Psychosis Precipitated by Acetyl-l-Carnitine in a Patient With Bipolar Disorder

Sir: Alternative and complementary medicine is popular in the United States, and interest in this type of medicine is growing. Approximately 55% of the U.S. population uses complementary and alternative medicines, at a cost of $337 million in 2001.¹ Knaudt et al.² found that 54% of outpatients with psychiatric conditions used alternative medicines in addition to conventional medicines to treat psychiatric symptoms.

Acetyl-l-carnitine (ALC) is a popular nutritional supplement used by patients with mood disorders, Alzheimer's disease, and other disorders. It is widely sold over the Internet as a safe and effective nutritional supplement. There is also a general perception among the public that nutritional supplements are safe, with few side effects. To our knowledge, there are no reports of ALC precipitating a psychiatric disorder. We report the first case of ALC precipitating a psychotic episode in a person with a previous history of bipolar disorder.

Case report. Mr. A, a 52-year-old white man, admitted as an inpatient to our psychiatric unit in 2005 after he became floridly psychotic. He presented with auditory hallucinations of the devil and persecutory delusions regarding his brother and mother, who were his primary caregivers. On admission, he demonstrated hostility and aggression toward the staff in the unit. He also was verbally threatening and physically assaultive toward staff.

Mr. A had a long history of bipolar disorder dating back to early adulthood. He had been stabilized on lithium treatment and had been symptom free for more than 10 years. His symptoms had reemerged about 2 years ago, and, prior to the current admission, the patient had been admitted 3 months ago for inappropriate sexual behaviors, which had been treated successfully with citalopram. He had been discharged on a treatment regimen of lithium, 150 mg b.i.d., and citalopram, 20 mg/day, and had been off treatment with antipsychotics for more than 3 months before the current admission (he had received aripiprazole, olanzapine, clozapine, and quetiapine in the past). His condition was stable, and he had been doing very well for 4 weeks. Five days before admission, the patient was started on treatment with nutritional supplements including vitamin C, vitamin E, and ALC, the latter at 500 mg/day. Five days after ALC was started, the patient suddenly became psychotic.

We believe that ALC was responsible for the precipitation of this current psychotic episode because of the temporal association of the onset of psychosis with the start of ALC treatment, the suddenness of the onset, and the severity of the psychosis, which was much greater than he had experienced in a long time.

ALC is a well-known nonessential organic nutrient. Because ALC is essential for the transport of long-chain fatty acids across the inner mitochondrial membrane, it has major importance in mitochondrial energy metabolism. ALC is easily transported across the blood-brain barrier and improves neuronal and repair mechanisms while modifying acetylcholine production in the central nervous system.³

Esters of carnitine (acetylcarnitine and propionylcarnitine) have pharmacologic value by virtue of their antioxidant properties and ability to deliver readily oxidizable carbon units to mitochondria. Alzheimer's disease and depression in the elderly, ischemia-induced myocardial dysfunction in angina pectoris, human immunodeficiency virus infection, and diabetic neuropathies may respond positively to ALC administration.

Animal studies have shown that ALC administration persistently increases dopamine outflow in the nucleus accumbens.⁴ Carnitine supplementation has been shown to significantly increase the levels of dopamine in the cortex, hippocampus, and striatum of rat brain.³

Dopamine dysregulation in this pathway has been shown to cause psychotic symptoms. This dysregulation may arise through a process of sensitization, which, in animals, can be caused by repeated administration of dopamine-releasing drugs. The same process may occur in humans, and some individuals may be particularly sensitive to the effects of such drugs either for genetic reasons or through early environmental damage.⁵

This case report illustrates the need for physicians to be aware of any complementary therapies that patients might be receiving and to routinely inquire about this during the initial interview. Psychiatrists need to be aware of the potential that these therapies have to exacerbate or worsen preexisting psychiatric disorders.