Shown: posts 40 to 64 of 64. Go back in thread:
Posted by ed_uk on November 9, 2004, at 9:54:54
In reply to Re: The Forbidden Combination: My AD list, posted by ed_uk on November 9, 2004, at 8:35:27
I promised above that i'd find the letter to the British Medical Journal called 'fatal hyperpyrexia with antidepressant drugs'.
I can't type it all out though because I'd be here for ages, it took me long enough to find it!........
At noon on 28 August 1964 a 41-year old woman was admitted to this hospital with a diagnosis of depression and 'hysterical' behaviour. She gradually became comatose and showed signs of sympathetic over-stimulation with dilated pupils, flushed skin, perspiration, hypersalivation, and rigid legs with ankle clonus. Her pulse was regular at 150, BP 130/70 mmHg, temperature 40 Celsius (104 F), and her respiration was shallow with increasing cyanosis. These signs suggested overdose with antidepressant drugs, it was confirmed that she has been taking phenelzine, desipramine and chlorpromazine. She was transferred to a general hospital, where she died at 5 p.m. the same day............ A report from the forensic science lab showed that chlorpromazine and desipramine had been found in the tissues, but only at therapeutic amounts. No phenelzine was found in the tissues but it was suggested that this could still have produced a reaction even if it had not been taken for a number of days. (after all MAO inhibition can persist, *addition by me!*) ..............she had been taking phenelzine regularly in doses of 15mg thrice daily until the day before her death. Six weeks previously she had been prescribed desipramine, 50mg thrice daily, but did not take this regularly and certainly not for 48 hours before her death, because she felt that it did not help her. The amount of tablets left in each bottle showed that there was no eveidence of overdose....
What does anyone think...Here are some possibilities that I thought of....
1. SS caused by interaction between phenelzine and desipramine (which is very selective as a NRI, but not completely devoid of effect on serotonin reuptake!). Maybe she was very sensitive to desipramine's very weak serotonin reuptake inhibition.
2. SS caused by phenelzine alone. (After all, there are cases of SS with SSRIs alone, but no fatalities).
3. NMS due to the chlorpromazine--- but her 'ankle clonus' is characteristic of the SS.
4. She had actually taken another drug that the pathologist did not test for eg. imipramine from a friend (imipramine is metabolised to desipramine).
Anyway, this was the only report I could find which suggested an interaction between an MAOI and a selective NRI in humans. Here is an excerpt from a rat study which also suggestes the possibility of interaction......
'Myoclonic phenomena such as forelimb flexor-extensor movements, head and body twitches, occurred in *phenelzine pretreated* rats after paroxetine, fluoxetine, clomipramine, imipramine, amitriptyline and *desipramine.* Wet dog shakes, the most intense phenomenon, were obtained *only* after paroxetine, fluoxetine, clomipramine and imipramine (SRIs). Myoclonic features were prevented when pretreatment included p-chlorophenylalanine but were unaffected when this incorporated alpha-methyl-p-tyyrosine; there were attenuated by methysergide, cyproheptadine, clozapine or pimozide. The myoclonic phenomena were reproduced by combination of 5-hydroxytryptophan but not L-3,4-dihydroxyphenylalanine with clomipramine.
Posted by SLS on November 9, 2004, at 10:27:23
In reply to Re:A Combination which has caused much controversy, posted by ed_uk on November 9, 2004, at 8:02:58
> Does anyone have any experience of combined MAOI/amitriptyline treatment??
I once combined Nardil 45mg + amitriptyline without sequalae. However, for me, I don't think I obtain adequate MAO inhibition until I get to 60mg of Nardil. I can't conclude that this combination would be without hazard.
Which serotonergic actions of amitriptyline do you think provide protection from serotonin syndrome? How about nortriptyline?
Posted by SLS on November 9, 2004, at 10:39:05
In reply to Re: The Forbidden Combination: My AD list, posted by darkhorse on November 9, 2004, at 8:31:57
> As for Septiline ,I took it while in Japan(I do not remember the brand name),as an addition to Fluoxetine,and all I know it it is very similar in action to Mianserin& Mirtazapine (5ht2,H2,NE2)so it helped reduce my anxiety and made a better sleep and increase my appetite...
Japan also has a drug called rolipram. I'm not sure what the brand name is. It is debatable how effective it is, but its mechanism is different from anything else out there. It is a phospodiesterase inhibitor, and works on second messengers.
> How was your experience with duloxetine?
I experienced a significant antidepressant effect in the third week that disappeared quickly. I went up to 90mg, but that did very little but make me sleepy and impacted negatively on motivation.
> what other AD that is closest in effect to it,and is it worth the money and the side effects?
I would say Effexor is pretty close. As to whether or not it is worth trying Cymbalta, some people here have reported improvements in both anxiety and depression. However, the posts I have seen have lacked descriptions of the severity of depression being treated, and the degree of improvement experienced. You might want to wait a month or two more to see how Cymbalta works for people more long-term. Perhaps you can start a new thread.
Posted by Willyee on November 9, 2004, at 13:44:57
In reply to Re: The Forbidden Combination, posted by vwoolf on November 9, 2004, at 6:21:37
> I have to put in a word here, to say that I agree with Squiggles. I have no interest in pharmacology, and seldom visit this board, but I suffer from suicidal ideation quite frequently, and was immediately caught by the word "fatal" in the posts. I was taking SSRI's for some time last year before I stopped and went onto MAOI's. This post has now made me aware that in my stash of left-over pills I have a potentially lethal combination. I would rather not have this information. I am fine at the moment, but on my next down cycle this knowledge will be in my head. I think one needs to be more careful on boards like this.
This has got to be a prime example.First i dont downplay your condition,i dont down play the seriousness of any emotional disorder,and i certaintly dont down play sucideal ideation.
However i dont see how someone posting information,someone who does not claim to be a health professional nor recomending anything to others,should be held responsable to someone reading that information and deceding to use it in a dangerous manner.
Maois seem to be the least of experimented medication,probualy because of the narrow margin in which it is and has been prescribed.SSRIS are prescribed more and there are tons upon tons of information regarding the use of it and other substances.
Here the few who are on Maois,are considering them have a chance to discuss in detail the medication,discuss to a degree that the data sheets certaintly dont.
Appliny that the initial post can provide a means to one intentionaly harming himself is absurd,first it was noted in almost every post that these meds are in fact dangerous,so therefore if one chooses to use this as a tool of self destruction is by no means the fault of the person writing it.
Sucudeal ideation is a horrid feeling,a dangerous vulnerable state,and if it gets to the boling point,and wont require any specific drug or combo,when one is sucideal the mind is working on a different level,and it is not hard for that person to find a means by which to hurt themeslves,chances are there are enough combos off over the counter substances in the medicine cabinet to do the job.
I do not think the orignal post was giving any intention for one to go and try it,more so to use the info in a self destructive way.
Luckly i had that feeling onlyonce in my disease,it was during an effexor withdrawal,i was not myself,thinking back not it frightnes me to think of how my mind can deprat itself from me to such a degree that i would try to hurt myself,i think it scares me more than the act itself.
I am sorry for you,or anyone who has to endure what i felt that one day on any type of reoccuring basis.
Posted by bethesdabob on November 9, 2004, at 17:17:09
In reply to Re:A Combination which has caused much controversy, posted by ed_uk on November 9, 2004, at 8:02:58
Ed the Brit
My 47 year old wife died last December from a seizure disorder. She had a bad liver, result of hepatitis, and was bipolar and epileptic.
She met a female psychiatrist in our HMO that she liked that treated her bipolar and epilepsy.
At the time of her death wife's p'doc had her taking:
20 mgs adderall 3X a day
600 mgs effexor XR
900 mgs trileptal
10 mgs ambien for sleep
90 mgs remeron
3 mgs risperdal
6 mgs clonazepam
1 bottle of Stadol NS weekly (2500 Ml)
Primary Care physician treated wife for high blood pressure and nausea / vomiting:
32 mgs atacand
30 mgs prevacid
The night before she died we bickered and I slept in the guest bedroom, when I woke up and went to the bedroom to get ready for work, she was thrashing around on the bed - said she felt really uncomfortable, said that she had to get up earlier and change her nightgown - that she had been having sweats and chills and perspiration had soaked through her gown, she told me that she felt very nautious and had thrown up several times, told me that her chest hurt - that it was very crampy and made her pretty uncomfortable, she seemed pretty disoriented and asked me to take the kids to school and if she did not feel better said she wanted to go to the doctors or hospital.
When I returned about an hour later I discovered her dead. The pathologist later told me that she died as a result of a seizure/seizure disorder.
It has been suggested to me by several people that my wife died as a result of a serotonin syndrome caused by the medications that she took.
Asking free advice as you state that you are a pharmacy student, do you see something in her medication that might have provoked a reaction.
Had tried to send this to you in private mail but message keeps getting blocked and sent back.
Very much appreciate any thoughts on the matter.
Posted by jujube on November 9, 2004, at 18:12:54
In reply to Re:A Combination which has caused much controversy, posted by bethesdabob on November 9, 2004, at 17:17:09
I am not responding because I have any answers to your question (I do not have the experience to do so). I did, however, just want to say that I am so sorry for your loss.
> Ed the Brit
> My 47 year old wife died last December from a seizure disorder. She had a bad liver, result of hepatitis, and was bipolar and epileptic.
> She met a female psychiatrist in our HMO that she liked that treated her bipolar and epilepsy.
> At the time of her death wife's p'doc had her taking:
> 20 mgs adderall 3X a day
> 600 mgs effexor XR
> 900 mgs trileptal
> 10 mgs ambien for sleep
> 90 mgs remeron
> 3 mgs risperdal
> 6 mgs clonazepam
> 1 bottle of Stadol NS weekly (2500 Ml)
> Primary Care physician treated wife for high blood pressure and nausea / vomiting:
> 32 mgs atacand
> 30 mgs prevacid
> The night before she died we bickered and I slept in the guest bedroom, when I woke up and went to the bedroom to get ready for work, she was thrashing around on the bed - said she felt really uncomfortable, said that she had to get up earlier and change her nightgown - that she had been having sweats and chills and perspiration had soaked through her gown, she told me that she felt very nautious and had thrown up several times, told me that her chest hurt - that it was very crampy and made her pretty uncomfortable, she seemed pretty disoriented and asked me to take the kids to school and if she did not feel better said she wanted to go to the doctors or hospital.
> When I returned about an hour later I discovered her dead. The pathologist later told me that she died as a result of a seizure/seizure disorder.
> It has been suggested to me by several people that my wife died as a result of a serotonin syndrome caused by the medications that she took.
> Asking free advice as you state that you are a pharmacy student, do you see something in her medication that might have provoked a reaction.
> Had tried to send this to you in private mail but message keeps getting blocked and sent back.
> Very much appreciate any thoughts on the matter.
Posted by vwoolf on November 10, 2004, at 4:25:25
In reply to Re: To vwoolf, posted by ed_uk on November 9, 2004, at 7:00:25
Hi Ed, I want to apologise for my knee-jerk reaction yesterday. Your post touched a sore spot and I reacted without thinking. Please ignore what I said, if you can.
PS I have now destroyed the left over pills.
Posted by ed_uk on November 10, 2004, at 6:57:37
In reply to To ed_uk, posted by vwoolf on November 10, 2004, at 4:25:25
Hi vwoolf :-)
Thank you for your apology. Please don't worry, I wasn't upset by your post. Everyone in this forum has problems, including myself, sometimes when people are feeling low they say things that they wouldn't say if they were feeling better. Personally, I've done and said many things which I have regretted afterwards. I'm relieved that you've got rid of the excess pills. I wouldn't want you to harm yourself.
All the best...
Posted by ed_uk on November 10, 2004, at 7:11:14
In reply to Re:A Combination which has caused much controversy, posted by bethesdabob on November 9, 2004, at 17:17:09
I'm not sure why the babblemail got blocked. I don't use that email address anymore anyway so I'm glad you contacted me by posting instead. If you'd sent me a babblemail I might not have received it for a few weeks.
Would you like me to send a reply by babblemail or should I post a reply?
Many other people might want to post their ideas as well, would that be ok? People might be holding back because you addressed your post to me.
Posted by bethesdabob on November 10, 2004, at 11:26:47
In reply to Re:To Bethesdabob, posted by ed_uk on November 10, 2004, at 7:11:14
Many thanks for your kind reply.
I have no reservations about people jumping into this thread and saying whatever they like, I welcome any and all opinions.
Following my wife's death a physician relative raised questions to me about wife's death, referred me to a legal group he thinks highly of, said it was worth a "free look". Group requested medical records of all her doctors, most were received within two weeks, waited 4 months for records from the psychiatrist.
Received word from the group two weeks ago that a board certified psychiatrist would testify on my behalf, was told that records were now being reviewed by a neurologist and psychopharmacologist.
Wife was diagnosed epileptic as a teenager, she had many small seizures in the months before her death, had visited a neurologist/headache specialist weeks before she died about her migraine headaches.
Wife lost her father to lung cancer when she was 14, she became depressed and suicidal after his death, her mother committed her to an institution in the 70's, she was diagnosed manic depressive.
Before we met she lived pretty recklessly when not institutionalized, had many drug and alcohol issues, engaged in all kinds of risky behavior, psychiatric medicines and Alcoholics Anonymous saved her life, we met and got married, she maintained her sobriety, contributed much of her time to church and our community and was a great mom to our three sons till she died.
There were times in our marriage when wife would get depressed or stop taking her meds and would need to be admitted and stablized, she would get bummed out and say that she was a burden to us and that the kids and I would be a lot better off if she were dead, I hope that she can look down on us from wherever she is and realize just how wrong she was.
I come to this board everyday and read what people post, I feel so bad for many of the folks and the pain that they suffer with, really had no idea about all that wife had to struggle with until she died and I started educating myself further. Regret that I was not more proactive in her care.
Posted by ed_uk on November 10, 2004, at 11:57:38
In reply to Re:To Bethesdabob, posted by bethesdabob on November 10, 2004, at 11:26:47
I was very sorry to hear that your wife died last December. I will try to give you some information, but Im not sure how useful it will be. I feel bad because Im not sure that Im really helping. Please don't be overwhelmed by all the studies I've posted.
Before I start, I need to say that I cant be sure what was responsible for your wifes death, I can only make suggestions about what might have been the cause. The main thing which concerned me about your wifes medication was the very high dose of Effexor, particularly for someone with epilepsy. The high dose of Remeron also stood out. The possibility of a drug interaction is always a worry when someone is on so many medications.
Restlessness, sweating, chills/shivering, nausea/vomiting and confusion could all have been symptoms of the Serotonin Syndrome (SS). I would expect that there are also many other medical conditions which might cause these symptoms. How did the pathologist explain these symptoms?
Seizures may also occur in severe cases of the SS. I also found a report stating that one of the symptoms which occurred in a woman diagnosed with SS was chest pain, a symptom that your wife experienced. Here it is....
'OBJECTIVE: To report a possible case of serotonin syndrome associated with coadministration of tramadol hydrochloride and sertraline hydrochloride. CASE SUMMARY: A 42-year-old woman developed **atypical chest pain**, sinus tachycardia, confusion, psychosis, sundowning, agitation, diaphoresis, and tremor......'
There have been numerous reports of the SS in patients taking venlafaxine(Effexor) and mirtazapine(Remeron). SS has occurred in people taking venlafaxine alone, venlafaxine combined with mirtazapine, venlafaxine in overdose, and venlafaxine combined with amphetamines (Adderall contains amphetamines).
Here are the abstracts of some relevent articles....
Ann Pharmacother. 2003 Feb;37(2):209-11. Related Articles, Links
Serotonin syndrome induced by low-dose venlafaxine.
Pan JJ, Shen WW.
Department of Psychiatry, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
OBJECTIVE: To report the case of a patient with serotonin syndrome induced by low-dose venlafaxine. CASE SUMMARY: A 29-year-old Taiwanese woman with major depressive disorder abruptly developed serotonin syndrome during low-dose (37.5 mg/d) venlafaxine monotherapy, with symptoms of restlessness, tremor, shivering, diarrhea, vomiting, ataxia, tachycardia, and myoclonus. The patient recovered in 2 hours after receiving prochlorperazine and lorazepam in the emergency department. Venlafaxine was discontinued, and she was discharged home. Two weeks later, the patient started to receive fluoxetine 20 mg/d and reported no adverse adverse effects during follow-up clinic visits. DISCUSSION: The clinical manifestations of this case meet Sternbach's criteria of serotonin syndrome. Its possible etiologic factors include panic attack, adverse drug reaction, pharmacodynamic interaction, and congenital absence of CYP2D6 enzyme activity. The Naranjo probability scale suggested a probable causality of venlafaxine treatment and serotonin syndrome. CONCLUSIONS: Clinicians should be aware of the risk of serotonin syndrome when the patient receives not only a combination of 2 antidepressants, but also the single potent serotonergic agent venlafaxine.
J Emerg Med. 1997 Jul-Aug;15(4):491-3. Related Articles, Links
Isolated venlafaxine-induced serotonin syndrome.
Department of Medical Toxicology, Good Samaritan Regional Medical Center, Phoenix, Arizona 85006, USA.
Serotonin syndrome is a potentially fatal complication of serotonergic drug therapy. Usually, serotonin syndrome occurs with the concomitant use of two serotonergic drugs; this case report describes a patient with a classic presentation of serotonin syndrome induced solely by a venlafaxine overdose. Emergency physicians need to be aware that the serotonin syndrome may occur not only with serotonergic drug combinations but also with overdoses of a single potent serotonergic agent such as venlafaxine.
Ann Pharmacother. 2002 Apr;36(4):641-3. Related Articles, Links
Severe serotonin syndrome induced by mirtazapine monotherapy.
Hernandez JL, Ramos FJ, Infante J, Rebollo M, Gonzalez-Macias J.
Department of Internal Medicine, Hospital Marques de Valdecilla, Santander, Spain. firstname.lastname@example.org
OBJECTIVE: To document a case of serotonin syndrome (SS) associated with mirtazapine monotherapy, review the previously reported cases of SS associated with this tetracyclic antidepressant, and discuss the possible pathogenic mechanisms leading to this serious adverse drug reaction. CASE SUMMARY: A 75-year-old man developed agitation, confusion, incoordination, and gait disturbance because of progressive rigidity. Mirtazapine had been started 8 days earlier to control major depression. Physical examination revealed diaphoresis, low-grade fever, hypertension, tachycardia, bilateral cogwheel rigidity, hyperreflexia, tremor, and myoclonus, symptoms and signs that are consistent with severe SS. DISCUSSION: A review of the cases of SS with implication of mirtazapine as the cause was performed. The possible pathogenic mechanisms leading to this adverse reaction in this patient are also discussed, and pathophysiologic hypotheses are formulated. CONCLUSIONS: Although mirtazapine offers clinicians a combination of strong efficacy and good safety, we suggest bearing SS in mind when prescribing this drug, especially in frail, elderly patients with underlying chronic conditions. In these patients, it might be more adequate to start mirtazapine therapy at a lower dose (<15 mg/d).
Clin Neuropharmacol. 2003 Mar-Apr;26(2):54-7. Related Articles, Links
Clin Neuropharmacol. 2003 Nov-Dec;26(6):287-8; author reply 289-90.
Clin Neuropharmacol. 2003 Nov-Dec;26(6):288-9; author reply 289-90.
Mirtazapine-induced serotonin syndrome.
Ubogu EE, Katirji B.
Division of Neuromuscular Diseases, Department of Neurology, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Hanna House 5th Floor, 11000 Euclid Avenue, Cleveland, OH 44106-5040, USA. email@example.com
An 85-year-old woman developed sudden confusion and dysarthria progressing to mutism, orobuccal dyskinesias, generalized tremors worse with activity, ataxia, and rigidity with cog wheeling without high-grade fevers or dysautonomia. These findings were related temporally to the institution of mirtazapine as monotherapy for a major depressive illness with superimposed anxiety disorder. Withdrawal of the agent resulted in early notable clinical resolution with only residual hypertonia after 2 weeks. This is a rare report of serotonin syndrome induced by mirtazapine monotherapy. The hypothesized pathophysiologic mechanism in this case is overstimulation of serotonin (5-hydroxytryptamine or 5-HT) type 1A receptors (5-HT(1A)) in the brainstem and spinal cord in an individual with risk factors for hyperserotoninemia resulting from reduced, acquired endogenous serotonin metabolism.
A LETTER TO THE MEDICAL JOURNAL OF AUSTRALIA
TO THE EDITOR: We report two episodes of serotonin toxicity (or serotonin syndrome) caused by drug interaction in one individual chronically treated with dexamphetamine. The interacting drugs were venlafaxine, then later citalopram. We are not aware of any previous reports of serotonin toxicity caused by dexamphetamine in combination with either venlafaxine or any selective serotonin reuptake inhibitor (SSRI).
A 32-year-old man presented after two days of marked agitation, anxiety, shivering and tremor. He was being treated with dexamphetamine, 5 mg three times daily, for adult attention deficit hyperactivity disorder. He had started venlafaxine (75 mg daily) two weeks previously, and this had been increased to 150 mg daily after a week. On examination, he was alert and oriented, but diaphoretic, shivering and had fine motor tremor. His heart rate was 140 bpm, blood pressure was 142/93 mmHg and temperature 37.3°C. Pupils were 3 mm diameter and reactive, with no nystagmus or ocular clonus. There was generalised hypertonia, hyperreflexia, 12 beats of inducible ankle clonus, frequent myoclonic jerking and tonic spasm of the right side of his orbicularis oris muscle. His abdomen was tense, but non-tender, with normal bowel sounds. An electrocardiogram showed sinus tachycardia with a baseline tremor, but no other abnormality.
Therapy with dexamphetamine and venlafaxine was ceased, and cyproheptadine (8 mg doses up to a total of 32 mg over three hours) was given. The patient had a stepwise reduction in heart rate, with complete resolution of his symptoms, and was discharged the next morning. Dexamphetamine therapy was restarted three days later and citalopram therapy was commenced one week after discharge. Two weeks after discharge, he reported similar symptoms, and ceased citalopram. Three days later he was still agitated, with nausea, diarrhoea and teeth clenching. There was no rigidity, tremor or diaphoresis, and his heart rate was 76 bpm. He was given two 8 mg doses of cyproheptadine and was asymptomatic two days later.
Some of this patient's symptoms could be attributed to noradrenaline excess. However, the combination of neuromuscular and autonomic features is more consistent with serotonin toxicity. The fact the symptoms resolved after administration of cyproheptadine (a 5-HT2-receptor antagonist) supports this hypothesis. There is no theoretical reason why the interaction of citalopram (a pure SSRI) and dexamphetamine should cause catecholamine excess, and again the more likely explanation is serotonin toxicity.
Dexamphetamine causes psychostimulation and increased peripheral sympathomimetic activity. Centrally it causes presynaptic release of serotonin,1 and dopamine and catecholamine release.2 Venlafaxine and its metabolite, O-desmethylvenlafaxine, inhibit both neuronal 5-HT reuptake and noradrenaline reuptake,3 whereas citalopram, an SSRI, has little effect on noradrenaline reuptake.4 The combination of serotonin reuptake blockade and either presynaptic release of serotonin or monoamine oxidase inhibition by dexamphetamine will cause increased serotonin levels in the central nervous system, and is the likely mechanism of toxicity in this patient. This is consistent with the mechanism for other reports of serotonin toxicity.5
Increased awareness and cautious monitoring is advised when using a combination of dexamphetamine and either venlafaxine or an SSRI. This is particularly important in people using amphetamines recreationally and in children taking dexamphetamine for attention deficit hyperactivity disorder.
I also found this reference to a report of SS due to a combination of venlafaxine and mirtazapine but could not get access to the article........
World J Biol Psychiatry. 2002 Jul;3(3):167. Related Articles, Links
Serotonin syndrome produced by a combination of venlafaxine and mirtazapine.
There is also a small amount of evidence that some patients treated with risperidone plus a serotonin reuptake inhibitor may experience neurotoxicity. Venlafaxine inhibits the reuptake of serotonin. Here are a couple of reports...........
Ann Pharmacother. 2003 Mar;37(3):388-91. Related Articles, Links
Ann Pharmacother. 2003 Oct;37(10):1531-2; author reply 1532-3.
Combination risperidone and SSRI-induced serotonin syndrome.
Karki SD, Masood GR.
School of Pharmacy, State University of New York at Buffalo, Buffalo, NY, USA. firstname.lastname@example.org
OBJECTIVE: To report 2 cases of serotonin syndrome associated with combined therapy of risperidone and selective serotonin-reuptake inhibitors (SSRIs) in elderly patients. CASE SUMMARIES: An 86-year-old white man was admitted to the emergency department because of increased confusion and generalized weakness over the past several days. His medication history indicated paroxetine 10 mg/d and risperidone 0.25 mg/d. The patient's confusion worsened and underwent acute changes that resembled delirium. He was placed in a geri chair and he became extremely agitated. He was then treated with escalating doses of risperidone. The patient died on day 5 of admission, at which time he was being treated with risperidone 2-3 mg/d. A 78-year-old white female nursing home resident was admitted to the emergency department because of increased confusion and generalized weakness. She was being treated with paroxetine for depression and risperidone for agitation. Her risperidone dose was increased to manage agitation. The patient's agitation worsened with increasing doses of risperidone; she developed tremor, dizziness, and muscle incoordination. After psychopharmacologic consultation, the risperidone and paroxetine were discontinued and she was treated with lorazepam. The patient recovered, returned to baseline status in 2 days, and was later transferred back to the nursing home. DISCUSSION: We believe that in both cases, serotonin syndrome was precipitated by risperidone in combination with SSRI antidepressants. A literature search indicated one report of serotonin syndrome with a combination of risperidone and paroxetine. CONCLUSIONS: An objective causality assessment revealed that the adverse drug event was probable in the first patient and definite in the second patient. We caution clinicians treating elderly patients with combined risperidone and SSRIs to include serotonin syndrome in differential diagnosis if the patient is showing signs of increasing agitation with escalating doses of risperidone.
Ann Pharmacother. 2002 Mar;36(3):440-3. Related Articles, Links
Ann Pharmacother. 2002 Jul-Aug;36(7-8):1293; author reply 1294.
Neurotoxic syndrome associated with risperidone and fluvoxamine (an SSRI)
Reeves RR, Mack JE, Beddingfield JJ.
GV (Sonny) Montgomery Veterans Administration Medical Center, Department of Psychiatry, Jackson, MS 39216-5116, USA. email@example.com
OBJECTIVE: To report a case of a neurotoxic syndrome in a patient undergoing concomitant treatment with risperidone and fluvoxamine. CASE REPORT: A 24-year-old African American woman hospitalized for psychosis was unresponsive to risperidone. Because of obsessive symptoms, low doses of fluvoxamine were added to her treatment regimen. Within 2 days, she developed confusion, diaphoresis, diarrhea, hyperreflexia, and myoclonus, which then progressed to rigidity, fever, and unresponsiveness, requiring endotracheal intubation. Symptoms resolved over 10 days with discontinuation of medication, hydration, and bromocriptine 5 mg 3 times daily. Ultimately, she was treated with olanzapine and fluvoxamine without adverse effects. DISCUSSION: This represents the first reported case of a neurotoxic syndrome secondary to treatment with risperidone and fluvoxamine. Differential diagnosis between neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS) could not be accurately determined because of the overlap of signs and symptoms of both syndromes. NMS and SS may represent different aspects of a more generalized neurotoxic syndrome. This could be an important consideration in formulating treatment for neurotoxic syndromes. CONCLUSIONS: Clinicians should be aware of potentially serious adverse reactions that may occur during concomitant treatment with antipsychotics and selective serotonin-reuptake inhibitors.
Overall, the thing which stands out the most when looking at your wife's medication is the very high dose of venlafaxine. As I already said, venlafaxine can cause the SS. Severe SS may cause seizures. Venlafaxine has also been reported to cause SS in the absense of the SS, particularly in overdose.
The association between Remeron and SS is much less certain, whether Remeron can actually cause SS seems to be quite controversial. The link between Risperdal and the SS is also doubtful.
It is important to notice that SS usually occurs quite rapidly after a change in medication eg. the addition of an extra med or an increase in dose. It is important to find out whether there were any changes in your wife's medication shortly before she died. Had there been a recent increase in the dose of Effexor or Remeron? Any Effexor dose changes are especially important.
Effexor, Remeron, Risperdal, Stadol and Adderall all need to be used with caution in epilepsy. It is possible that these meds may cause seizures. The link between seizures and Effexor is probably the strongest, there is less information about the effect of the other medications on epilepsy. I did notice the dose of Remeron was very high though, perhaps this could have caused a seizure, I don't know. Some animal research has been done to examine the link between venlafaxine and seizures, the introduction to the study noted that.....
'Clinical seizures after venlafaxine treatment have occasionally been reported when the drug was used at very high doses or in combination with other medications.'
I was concerned when you mentioned that your wife may have had abnormal liver function resulting from hepatitis. Again, it was the very large dose of venlafaxine which was the problem. Here is what the BNF says about venlafaxine....
'Halve dose in moderate hepatic(liver) impairment; avoid if severe'.
The implication is that mild impairment of liver function may not be relevant. The BNF always mentions mild impairment if it is thought to be relevant. Did you wife have any liver function tests performed which showed persistent damage from the hepatitis? Or had the liver healed?
When you mentioned the clonazepam I wondered whether your wife had missed a dose by mistake (or maybe a few doses). Abruptly stopping clonazepam can induce severe withdrawal symptoms and convulsions. Seizures may also occur on stopping Trileptal suddenly but this is probably not so likely. The problem with using clonazepam as a long-term anti-epileptic is that its anticonvulsant effect decreases significantly after a few weeks or months of continuous treatment, increasing the dose is not always effective in restoring its efficacy. It is possible that some of your wifes symptoms may have been due to withdrawal.
I think the your wifes psychiatrist had some very difficult decisions to make. In general, it is recommended that if anyone suffers seizures while taking meds which can cause seizures, the possible culprits should be stopped. Eg. Stop the effexor, adderall etc. This can be very difficult, however, because the medication may be necessary to control other conditions such as bipolar disorder.
A FINAL POINT ..
Trileptal (an anticonvulsant/anti-manic) and Effexor (an antidepressant) can both cause hyponatremia (low blood sodium concentration) as a side effect. Here is the official English warning on the risk of hyponatremia with antidepressants....
'Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants; however, it has been reported more frequently with SSRIs than with other antidepressants. The CSM has advised that hyponatraemia should be considered in all patients who develop **drowsiness, confusion, or convulsions** while taking an antidepressant.'
Hyponatremia would not explain your wife's other symptoms though, SS is probably a better explanation.
I hope this information is helpful and not too upsetting.
Posted by bethesdabob on November 10, 2004, at 12:41:15
In reply to Re:To Bethesdabob, posted by ed_uk on November 10, 2004, at 11:57:38
Not upsetting at all, very informative, thank you very much.
Posted by lorilu on November 10, 2004, at 21:22:46
In reply to Re: The Forbidden Combination » vwoolf, posted by Larry Hoover on November 9, 2004, at 7:33:47
Make sure you follow your own advice and get rid of your old stash. We would sure miss you!
Posted by ed_uk on November 11, 2004, at 9:03:59
In reply to Re:A Combination which has caused much controversy » ed_uk, posted by SLS on November 9, 2004, at 10:27:23
RE: amitriptyline+MAOI versus nortriptyline+MAOI
I think it's very difficult to compare the risk of SS with these two combinations. Amitriptyline is more potent that nortriptyline as a serotonin reuptake inhibitor, at a glance it might be expected that the risk of SS would be higher with amitriptyline. On the other hand, amitriptyline appears to be more potent as an antagonist at 5-HT2a receptors. It seems likely that this might provide some protection from the SS.
This rather dubious little table claims that amitriptyline is more potent at the 5-HT2a receptor than nortriptyline. I took it from Dr. Gillman's psychopharmacology website, it doesn't say where the information came from! .......
Low numbers means high potency, ie bigger effect.
SSRIs nil sig except
This study (in rats) claims that the SS can be attenuated by 5-HT2a antagonists.........
Brain Res. 2001 Jan 26;890(1):23-31. Related Articles, Links
Potent serotonin (5-HT)(2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome.
Nisijima K, Yoshino T, Yui K, Katoh S.
Department of Psychiatry, Jichi Medical School, Minamikawachi-Machi, Kawachi-Gun, Tochigi-Ken, 329-0498, Japan. firstname.lastname@example.org
The serotonin (5-HT) syndrome is the most serious side effect of antidepressants, and it often necessitates pharmacotherapy. In the present study, the efficacy of several drugs was evaluated in an animal model of the 5-HT syndrome. When 2 mg/kg of clorgyline, a type-A monoamine oxidase inhibiting antidepressant, and 100 mg/kg of 5-hydroxy-L-tryptophan, a precursor of 5-HT, were administered intraperitoneally to rats to induce the 5-HT syndrome, the rectal temperature of the rats increased to more than 40 degrees C, and all of the animals died by 90 min after the drug administration. The noradrenaline (NA) levels in the anterior hypothalamus, measured by microdialysis, increased to 15.9 times the preadministration level. Pretreatment with propranolol (10 mg/kg), a 5-HT(1A) receptor antagonist as well as a beta-blocker, and dantrolene (20 mg/kg), a peripheral muscle relaxant, did not prevent the death of the animals, even though these two drugs suppressed the increase in rectal temperature to some extent. Chlorpromazine and cyproheptadine prevented the lethality associated with the 5-HT syndrome only at high doses. By contrast, pretreatment with ritanserin (3 mg/kg) and pipamperone (20 mg/kg), both potent 5-HT(2A) receptor antagonists, completely prevented the increase in rectal temperature and death of the animals, and the hypothalamic NA levels in these two groups increased less than that in the other groups. These results suggest that potent 5-HT(2A) receptor antagonists are the most effective drugs for treatment of the 5-HT syndrome, and that NA hyperactivity occurs in the 5-HT syndrome.
As you mention in your psychiatric drug chart, ritanserin is not selective for the 5-HT2a receptor. Here is another study which examined the importance of the different 5-HT(2)R subtypes in the SS. It looks like 5-HT2a antagonists can reduce some of the signs of SS in rats. Other receptors such as the 5-HT(2c)R may also be important, however................
Behav Pharmacol. 2002 Jul;13(4):313-8. Related Articles, Links
Role of 5-HT(2) receptors in the tryptamine-induced 5-HT syndrome in rats.
Van Oekelen D, Megens A, Meert T, Luyten WH, Leysen JE.
Discovery Research, Janssen Research Foundation, Beerse, Belgium.
We distinguished the functions of the different 5-hydroxytryptamine-2 (5-HT(2)) receptor (5-HT(2)R) subtypes in the tryptamine-induced 5-HT syndrome in rats using (1) the 5-HT(2A)R antagonist R93274 (N-[(3-p-fluorophenyl-1-propyl)-4-methyl-4-piperidinyl]-4-amino-5-iodo-2-methoxybenzamide), the 5-HT(2A/C)R antagonist R99647 (2-(dimethylaminomethyl)2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine), the 5-HT(2B/C)R antagonist SB-242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline), and several 5-HT(2)R antagonists (ketanserin, risperidone, pipamperone and mianserin); and (2) chronic 5-HT(2)R activation by 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). In contrast to SB-242084, the selective 5-HT(2A)R antagonist R93274 as well as the non-selective 5-HT(2A)R antagonists (R99647, ketanserin, risperidone, pipamperone and mianserin) significantly inhibited tryptamine-induced forepaw treading and tremors, and reversed peripherally mediated cyanosis into hyperaemia; only the 5-HT(2A/C)R antagonists R99647 and mianserin inhibited the tryptamine-induced hunched back. Intermittent DOM administration (intravenously every 48 h for 12 days) did not change the centrally mediated tryptamine-induced forepaw treading, tremors and hunched back at 1, 4 or 7 days after the last DOM pretreatment. The DOM-induced head twitch response, measured immediately after every DOM injection, was not affected. In contrast, peripherally mediated cyanosis was reversed into hyperaemia in 75, 11 and 20% of all pretreated rats at 1, 4 and 7 days, respectively, after the last DOM administration. Taken together, these finding suggest that central 5-HT(2A)Rs mediate tryptamine-induced forepaw treading and tremors, that peripheral 5-HT Rs mediate tryptamine-induced cyanosis, and that 5-HT(2A)Rs mediate tryptamine-induced hunched back. Peripheral 5-HT(2C)Rs are more sensitive to desensitization after intermittent treatment with an agonist than central 5-HT(2A)Rs.
After all that, it's still difficult to compare the risks associated with combining amitriptyline or nortriptyline with an MAOI.
Did you say you experienced SS with nort but not with ami? Have you ever taken a high dose of an MAOI with ami? Were you on a high dose of an MAOI when you were taking nort and experienced symptoms of the SS?
Have a look at this article from Stockley's if you're interested...........
Monoamine oxidase inhibitors (MAOIs) + Tricyclic antidepressants
Because of the very toxic and sometimes fatal reactions (similar to or the same as the serotonin syndrome) which have very occasionally taken place in patients taking both MAOIs and tricyclic antidepressants, concurrent use came to be regarded as totally contraindicated, but informed opinion now considers that with extremely careful control it is permissible and advantageous to use both these drugs together for some refractory patients.
(a) Toxic reactions or other interactions
The toxic reactions have included (with variations) sweating, flushing, hyperpyrexia, restlessness, excitement, tremor, muscle twitching and rigidity, convulsions and coma. An illustrative example:
A woman who had been taking 20 mg tranylcypromine daily for about 3 weeks, stopped taking it 3 days before taking a single tablet of imipramine. Within a few hours she complained of an excruciating headache, and soon afterwards lost consciousness and started to convulse. The toxic reactions manifested were a temperature of 40°C, pulse rate of 120, severe extensor rigidity, carpal spasm, opisthotonos and cyanosis. She was treated with amobarbital and phenytoin, and her temperature was reduced with alcohol-ice-soaked towels. The treatment was effective and she recovered. 1
Similar reactions have been recorded on a number of other occasions with normal therapeutic doses of iproniazid, 2 isocarboxazid, 2,3 pargyline, 4 or phenelzine 5-11 with imipramine; phenelzine with desipramine 12 or clomipramine; 13-15 tranylcypromine 16-19 with clomipramine; and moclobemide with imipramine. 20. Moclobemide is reported not to interact with amitriptyline or desipramine 17,21-23 but a reaction similar to the serotonin syndrome occurred in 2 patients when clomipramine (50 mg daily) was replaced by moclobemide, 24,25 and 4 patients developed the serotonin syndrome (3 of them died) after taking moderate overdoses of moclobemide and clomipramine. 26-29 However another study found that doses of up to 300 mg moclobemide could be given 24 h after the last dose of treatment with either amitriptyline or clomipramine without any major risks. 23 Another study found a 39% rise in serum trimipramine levels in 15 patients and a 25% rise in serum maprotiline levels of 6 other patients when concurrently treated with moclobemide. No serious toxic reactions were reported. 30 Only a minor and clinically unimportant change in the pharmacokinetics of amitriptyline occurs in patients given toloxatone. 31
Some other reports are confused by overdosage with one or both drugs, or by the presence of other drugs and diseases. There have been fatalities. 12,16,32 In some instances the drugs were not taken together but were swapped without a washout period in between. There are far too many reports of these interactions to list all of them here, but they are extensively reviewed elsewhere. 33-35 Three patients with bipolar disorder developed mania when treated with isocarboxazid and amitriptyline. 36
(b) Advantageous or uneventful concurrent use
Dr GA Gander of St Thomass Hospital, London, has stated 37 that 98 out of 149 patients on combined therapy (phenelzine, isocarboxazid or iproniazid with imipramine or amitriptyline) over periods of 124 months improved significantly and that the side-effects were . . . identical in nature and similar in frequency to those seen with a single antidepressant. . .. Side effects were easily controlled by adjusting the dosage. None of the serious side-effects previously reported, such as muscle twitching or loss of consciousness was seen. He also states that more than 1400 patients having combined antidepressants over a period of 4 years . . . tend to confirm these findings described. Dr William Sargant from the same department has also written 38 that . . . we have used combined antidepressant drugs for nearly 10 years now on some thousands of patients. We still wait to see any of the rare dangerous complications reported.
There are a number of other reports and reviews describing the beneficial use of MAOI/tricyclic antidepressant combinations. 34,35,39-42
Not understood. One idea is that both drugs cause grossly elevated monoamine levels (5-HT, norepinephrine (noradrenaline)) in the brain which spill-over into areas not concerned with mood elevation. It may be related to, or the same as the serotonin-syndrome seen with selective serotonin re-uptake inhibitors. 14,20 Some of the tricyclics (e.g. clomipramine, imipramine) are potent inhibitors of serotonin uptake. Less likely suggestions are that the MAOIs inhibit the metabolism of the tricyclic antidepressants, or that active and unusual metabolites of the tricyclic antidepressants are produced. 34
Importance and management
An established, serious and life-threatening but apparently uncommon interaction. There is no precise information about its incidence but it is probably much lower than was originally thought. No detailed clinical work has been done to find out precisely what sets the scene for it to occur, but some general empirical guidelines have been suggested so that it can, as far as possible, be avoided when concurrent treatment is thought appropriate: 11,33-35,43
Treatment with both types of drug should only be undertaken by those well aware of the problems and who can undertake adequate supervision.
Only patients refractory to all other types of treatment should be considered.
Tranylcypromine, phenelzine, clomipramine and imipramine appear to be high on the list of drugs which have interacted adversely. Amitriptyline, trimipramine and isocarboxazid are possibly safer.
Drugs should be given orally, not parenterally.
It seems safer to give the tricyclic antidepressants first, or together with the MAOI, than to give the MAOI first. If the patient is already taking an MAOI, it may not be safe to start the tricyclic antidepressant until recovery from MAO-inhibition is complete.
Small doses should be given initially, increasing the levels of each drug, one at a time, over a period of 23 weeks to levels generally below those used for each one individually.
Do not exchange either the MAOI or the tricyclic antidepressant for other members of these drug groups without taking full precautions. A good washout period between the drugs is advisable. In the case of moclobemide, not less than 24 h, but with other MAOIs the usual advice is that washout should be up to 3 weeks. However one study reported switching 178 patients from tricyclics to MAOIs within 4 days or less. 63 of these patients were given the MAOI while still being tapered from the tricyclic, all without any apparent problems. 42
Doses of 50 and 100 mg chlorpromazine given intramuscularly have been used successfully in the treatment of this adverse interaction 17,19 and one report suggests that patients should carry 300 mg chlorpromazine and take it if a sudden, throbbing, radiating occipital headache occurs, and seek medical help at once. 44 It has been suggested that dantrolene can probably be used to reduce the muscle rigidity and hyperpyrexia, and possibly methysergide which is a 5-HT receptor antagonist. 26
1. Brachfeld J, Wirtshafter A, Wolfe S. Imipramine-tranylcypromine incompatibility. Near-fatal toxic reaction. JAMA (1963) 186, 11723.
2. Ayd FJ. Toxic somatic and psychopathological reactions to antidepressant drugs. J Neuropsychiatry (1961) 2 (Suppl 1), S119S120.
3. Kane FJ, Freeman D. Non-fatal reaction to imipramine-MAO inhibitor combination. Am J Psychiatry (1963), 120, 7980.
4. McCurdy RL, Kane FJ. Transient brain syndrome as a non-fatal reaction to combined pargyline imipramine treatment. Am J Psychiatry (1964), 121, 3978.
5. Loeb RH. Quoted in ref 10 below as written communication (1969).
6. Hills NF. Combining the antidepressant drugs. BMJ (1965) 1, 859.
7. Davies G. Side effects of phenelzine. BMJ (1960) 2, 1019.
8. Howarth E. Possible synergistic effects of the new thymoleptics in connection with poisoning. J Ment Sci (1961) 107, 100103.
9. Singh H. Atropine-like poisoning due to tranquillizing agents. Am J Psychiatry (1960) 117, 3601.
10. Lockett MF, Milner G. Combining the antidepressant drugs. BMJ (1965) 1, 921.
11. Graham PM, Potter JM, Paterson JW. Combination monoamine oxidase inhibitor/tricyclic antidepressant interaction. Lancet (1982) ii, 440.
12. Bowen LW. Fatal hyperpyrexia with antidepressant drugs. BMJ (1964) 2, 1465.
13. Beeley L, Daly M (eds). Bulletin of the W. Midlands Centre for Adverse Drug Reaction Reporting. (1986) 23, 16. (1986) 23, 16.
14. Nierenberg DW, Semprebon M. The central nervous system serotonin syndrome. Clin Pharmacol Ther (1993) 53, 848.
15. Stern TA, Schwartz JH, Shuster JL. Catastrophic illness associated with the combination of clomipramine, phenelzine, and chlorpromazine. Ann Clin Psychiatry (1992) 4, 815.
16. Beaumont G. Drug interactions with clomipramine (Anafranil). J Int Med Res (1973) 1, 480.
17. Tackley RM, Tregaskis B. Fatal disseminated intravascular coagulation following a monoamine oxidase inhibitor/tricyclic interaction. Anaesthesia (1987) 42, 7603.
18. Richards GA, Fritz VU, Pincus P, Reyneke J. Unusual drug interactions between monoamine oxidase inhibitors and tricyclic antidepressants. J Neurol Neurosurg Psychiatry (1987) 50, 12401.
19. Gillman PK. Successful treatment of serotonin syndrome with chlorpromazine. Med J Aust (1996) 165, 345.
20. Brodribb TR, Downey M, Gilbar PJ. Efficacy and adverse effects of moclobemide. Lancet (1994) 343, 4756.
21. Zimmer R, Gieschke R, Fischbach R, Gasic S. Interaction studies with moclobemide. Acta Psychiatr Scand (1990) (Suppl 360), 846.
22. Korn A, Eichler HG, Fischbach R, Gasic S. Moclobemide, a new reversible MAO inhibitor interaction with tyramine and tricyclic antidepressants in healthy volunteers and depressive patients. Psychopharmacology (Berl) (1986) 88, 1537.
23. Dingemanse J, Kneer J, Fotteler B, Groen H, Peeters PAM, Jonkman JHG. Switch in treatment from tricyclic antidepressants to moclobemide: a new generation monoamine oxidase inhibitor. J Clin Psychopharmacol (1995) 15, 418.
24. Spigset O, Mjorndal T, Lovheim O. Serotonin syndrome caused by a moclobemide-clomipramine interaction. BMJ (1993) 306, 248.
25. Gillman PK. Serotonin syndrome clomipramine too soon after moclobemide? Int Clin Psychopharmacol (1997) 12, 33942.
26. Neuvonen PJ, Pohjola-Sintonen S, Tacke U, Vuori E. Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses. Lancet (1993) 342, 1419.
27. Hernandez AF, Montero MN, Pla A, Vllaneuve E. Fatal moclobemide overdose or death caused by serotonin syndrome? J Forensic Sci (1995) 49, 12830.
28. Franηois B, Marquet P, Desachy A, Routson J, Lachatre G, Gastinne H. Serotonin syndrome due to an overdose of moclobemide and clomipramine: a potentially life-threatening association. Intensive Care Med (1997) 23, 1224.
29. Ferrer-Dufol A, Perez-Aradros C, Murillo EC. Fatal serotonin syndrome caused by moclobemide-clomipramine overdose. Clin Toxicol (1998) 36, 312.
30. Kφnig F, Wolfersdorf M, Lφble M, Wφssner S, Hauger B. Trimipramine and maprotiline plasma levels during combined treatment with moclobemide in therapy-resistant depression. Pharmacopsychiatry (1997) 30, 1257.
31. Vandel S, Bertschy G, Perault MC, Sandoz M, Bouguet S, Chakroun R, Guibert S, Vandel B. Minor and clinically non-significant interaction between toloxatone and amitriptyline. Eur J Clin Pharmacol (1993) 44, 979.
32. Wright SP. Hazards with monoamine-oxidase inhibitors: a persistent problem. Lancet (1978) i, 2845.
33. Schuckit M, Robins E, Feighner J. Tricyclic antidepressants and monoamine oxidase inhibitors. Combination therapy in the treatment of depression. Arch Gen Psychiatry (1971) 24, 50914.
34. Ponto LB, Perry PJ, Liskow BI, Seaba HH. Drug therapy reviews: tricyclic antidepressant and monoamine oxidase inhibitor combination therapy. Am J Hosp Pharm (1977) 34, 95461.
35. Ananth J, Luchins D. A review of combined tricyclic and MAOI therapy. Compr Psychiatry (1977) 18, 22130.
36. De la Fuente JR, Berlanga C, Leon-Andrade C. Mania induced by tricyclic-MAOI combination therapy in bipolar treatment-resistant disorder. Case reports. J Clin Psychiatry (1986) 47, 401.
37. Gander GA. In Antidepressant Drugs Proc 1st Int Symp Milan (1966). Int Congr Ser No 122, p 336. Excerpta Medica.
38. Sargant W. Safety of combined antidepressant drugs. BMJ (1971) 1, 5556.
39. Stockley IH. Tricyclic antidepressants. Part 1. Interaction with drugs affecting adrenergic neurones. In Drug Interactions and Their Mechanisms p 14. (1974) Pharmaceutical Press, London. (1974) Pharmaceutical Press, London.
40. White K, Pistole T, Boyd JL. Combined monoamine oxidase inhibitor-tricyclic antidepressant treatment: a pilot study. Am J Psychiatry (1980) 137, 14225.
41. Berlanga C. Ortego-Soto HA. A 3-year follow-up of a group of treatment-resistant depressed patients with a MAOI/tricyclic combination. J Affect Disord (1995) 34, 18792.
42. Kahn D, Silver JM, Opler LA. The safety of switching rapidly from tricyclic antidepressants to monoamine oxidase inhibitors. J Clin Psychopharmacol (1989) 9, 198202.
43. Beaumont G. Personal communication (1978).
44. Schildkraut JJ, Klein DF. The classification and treatment of depressive disorders. In Manual of Psychiatric Therapeutics p 61. Shader RI (ed). (1975). Little, Brown, Boston, Mass. (1975). (1975).
Posted by Chairman_MAO on November 11, 2004, at 12:59:40
In reply to Re: The Forbidden Combination: My AD list » darkhorse, posted by SLS on November 9, 2004, at 10:39:05
Have you considered trying parnate + amisulpride? Or Parnate + amisulpride + memantine/lamictal/other NMDA antagonist?
I've also been wondering about whether amisulpride would prevent DA agonists from eventually causing lethargy by preventing them from stimulating the autoreceptors.
Posted by Willyee on November 11, 2004, at 19:38:32
In reply to Re: What do you think of Parnate + amisulpride? » SLS, posted by Chairman_MAO on November 11, 2004, at 12:59:40
> Have you considered trying parnate + amisulpride? Or Parnate + amisulpride + memantine/lamictal/other NMDA antagonist?
> I've also been wondering about whether amisulpride would prevent DA agonists from eventually causing lethargy by preventing them from stimulating the autoreceptors.
I think this combo was mentioned by the people who put out the GOOD DRUG GUIDE,which in my opinion is one of the best articles ever written.
I know for sure one of the combos they mentioned with parnate that showed success was parnate and the beta blocker clonodine,it appearently ehnaced the anti depressant action of the med,right now with slow careful montiering im still finding tagamet,and vivarin at times to be the most beneficial augment to parnate,but im still not satisfied the search goes on.
Posted by SLS on November 12, 2004, at 7:29:40
In reply to Re: A little message to Scott, posted by ed_uk on November 11, 2004, at 9:03:59
Posted by SLS on November 12, 2004, at 7:56:07
In reply to Re: What do you think of Parnate + amisulpride? » SLS, posted by Chairman_MAO on November 11, 2004, at 12:59:40
> Have you considered trying parnate + amisulpride?
Not really, although it's a good thought. In the past, I have tried adding Risperdal and Zyprexa to a combination of Parnate + desipramine. My reactions were the same. I experienced a significant (25% improvement) antidepressant within the first few days that lasted for 5 days or so.
> Or Parnate + amisulpride + memantine/lamictal/other NMDA antagonist?
If I do try adding amisulpride, I will definitely be taking Lamictal 300mg.
> I've also been wondering about whether amisulpride would prevent DA agonists from eventually causing lethargy by preventing them from stimulating the autoreceptors.
Isn't that something how consistently Mirapex produces a latent lethargy? I guess something is happening presynaptically, as this phenomenon looks similar to low-dose apomorphine-induced sedation. I think the success of your strategy would depend upon the relative affinities of the two drugs for the receptor. Amisulpride is an extremely potent ligand for the presynaptic receptor, much more so than sulpiride. I don't know how it compares to the various agonists, though. One would like amisulpride to be a stronger ligand than the agonist. The following values that I found on the Internet represent the affinity of ligand for the D2 receptor. However, it doesn't diffentiate between presynaptic versus postsynaptic affinities. Presynaptic receptors are of substantially higher binding affinity than postsynaptic. If we assume that the ligands bind to both pre- and post- synaptic receptors in the same relative order of affinity, then your strategy might work.
K(i) for D2
amisulpride 1.3 - 3.8 nM
pramepexole 750 - 1500 nM
ropinerole 650 - 1000 nM
I appreciate your input.
Posted by SLS on November 12, 2004, at 8:13:18
In reply to Re: A little message to Scott, posted by ed_uk on November 11, 2004, at 9:03:59
> RE: amitriptyline+MAOI versus nortriptyline+MAOI
> I think it's very difficult to compare the risk of SS with these two combinations. Amitriptyline is more potent that nortriptyline as a serotonin reuptake inhibitor, at a glance it might be expected that the risk of SS would be higher with amitriptyline. On the other hand, amitriptyline appears to be more potent as an antagonist at 5-HT2a receptors. It seems likely that this might provide some protection from the SS.
When I was tried on a combination of Nardil 45mg + amitriptyline 150mg, I experienced no untoward reactions. However, I believe that the dosage of Nardil was too low to achieve clinically sufficient MAO inhibition. I have never profited from Nardil unless the dosage was at least 60mg. I did experience what I believe were the beginnings of SS when I added nortriptyline to the Nardil 75mg I had been taking. Obviously, I can't report with certainty the safety of adding amitriptyline to the same dosage of Nardil because I have never tried it.
Right now, I believe that desipramine should be the only TCA to be combined with Nardil. However, I think Parnate is less likely to produce these reactions, and would probably be a better drug to use in combinations with the other TCAs. I have taken a high dose of Parnate + imipramine and tolerated it well. I experienced a significant SS reaction to Nardil 60mg + imipramine.
> As you mention in your psychiatric drug chart, ritanserin is not selective for the 5-HT2a receptor.
It would still be great if ritanserin were available to use as an augmentor of antidepressants. Ritanserin is a great drug without an indication. I imagine the patent has expired, and we will never see it unless it is manufactured as an orphan drug.
Posted by ed_uk on November 12, 2004, at 9:36:16
In reply to Re: A little message to Scott » ed_uk, posted by SLS on November 12, 2004, at 8:13:18
Did you ever benefit from taking TCAs with MAOIs? Would you ever consider taking amitriptyline plus tranylcypromine? Ed
Posted by Shalom34Israel on November 12, 2004, at 19:02:38
In reply to The Forbidden Combination, posted by ed_uk on November 8, 2004, at 10:13:02
hello from Israel. I actually had psychiatrist at University recommend this combination to me. Very bad advice. I turned it down. Later I took parnate alone and still experienced hypertensive crisis from accidentally eating goat cheese.
MAOI plus SSRI? very bad advice
Posted by ed_uk on November 13, 2004, at 16:46:14
In reply to Re: The Forbidden Combination, posted by Shalom34Israel on November 12, 2004, at 19:02:38
Please read my original post carefully. As you will see, I was not advocating the use of SSRI+MAOI.
Posted by Questionmark on November 16, 2004, at 2:51:26
In reply to Re: The Forbidden Combination, posted by ed_uk on November 8, 2004, at 11:23:54
i have used *extremely* low-dose Paxil a few times while i have been on Nardil-- not by doctor's instruction, of course. i believe each time i was short on my Nardil for a couple days or so (though i think the first time may have been out of curiosity and the need for extra extra help with sociability and happiness that particular day).
(By the way, i know it goes without saying, but still-- this is NOT a good idea.)
Each time was roughly between 2.5mg and 5mg of Paxil (cut 10mg or 20mg pills), and i had been taking either 45mg or 60mg Nardil previously or presently. The effects of even this low dose of Paxil was profound: hypomania, euphoria, nervousness and excitability but not of the extremely unpleasant kind, moderate to more-than-moderate muscle tension and the desire to clench/contract muscles fairly hard, jaw clenching, obnoxious self-amusing behavior and speech (so to speak), increased body temperature, flushing, pupil dilation, and restlessness (e.g., my leg shaking even more rapidly than usual when sitting; exaggerated facial movements such as stretching mouth a lot and such). There certainly may have been a number of negative physiological effects that went unnoticed as well, such as excessive muscle protein breakdown (or something along those lines), kidney stress, and who knows what kinds of possiblly harmful brain effects?.
Anyway, i wanted to give my account so i could give my opinion on this matter and do so with a little added credence. i am really really open to the cautious use of oft-touted "contraindicated" med combinations. However, i fully believe that the combined use of an MAOI and an SSRI (any SRI probably) is never worthwhile. Aside from the significant danger and narrow margin of safety with efficacy, any desired effects that may be obtained from this combination can easily, safely, and still effectively be obtained via an increase in SSRI or MAOI dosage alone.
The reason i used the added Paxil was because i wanted an immediate effect for that particular day, but i'm foolish, desperate, overly curious, and Rx dependent (not any Rx in particular-- per se-- but Rxes in general). You get the idea.
Posted by ed_uk on November 16, 2004, at 7:45:59
In reply to Re: The Forbidden Combination, posted by Questionmark on November 16, 2004, at 2:51:26
Thank you Questionmark for your response- it was exactly the sort of thing that I was looking for. (I was very relieved that you'd read my post properly so you knew that I wasn't recommeding the combination :-)
Clearly the combination can be very dangerous, especially if the SSRI dose is high. Perhaps you should have taken just 1mg Paxil rather than 2.5mg!!
It would be very interesting to know whether any tolerance to the symptoms of the SS can occur if someone has taken an MAOI plus a very low dose of an SSRI on a long term basis. Unsurprisingly, I have never come across anyone who has done this.
Does anyone else have any experiences to share?
Posted by Questionmark on November 18, 2004, at 14:45:48
In reply to Re: What do you think of Parnate + amisulpride? » Chairman_MAO, posted by SLS on November 12, 2004, at 7:56:07
What a great idea-- adding amisulpride or another D2 antagonist to a D2 agonist to counter the lethargy. And what a smart way to help determine if that would work-- looking at the respective binding affinities of those three drugs on the D2 receptor. You guys are brilliant.
Anyway, are there autoreceptors of DA other than D2? If not, or not to a strong degree, then why aren't there dopamine agonists that just bind to D1 and/or D3 and/or D4 receptors? (Are there D1 autoreceptors?)
Oh and by the way, i've been wondering for quite some time now why D2 agonists are capable of causing such drowsiness and lethargy, and now i know why. So thank you. It eases some confusion that i had.
> Hi CM.
> > Have you considered trying parnate + amisulpride?
> Not really, although it's a good thought. In the past, I have tried adding Risperdal and Zyprexa to a combination of Parnate + desipramine. My reactions were the same. I experienced a significant (25% improvement) antidepressant within the first few days that lasted for 5 days or so.
> > Or Parnate + amisulpride + memantine/lamictal/other NMDA antagonist?
> If I do try adding amisulpride, I will definitely be taking Lamictal 300mg.
> > I've also been wondering about whether amisulpride would prevent DA agonists from eventually causing lethargy by preventing them from stimulating the autoreceptors.
> Isn't that something how consistently Mirapex produces a latent lethargy? I guess something is happening presynaptically, as this phenomenon looks similar to low-dose apomorphine-induced sedation. I think the success of your strategy would depend upon the relative affinities of the two drugs for the receptor. Amisulpride is an extremely potent ligand for the presynaptic receptor, much more so than sulpiride. I don't know how it compares to the various agonists, though. One would like amisulpride to be a stronger ligand than the agonist. The following values that I found on the Internet represent the affinity of ligand for the D2 receptor. However, it doesn't diffentiate between presynaptic versus postsynaptic affinities. Presynaptic receptors are of substantially higher binding affinity than postsynaptic. If we assume that the ligands bind to both pre- and post- synaptic receptors in the same relative order of affinity, then your strategy might work.
> K(i) for D2
> amisulpride 1.3 - 3.8 nM
> pramepexole 750 - 1500 nM
> ropinerole 650 - 1000 nM
> I appreciate your input.
> - Scott
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD, email@example.com
Script revised: October 4, 2007
Copyright 2006-08 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.