Creutzfeldt-Jakob Disease Presenting as Psychosis

Letters to the Editor Quetiapine for Chronic Motor Tic Disorder

4. Huang SC, Lai TJ, Tsai SJ: A case report of quetiapine-related ticlike symptoms. J Clin Psychiatry 2002; 63:1184–1185

TO THE EDITOR: There have been few case reports on the successful use of quetiapine for the treatment of Tourette’s syndrome and other tic disorders in children and adolescents (1– 3). We discuss our successful treatment of a patient with such a disorder. Mr. A was a 26-year-old single African American man who had been diagnosed with chronic motor tic disorder at age 7. He had symptoms of social phobia, including difficulties with public speaking and daily social interactions. His tic disorder was familial. Trials of medications since grade school included haloperidol, pimozide, clonidine, sertraline, alprazolam, propranolol, diazepam, olanzapine, and risperidone. These trials included full therapeutic doses for a sufficient duration. Risperidone was the most effective medication in relieving his symptoms but caused extensive weight gain, which led to discontinuation. The weight gain stopped after the risperidone was tapered; however, the tics reappeared. Diazepam and alprazolam exacerbated the tics. Clonidine and olanzapine were not effective in controlling the tics. Mr. A was then given quetiapine, 25 mg/day, which was titrated to 400 mg/day over several weeks. Within a month, he reported that he could socialize with more ease and was not having any tics. For the first time ever, he was able to speak publicly without any tics or problems initiating speech. Weight gain occurred, although not as much as when he was treated with risperidone.

The few case reports on this topic include patients who had not responded or had intolerable side effects to trials of haloperidol, risperidone, and clonidine. In contrast, Huang et al. (4) reported that an adult developed tics after 1 month of treatment with quetiapine. With any antipsychotic medication, tardive dyskinesia may occur and mimic a new onset of tic disorder. There are several possible mechanisms to explain the effect of quetiapine on tics. Quetiapine is unique among the atypical antipsychotics because it has a high serotonin-to-dopamine binding ratio. Parraga and Woodward (2) suggested that quetiapine’s unique binding profile to dopamine D4 receptors and serotonin 5-HT6 receptors, its selective inactivation of the mesolimbic cortical dopamine neurons, and/or its effect on excitatory amino acids might lead to its effectiveness in improving tics. To our knowledge, this is the first case report of the successful use of quetiapine for the treatment of a tic disorder in an adult. Further controlled trials to determine whether quetiapine is effective in the treatment of tic disorders in adults are warranted. References 1. Schaller JL, Behar D: Quetiapine treatment of adolescent and child tic disorders: two case reports. Eur Child Adolesc Psychiatry 2002; 11:196–197 2. Parraga HC, Woodward RL: Quetiapine for Tourette’s syndrome. J Am Acad Child Adolesc Psychiatry 2001; 40:389–390 3. Chan-Ob T, Kuntawongse N, Boonyanaruthee V: Quetiapine for tic disorder: a case report. J Med Assoc Thai 2001; 84:1624– 1628

Am J Psychiatry 161:7, July 2004

DREW BARZMAN, M.D. BETH GERNERT, B.A. MELISSA DELBELLO, M.D. Cincinnati, Ohio

Creutzfeldt-Jakob Disease Presenting as Psychosis TO THE EDITOR: The onset of sporadic Creutzfeldt-Jakob disease is usually characterized by dementia and/or neurological symptoms. The frequency of the prodromal psychiatric manifestations in sporadic Creutzfeldt-Jakob disease ranges between 18% and 39% (1), with mainly depressive disorders, personality changes, and emotional lability. Cases of the onset of sporadic Creutzfeldt-Jakob disease with psychotic disorders are rare (2). We report the case of a patient with sporadic Creutzfeldt-Jakob disease presenting as psychosis. Mr. A was a 31-year-old Caucasian man who was hospitalized for delusions of being controlled and persecutory, megalomanic auditory hallucinations, somatic tactile hallucinations, and visual hallucinations. He had no history of iatrogenic exposure, psychiatric disorders, or substance abuse disorders and no family history of psychiatric illness. The onset of the disorder was insidious. According to his family, Mr. A had had psychiatric symptoms for 9 months before the hospitalization: sleep disorders, auditory hallucinations, and delusional beliefs of persecution, and subsequently, social withdrawal, affective nonresponsivity, ideas of reference, physical transformation beliefs, and aggressive behaviors. His first EEG, performed 1 month before the hospitalization, was normal. At the onset of the hospitalization, Mr. A had memory problems characterized by an impaired ability to learn new information and daytime wandering, verbal stereotypies, inappropriately smiling, and reduced speech. Haloperidol, 15 mg/day, was used over 3 weeks with no improvement. His memory impairment gradually worsened. Neurological symptoms, such as hyperreflexia and hypertonia, appeared 16 months after his first psychiatric symptoms. He never had myoclonus. His condition deteriorated subsequently, with ataxia, mutism, and incontinence. He died 22 months after appearance of the first psychiatric symptoms. During hospitalization, repetition of the EEG showed nonspecific cortical abnormalities, without the periodic triphasic waves typical of sporadic Creutzfeldt-Jakob disease. A computerized tomographic scan showed diffuse cortical atrophy. The results of laboratory tests and CSF analysis were normal. The neuropathological findings at autopsy confirmed the diagnosis of sporadic CreutzfeldtJakob disease, including frontal and temporal atrophy, extensive cortical spongiform changes, neuronal loss, and gliosis throughout the cerebral cortex.

We report an unusual initial presentation of sporadic Creutzfeldt-Jakob disease characterized by psychotic symptoms, confirming the initial report of Dunn et al. (2). However, the hypothesis of sporadic Creutzfeldt-Jakob disease and schizophrenia comorbidity cannot be ruled out. The psychotic features in sporadic Creutzfeldt-Jakob disease are usually fleeting and transient, while our patient fulfilled the http://ajp.psychiatryonline.org

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LETTERS TO THE EDITOR

DSM-IV characteristic symptoms, the social dysfunction, and the duration criteria for schizophrenia. The psychiatric presentation of our patient could be linked with an early age at onset and a long duration of the disease and could be influenced by genetic factors, in particular, polymorphism of the codon 129 of the prion protein gene (3). References 1. Will RG, Matthews WB: A retrospective study of Creutzfeldt-Jakob disease in England and Wales 1970–1979, I: clinical features. J Neurol Neurosurg Psychiatry 1984; 47:134–140 2. Dunn NR, Alfonso CA, Young RA, Isakov G, Lefer J: CreutzfeldtJakob disease appearing as paranoid psychosis (letter). Am J Psychiatry 1999; 156:2016–2017 3. Rossetti AO, Glatzel M, Aguzzi A, Janzer R, Bogousslavsky J: Clinical and radiological mimicry of vCJD in a valine homozygous PrP(Sc) type 1 sCJD patient (letter). J Neurol 2003; 250:491–493

ALAIN DERVAUX, M.D. HUBERT LAINÉ, M.D. MARCEL CZERMAK, M.D. GÉRARD MASSÉ, M.D. Paris, France

Worsening Schizoaffective Disorder With Aripiprazole TO THE EDITOR: Effective in patients with schizophrenia, schizoaffective disorder, and acute bipolar mania, aripiprazole is the first drug with clear antipsychotic effects that is not a dopamine D2 receptor antagonist, and it represents a novel treatment development for psychotic disorders (1, 2). We report on a patient whose symptoms worsened after treatment with aripiprazole. Mr. A, a 50-year-old man with schizoaffective disorder, bipolar type, since his mid-20s, was treated with quetiapine, 400 mg b.i.d., and divalproex, 1000 mg b.i.d. He did reasonably well with this regimen but sometimes expressed grandiose delusions and had occasional auditory hallucinations and poor impulse control. Previous response to treatment with risperidone had been poor. He was moderately obese but had no other medical problems. He lived with his mother, who administered his medications and ensured that he was compliant with treatment. He did not drink alcohol or use illicit drugs. Aripiprazole, 15 mg/day, was added to his treatment regimen. A week later, he was more grandiose and sometimes responded to internal stimuli. His aripiprazole dose was then increased to 30 mg/day. Several days later, he became agitated, began threatening others, and would spend hours wandering in the streets. His mother stopped the aripiprazole because she felt it made him worse. His other medications were continued as prescribed. A week later, she brought Mr. A to the clinic and related that he was better after discontinuing aripiprazole. Mr. A was hospitalized to adjust his medications under controlled conditions. Divalproex and quetiapine were continued as before; aripiprazole, 15 mg/day, was resumed. After 6 days, he became more irritable and grandiose, and his hallucinations increased. Aripiprazole was discontinued, and 4 days later, his status was similar to that at admission. Ultimately, he responded best to divalproex, 1000 mg b.i.d., and olanzapine, 20 mg at bedtime.

The concurrence of the exacerbation of psychotic symptoms with our patient’s treatment with aripiprazole suggests

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that aripiprazole contributed to the occurrence of his symptoms. His rechallenge symptoms also strengthen the association. The most likely explanation for this phenomenon is aripiprazole’s partial agonism at dopamine D 2 receptors. Aripiprazole acts as a functional antagonist at D2 receptors under hyperdopaminergic conditions but exhibits functional agonist properties under hypodopaminergic conditions (1). Quetiapine shows a transiently high (up to 70%) D 2 occupancy at doses of 300 to 600 mg/day (2). We postulate that treatment with high doses of quetiapine created a functional hypodopaminergic state that allowed aripiprazole to act as a dopaminergic agonist, leading to increased psychotic symptoms. Clinicians may need to exercise caution when using aripiprazole in combination with other antipsychotic agents and consider cross-titration early on, with reduction of the first antipsychotic when aripiprazole is introduced. References 1. Kane JM, Carson WH, Saha AR, McQuade RD, Ingenito GG, Zimbroff DL, Ali MW: Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2002; 63:763–771 2. Kapur S, Zipursky R, Jones C, Shammi CS, Remington G, Seeman P: A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Arch Gen Psychiatry 2000; 57:553–559

ROY R. REEVES, D.O., PH.D. JAMES E. MACK, PH.D. Jackson, Miss.

Genetics in Pharmacokinetics? TO THE EDITOR: Greer M. Murphy, Jr., M.D., Ph.D., et al. (1) evaluated the importance of the cytochrome P450 CYP2D6 polymorphism (pharmacokinetic effect) and a single nucleotide polymorphism (SNP) in the serotonin (5-HT) subtype 2A receptor locus (5-HTR2A 102) as a pharmacodynamic effect on tolerance to the antidepressants paroxetine and mirtazapine. They described a major effect of the 5-HTR2A 102 T/C SNP with significantly more discontinuations due to side effects in paroxetine-treated patients carrying the C/C allele. In mirtazapine-treated patients, no differences were found in the occurrence of side effects with respect to the 5-HTR2A 102 genotype. Moreover, the CYP2D6 polymorphism obviously had no influence on the incidence of side effects in patients treated with either paroxetine or mirtazapine. The latter is surprising because mirtazapine and especially paroxetine are suggested substrates of CYP2D6. However, it is well documented that paroxetine inhibits its own metabolism, and at a final dose of 40 mg/day, there is no difference at all in the CYP2D6 activity (phenotype) between genotypical poor, intermediate, extensive, and ultra-rapid metabolizers (2, 3). This is nicely documented in the article by Dr. Murphy et al. by the plasma drug levels at day 28. At lower doses of paroxetine, when CYP2D6 is not completely inhibited, pharmacokinetic differences should become visible and are likely to affect the pharmacodynamics. The role of CYP2D6 in the pharmacokinetics of mirtazapine in vivo in patients is also questionable (4). The results of Dr. Murphy et al. with respect to the 5-HT2A receptor are of great clinical importance. However, my impression of the article was that Dr. Murphy and co-workers had Am J Psychiatry 161:7, July 2004