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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by ed_uk on December 6, 2004, at 13:48:36
Hi,
In animals, MAO type A deficiency has been associated with aggressive behaviour. Similarly, humans will low platelet MAO activity appear to be more aggressive. I was wondering how this might relate to treatment with an MAO inhibitor such as Nardil, Marplan, Parnate or Manerix/Aurorix.
To those who have taken an MAOI, did it produce an increase in aggression?
Someone did once tell me that Parnate made them unsympathetic. Perhaps the clinical efficacy of MAOIs in making people less anxious and less sensitive might also tend to make them more aggressive under certain circumstances.
.........If you are not interested in what I'm saying stop here, if you are interested then read on...........
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Here are some quotes from studies on PubMed.............'MAO A knock-out mice have elevated brain levels of serotonin, norephinephrine, and dopamine and manifest aggressive behavior similar to human males with a deletion of MAO A.'
'There was lower (platelet) MAO activity among violent offenders than among nonviolent offenders.'
'Violent behavior has been associated with certain personality traits like poor impulse control, sensation seeking, and monotony avoidance, which predispose to increased risk for violent acts. Low platelet monoamine oxidase (MAO) activity has been found in subjects with such traits, as well as in imprisoned violent offenders.'
'Patients who were diagnosed as psychopaths according to the criteria of Cleckley had significantly lower platelet MAO activity than the control group.'
'We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. ................. Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems.'
'Criminal offenders displayed significantly lower MAO activity in comparison to noncriminals. High levels of norm-breaking behavior in adolescence were associated with adult high impulsiveness, low socialization, and low platelet MAO activity in both male and female subjects.'
Ed.
Posted by linkadge on December 6, 2004, at 14:00:33
In reply to MAOIs and aggression, posted by ed_uk on December 6, 2004, at 13:48:36
I was just about to post the exact same thing. When you mentioned the SSRI's/agression link in some of the above posts I thought It might be advantageious to mention that there has been a link found in both animals and humans, between low MAO-A and agression, particulary agression under stress.
An MAO-A inhibitor would have a similar effect to say effexor, raising norepinephrine and serototonin. Yes I did find that effexor made me more agressive, not physically, but verbally, and just the way I felt about myself. I felt *meaner*
and more "punklike"Serotonin at the 5ht1a,1b receptors can *tame* agresssion, but serotonin particularly at the 5-ht2c receptor can cause agression.
It is interesting (and almost paradoxical in our thinking) to find that MAO-B inhibitors have *not* been linked to agression.
I would think that a perfect serenic would be a 5-ht1a/b receptor agonist combined with a selective MAO-B inhibitor.
Linkadge
Posted by ed_uk on December 7, 2004, at 7:41:00
In reply to Re: MAOIs and aggression, posted by linkadge on December 6, 2004, at 14:00:33
Hi,
Serotonin/aggression
Have scientists got it wrong?Some investigators have linked low 5-HIAA concentrations to aggression. It has been suggested that low 5-HIAA concentrations resulted from low serotonin levels. Hence, it has been suggested that low serotonin may lead to aggression. (BTW, I know that this is an oversimplification!)
Anyway, inhibition of MAO raises serotonin levels but reduces 5-HIAA levels. Perhaps the association between low serotonin and aggression was incorrect. The low 5-HIAA concentration observed in aggression may have resulted from low MAO activity. Perhaps, in some people, the high levels of serotonin resulting from the use of SSRIs or MAOIs may cause aggressive behaviour.
Maybe, as Linkadge suggested, stimulation of 5-HT(2) receptors is partly resonsible for serotonin-induced increase in aggression..............................................'Mice deficient in monoamine oxidase A (MAO A) have elevated brain levels of 5-HT and manifest enhanced aggression. We used these mice as a model to study the role of 5-HT in aggression. Our results show that ketanserin and tetrabenazine (TBZ) strikingly abolished the aggressive behavior of MAO A-deficient mice. The anti-aggressive effect of ketanserin may be primarily mediated by 5-HT(2A) receptors. 'Ed.
Posted by linkadge on December 7, 2004, at 10:14:10
In reply to Re: MAOIs and aggression, posted by ed_uk on December 7, 2004, at 7:41:00
SSRI and tryciclics might not cause the same decreases in 5-htaa levels that MAOI's do.
And you are right, these are antidepressants, and not antiagressive agents. (a) Do they increase agression, (b) does this have any effect on their clinical effect.
What I think is stupid is the forced rat swim test. I can be agressive and yet still depressed.
Ie, I might swim for hours and yet still be depressed. Ie the drug might just prolong swimming by inducing agression. This does not mean the mice are any happier about it.Lithium is interesting. when used as a sole agent, it almost always decreases agression.
It increases overall 5-ht1a/b activity, but decreases serotonin at other receptors.
Ie. SSRI's are terrably blunt tools. Saying this or that is caused by high or low serotonin is stupid because it's really the receptors that determine what serotonin does.
We need a series of potent and selective serotonin agonists, in order to figure out one receptor from the next.
Linkadge
Posted by SDW on December 7, 2004, at 12:31:12
In reply to Re: MAOIs and aggression, posted by linkadge on December 7, 2004, at 10:14:10
I wonder if substantial inhibition of MAO in a "healthy" subject, who is ostensibly not suffering from depression, would become agressive due to increased levels of any of the neurotransmitters. In other words, you could theoretically "ovecorrect" for a deficency of amines, and agression (or mania...) could be the outcome. Depressed people who improve on MAOIs would have increased self-confidence and more assertiveness...but as long as it's appropriate and controllable it probably wouldn't be considered agression in the common definition of the term. Parnate makes me a much nicer guy when it works...I'm more agressive (irritable/hostile) when I'm depressed...
Just a few thoughts on the subject...
Steve
Posted by linkadge on December 7, 2004, at 13:57:05
In reply to Re: MAOIs and aggression, posted by SDW on December 7, 2004, at 12:31:12
I think you're absolutely right SDW. I was certainly not agressive on Parnate either. It calmed me down and made me more agreeable.
I think that a lot more work needs to be done.
Perhaps low MAO function coupled with prefrontal dammage might make someone more agressive, and impulsive.
Linkadge
Posted by djmmm on December 9, 2004, at 8:12:11
In reply to Re: MAOIs and aggression, posted by linkadge on December 7, 2004, at 13:57:05
lots of MAOI info..enjoy:
Monoamine Oxidase: Basic and Clinical Perspectives
D.P. Holschneider, M.D. and J.C. Shih, Ph.D.
Posted by KaraS on December 9, 2004, at 15:21:04
In reply to Re: MAOIs and aggression, posted by djmmm on December 9, 2004, at 8:12:11
Thanks! Lots of great info there. I was surprised to read about a suspected relationship between PEA and panic. Another reason why MAOIs may be best for anxiety/panic disorder.
Posted by jclint on December 9, 2004, at 17:03:52
In reply to Re: MAOIs and aggression » djmmm, posted by KaraS on December 9, 2004, at 15:21:04
Yeah its very interesting. Interesting theories on the cause of the anti-anxiety properties of MAOIs.
I'm a little suspicious of some of the statements though:
"In the treatment of social phobia, characterized by an exaggerated fear of exposing oneself to the scrutiny of others, the response rate of phenelzine is 60–70% (142,145). Moclobemide has similar efficacy (146)."
I know there is little research into Moclobemide and SP, but I'm strongly skeptical about this drug. I certainly haven't seen any anecdotes of people getting a robust anti-sp effect from it.
Posted by djmmm on December 9, 2004, at 18:27:16
In reply to Re: MAOIs and aggression, posted by jclint on December 9, 2004, at 17:03:52
> Yeah its very interesting. Interesting theories on the cause of the anti-anxiety properties of MAOIs.
>
> I'm a little suspicious of some of the statements though:
>
> "In the treatment of social phobia, characterized by an exaggerated fear of exposing oneself to the scrutiny of others, the response rate of phenelzine is 60–70% (142,145). Moclobemide has similar efficacy (146)."
>
> I know there is little research into Moclobemide and SP, but I'm strongly skeptical about this drug. I certainly haven't seen any anecdotes of people getting a robust anti-sp effect from it.This is the study:
Versiani M, Nardi AE, Mundim FD, Alves AB, Liebowitz MR, Amrein R. Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine. Br J Psychiatry 1992;161:353-360.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1393304
Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine.
Versiani M, Nardi AE, Mundim FD, Alves AB, Liebowitz MR, Amrein R.
In a double-blind, parallel group trial, 78 subjects with social phobia received moclobemide (a new reversible inhibitor of monoamine oxidase A) phenelzine, or placebo. After eight weeks, both active drugs-phenelzine somewhat more than moclobemide--were clinically and statistically significantly more effective than placebo, as assessed by rating scales. There was some further improvement between weeks 8 and 16, particularly in the moclobemide group; at week 16, 82% of the moclobemide and 91% of the phenelzine-treated patients were almost asymptomatic. Moclobemide was, however, much better tolerated than phenelzine. Patients withdrawn from active drugs had relapsed by week 24, providing additional support for the efficacy of the active drugs.
Posted by banga on December 9, 2004, at 20:15:10
In reply to Re: MAOIs and aggression, posted by djmmm on December 9, 2004, at 18:27:16
I have seen conflicting information RE serotonin levels and aggression.
I definietely think there is a link between high serotonin levels and aggression (and impulsivity). When I was on a higher dose of Lexapro, I began to have very aggressive thoughts. I even felt some aggression towards a baby, which was extremely disturbing. When I dropped the dose, it got better.
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