you should investigate the interaction issue carefully -- serzone's metabolites are processed by various *other* liver enzymes and taking multiple meds that inhibit these enzymes can create a contraindication or at the least necessitate dosage adjustments. oh yeah, and you can't drink grapefruit juice!
i can't comment on the combo with wellbutrin you're considering because i've never combined serzone with another drug classified strictly as an AD nor have i taken wellbutrin -- i might try it someday, but i've always felt it would be too "activating" for my overly-anxious self. who knows, i might have a "paradoxical reaction" to it and calm down. if i try another AD soon, it might be remeron, though i wish they hadn't made it with such potent antihistamine effects -- i fear it will leave me exhausted all of the time due to this factor.....so i'm waiting to see if i can get some samples without springing for a whole month's supply.
aside from the meds i mentioned, i occassionally take 25 mg of trazodone before bed (my tolerance for it is low these days) and i also take low-dose mirapex (D2/D3 dopamine agonist) for restless legs syndrome -- it also reduces anxiety a bit. i have tried to taper some of these down with the ultimate goal of discontinuing some, but i seem to have great difficulty with that -- i don't feel like my program is working very well and i'm still acutely anxious and depressed......but if i try to phase a med out, i feel MUCH worse, so i'm currently stuck in a rut.
thanks for listening,
Stan
Posted by Anyuser on August 2, 2002, at 10:09:38
In reply to Re: Serzone » Anyuser, posted by Stan on August 2, 2002, at 2:27:41
This is from J Clin Psychiatry 2002;63, notes omitted by Anyuser. It was funded by Bristol-Meyers.
Once-Daily Dosing
Early studies documenting the efficacy of nefazodone used a b.i.d. dosing schedule partly based on the short half-life of the drug (i.e., 4-8 hours). More recent data, however, show no significant differences with once- versus twice-daily nefazodone. Markovitz and Wagner conducted a study of 209 patients with major depression to compare once-daily dosing at bedtime with b.i.d. dosing of nefazodone. The titration schedules utilized, mean daily dose, and mean length of therapy are noted in Table. 2 [omitted by Anyuser]. According to CGI scores, 77% of bedtime-treated patients and 75% of b.i.d.-treated patients improved (defined as > 50% improvement in depressive symptoms); 51% and 43% of bedtime- and b.i.d.-treated patients, respectively, were complete responders. Dropout rates were 11.3% and 8.2%. for bedtime- and b.i.d.-treated patients, respectively. The investigators concluded that the efficacy and tolerability of nefazodone administered once daily at bedtime are comparable to those of b.i.d. administration.
To determine whether efficacy and tolerability would be maintained with the bedtime dosing, Preskorn and colleagues conducted a 12-week, open-label continuation study in 47 depressed patients who responded to 12 weeks of nefazodone b.i.d. therapy (300--600 mg/day). At the end of the l2-week acute phase, patients' morning doses of nefazodone were halved and evening doses were increased by 50%; after 1 week, the entire daily dose was administered in the evening. Of 41 evaluable patients, antidepressant response was maintained or improved in 39 patients (95%) according to CGI-Improvement and -Severity of Illness subscales. Most patients (89%) tolerated the switch to a bedtime dose regimen without difficulty. Five patients (11%) discontinued treatment during the initial 2-week period of dose transition, primarily for adverse events. Overall, patients maintained good clinical response, or experienced further improvement, with bedtime nefazodone continuation therapy, based on results of both clinician and patient ratings. The tolerability of once-daily nefazodone dosing was excellent, and no safety concerns were evident during this extended treatment. This open study suggests that once-daily dosing of nefazodone is a convenient and safe treatment option.
Posted by Anyuser on August 2, 2002, at 10:26:42
In reply to Re: Serzone » Anyuser, posted by Stan on August 2, 2002, at 2:27:41
This is the end of the thread.
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