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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 20 of 20. This is the beginning of the thread.
Posted by Anna Laura on July 18, 2001, at 13:54:57
Hi all,
I called my pdoc today, 'cause lately i've been suffering from "micro-bouts" of depression. He told me i might switch to effexor (i'm currently taking amytriptyline, 50 mg., plus 100 mg. of an atypical antipsicotic). He was quite reluctant, though. He told me it might be counterproductive since switching could be stressful and i don't need that. He finally told me that i could go ahead and take it. I'm puzzled: don't know what to do.
I recall months ago i read a research article which showed that switching might be dangerous in the long run. I switched already from Tofranil to Prozac and then from Prozac to amytryptiline and levo-sulpiride without any trouble ; (i didn't get any big results either).
Considering that i currently don't feel stable enough, switching could be a problem. Or not?I suffer from double depression, until the last month felt quite stable since my major problem was anhedonia. In the last few weeks i grew more nervous and apathetic. I don't know if i'm going backwards again or if it's just a false alarm ( I hope that).
What do you guys think?
Should i stay on my current medication or not?
Posted by SalArmy4me on July 19, 2001, at 1:15:36
In reply to Is switching stressful for your nervous system?, posted by Anna Laura on July 18, 2001, at 13:54:57
Switching to a newer medication is always a good idea, considering how the newer medications like effexor: require no blood tests, affect more wanted chemicals and less unwanted receptor sites, generally have less side-effects, and have overall better efficacy and compliance ratings among outpatients.
Posted by stjames on July 19, 2001, at 1:37:33
In reply to Is switching stressful for your nervous system?, posted by Anna Laura on July 18, 2001, at 13:54:57
Could you try taking more of the amytriptyline ?
I think the depression is back and you need to treat it. Isn't being depressed clearly bad for your health and nervous system ?
Posted by Elizabeth on July 19, 2001, at 7:56:38
In reply to Is switching stressful for your nervous system?, posted by Anna Laura on July 18, 2001, at 13:54:57
> I called my pdoc today, 'cause lately i've been suffering from "micro-bouts" of depression. He told me i might switch to effexor (i'm currently taking amytriptyline, 50 mg., plus 100 mg. of an atypical antipsicotic).
Which antipsychotic? They have different potencies.
> He was quite reluctant, though. He told me it might be counterproductive since switching could be stressful and i don't need that.
That's true. My idea would be to decrease the amitriptyline gradually, then start adding Effexor slowly. It might make the transition easier. I'm not sure of the exact details of how you might do this (like, a schedule). (There's the potential for Effexor to decrease the clearance of the amitriptyline, which could be bad; that you only take 50 mg of ami for depression suggests to me that you might already be metabolising it poorly, and I'm not sure what the right thing to do would be under those circumstances.)
> I suffer from double depression, until the last month felt quite stable since my major problem was anhedonia. In the last few weeks i grew more nervous and apathetic. I don't know if i'm going backwards again or if it's just a false alarm ( I hope that).
> What do you guys think?
> Should i stay on my current medication or not?I'd go for it with the Effexor, but slowly.
-elizabeth
Posted by Janelle on July 19, 2001, at 16:32:46
In reply to Is switching stressful for your nervous system?, posted by Anna Laura on July 18, 2001, at 13:54:57
Switching probably IS "stressful" to the nervous system, BUT it's probably something the system CAN handle and also isn't it "better" (so to speak!) to switch to another med if the one(s) a person is on are NOT working? JMHO (Just My Humble Opinion)
I'm far from stable (though I am improving) and my pdoc is doing switches to fine-tune my meds, so I don't think your not being stable should be a problem. In fact, your not being stable could be due to not finding the right meds yet, therefore NEEDING to switch!
I'd say go ahead and try the EffexorXR (GRADUALLY) but be careful since you said you are feeling "nervous" - I have that problem (nervousness) and Effexor is making it worse, so next visit to pdoc I'm gonna taper off and try a different a-d.
Good luck!
-Janelle
Posted by Elizabeth on July 19, 2001, at 17:35:15
In reply to Re: Is switching stressful for your nervous system?, posted by SalArmy4me on July 19, 2001, at 1:15:36
> Switching to a newer medication is always a good idea, considering how the newer medications like effexor: require no blood tests, affect more wanted chemicals and less unwanted receptor sites, generally have less side-effects, and have overall better efficacy and compliance ratings among outpatients.
The main down sides are that Effexor could raise blood pressure and is more likely to cause jitteriness than tricyclics are. Amitriptyline is one of the worst offenders among the tricyclics; I'm always surprised when I hear of someone who's taking it.
A healthy person shouldn't require any blood tests to take tricyclics, although it's a good idea to get an echocardiogram confirming that you don't have certain kinds of arrhythmias, and some people might want to get a serum level (although that's not usually done).
-elizabeth
Posted by SalArmy4me on July 19, 2001, at 18:10:26
In reply to Re: Is switching stressful for your nervous system? » SalArmy4me, posted by Elizabeth on July 19, 2001, at 17:35:15
I'm talking about the blood-tests needed to determine adequate treatment levels of imipramine, desipramine, and nortriptyline. Jitteriness? Venlafaxine XR is the only antidepressant also approved for Generalized Anxiety Disorder.
Posted by Elizabeth on July 20, 2001, at 0:22:21
In reply to Re: Is switching stressful for your nervous system?, posted by SalArmy4me on July 19, 2001, at 18:10:26
> I'm talking about the blood-tests needed to determine adequate treatment levels of imipramine, desipramine, and nortriptyline.
That's something that isn't really done very much unless there's a particular reason to believe a patient is a slow hydroxylator or there's an interaction (e.g., if the person is taking an SSRI too). Effective doses, for the most part, have been established. (Probably what ends up happening is that people who don't metabolise tricyclics properly just get a lot of side effects and stop taking them.)
> Jitteriness? Venlafaxine XR is the only antidepressant also approved for Generalized Anxiety Disorder.
That doesn't mean the other ones don't work. Nardil, e.g., is great for GAD. Plus I think that Paxil (at least) has been approved for GAD now, too.
-e
Posted by Elizabeth on July 20, 2001, at 0:24:44
In reply to Re: Is switching stressful for your nervous system?, posted by SalArmy4me on July 19, 2001, at 18:10:26
> Jitteriness? Venlafaxine XR is the only antidepressant also approved for Generalized Anxiety Disorder.
I forgot to mention this: Effexor and SSRIs tend to make people with anxiety or panic more anxious at first. The jitteriness goes away with time, but the first few weeks can be really hard unless you start at a very minimal dose and increase it very gradually. SSRIs and Effexor are more likely to cause this problem than tricyclics (or, I suspect, MAOIs) are.
-elizabeth
Posted by SalArmy4me on July 20, 2001, at 1:10:56
In reply to Re: Is switching stressful for your nervous system? » SalArmy4me, posted by Elizabeth on July 20, 2001, at 0:22:21
Clinicians sure do serum levels of imipramine, desipramine, and nortriptyline--I could consider a psychiatrist inept if he didn't do them, knowing how vital serum levels are to those drugs' successes:
Clinical Psychopharmacology Seminar
http://www.vh.org/Providers/Conferences/CPS/11.html
Treatment of Refractory Depression
Original Author(s): Bruce Alexander, Pharm.D.
Latest Reviser(s): Bruce Alexander, Pharm.D.,
Creation Date: 1996
Last Revision Date: January 2000"That serum level monitoring might lead to an improved response rate in the treatment of depression has been suggested (Perry et al 1987, Glassman et al 1977). (see table 1). The remaining TCAs and other antidepressants have inadequate data to make conclusions about therapeutic ranges. This topic is extensively reviewed in the monograph dealing with antidepressant dosing.
Glassman et al (1977) has reported that 40 to 50% of depressive patients do not achieve recommended serum levels with imipramine 200 to 225 mg/d. In this study, of the 13/16 patients that did not respond to levels < 180 ng/ml, 7 responded promptly when a level >200 ng/ml was achieved."
Posted by Anna Laura on July 20, 2001, at 2:45:47
In reply to Tricyclic Serum Levels » Elizabeth, posted by SalArmy4me on July 20, 2001, at 1:10:56
Thanks for answering everybody !!!
I feel a little bit reassured now.
Hope switching to Effexor it's going to be a good idea.Wishing you all the best,
Anna Laura
Posted by Elizabeth on July 20, 2001, at 15:44:21
In reply to Tricyclic Serum Levels » Elizabeth, posted by SalArmy4me on July 20, 2001, at 1:10:56
> Clinicians sure do serum levels of imipramine, desipramine, and nortriptyline--I could consider a psychiatrist inept if he didn't do them, knowing how vital serum levels are to those drugs' successes:
That may be true, but in actual practise, most psychiatrists only order a serum level if there's some specific reason to believe that the patient might not be metabolising the tricylic properly (or in the presence of another drug which may alter its metabolism). Some consider it important to monitor serum levels of amitriptyline and nortriptyline because of their atypical dose-response curves (they have a therapeutic window). Anyway, even if serum levels are tested, you only need to do it when you first start taking the drug -- it's not like taking lithium or Clozaril or somesuch.
Therapeutic levels haven't even been established for most of the tricyclics.
-elizabeth
Posted by SalArmy4me on July 20, 2001, at 21:37:13
In reply to Re: Tricyclic Serum Levels » SalArmy4me, posted by Elizabeth on July 20, 2001, at 15:44:21
Where is your proof of what you say?
> > Clinicians sure do serum levels of imipramine, desipramine, and nortriptyline--I could consider a psychiatrist inept if he didn't do them, knowing how vital serum levels are to those drugs' successes:
>
> That may be true, but in actual practise, most psychiatrists only order a serum level if there's some specific reason to believe that the patient might not be metabolising the tricylic properly (or in the presence of another drug which may alter its metabolism). Some consider it important to monitor serum levels of amitriptyline and nortriptyline because of their atypical dose-response curves (they have a therapeutic window). Anyway, even if serum levels are tested, you only need to do it when you first start taking the drug -- it's not like taking lithium or Clozaril or somesuch.
>
> Therapeutic levels haven't even been established for most of the tricyclics.
>
> -elizabeth
Posted by Waterlily on July 21, 2001, at 20:02:56
In reply to Re: Tricyclic Serum Levels » SalArmy4me, posted by Elizabeth on July 20, 2001, at 15:44:21
> > Clinicians sure do serum levels of imipramine, desipramine, and nortriptyline--I could consider a psychiatrist inept if he didn't do them, knowing how vital serum levels are to those drugs' successes:
>
> That may be true, but in actual practise, most psychiatrists only order a serum level if there's some specific reason to believe that the patient might not be metabolising the tricylic properly (or in the presence of another drug which may alter its metabolism).Just an interesting note on this topic - I'm a healthy 32 year old woman, 125 lbs, 5'8" tall. My psychiatrist had a serum imipramine level drawn about a month after I started on imipramine. I was on 75 mg., a dose that normally is not enough to be therapeutic. However, the blood test showed that the level was in the high therapeutic range, near being too much. My psychiatrist says that you never know when you'll encounter someone like this, so he always has the blood level monitered. I had a test back in November and I'm scheduled to have another test in a week or so.
Posted by Elizabeth on July 21, 2001, at 22:28:04
In reply to Re: Tricyclic Serum Levels, posted by SalArmy4me on July 20, 2001, at 21:37:13
> Where is your proof of what you say?
It's just my observation. Where's *your* proof that tricyclic serum levels are commonly monitored? You cite recommendations and you give your own opinion, but that doesn't mean that's the actual practise.
-e
Posted by Elizabeth on July 21, 2001, at 22:32:47
In reply to Re: Tricyclic Serum Levels, posted by Waterlily on July 21, 2001, at 20:02:56
Waterlily,
You're probably a slow hydroxylator. That's fairly common. In most cases when a person tries a tricyclic but isn't metabolising it properly, they get a lot of side effects and can't tolerate the drug. Some doctors will think to get a serum level, but many won't.
-elizabeth
Posted by Elizabeth on July 22, 2001, at 15:34:38
In reply to Re: Tricyclic Serum Levels, posted by SalArmy4me on July 20, 2001, at 21:37:13
OK, since you seem to think that an appeal to authority constitutes "proof," here's what Schatzberg & Nemeroff have to say:
"Despite a current appreciation for the great variability in metabolism of tricyclic drugs and a consequent need to individualize treatment, definitive therapeutic concentrations are not well established for all TCAs. Most critical analyses agree that therapeutic levels have been defined for only nortriptyline, imipramine, and desipramine (American Psychiatric Association Task Force 1989; Perry et al. 1987; Rudorfer and Potter 1987). Nonetheless, attempts have been made to provide estimates of reasonable therapeutic ranges for all marketed TCAs based on cumulative experience with therapeutic monitoring rather than on prospective controlled studies (Orsulak 1989). Lack of response, toxicity, minimizing adverse effects by using the minimal effective dose, and suspected pharmacokinetic interactions (e.g., with neuroleptics or SSRIs) are indications for measurements of plasma drug levels. Even without such measurements, daily doses of tricyclic drugs other than nortriptyline or protriptyline can be increased to 300-350 mg of imipramine or the equivalent if side effects allow. Dose increases of nortriptyline require monitoring because plasma levels greater than 150 ng/mL are as ineffective as those yielding a subtherapeutic (< 50 ng/mL) level."
IOW, tricyclic serum level monitoring is something that's only done when there's a specific reason to do it: it's not necessary as a general rule. In reality, a lot of doctors don't do it even when it is called for.
If there is a need for measurement of serum levels, you should arrange for the blood to be drawn about 10 hours after your last dose.
-e
Posted by stjames on July 22, 2001, at 16:24:13
In reply to Re: Tricyclic Serum Levels, posted by SalArmy4me on July 20, 2001, at 21:37:13
> Where is your proof of what you say?
>Look to the internet or "Listening to Prozac"
Blood levels of TCA's are not very predictive
of outcome. After all it is not blood that has the synapse.
They are done just to get an idea if
a patient is a rapid metabolizer.James
Posted by Sunnely on July 22, 2001, at 21:22:12
In reply to Re: Tricyclic Serum Levels, posted by stjames on July 22, 2001, at 16:24:13
Although not all psychotropic drugs require therapeutic drug monitoring (TDM), there are situations in which psychotropic TDM is useful:
1. When the possibility of genetic polymorphism exists in one of the cytochrome P450 enzyme families, rendering them extensive metabolizers (EMs) or poor metabolizers (PMs) of certain drugs. For example, about 8% of Caucasians are genetically deficient in CYP2D6 enzymes making them more prone to dangerous blood levels of a psychotropic drug that depends on this enzyme for metabolism such as desipramine (Norpramin). Genetic deficiency of CYP2D6 may also explain the lack of response to adequate dosage of analgesics such as codeine preparations and tramadol (Ultram) as these drugs require the presence of CYP2D6 to be converted to their active metabolites, morphine and M1, respectively.
2. Drug-drug interactions. Certain medications can affect the metabolism of some of the psychotropic drugs. For example, carbamazepine (Tegretol) can decrease the blood levels of haloperidol (Haldol) by as much as 50% via induction of hepatic metabolism leading to decreased blood level of haloperidol and subsequent psychotic relapse. On the other hand, cimetidine (Tagamet) increases the blood level of haloperidol leading to increased haloperidol side effects (e.g., tremor, rigidity, motor restlessness). Fluoxetine (Prozac) and paroxetine (Paxil) can increase the blood level of desipramine (Norpramin) leading to increased desipramine side effects and potentially dangerous electrocardiogram abnormality.
The antibiotic ciprofloxacin (Cipro) and the antidepressant fluvoxamine (Luvox) can significantly increase the blood level of clozapine (Clozaril), and also olanzapine (Zyprexa), which can cause increase side effects (even acute delirium and/or seizures with clozapine). On the other hand, cigarette smoking can decrease the blood levels of clozapine and olanzapine leading to loss of effectiveness and psychotic relapse. Conversely, abrupt discontinuation of cigarette smoking may lead to an increase in clozapine (and olanzapine) blood level leading to toxicity.
3. For certain drugs which induce their own metabolism resulting in declining blood levels (e.g., carbamazepine or Tegretol). Tegretol is an "autoinducer," it induces its own metabolism.
4. When drug toxicity may be confused with the disease being treated. Akathisia (motor restlessness) and anxiety/agitation are difficult to differentiate. Increasing the dose of the antipsychotic drug may worsen the akathisia. Checking the antipsychotic blood level (e.g., haloperidol) may help resolve this problem.
Dry mouth, constipation, and lethargy can be symptoms of depression as well as adverse effects of TCAs. Without TDM, the doctor may increase the dose of TCA due to presumed worsening of the mood disorder, leading to further increase in TCA toxicity.
5. Suspected noncompliance. Forty percent of patients are noncompliant with psychotropic drugs. Erratic compliance can lead to subtherapeutic blood concentrations, leading to prolonged duration of illness.
6. For drugs with narrow therapeutic index (margin of safety between therapeutic blood level and toxic blood level) such as lithium. This is of particular importance especially in the elderly patients, those with concomitant medical illness, taking other drugs, and children.
7. For drugs whose activity is dependent upon the parent and active metabolites (e.g., several TCAs, antipsychotics, and anti-anxiety drugs).
8. For maintenance treatment when minimum effective blood level is required for prophylaxis (e.g., lithium). Although lithium levels between 0.8 - 1.2 is the general guideline to the treatment of acute mania of bipolar disorder, lower blood levels may suffice once mania has been stabilized.
9. For emergency management of psychotropic drug overdose. For example, serial blood levels (among other measures) of lithium or TCA in the medical management in cases of acute overdoses are of utmost importance.
10. Prediction of dose needed to achieve a therapeutic blood level at steady state. For example, following a single 600-mg dose of lithium, a 24-hour blood lithium level can be used to determine the dosage that will be required to achieve a steady-state blood level between 0.6 to 1.2. Similar nanograms are available for some TCAs, although therapeutic blood levels for these drugs are less well established. Also, checking for valproate blood level a few days after insitituting a loading dose of Depakote.
11. To document the level of a therapeutic dose for an individual patient, especially those patients requiring unusually high or low doses (may be helpful for legal purpose). For example, some extremely rapid metabolizers require unusually high doses that exceed usual guide; slow metabolizers should be treated with extremely low doses that would usually be considered subtherapeutic. Lack of TDM in the case of a sudden death with substantially elevated postmortem blood drug concentrations may be seen as negligence.
12. Minimize cost. For example, noncompliance and subtherapeutic blood levels usually delay the improvement of the illness, leading to prolonged hospital stay or additional outpatient visits. Identifying excessive psychotropic blood levels avoids toxicity, further avoiding unnecessary or prolonged hospitalization (and additional and costly laboratory tests).
SOME TIPS for TDM:
1. Drug levels are most reliably measured as "trough" levels; sample is drawn sometime after the elimination commences, usually 10 to 12 hours after the last dose. It is usually drawn in the morning, before the morning dose is taken, if one is scheduled.
2. The patient should be at pharmacokinetically stable blood level; after at least 4 to 5 half lives before checking for TDM. However, a doctor can order a psychotropic blood level anytime if he/she suspects toxicity, noncompliance, or drug-drug interactions.
3. As with any laboratory test, results should be interpreted with the patient's clinical condition in mind. For example, even if a patient's lithium blood level says 0.8-1.2 (within therapeutic range) but the patient is experiencing symptoms such as lethargy, confusion, increased tremor, unsteadiness, diarrhea, primary consideration should be lithium toxicity despite the "normal" lithium level. Lithium must be stopped immediately.
4. If you adjust for an interactive drug and take the interactive drug away, you've got to readjust. (For example, effect of cigarette smoking and abrupt discontinuation of smoking on certain drugs such as clozapine or olanzapine.)
> > Where is your proof of what you say?
> >
>
> Look to the internet or "Listening to Prozac"
> Blood levels of TCA's are not very predictive
> of outcome. After all it is not blood that has the synapse.
> They are done just to get an idea if
> a patient is a rapid metabolizer.
>
> James
Posted by Elizabeth on July 23, 2001, at 16:21:14
In reply to Re: Tricyclic Serum Levels, posted by stjames on July 22, 2001, at 16:24:13
> Look to the internet or "Listening to Prozac"
> Blood levels of TCA's are not very predictive
> of outcome. After all it is not blood that has the synapse.
> They are done just to get an idea if
> a patient is a rapid metabolizer.Exactly; or if there's something else that might be going on (such as a pharmacokinetic interation with another drug).
Sunnely goes on in more detail about when monitoring the dose is necessary or helpful. (BTW, Lamictal, as well as Tegretol, is an autoinducer.)
-elizabeth
This is the end of the thread.
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