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Copyright ª Blackwell Munksgaard 2005 A psychotic episode associated with the AtkinsDiet in a patient with bipolar disorder talcum powder, and flooding the apartment withwater from his bathtub, resulting in the collapse of Studies have suggested that a ketogenic diet is the ceiling of the apartment downstairs. The time beneficial for epilepsy, both in adults (1) and in course of the patient’s diet and symptoms is children (2). As antiseizure medications have proved to be effective treatment for bipolar At presentation to the hospital, the patient’s disorder, the question has arisen whether the weight was recorded as 189 pounds. Mood was ketogenic diet, or other diets, may be effective in irritable and expansive. Thought process was the treatment of bipolar disorder (3). Dietary rambling and tangential. Thought content included omega-3 fatty acids have been found to lengthen somatic preoccupation and delusions with religious remissions in bipolar disorder (4). But in one study references. He was not oriented to day or date.
that examined the effect of the ketogenic diet on He was placed on a regular diet, and treated with bipolar disorder in valproate-resistant patients, no a continuation of his preadmission medications.
effect was found (5). We describe the case of a His weight increased rapidly, his mood stabilized, patient with bipolar disorder maintained on val- and his delusions gradually improved until his proic acid, who developed mania shortly after One possible connection between diet and the The patient is a 54-year-old veteran who first development of mania in this patient is a relation- developed bipolar disorder in the mid-1990s. His ship between ketosis and valproate metabolism.
most recent psychiatric admission was in October2001. Discharge psychiatric medications weredivalproex, 1.5 g total per day, clonazepam, 1 mgat HS, and quetiapine, total daily dose 700 mg.
From October 2001 until June 2003, the patient had no psychiatric complaints recorded by hiscaseworker with the exception of mild anxiety. On June 12, 2003, the patient told his caseworker that he started the Atkins diet. On June 25, the patient reported that he was not sleeping well, and clonazepam was increased to 1.5 mg. On July 10, because of continued insomnia, his divalproex was increased to 2 g/day. On July 22, the patient’s family voiced concerns over his increasingly bizarrebehavior and paranoia. On July 24, the patient had multiple somatic complaints, and on July 30, he complained of multiple odors and was hyperverbal.
A total of 25 mg of diazepam/day was added to his Fig. 1. Patient weight and severity of manic symptoms prior to medication regimen. On August 8, the caseworker admission. Symptoms were recorded from notes made by the noted that money was missing from the patient’s patient’s caseworker. Shaded area represents the period of the bank account. The patient continued to refuse patient’s diet. Symptom severity was divided on a 6-pointscale: 1 ¼ stable mood; 2 ¼ some complaints of anxiety; hospital admission until August 12, when he was 3 ¼ insomnia; 4 ¼ bizarre behavior with intact reality testing; evicted after covering the entire apartment in 5 ¼ disorientation, primarily to date; and 6 ¼ severe psychosis.
branched-chain fatty acid that is metabolized both 1. Sirven J, Whedon B, Caplan D et al. The ketogenic diet for by glucuronization and oxidation. There is signif- intractable epilepsy in adults: preliminary results. Epilepsia icant variation in the pattern of valproate metab- olism within and between individuals (6). The 2. Vining EP, Freeman JM, Ballaban-Gil K et al. A oxidative pathway occurs within the mitochondria multicenter study of the efficacy of the ketogenic diet.
Arch Neurol 1998; I55: 1433–1437.
and is subject to auto-induction (7) and is capable 3. El-Mallakh RS, Paskitti ME. The ketogenic diet may have of complete metabolism of valproate via beta mood-stabilizing properties. Med Hypotheses 2001; 57: oxidation to carbon dioxide and ketone bodies (8). During low-carbohydrate diets or starvation, 4. Stoll AL, Severus WE, Freeman MP et al. 3 Fatty gluconeogenesis is stimulated through multiple acids in bipolar disorder: a preliminary double-blind,placebo-controlled trial. Arch Gen Psychiatry 1999; 56: mechanisms, including increased mitochondrial transport of fatty acids, resulting in the formation 5. Yaroslavsky Y, Stahl Z, Belmaker RH. Ketogenic diet in of ketones. It is conceivable that the stimulation of bipolar illness. Bipolar Disord 2002; 4: 75.
fatty acid transport and metabolism by dietary 6. Kreher U, Darius J, Wien F. Establishing individual changes could lower plasma levels of valproate.
metabolite patterns for patients on valproate therapy. EurJ Drug Metab Pharm 2001; 26: 99–107.
An alternative explanation in the present case is 7. McLaughlin DB, Andrews JA, Hooper WD, Cannell GR, that metabolic conditions related to the diet Eadie MJ, Dickinson RG. Apparent autoinduction of contributed directly to the development of mania, valproate beta-oxidation in humans. Br J Clin Pharmacol independently of changes in the plasma level of valproate. Mania has been precipitated in Muslim 8. Silva MF, Ruiter JP, Overmars H et al. Complete beta- oxidation of valproate: cleavage of 3-oxovalproyl-CoA by bipolar patients by changes in Ôsocial rhythmÕ a mitochondrial 3-oxoacyl-CoA thiolase. Biochem J 2002; is observed (9). Elevation of mood has been 9. Kadri N, Mouchtaq N, Hakkou F, Moussaoui D.
reported in obese patients during low-calorie, Relapses in bipolar patients: changes in social rhythm? Int limited-carbohydrate diets, whether or not ketosis J Neuropsychopharmacol 2000; 1: 45–49.
10. Rosen JC, Gross J, Loew D, Sims EA. Mood and develops (10). Mood changes during fasting may appetite during minimal-carbohydrate and carbohydrate- be related to changes in neuroendocrine function supplemented hypocaloric diets. Am J Clin Nutr 1985; 42: In summary, the close temporal relationship 11. Michalsen A, Schneider S, Rodenbeck A, Ludtke R, between the initiation of the Atkins diet by this Huether G, Dobos GJ. The short-term effects of fasting onthe neuroendocrine system in patients with chronic pain patient and the subsequent development of mania syndromes. Nutr Neurosci 2003; 6: 11–18.
suggests a relationship between diet and bipolardisorder. Further studies are necessary to elucidate this relationship, as well as to investigate the effects of dietary changes on the metabolism of valproic Department of Psychiatry and Behavioral Medicine Medical College of Wisconsin8701 Watertown Plank RoadMilwaukee, WI 53226, USA


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