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Below are many references to the fact that lithium is helpful for aggression, irritability and violent behavior.  The concern over using the pharmaceutical drug lithium is always one of detrimental side effects and the possibility of lithium toxicity.  However, the bioavailibility of lithium orotate allows very small amounts to be used effectively.  The same positive results may be achieved without any of the negative effects of the drug forms of lithium.




The National Institute of Mental Health (NIMH) states that “Lithium is the most promising agent for the treatment of aggression in children and adolescents." (January 2004)




In The Biology of Aggression, Vol 3, Spring 1999, it states that “Lithium is impressive in treating antisocial, aggressive and assaultive behavior” (citing Bloom and Kupfer, 1994; Sheard et al., 1976; Tupin et al., 1973).


(continuing) "Michael Sheard., a biologist at Yale, had been working with the anti-manic agent lithium carbonate. In a four-month study, Sheard gave lithium or placebo (a sugar pill) to approximately 40 prison inmates. The results were remarkable. While lithium had no effect on nonviolent behavior (stealing, lying), it appeared to fully suppress serious assault in inmates as observed and documented by prison guards.

Even more important was the observation that impulsive aggression returned to previous levels in the lithium-treated subjects after they were switched to the placebo condition."




In research supported by the National Institute of Mental Health, Dr. Paul H. Soloff concluded that,


Studies of impulsive, criminal adults and of delinquent adolescents demonstrate a strong effect for lithium against impulsive-aggressive symptoms……. The double-blind studies and additional case reports (e.g., Shader, Jackson, & Dodes, 1974) support an 'A' recommendation for the use of lithium for this indication.”   (Dr. Paul H. Soloff, M.D., March 1997.   Dr. Soloff is professor of psychiatry, Department of Psychiatry, University of Pittsburgh School of Medicine. )




Journal of the American Medical Association


Archives of General Psychiatry

Vol. 57 No. 7, July 2000


A Double-Blind Placebo-Controlled Study of Lithium in Hospitalized Aggressive Children and Adolescents with Conduct Disorder


Richard P. Malone, MD; Mary Anne Delaney, MD; James F. Luebbert, MD; Jacqueline Cater, PhD; Magda Campbell, MD


Background:  A subgroup of children and adolescents with conduct disorder are characterized by severe and persistent aggression. Although there is no agreed on treatment for such aggression, lithium carbonate has shown promise in some studies involving children. Our study was designed to critically assess the efficacy of lithium in the treatment of aggression in children and adolescents using a measure specific for aggression.


Methods:  Subjects were inpatients with conduct disorder hospitalized because of severe and chronic aggression. A parallel-groups design was used in this double-blind, placebo-controlled trial with randomization to lithium or placebo. Only those who met the aggression criterion during the 2-week placebo-baseline period were randomized to 4 weeks of treatment. Outcome measures included Clinical Global Impressions, the Global Clinical Judgments(Consensus) Scale, and the Overt Aggression Scale.


Results  Eighty-six inpatients enrolled in the study; 40(33 male and 7 female; median age, 12.5 years) entered and completed the treatment phase. Lithium was statistically and clinically superior to placebo. Sixteen of 20 subjects in the lithium group were responders on the Consensus ratings vs. 6 of 20 in the placebo group (P=.004). Ratings on the Overt Aggression Scale decreased significantly for the lithium group vs. the placebo group (P=.04).More than half of the subjects in the lithium group experienced nausea, vomiting, and urinary frequency.


(**Website note** These are side effects of the drug form of lithium carbonate. Lithium orotate does not cause these or any other side effects.)


Conclusions:  Lithium is a safe and effective short-term treatment for aggression in inpatients with conduct disorder, although its use is associated with adverse effects (**Website note** referring to the 'adverse effects' of lithium carbonate which lithium orotate would not have.)




Lithium in the treatment of aggression in mentally handicapped patients.

M Craft, IA Ismail, D Krishnamurti, J Mathews, A Regan, RV Seth and PM North Bryn-y-Neuadd Hospital, Llanfairfechan.

In a double-blind trial lasting 4 months in 42 mentally handicapped patients, the effect of lithium on aggression was assessed in comparison with placebo. In the lithium-treated group, 73% of patients showed a reduction in aggression during treatment. There were significant differences in mean weekly aggression scores and in the frequency of aggressive episodes between the lithium and placebo groups. Side-effects were noted in 36% of the lithium group (and 20% of the placebo group), but were mainly transitory. There were no episodes of toxicity, and no patients had to be withdrawn from the trial. Lithium appears to be worth a 2-month trial in such patients, where repeated aggression has not been relieved by more appropriate placement, occupation or company.


Lithium for irritability in post-traumatic stress disorder.

Forster PL, Schoenfeld FB, Marmar CR, Lang AJ.

University of California, San Francisco.

Irritability is often a problem for patients with Post-Traumatic Stress Disorder (PTSD). We describe two cases that illustrate the use of lithium in the treatment of veterans with PTSD who complained of serious problems with irritability or angry outbursts. These cases are discussed in the context of evidence that lithium may be useful in other patients with disorders of impulse control. The evidence linking disorders of anger and impulse control to a dysregulation in neurotransmitter regulation, particularly in serotonergic pathways, supports a psychopharmacologic approach to treatment. These findings should lead to further study of the role of lithium in the treatment of this symptom complex in patients with PTSD.



Current Psychiatry  

Vol. 2, No. 2 / February 2003

Benefits of low-dose lithium

In “Rediscovering the art of lithium therapy” (Current Psychiatry, December 2002), James W. Jefferson, MD, remarked that “Many patients on maintenance therapy do well at (lithium blood) levels between 0.6 and 0.8 mEq/L, and some prosper at even lower levels.”

Extremely low dosages of lithium may help well-functioning individuals who tend to be impatient or easily irritated. These persons are not impulse-ridden, are neither aggressive nor manic, and may not act out in an obvious way. They simply fume when waiting in a long line, or when someone cuts in front of them in traffic. They may complain excessively, and their blood pressure might be significantly elevated when agitated. The intensity and duration of their anxiety over mundane tribulations are the identifying characteristics. Such individuals might be classified as “bipolar III;” their depressive episodes are all but indistinguishable from the low end of the normal mood spectrum.

Hyperirritability has historically been included in diagnoses such as atypical depression or dysthymic disorder and may respond to antidepressants. This symptom, however, could also indicate a mild bipolar variant that is better treated with low-dose lithium. Starting such patients on lithium, 300 mg/d or even 150 mg qd, can bring significant relief, usually without side effects. In extremely low dosages, a therapeutic response may be obtained even though the blood level is well below 0.5 mEq/L. Patients who respond to low-dose lithium therapy typically report that they hardly notice the minor stressors that once angered them.

Other classes of drugs, such as MAO inhibitors, have also undeservedly fallen from grace as has lithium. Newer drugs should not replace older, effective ones without a clear rationale. Too often, psychiatric patients relapse while taking a newer medication; they stop taking the older agent “because my doctor said a newer, better one is out now."

Lorraine S. Roth, MD
Staff Psychiatrist,
Boston VA Outpatient Clinic

Dr. Jefferson responds:

Lithium does appear to be beneficial in aggressive impulsivity, although to my knowledge it has not been studied formally at the low dosages that Dr. Roth has found to be effective. Kitchner and Greenstein1 did describe five Vietnam veterans with posttraumatic stress disorder whose anger, insomnia, irritability, and anxiety responded to 300 to 600 mg/d of lithium carbonate.

Although the individuals Dr. Roth describes do not fit a conventional bipolar profile, they might have a place within the ever-expanding softer bipolar spectrum (well beyond the drug-induced manias and hypomanias of bipolar III). Perhaps her intriguing observation can help the road-ragers who roam the freeways of Los Angeles and other large cities.

James W. Jefferson, MD
Madison, WI


Nutritional Influences on Illness

The Effects of Dietary Lithium upon Mood and Behavior (excerpts)
by Melvyn R. Werbach, MD

"There is evidence that low levels of lithium in tap water correlates with higher mental hospital admissions due to diagnoses of psychosis, neurosis, schizophrenia, personality disorders and homicides.

Such nutritional lithium levels appear to be particularly related to aggressiveness. Violent criminals have been found to have reduced hair lithium levels. Moreover, a study of 27 counties found that the incidences of suicide, homicide and rape were significantly higher in counties whose drinking water supplies contained little or no lithium compared to counties with higher water lithium levels, even after correcting for population density. Corresponding associations with the incidences of robbery, burglary and theft were also significant, as were associations with the incidences of arrests for possession of opium, cocaine and their derivatives.

Results of a few early human intervention studies suggest that providing a nutritional level of lithium supplementation can have substantial mental and emotional benefits. In a 4-week study, the 16 male and 8 female subjects were all former drug users; some were violent offenders or had a history of domestic violence. They randomly received 400 mcg daily of lithium in tablets composed of lithium-rich brewer’s yeast, or similar tablets in which the brewer’s yeast was lithium-free. Each week they completed questionnaires measuring mental and physical activity, ability to think and work, mood and emotionality. In the lithium group only, total mood test scores increased steadily and significantly during supplementation.

Assuming that a person consumes about one liter of water daily from municipal supplies, it is striking that the therapeutic level of lithium from natural sources is so similar to the level consumed by residents of the counties with higher lithium levels in the study cited earlier. In the Texas drinking water study, the lithium level of drinking water in those counties with higher levels (and decreased violence) was between 70 and 170 mcg per liter, which lends further support to the hypothesis that only 50 mcg of lithium taken 3 times daily with meals may have substantial positive effects on mood and behavior – especially for people who live in areas where the levels of lithium in drinking water are low."

Effects of Nutritional Lithium Supplementation on Mood

N. Schrauzer and E. Devroey, 1994

The results of an intensive study of former drug users, violent offenders or those with a history of domestic violence assert that lithium supplementation has a mood improving and stabilizing effect. Authors suggest that a nutritional lithium supplement may be a valuable tool in violence and suicide prevention programs.

Understanding and Preventing Violence, Volume 2, 1994

"There are numerous demonstrations of antiaggressive effects in lithium responders among institutionalized individuals with diagnoses ranging from mental retardation to epilepsy, psychosis, and antisocial personality (e.g., Dostal and Zvolsky, 1970; Tupin, 1972; Goetzl et al., 1977; Dale, 1980; Craft et al., 1987; Glenn et al., 1989; Luchins and Dojka, 1989).

The most convincing evidence for lithium's effectiveness as an antiaggressive medication was gathered in violent prisoners (Sheard, 1971, 1977b; Sheard and Marini, 1978; Marini and Sheard, 1976, 1977; Tupin et al., 1973). Sheard's initial placebo-controlled study on 12 male volunteer prisoners in whom lithium given three times a day decreased assaultive behavior and verbal hostility as assessed by the prison staff was confirmed in a larger double-blind study with 66 highly aggressive prisoners (Sheard et al., 1976.)

In both a Connecticut and a California sample of violent convicts, lithium achieved a near elimination of aggressive feelings and violent behavior over the entire 3-18 months of treatment (Tupin et al., 1973; Sheard and Marini, 1978.)

Concluding Statement

The preclinical and clinical evidence establishes lithium as an effective long-term antiaggressive substance."