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Re: Drug-related Violence - Scott

Posted by Cam W. on May 31, 2000, at 1:07:30

In reply to Re: Drug-related Violence - Andrew, posted by SLS on May 30, 2000, at 8:04:05

Scott - Thank you for pleading my case with andrew. I don't think I could have said it as eloquently as you. You basically said what I had meant. I agree with much of what andrew said (but I would like proof of the hush money claim) and I will still stand by all of what I said.

In your previous post, you have no need to apologize for your beliefs. Yes, I agree that some people (about 10%) do get akasthesia-like or agression as a side effect of a number of medications. Aggression is probably due to the medications or aggressive disorders causing (or caused by) a neurotransmitter imbalance in areas of the brain regulating emotion (Is it the prefrontal cortex, hippocampus and amygdala? - I didn't have time to look this up and I can't remember, off-hand). Evidence for this (only a quick search done) is as follows:

"There are clear genetic contributions to impulsivity and aggression, although the exact details remain to be elucidated. Abnormalities in neurotransmitters, including decreased serotonergic function as well as increased noradrenergic function, have been related to aggressive behavior."[1]

"Cocarro and colleagues have demonstrated an inverse relationship between several measures of serotonin function and impulsive aggression in a group of individuals with personality disorder. Cerebral spinal fluid (CSF) vasopressin levels appear to be positively correlated with impulsive aggression, while there is an inverse correlation between serotonin function and vasopressin."[2]

Remember, vasopressin is needed in conjunction with CRH to efficiently stimulate the pituitary to release ACTH. Lack of vasopression can dysregulate the HPA axis, resulting in depressive symptoms [from a paper on CRH antagonists in anxiety that I have at work; I believe the author was F.Hoeboer(sp?) - reference available upon request]

"PET scan studies have demonstrated that individuals with intermittent explosive disorder have less serotonin activity in the orbital-frontal cortex than controls. A number of studies indicate that dysregulation of the serotonin system plays a role in impulsive aggression. For example, CSF 5-HIAA, the major metabolite of serotonin, is decreased in individuals with a history of impulsive aggression compared with those who suffer from nonimpulsive aggression and with normal controls...
... Depression and violent behavior are significantly correlated with moderate to severe outwardly directed irritability, as demonstrated by a study in which 37% of depressed patients reported having such irritability...
...Compared with controls, outpatients with major depressive disorder (MDD) have a significantly higher rate of anger attacks. As many as 38% to 44% of depressed outpatients report anger attacks, which are more common in individuals with unipolar depression than in those with bipolar disorder."[2]

So, is the antidepressant causing the anger and aggression or is it the drug or is it a combination of the two? I believe that it is probably the latter.

"...amitriptyline has been shown to increase aggression in some individuals with borderline personality disorder."[2: see ref.3]
"Tricyclic antidepressants may increase irritability because they stimulate the norepinephrine system."[4]

"In individuals with MDD, there are marked signs of autonomic arousal associated with anger attacks, including tachycardia, hot flashes, and sweating."[2]

More evidence of an imbalance in the body's chemistry causing anger responses?

"A number of studies have suggested that aggression is associated with reduced serotonin function. Dr.Fava reported that he and his colleagues found a blunting of the prolactin response to fenfluramine, a measure of serotonin function, in depressed individuals with anger attacks as compared to depressed individuals without anger attacks. This finding suggests a greater dysregulation of serotonergic neurotransmission in MDD with anger attacks than in MDD alone."[2]

More evidence of decreased serotonin function causing anger. Could this be used as a marker for determining if a depression is caused by a lack of serotonin or a lack of norepinephrine? It is increased norepinephrine that can cause aggressive behavior. [see 3rd paragraph of this post - Re: ref.1]

"A number of open-label studies have demonstrated that antidepressive agents, particularily the serotonin reuptake inhibitors, are effective in decreasing anger attacks. The depression response to these agents is equally robust in depressed individuals with or without anger attacks. In individuals with depression without anger attacks. treatment with either fluoxetine or sertraline is associated with less emergence of anger attacks than treatment with placebo."[2: see ref.5]
"These studies indicate that serotonin reuptake inhibitors can be safely used and show substantial promise in the treatment of anger attacks."[2]

While having a slight propensity to cause anger attacks, SRIs seem to be the treatment of choice for depression-related anger management. Other medications can also be used for aggression control:

"A number of studies have demonstrated a decrease in the use of seclusion and improvement in measures of aggression and irritability in hospital-based settings since the introduction of clozapine."[2: see ref.6]

"Similar comparisons for riseridone have demonstrated a decrease in physical assault, seclusion, and restraint."[2]

"Olanzapine has been found to decrease aggression in the treatment of acute mania..."[2: see ref.7]

Yes Scott, I agree with you that drug-induced aggression and anger can be a problem in some instances, but with proper case management and an astute physician, the risks can be held to a minimum.

I also agree with your views on psychological versus biological causes and remedies of depression. The stress/diasthesis model of mental illnesses (esp. depression, bipolar disorder and schizophrenia) has been championed by some great minds (Charles Nemeroff of Emory, Ming Tsang of Harvard, and, I believe, Nancy Andreasen, editor of the American Journal of Psychiatry).

[1] Korn ML. Various perspectives on violence. American Psychiatric Association 153rd Annual Meeting, Day 3, May 16, 2000, Chicago, Illinois.

[2] Brady K. The treatment and prevention of violence. American Psychiatric Association 153rd Annual Meeting, Day 2, May 15, 2000, Chicago, Illinois.

[3] Soloff PH, George A, Nathan RS, Schulz PM, Perel JM. Paradoxical effects of amitriptyline on borderline patients. Am J Psychiatry. 1986; 143: 1603-1605.

[4] Korn ML. Treatment of aggression. American Psychiatric Association 153rd Annual Meeting, Day 5, May 18, 2000, Chicago, Illinois.

[5] Coccaro EF, Kavoussi RJ. Fluoxetine and impulsive aggressive behavior in personality-disordered subjects. Arch Gen Psychiatry. 1997; 54: 1081-1088.

[6] Chiles JA, Davidson P, McBride D. Effects of clozapine on use of seclusion and restraint at a state hospital. Hosp Community Psychiatry. 1994; 45: 269-271.

[7] Tohen M, Sanger TM, McElroy SL, et al. Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group. Am J Psychiatry. 1999; 156: 702-709.

For further reading; a good commentary (available online at

Hirschfield RMA, Suicide and antidepressant treatment. Arch Gen Psychiatry; Apr 2000; 57: 325-326.

Scott, your opinions on my postings are greatly appreciated (as are yours andrew). Do not feel sorry for believing in something. I am not always right and sometimes I state my opinions as fact. The original comments I made in the post that started all this fun, I truly believe (but my beliefs can be modified, I'm not that old, yet).

Take care my friend - Sincerely - Cam

P.S. If I'd known I was going to get this kind of reaction, I would have gone back and corrected my spelling mistakes. There may be some in this post as well, but I'm tired and I don't care (bob - edit this for me, please) ;^

andrew, I hope you don't think that I have left you out. My comments were not made with any sort of value judgements at all. I do not wish anyone harm and I believe that life should be lived to it's fullest. Having MDD is not what I would consider a fulfilling life (I've been there, and lately I'm not sure if I am headed back). I, myself would risk the aggression/violence/suicidal side effects of medications; if only to enjoy a nice sunny day, sitting on the side of a grassy hill with nothing to do but watch billowy clouds float by in a calm breeze and listen to the rustle of the leaves in nearby trees. Thanks for taking time to respond to my post. I must go to bed now, as I am exhausted from another trying day at work and karate (BTW - I finished dead last in my division in both categories at the provincial karate tournament on Saturday, and you know what, I don't care - the job action by the nurses and support staff last week has left me absolutely drained). Sincerely - Cam




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