Catherine Chiles

Medical Student Beliefs and Attitudes Toward Mental Illness Across Five Nations.

Abstract Negative attitudes toward people with mental illness are a widespread concern and may vary across countries. This study used a 36-item questionnaire to compare attitudes toward people with mental illness and beliefs about the causes of mental illness among medical students from the United States, Brazil, Ghana, Nigeria, and China (N = 1131). Exploratory factor analysis identified the underlying factor structure of the questionnaire, and analysis of covariance was then used to compare factors representing four nonstigmatized attitudes across students from the five countries. US Medical students scored highest on all four factors, followed by those from Brazil. Nigerian and Ghanaian students scored lowest on nonsupernatural etiology of mental illness, and Chinese students showed the lowest score on personal social acceptance and public policy acceptance of people with mental illness. Differences in medical student attitudes between these five countries suggest underlying sociocultural differences in attitudes with the more stigmatized attitudes in developing countries.

Clozapine-induced euphoria: a case report.

To the Editor: We describe a case of treatment-resistant schizophrenia in which clozapine initiation and titration caused transient euphoria. Case report. Mr A is a 64-year-old man with a 35-year history of treatment-refractory schizophrenia (DSM-IV criteria), who was experiencing chronic delusions and auditory and visual hallucinations. He underwent multiple trials of different antipsychotics in the past, including trifluoperazine, chlorpromazine, olanzapine, and haloperidol, with minimal improvement in the psychotic symptoms. Past medical history included obesity, chronic obstructive pulmonary disease, and benign prostatic hypertrophy. He reported smoking 1 pack of cigarettes per/day and sporadic alcohol and cannabis abuse. He also reported experimenting with opioids in his adolescence. Current medications included haloperidol decanoate 200 mg intramuscular/monthly and finasteride 5 mg and terazosin 10 mg by mouth at bedtime. Medical assessment revealed normal physical examination, electrocardiogram, and laboratory values and no known drug allergies. To target the chronic delusions and auditory and visual hallucinations, clozapine was started on an outpatient basis at 12.5 mg and increased weekly in 12.5–25-mg increments, with regular weekly follow-ups and monitoring of vital signs and complete blood count values. Mr A tolerated initiation and titration fairly well. He developed mild tachycardia, ranging from 105–120 beats/min. His blood pressure remained within normal values; however, on several occasions, transient orthostatic hypotension with a 10-point drop in systolic and diastolic blood pressure was observed. Shortly following initiation of clozapine, Mr A started reporting feeling “high.” He described feeling elated, followed by intense feelings of euphoria and happiness starting 10 to 20 minutes after clozapine administration and lasting up to 2 hours. He also endorsed mild dizziness that initially paralleled euphoric feelings and then stopped. He described these sensations as being very similar to the effect of opioids that he had abused in adolescence. He denied experiencing a similar effect from other neuroleptics that he was given in the past. Mr A continued to experience this effect for 2 months while still undergoing clozapine titration. Once the clozapine level reached the total daily dose of 150 mg, the effect diminished in its strength and intensity and eventually disappeared. This is a first report in the literature describing clozapine-induced euphoria that started shortly after clozapine initiation and lasted for several months into clozapine titration; the effect resembled that of opioids in this case. Clozapine1 and opioids2 share certain pathophysiologic effects that can be responsible for the above-described effect. First, both clozapine and opioids can produce orthostatic hypotension that can be responsible for reduced brain oxygenation, creating the feeling of euphoria that initially occurred in this case. Second, opioid-induced euphoria and feeling “high” are related to the dose-dependent increase of dopamine in certain brain areas, for example, in the nucleus accumbens,2 which is believed to have a central role in addiction physiology. Interestingly, studies in animal models show that clozapine administration can produce an increase of dopamine in the nucleus accumbens,3 which could, in part, explain the euphoric feelings experienced by Mr A. Additionally, it appears that clozapine can affect D1 and D2 receptors and that modulation of D1 and D2 receptors could either reduce or increase, respectively, craving for substance abuse.4,5 Therefore, it is possible that the clozapine-related increase in dopamine concentration, in the case of Mr A, transiently experienced as the subjective feeling of being “high,” could reactivate opioid-induced synaptic plasticity of dopamine reward pathways. This hypothesis requires further investigation.

A case of cardiac arrest and pulmonary embolism after clozapine titration.

To the Editor: We describe a case in which a patient was started on clozapine treatment and subsequently developed pericardial tamponade and cardiac arrest complicated by pulmonary embolism. Case report. Mr A, a 52-year-old man with a history of severe, treatment-resistant schizophrenia (DSM-IV criteria), was hospitalized in 2010 to start a clozapine trial. Medical assessment revealed no abnormalities upon physical examination, laboratory values within normal limits, and no abnormalities in vital signs. At the time of his admission, he was treated with divalproex sodium 1,500 mg and perphenazine 16 mg daily and risperidone 50 mg every 2 weeks via depot injection. Past medical history included mild obesity, hyperlipidemia, well-controlled hypertension, and benign prostatic hypertrophy. Nonpsychiatric medications included simvastatin 80 mg, furosemide 20 mg, finasteride 5 mg, and tamsulosin 0.4 mg daily; the patient had remained medically stable for over 1 year prior to admission. Clozapine was started at 12.5 mg and increased daily in 12.5-25–mg increments up to 300 mg/d in divided doses, as perphenazine was tapered off. Divalproex sodium was continued at the same dose. Fifteen days after initiation of clozapine treatment, Mr A developed a fever of 102.5°F and tachycardia and was transferred to the medical unit with a pulse rate ranging from 110 to over 120 bpm. Laboratory investigations for neuroleptic malignant syndrome and infectious etiologies were negative. On the 17th day after clozapine initiation, the patient experienced respiratory depression, hypoxia, and hypotension. Chest computed tomography (CT) and echocardiogram revealed large pericardial effusion. The patient was scheduled for right heart catheterization to evaluate for cardiac tamponade and was emergently intubated due to progressive hypoxemia of 85% O2 saturation. At the time of intubation, the patient went into pulseless electrical activity and was resuscitated after administration of 1 mg of epinephrine. Subsequently, right heart catheterization was performed with a Swan-Ganz inguinal catheter. Thoracocentesis obtained 750 mL of serosanguineous liquid that was negative for infectious, malignant, or immunologic etiology; however, pericardial biopsy revealed inflammatory cells. After the diagnosis of pericarditis was made, clozapine was discontinued. On the second day after thoracocentesis, Mr A became progressively hypoxemic and hypotensive while continuing to have mild fever of unknown origin. Subsequent chest CT revealed a large right pulmonary embolism and bilateral pleural effusions. Risperidone injections ceased following this diagnosis. At that time, the patient was continued on mechanical ventilation and started on intravenous heparin, and the Swan-Ganz catheter was removed. This slowly resulted in hemodynamic stabilization. Mr A was started on broad-spectrum antibiotic coverage, although the extensive work-up continued to be negative. His temperature normalized 7 days after stopping clozapine, and he improved further. This patient developed severe cardiopulmonary symptoms leading to cardiac arrest shortly after initiation of clozapine treatment. Multiple etiologies can be implicated in the pathogenesis of pericarditis, including infections, malignancy, autoimmunity, and uremia. Rapid development of cardiac tamponade leading to cardiac arrest combined with the extensive negative baseline workup coincides with the initiation of clozapine treatment and is consistent with previously described cases of clozapine-related cardiopulmonary complications that include polyserositis.1,2 What makes this case unique, however, is the severity and lethality of symptoms and the development of pulmonary embolism. Inguinal catheterization could be a potential source of emboli, although in this case several other risk factors could contribute to their development, including obesity, hypertension, and hyperlipidemia. In addition, clozapine could be an independent risk factor for development of pulmonary embolism,3 but to what degree is unclear. Although the patient presented with some heart disease–related risk factors, these were not contraindications for initiation of clozapine treatment.