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Dr. Bob is Robert Hsiung, MD,
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Posted by Ritch on December 29, 2004, at 17:03:42
In reply to Re: What to combine with a mood stabilizer? » Ritch, posted by tensor on December 29, 2004, at 13:24:37
> I was actually thinking of get rid of both remeron and zoloft. And then start with nortrip+mood stab. But do have i have to check blood levels for nortrip?
Some people don't get them checked if they show no signs of toxicity and they are responding to the nortriptyline (as Ed mentioned). I just thought it might be a good idea should you combine the Zoloft with it--- because the Zoloft (and other SSRI's) will inhibit liver enzymes that break down the nortriptyline, which may cause very high levels of the nortriptyline at a "standard" dosage and possible toxicity. Some people are "poor metabolizers" of TCA's like nortiptyline as well (without taking an SSRi). Combining SSRI and TCA can raise blood levels of the TCA ten-fold in some cases. Just being cautious. When I took Zoloft+Nortiptyline I was only taking 20-30mg of NT, didn't get blood level done, the only side effects I got from nortrip. besides some dry mouth was a little shakiness with "pins and needles" skin sensations(like from watching a scary movie) and an elevated heart rate. Oh, you might get a decent mood boost when you stop the Remeron.. I definitely did! Good luck!
Posted by banga on December 29, 2004, at 17:12:59
In reply to Re: What to combine with a mood stabilizer? » banga, posted by tensor on December 29, 2004, at 13:30:20
>
> Did it help you for depression/anxiety?
>
> Kind regards,
> MattiasIf you mean did nortryptiline help me, I haven't been on it long enough to find out. I did not have any other side effects other than the weight gain. My body seems to not mind tricyclics.
I also have some cognitive dysfunction..with the nortryp, I had hoped for some activating effects, perhaps for my mind too. I may be adding a stimulant down the line...
>
Posted by ed_uk on December 29, 2004, at 17:31:12
In reply to Re: What to combine with a mood stabilizer? » tensor, posted by Ritch on December 29, 2004, at 17:03:42
> Some people don't get them checked if they show no signs of toxicity and they are responding to the nortriptyline (as Ed mentioned). I just thought it might be a good idea should you combine the Zoloft with it--- because the Zoloft (and other SSRI's) will inhibit liver enzymes that break down the nortriptyline, which may cause very high levels of the nortriptyline at a "standard" dosage and possible toxicity. Some people are "poor metabolizers" of TCA's like nortiptyline as well (without taking an SSRi). Combining SSRI and TCA can raise blood levels of the TCA ten-fold in some cases. Just being cautious. When I took Zoloft+Nortiptyline I was only taking 20-30mg of NT, didn't get blood level done, the only side effects I got from nortrip. besides some dry mouth was a little shakiness with "pins and needles" skin sensations(like from watching a scary movie) and an elevated heart rate. Oh, you might get a decent mood boost when you stop the Remeron.. I definitely did! Good luck!
Hi Mattias,
Ritch is right, getting a plasma level is more important if you were going to combine nort with sertraline. In my last post I was assuming that you'd be taking the nort on its own.
Although sertraline certainly can raise nort plasma levels, it is considerably less problematic than some of the other SSRIs in this respect. Here is a summary of a little study...........
'A study in 14 elderly patients on nortriptyline found that when additionally given 50 mg sertraline daily, the median increase in plasma nortriptyline levels was only 2% (with a range of –26 to 117%), but two of them showed increases of 51% and 117% respectively, changes the authors considered clinically meaningful. For those taking higher doses of sertraline (100 to 150 mg daily) the median increase in nortriptyline plasma levels was 40% (with a range of −12% to +239%).'
Because some people are very sensitive to nortriptyline (eg. poor metabolizers) it is important to start with a very low dose and to increase gradually if necessary. Careful dose titration based on efficacy and tolerability is in many ways as useful as plasma concentration monitoring. People who suffer 'strong' side effects at very low doses are likely to be poor metabolizers.
A suitable starting dose for nortriptyline is 10mg. In the absense of other medication, most people need 50-100mg/day of nort to get a good antidepressant effect. As ever, YMMV, some people will need more (it is unusual to exceed 150mg/day) and others will do well on less. As Ritch said, lower doses of nort may be sufficient for a person taking sertraline.
If severe side effects are present at very low doses it would be useful to get a plasma level- a high plasma conc would suggest that the person may be a poor metabolizer.
If a person fails to improve on nort, a plasma level can tell you whether you should increase or decrease the dose in order to maximize effectiveness. With nort, too high a dose may make the treatment less effective ie. it has a 'therapeutic window'.
Ed.
Posted by ed_uk on December 29, 2004, at 18:34:13
In reply to Re: What to combine with a mood stabilizer?, posted by banga on December 29, 2004, at 17:12:59
Hi!
You may prefer desipramine to nort. Desipramine is more 'activating' than nort and should be less likely to cause weight gain! Have you tried desip already?
Regards,
Ed.
Posted by linkadge on December 31, 2004, at 14:56:36
In reply to To banga, posted by ed_uk on December 29, 2004, at 18:34:13
Why is desipramine considered more activating than nortryptaline ??
Desipramine is a mixed ser/nor reuptake inhibitor while nortryptaline is selective to the norepinephrine transporter.
Linkadge
Posted by ed_uk on December 31, 2004, at 15:25:30
In reply to to Ed_UK, posted by linkadge on December 31, 2004, at 14:56:36
Desipramine is a selective norepinephrine reuptake inhibitor, as is nortriptyline. Nortriptyline has a greater affinity for H1 receptors than desipramine, which might explain why nort sometimes causes drowsiness. As far as I know, nortriptyline also blocks 5-HT2 receptors, which might possibly cause drowsiness as well.
Ed.
Posted by banga on December 31, 2004, at 16:24:18
In reply to Re: TCAs » linkadge, posted by ed_uk on December 31, 2004, at 15:25:30
I have not tried desipramine. If it causes less weight gain, wow it could be a great option. Somehow I find it easier to find detailed info on SSRIs than on TCAs, except for one article that describes how much each acts on serotonin as opposed to norepinephrine.
But in terms of 5HT2a blocking...doesn't that help with anxiety in some cases? I also looked at notrtyp because this seems to be a common element in many (well, "many" being rather relative!)drugs that have helped me w/anxiety (clomipramine, geodon). Of course this was just a guess, that this mechanism is helpful for me...
But thanks for the desipramine hint. Now I have to think how I will pose this to my pdoc after just convincing her that nortryp is the next logical choice.
Posted by ed_uk on December 31, 2004, at 17:04:27
In reply to Re: TCAs-desipramine, posted by banga on December 31, 2004, at 16:24:18
> I have not tried desipramine. If it causes less weight gain, wow it could be a great option.
Hi Banga!!
Weight gain isn't often reported with desipramine but I'm sure that it's possible! Some people have even reported weight loss. As far as I know, desipramine is a weaker antihistamine than nortriptyline and also a weaker 5-HT2 antagonist- this suggests that it would be less likely to cause weight gain.
> But in terms of 5HT2a blocking...doesn't that help with anxiety in some cases?
Yes, I think that it probably does in some cases. Noradrenergic drugs such as nortriptyline, lofepramine and desipramine do at times cause anxiety as a side effect. On the other hand, NRIs can be useful in treating panic disorder. Personally, I haven't noticed any change in my anxiety since I've been taking lofepramine.
> But thanks for the desipramine hint. Now I have to think how I will pose this to my pdoc after just convincing her that nortryp is the next logical choice.
Well, it is usually necessary to try several different drugs to see which you prefer..... if only our responses to drugs were more predictable.
Regards,
Ed.PS. Happy New Year!
Posted by ed_uk on December 31, 2004, at 17:22:31
In reply to Re: TCAs » banga, posted by ed_uk on December 31, 2004, at 17:04:27
You might be interested in this.......
J Clin Psychiatry. 1987 Jan;48(1):27-8.
The effect of desipramine on body weight in depression.
Levitt AJ, Joffe RT, Esche I, Sherret D.
Twenty-six patients with major depressive disorder were treated with desipramine for 4 weeks to determine the effect of the drug on body weight. Responders to desipramine showed a weight gain only at Weeks 3 and 4; nonresponders had a nonsignificant loss of weight. The increase in body weight of the responders was independent of dosage, sex, and hospitalization status. These findings suggest that the small increase in body weight that occurs in patients taking desipramine is associated with treatment response. In addition, desipramine may be a valuable treatment alternative for those patients in whom excessive weight gain is undesirable.
Posted by ed_uk on December 31, 2004, at 17:41:13
In reply to Re: TCAs » banga, posted by ed_uk on December 31, 2004, at 17:04:27
On the other hand this is not good.....
Fernstrom and Kupfer (Psychiatry Research, 26: 256-271, 1988) compared weight change in patients treated with amitriptyline, nortriptyline, desipramine, and zimelidine. They reported weight gain in 89% of patients treated with amitriptyline, 67% of patients treated with nortriptyline, 58% of patients treated with desipramine, and 8% of those treated with zimelidine.
Well, at least desipramine wasn't as bad as nortriptyline! I still think that you should try it!
Ed.
Posted by banga on January 3, 2005, at 0:59:24
In reply to Re: TCAs..... to Banga, posted by ed_uk on December 31, 2004, at 17:41:13
Thank you Ed for the info! I know of course no antidepressant is a guarantee for working; and the nortryp--and maybe then desipramine--will be a first try in the more norepinephrine direction..I suppose on the one hand I should be thankful that TCAs seem to agree with me, as my pdoc said--she was mightliy impressed that the only side effect I had at all from clomipramine was weight gain..and some mild postural hypotension. For the brief time on nortryptiline, I did not notice anything bothersome other than the weight. I will see my pdoc Tuesday, discuss options...perhaps adding zonegran to counteract TCA weight gain? Right now I am only on 100 mg lamictal, amazing I am doing so well, although the past few days I fear I may be losing effectiveness.
Posted by banga on January 3, 2005, at 19:59:51
In reply to Re: TCAs -ed_uk, posted by banga on January 3, 2005, at 0:59:24
Now about TCAs and sexual side effects...does it seem as though the less serotogenic ones, say like desipramine, have less effect on libido etc? or is that just wishful thinking?
Posted by ed_uk on January 3, 2005, at 20:20:45
In reply to Re: TCAs-desipramine, posted by banga on January 3, 2005, at 19:59:51
Hi!
Yes, desipramine does seem to have less effect on libido than most ADs.
BTW, have you considered maprotiline (Ludiomil)? It is a NRI which would be expected to cause little weight gain or sexual side effects.
Regards,
Ed.
Posted by banga on January 3, 2005, at 20:59:16
In reply to Re: TCAs-desipramine » banga, posted by ed_uk on January 3, 2005, at 20:20:45
Ludiomil--that's a really old one, isn't it? I dont know why some of these old ones are simply not heard about these days. If you know off-hand any links with info on it, let me know! Ill do a search myself now, it's just that I am not search engine whiz kid of the century. Plop me in a physical med library, it's a different story.
Thanks yet again for the advice.
Posted by KaraS on January 3, 2005, at 22:00:48
In reply to Re: TCAs-desipramine, posted by banga on January 3, 2005, at 20:59:16
> Ludiomil--that's a really old one, isn't it? I dont know why some of these old ones are simply not heard about these days. If you know off-hand any links with info on it, let me know! Ill do a search myself now, it's just that I am not search engine whiz kid of the century. Plop me in a physical med library, it's a different story.
>
> Thanks yet again for the advice.
I used to take a small amount of maprotiline/Ludiomil (25-50 mg. I think) for several years to help me sleep. I found it very easy to tolerate. I didn't feel as drugged in the morning as I used to on doxepin. That little bit would keep me from having anxiety problems and panic attacks. I did gain weight on it though.
Posted by ed_uk on January 3, 2005, at 22:14:20
In reply to Re: TCAs-maprotiline » banga, posted by KaraS on January 3, 2005, at 22:00:48
>I did gain weight on it though.
Oh dear! Maybe desipramine would be better.
Ed.
Posted by ed_uk on January 3, 2005, at 22:20:33
In reply to Re: TCAs-maprotiline » banga, posted by KaraS on January 3, 2005, at 22:00:48
I think I may have made a mistake about maprotiline and weight gain :-( Don't think it's too bad in the sexual department though!
Here is some info. The risk of skin rashes and seizures is emphasized.
Adverse Effects, Treatment, and Precautions
Adverse effects with maprotiline, a tetracyclic antidepressant, are broadly similar to those with tricyclic antidepressants (see Amitriptyline, ) but antimuscarinic effects are less frequent.Skin rashes seem more common with maprotiline than with tricyclic antidepressants. Seizures have occurred in patients with no prior history of such disorders as well as in those with a history of epilepsy and the risk is increased if high doses of maprotiline are employed. It should not be used in patients with epilepsy or a lowered seizure threshold.
Incidence of adverse effects.
By March 1985 the UK Committee on Safety of Medicines1 had received reports of the following adverse reactions associated with maprotiline from a cumulative total of 2.5 million prescriptions: convulsions (124 cases), hepatic reactions (4 cases), and haematological reactions (8 cases). There had also been 454 reports of skin rashes.1. Committee on Safety of Medicines. Dangers of newer antidepressants. Current Problems 15 1985.
Effects on the skin.
In addition to many recorded instances of skin rashes with maprotiline (see ) cutaneous vasculitis, which resolved on discontinuation of therapy, has also been observed.11. Oakley AMM, Hodge L. Cutaneous vasculitis from maprotiline. Aust N Z J Med 1985; 15: 256–7. PubMed
Epileptogenic effect.
In a retrospective review of 186 psychiatric patients with no history of seizures, 5 of 32 patients receiving maprotiline developed generalised tonic-clonic seizures, compared with 1 of 45 receiving a tricyclic antidepressant.1 There were no seizures in the remaining patients who received other medications, or no drug treatment. Two of the 5 patients experiencing seizures with maprotiline were receiving doses of 75 to 150 mg daily, 2 were receiving daily doses of 200 to 300 mg, and one patient experienced partial complex seizures with a daily dose of 150 mg and generalised tonic-clonic seizures after increasing the daily dose to 300 mg.1. Jabbari B, et al Incidence of seizures with tricyclic and tetracyclic antidepressants. Arch Neurol 1985; 42: 480–1. PubMed
Overdosage.
Apart from seizures being more common with maprotiline, features of overdosage are similar to those experienced with tricyclic antidepressant poisonings (see under Adverse Effects of Amitriptyline, ).For a discussion of choice of antidepressant with respect to toxicity in overdosage, see under Depression, .
References.
1. Crome P, Newman B. Poisoning with maprotiline and mianserin. BMJ 1977; 2: 260. PubMed
2. Curtis RA, et al. Fatal maprotiline intoxication. Drug Intell Clin Pharm 1984; 18: 716–20. PubMed
3. Knudsen K, Heath A. Effects of self poisoning with maprotiline. BMJ 1984; 288: 601–3. PubMed
4. Crome P, Ali C. Clinical features and management of self-poisoning with newer antidepressants. Med Toxicol 1986; 1: 411–20. PubMed
Porphyria.
Maprotiline hydrochloride is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in animals.Interactions
Interactions associated with maprotiline are similar to those associated with tricyclic antidepressants (see Amitriptyline, ).Pharmacokinetics
Maprotiline is slowly but completely absorbed from the gastrointestinal tract. It is widely distributed throughout the body and is extensively bound to plasma protein.Maprotiline is extensively demethylated in the liver to its principal active metabolite, desmethylmaprotiline; paths of metabolism of both maprotiline and desmethylmaprotiline include N-oxidation, aliphatic and aromatic hydroxylation, and the formation of aromatic methoxy derivatives. In addition to desmethylmaprotiline, maprotiline-N-oxide is also reported to be pharmacologically active. The average elimination half-life of maprotiline is reported to be about 43 hours and that of its active metabolite even longer (range 60 to 90 hours). Maprotiline is excreted in the urine, mainly in the form of its metabolites, either in free or in conjugated form; appreciable amounts are also excreted in the faeces.
Maprotiline is distributed into breast milk (see Breast Feeding under Precautions of Amitriptyline, ).
References.
1. Maguire KP, et al An evaluation of maprotiline: intravenous kinetics and comparison of two oral doses. Eur J Clin Pharmacol 1980; 18: 249–54. PubMed
2. Alkalay D, et al. Bioavailability and kinetics of maprotiline. Clin Pharmacol Ther 1980; 27: 697–703. PubMed
3. Firkusny L, Gleiter H. Maprotiline metabolism appears to co-segregate with the genetically-determined CYP2D6 polymorphic hydroxylation of debrisoquine. Br J Clin Pharmacol 1994; 37: 383–8. PubMed
Uses and Administration
Maprotiline is a tetracyclic antidepressant with actions and uses similar to those of tricyclic antidepressants (see Amitriptyline, ). It is one of the more sedating antidepressants but antimuscarinic effects are less marked. Like the tricyclics, maprotiline is an inhibitor of the reuptake of noradrenaline; it also has weak affinity for central adrenergic (α1) receptors.Maprotiline is usually given by mouth as the hydrochloride but it has also been given by injection as the mesilate and in oral drops as the resinate.
In the treatment of depression () maprotiline hydrochloride is given by mouth in doses of 25 to 75 mg daily in three divided doses, gradually increased to 150 mg daily if necessary; up to 225 mg daily may be required in severely depressed patients in hospital. The dosage should be adjusted after 1 or 2 weeks according to response. Because of the prolonged half-life of maprotiline the total daily dose may also be given as a single dose, usually at night. A suggested initial dose for elderly patients is 10 mg three times daily or 30 mg at night gradually increased according to response over a period of 1 to 2 weeks to 25 mg three times daily or 75 mg at night.
Maprotiline should be withdrawn gradually to reduce the risk of withdrawal symptoms.
Preparations
Single-ingredient Preparations
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.Austria: Ludiomil; Belg.: Ludiomil; Braz.: Ludiomil; Canad.: Ludiomil; Denm.: Ludiomil; Maludil; Fr.: Ludiomil; Ger.: Aneural¤; Delgian¤; Depressase¤; Deprilept; Kanopan¤; Ludiomil; Mapro-GRY¤; Mapro-Tablinen¤; Maprolu; Mirpan¤; Psymion¤; Gr.: Aprotilin; Ludiomil; Hong Kong: Ludiomil; Hung.: Ludiomil; Maprolu; Irl.: Ludiomil¤; Israel: Ludiomil¤; Melodil; Ital.: Ludiomil; Maprolit¤; Malaysia: Ludiomil; Mex.: Ludiomil; Neth.: Ludiomil; NZ: Ludiomil; Port.: Ludiomil; S.Afr.: Ludiomil; Singapore: Ludiomil; Spain: Ludiomil; Swed.: Ludiomil; Switz.: Ludiomil¤; Ludiomil; Ludiomil; Thai.: Ludiomil; UK: Ludiomil; USA: Ludiomil¤;
Pharmacopoeial Preparations
USP 27: Maprotiline Hydrochloride Tablets;
Posted by ed_uk on January 3, 2005, at 22:35:49
In reply to Re: Maprotiline, posted by ed_uk on January 3, 2005, at 22:20:33
Yep, I'm pretty sure that maprotiline does cause quite a bit of weight gain! Oops, sorry. Stick with the desipramine idea!
Ed.
Posted by banga on January 4, 2005, at 11:10:21
In reply to Re: Maprotiline, posted by ed_uk on January 3, 2005, at 22:35:49
Thanks again Ed! Probably why we don't see maprotiline around much anymore.....
Any reason you can think of offhand why Strattera is thought to act better for ADHD than something like desipramine?
Posted by ed_uk on January 4, 2005, at 13:19:41
In reply to Re: Maprotiline, posted by banga on January 4, 2005, at 11:10:21
>Any reason you can think of offhand why Strattera is thought to act better for ADHD than something like desipramine?
Hi!
I don't think it actually is any better!
Ed.
Posted by SLS on January 4, 2005, at 14:49:57
In reply to Re: Strattera » banga, posted by ed_uk on January 4, 2005, at 13:19:41
> >Any reason you can think of offhand why Strattera is thought to act better for ADHD than something like desipramine?
>
> Hi!
>
> I don't think it actually is any better!
>
> Ed.
My doctor treats a lot of people with ADD. He seems to like Strattera, and is not at all averse to prescribing TCA for various conditions. I saw Strattera work a miracle with an adult with ADD. I don't know if he ever tried desipramine, though. I bet desipramine would be better for any behavioral component whereas Strattera might be better for the cognitive and inattention disturbances.
- Scott
Posted by SLS on January 4, 2005, at 14:51:25
In reply to Re: Strattera, posted by SLS on January 4, 2005, at 14:49:57
Strattera doesn't seem to make for a good antidepressant.
- Scott
Posted by zeugma on January 4, 2005, at 18:42:18
In reply to Re: Strattera, posted by SLS on January 4, 2005, at 14:51:25
I haven't taken desipramine, but I'll assume nortriptyline is similar enough to make a comparison. Strattera is far better than nortriptyline for symptoms of inattention. Unfortunately it is a far worse antidepressant, and actually induced a severe depression about eight months into treatment.
I used Strattera PRN earlier this year to get through a rocky patch, and it worked, but the dysphoria became quickly evident too, so for me it is not a viable option. There is also a fatiguing effect that Strattera induces which is unlike any other drug I have experienced. Neuroleptics and high doses of buspirone cause lethargy, which is of course intolerable, but there the body and mind feel equally drained. Strattera made me feel alert and exhausted at once. This was a uniquely wretched feeling.
I also think that complete clarity of the mental processes may not be the most desired effect for all ADD'ers, even inattentive ones. A little mental static may be good for the nervous system.
-z
Posted by ed_uk on January 4, 2005, at 20:01:28
In reply to Re: Strattera » SLS, posted by zeugma on January 4, 2005, at 18:42:18
Hi Z!!
> Strattera is far better than nortriptyline for symptoms of inattention.
I suppose that might be because of nort's anticholinergic properties. Nort's also a weak antihistamine, maybe that plays a role. I'd expect desipramine to be better for ADD than nortriptyline.
Regards,
Ed.
Posted by banga on January 5, 2005, at 9:45:51
In reply to Re: Strattera » zeugma, posted by ed_uk on January 4, 2005, at 20:01:28
Yeah, I have not been impressed by people's reports on Strattera. My pdoc mentioned it as an option if I am diagnosed ADHD, but I know I don't even want to give it a trial.
Desipramine will then be my request next Friday.
This is the end of the thread.
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