Letters to the Editor

Letters to the Editor

Mirtazapine for Treatment of Nausea Induced by Selective Serotonin Reuptake Inhibitors
Dear Editor: Nausea appears to be a dosagerelated side effect in as many as 26% of patients treated with selective serotonin reuptake inhibitors (SSRIs) (1,2). SSRIs increase the concentration of serotonin (5-HT) at neuronal synapses. Emesis may result from subsequent activation of central or peripheral 5-HT3 receptors (2,3). Antagonism of 5-HT3 by drugs like ondansetron is known to reduce emesis in chemotherapy patients a n d ma y h a v e s o me a p p l i c a t i o n i n SSRI-induced nausea, but the effect is short-lived and the cost is prohibitive (2,3). The 5-HT antagonist cyproheptadine may have some efficacy for SSRI-induced nausea, but it has been associated with worsening of depressive symptoms when used to treat SSRI-induced sexual dysfunction (4). The antidepressant mirtazapine, an antagonist at presynaptic alpha 2 adrenergic inhibitory autoreceptors and heteroreceptors (where it enhances noradrenergic and serotonergic activity), is also a potent antagonist of 5-HT2 and 5-HT3 receptors (5). We report a case of SSRI-induced nausea successfully treated with mirtazapine. To control her nausea, mirtazapine 15 mg at bedtime was substituted for trazodone. Nausea symptoms decreased the day after starting mirtazapine and completely disappeared within 4 days. However, she had difficulty sleeping and had to restart her trazodone. The combination of mirtazapine and trazodone left her with excess daytime sedation plus restless legs when falling asleep. Mirtazapine was subsequently discontinued, and her nausea returned within 4 days. Resumption of mirtazapine 15 mg at bedtime once more relieved all nausea. Replacement of trazodone with clonazepam 0.5 mg at bedtime allowed her to have a good sleep with no daytime sedation and no restless legs.

Effects of Propofol on Electroconvulsive Therapy Seizure Duration

Dear Editor: Propofol is an anesthetic agent alternative to methohexital. It is widely used because it is associated with smaller hemodynamic response during electroconvulsive therapy (ECT) (1). Studies have shown that propofol reduces seizure duration, and reports of reduced seizure duration with ECT under propofol anesthesia have led to concerns that propofol may diminish the efficacy of this treatment (2,3). However, although propofol has been associated with shorter seizures when given for ECT anesthesia, the reduced seizure duration has not been associated with smaller therapeutic effect Discussion We describe a patient who experienced reso- when compared with methohexital anesthesia lution of SSRI-induced nausea with low- (4,5). dosage mirtazapine. The use of this agent to We compared the effects of propofol on seicontrol nausea associated with SSRIs was first zure duration with ECTs performed without discussed by Pedersen and others in 1997 (6). anesthesia. We retrospectively studied 26 In their report, 3 patients experienced relief of patients consecutively referred for ECT. All nausea approximately 2 to 3 days after the patients were hospitalized and treated in addition of mirtazapine 15 mg daily. In 2 Trakya University Psychiatry Clinic, Edirne, patients, nausea resumed when mirtazapine Turkey, between January 1, 2001, and was discontinued and lessened when it was December 31, 2003. Until March 2002, ECT restarted. We observed a similar pattern in our treatments in this clinic were performed withcase. out anesthesia. Of the 26 patients, 15 had ECT

Case Report

References

Ms K, aged 46 years, is a single white woman 1. Trindale E, Menon D, Topfer LA, Coloma C. who has suffered for 10 years from a recurrent Adverse effects associated with selective serotonin unipolar major depressive disorder associated reuptake inhibitors and tricyclic antidepressants: a meta-analysis. CMAJ 1998;159:124552. with insomnia; she also suffers from 2. Bergeron R, Blier P. Cisapride for the treatment of obsessivecompulsive disorder (OCD). For nausea produced by selective serotonin reuptake the last 3 years, her symptoms have been inhibitors. Am J Psychiatry 1994;151:1084 6. partly controlled with sertraline 300 mg daily, 3. Coupland NJ, Bailey JE, Potokar JP, Nutt DJ. 5-HT3 bupropion slow release 150 mg twice daily, receptors, nausea, and serotonin-reputake inhibition. J Clin Psychopharmacol 1997;17:1423. and trazodone 100 mg at bedtime. During 4. Woodrum ST, Brown CS. Management of treatment, she experienced recurring episodes SSRI-induced sexual dysfunction. Ann of nausea associated with the administration Pharmacother 1998;32:120915. of SSRIs. With sertraline, the nausea was 5. Bezchlibnyk-Butler K, Jeffries J, editors. Clinical partly controlled by her taking the dosage in handbook of psychotropic drugs. 13th ed. Toronto (ON): Hogrefe & Huber; 2003. p 30 2. 100 mg increments 3 times daily, approxi6. Pederesen L, Klysner R. Antagonism of selective mately one-third of the way into a meal. serotonin reuptake inhibitor-induced nausea by Despite these efforts, her symptoms were mirtazapine. Int Clin Psychopharmacol occasionally sufficient to cause projectile 1997;12(1):59 60. vomiting, which forced her to reduce her total daily dosage. Attempts to decrease the Efstratios V Caldis, MB, ChB, FRCPCP sertraline dosage permanently increased her Robert D Gair, BSc (Pharm) Vancouver, British Columbia OCD symptoms.
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treatments under anesthesia, and 11 had treatments without anesthesia. Propofol was used as an anesthetic agent and succinylcholine was used as a muscle relaxant in the 15 patients who received anesthesia. Patients in both groups were treated with the same ECT machine (ThymatronTM DGx, Somatics Inc, Lake Bluff, IL). Bilateral electrode placement was applied for all patients. Seizure duration measurements were based on the machines automated seizure duration determinations. The groups were compared without taking into consideration the patients diagnosis, the drugs that they used, or their psychiatric outcomes.

Results
The groups were similar in terms of sex and mean age. Major depression was the most frequent diagnosis in both groups. The number of ECT treatments in the propofol anesthesia group (mean 9.67, SD 2.99) did not differ significantly from the nonanesthesia group
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(mean 9.27, SD 2.05; t = 0.37; P = 0.71). When the seizure durations were compared, seizure duration was longer in the propofol anesthesia group (mean 44.38, SD 14.52) than in the nonanesthesia group (mean 39.45, SD 3.47). However, this difference was not significant (t = 1.26, P = 0.22). Mean (SD) propofol dosage was 98.68 (4.48) mg. We found no linear correlation between the propofol dosage and seizure duration (r = 0.24, P = 0.41). We assessed the effect of both the number of ECTs and having anesthesia on seizure duration; no effects for ECT number (F1,11 = 1.80, P > 0.05) or patient group (F = 0.81, P < 0.05) were revealed, nor was there any significant interaction between the number of ECTs and the patient group (F1,11 = 1.55, P < 0.05).

Discussion
Contrary to previous studies (68), we did not find that propofol had any considerable effect on seizure duration. Our study design was different from other studies in that they compared 2 different induction agents (911); in our study, seizure durations of patients who received propofol anesthesia were compared with seizure durations of patients who received ECT treatments without anesthesia. Current standards, especially for research purposes, would preclude the use of ECT without anesthesia, but because our study was retrospective, we must assume that this ethical concern was not an issue. Our study found that propofol did not shorten seizure duration. Although anesthesia with propofol has been associated with shorter ECT seizures, other anesthetic agents used for comparison with the propofol may have affected earlier results. Our study suggests the importance of the control group who received ECTs without anesthesia for comparing the effects of anesthetic agents on seizure duration: results that are more reliable could be obtained and controversial conclusions minimized.

4. Fredman B, dEtienne J, Smith I. Husain MN. Anesthesia for electroconvulsive therapy: effects of propofol and methohexital on seizure activity and recovery. Anesth Analg 1994;79:759. 5. Malsch E, Gratz I, Mani S, Backup C, Levy S. Efficacy of electroconvulsive therapy after propofol and methohexital anesthesia. Convuls Ther 1994;10:2129. 6. Stadtland C, Erfurth A, Ruta U, Michael N. A switch from propofol to etomidate during an ECT course increases EEG and motor seizure duration. J ECT 2002;18(1):225. 7. Martensson B, Bartfai A, Hallen B, Hellstorm C, Junthe T, Olander M. A comparison of propofol and methohexital as anesthetic agents for ECT: effects on seizure duration, therapeutic outcome, and memory. Biol Psychiatry 1994;35:17989. 8. Simpson KH, Halsall PJ, Carr CM, Stewart KG. Propofol reduces seizure duration in patients having anaesthesia for electroconvulsive therapy. Br J Anaesth 1988;61:343 4. 9. Krystal AD, Weiner RD, Dean MD, Lindhal VH, Tramontozzi LA, Falcone G, and others. Comparison of seizure duration, ictal EEG, and cognitive effects of ketamine and methohexital anesthesia with ECT. J Neuropsychiatry Clin Neurosci 2003;15(1):2734. 10. Geretsegger C, Rochowanski E, Kartnig C, Unterrainer AF. Propofol and methohexital as anesthetic agents for electroconvulsive therapy (ECT): a comparison of seizure-quality measures and vital signs. J ECT 1998;14(1):2835. 11. Nguyen TT, Chhibber AK, Lustik SJ, Kolano JW, Dillon PJ, Guttmacher LB. Effect of methohexitone and propofol with or without alfentanil on seizure duration and recovery in electroconvulsive therapy. Br J Anaesth 1997;79:8013.

on room air. Immediate treatment included subcutaneous epinephrine 0.3 cc at 1:1000 dilution, intravenous diphenhydramine 50 mg, and intravenous solumedrol 125 mg. His symptoms resolved within 30 minutes, after which he was observed for another 3 1/2 hours. Later, he acknowledged that the peanut butter ingestion was a deliberate suicide attempt. He was subsequently placed on a suicide watch and denied access to all peanutcontaining products. While there are rare reports of patients with asthma who use their disease as a modality for suicide (either through deliberate avoidance of medications or deliberate induction of a severe attack) (1), no cases are thus far reported of deliberate induction of anaphylactic reactivity. This is the first reported case of a patient exploiting allergic sensitivity in this manner, demonstrating a possible avenue of suicidal attempt. Upon admission to a psychiatric ward, food allergies should be welldocumented; foods with anaphylactic potential should not be accessible to patients. Note An abstract of this case was previously presented at the Canadian Society of Allergy and Clinical Immunologoy Meeting; 2002; Quebec (QC).

Okan Caliyurt, MD Erdal Vardar, MD Cengiz Tuglu, MD Ercan Abay, MD Edirne, Turkey

Deliberate Ingestion of Peanut as a Suicide Attempt

Dear Editor: I report the case of a man, aged 24 years, with an established history of severe anaphylaxis to peanuts, who deliberately ingested peanut butter as a suicide attempt while admitted to hospital. The patient was admitted to the psychiatry service for severe depression but had not revealed overt suicidal ideation. His medical history was significant for severe anaphylactic reactivity to peanuts. During his admission, he prepared himself a sandwich that he later admitted was intentionally contaminated with peanut butter. Within 5 minutes of consuming the sandwich, he developed shortness of breath and swelling of the lips and throat, followed by an erythematous, pruritic rash involving his entire body. He was admitted to the emergency department, where he was noted to be tachycardic and hypoxic, with an oxygen saturation of 91%

References
1. Lewiston NJ, Rubinstein S. Sudden death in adolescent asthma. N Engl Reg Allergy Proc 1986;7:448 53.

Anne K Ellis, MD Kingston, Ontario

Postoperative Manic Outburst: A Case Report

Dear Editor: Immediate postoperative psychosis is common after coronary artery bypass grafting (CABG). It is usually shortlived. A clinical profile akin to mania is less common, as most acute postoperative psychoses are hallmarked either by purposeless agitation or by paranoid features. The following clinical report aims to break some ground on these transient psychic processes to foster better understanding of the psychological issues faced by patients in the immediate postoperative period.

References
1. Avramov MN, Husain MM, White PF. The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy. Anesth Analg 1995;81:596 602. 2. Mitchell P, Torda T, Hickie I, Burke C. Propofol as an anaesthetic agent for ECT: effect on outcome and length of course. Aust N Z J Psychiatry 1991;25:255 61. 3. Fear CF, Littlejohns CS, Rouse E, McQuail P. Propofol anaesthesia in electroconvulsive therapy: reduced seizure duration may not be relevant. Br J Psychiatry 1994;165:506 9.

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Case Report
A man, aged 84 years, underwent a scheduled CABG without incident. There was no history of personal or familial psychiatric problems and no history of excessive alcohol intake. On day 1 after surgery, the psychiatric consultant was called to see the patient because he asserted that he was to be filmed. When first seen, the patient was calm and cooperative, the sensorium was clear, and he denied any worries. He displayed a euphoric affect and felt himself to be extraordinarily well. He reported that, when he awoke from anesthesia, he was convinced that he had not been operated upon because he felt no pain and everything appeared so smooth. He then said that television crews could film him and that the marvelous medication he had been given should be publicized. Toward nighttime, he became demanding, wished to leave for home, and was irritable when given instructions to follow regarding his care. He was sleepless the whole night, and his agitation in regard to going home mounted, despite his having received 12 mg of haloperidol. The next day, he opposed any attempts to talk him down, requested that he be discharged, and was more irritable and expansive. He said he could not believe he was still alive and that the operation was such an easy matter that it was almost a miracle. He said that his father had died from heart disease without the benefit of such an operation and that he had known friends that had refused CABG and had died. He denied any worries. He was not sure that he was not dreaming and rambled about someone during the night wanting to set a fire to cover a murder. Within an hour, he was given 20 mg intravenous haloperidol and during the rest of the day received another 18 mg intravenously. Stimulation was kept to a minimum, light was dimmed, and he recovered some sleep. The next morning he awoke rested, was calm, and requested that he be shaved and groomed. He had almost no recall of the previous day, remembering only a strange, dreamy state. He again said how easy it was to go through such an operation. He was transferred to ward care. Later, he admitted that he had had some fear of passing away and was so happy that his surgery went well that he could hardly believe it. His subsequent hospital stay was uneventful, and he was discharged home less than a week after surgery.

clinical syndrome should be distinguished from both toxic-organic mania occurring frequently secondary to cerebrovascular lesions (1,2) and secondary mania as described by Krauthammer and Klerman (3), wherein a true manic episode occurs some time after surgery (4,5), physical illness, or drug use, usually after discharge from hospital. The case presented here focuses on the importance of the manic defense in the configuration of immediate postoperative psychosis. Such a symptomatic pattern meets the clinical aspects of the manic presentation. The clinical triad of elated mood, expansive talking, and increased behavioural activity was present in this case along with a clear sensorium and the absence of significant confusion, purposeless agitation, or important paranoid features accompanied by mistrust. The patients elated mood was expressed in the wish to have a television crew film him to publicize the event. The psychiatric consultant equated this to an anti-necrologic noticea major defense against denied death anxiety. Such massive anxiety, experienced soon after awakening from anesthesia, can rarely be expressed as such so early in a patients postoperative course; it is either acted upon or formulated in a deluded fashion. The psychological usefulness of such a transient and benign psychotic flare-up can be conceptualized as a kind of fast-track metabolic pathway to reduce excessive anxiety until postoperative experience reassures the patient.

Road Rage: Old Wine in a New Bottle

Dear Editor: In driving research, the debate about the relevance of temperamental factors and psychopathology has a long history. Tillman and Hobbs classic 1949 article, The Accident Prone Automobile Driver, is the first in the psychiatric literature to describe a link between psychiatric illness and driving problems (1). These researchers recruited 96 drivers who had 4 or more accidents and compared them with accident-free drivers. Clinical evaluation showed that the accident repeaters were more aggressive, impulsive, resentful of authority and lacking in social responsibility. The authors coined the phrase, often repeated in the literature , that a man drives as he lives. The debate continues. Smart and others timely article Psychiatric Distress Among Road Rage Victims and Perpetrators (2) raises several important points regarding underlying psychopathology in this condition. Intermittent explosive disorder is a condition that falls within the impulse-control disorder spectrum. One of the most common categorical diagnoses that underlie impulsecontrol disorder in adults is attention-deficit hyperactivity disorder (ADHD)often unrecognized. A good developmental history would usually reveal a childhood diagnosis of this condition. This is significant: the bestdocumented evidence for psychiatric illness and impulsive driving relates to ADHD (3,4). This differential diagnosis of impulsivity is very important with regard to clinical management. We now have evidence from Cox and others that, in driving simulator studies, stimulant medication significantly improves driving performance by subjects with uncontrolled ADHD, as well as preliminary evidence that stimulants may also improve driving behaviour on the road (5). Jerome and Segal reported on 100 consecutively presenting patients with ADHD (6). Some 80% of these had ADHD, including a combination of both inattentive and hyperactive and impulsive symptoms (combined type). Self-report and collateral data collected with a structured interview questionnaire, the Jerome Driving Questionnaire, indicated that subjects with ADHD, combined type, experienced high levels of frustration and impulsive behaviours in relation to other drivers on the road. Their reported driving behaviours fulfilled the criteria for road rage described by Smart and others (2). Cloningers Temperament and
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References
1. Starkstein SE, Boston JD, Robinson RG. Mechanisms of mania after brain injury: twelve case reports and a review of the literature. J Nerv Ment Dis 1988;176:87100. 2. Cummings JL, Mendez MF. Secondary mania with focal cerebrovascular lesions. Am J Psychiatry 1984;141:1084 7. 3. Krauthammer C, Klerman JL. Secondary mania: manic syndromes associated with antecedent physical illness or drugs. Arch Gen Psychiatry 1978;35:13339. 4. Isles LJ, Orrell MW. Secondary mania after open-heart surgery. Br J Psychiatry 1991;159:280 2. 5. Porter KA, Rosenthal SH. Postoperative mania. Psychosomatics 1993;43:1713

This report stresses the manic aspect of the Franois Sirois, MD short postoperative psychotic flare-up. Such a Sainte Foy, Quebec
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Character Inventory was used to establish personality profiles from this group and a similar group of patients with ADHD, combined type, attending an outpatient clinic at the Centre for Addiction and Mental Health. These profiles showed a high prevalence of externalizing personality disorder (7; personal communication, Dr Umesh Jain, 2003). When treated with stimulants, these patients described a parallel improvement on the JDQ and resolution of ADHD symptoms. Impulsivity also occurs in a range of unconnected categorical conditions that have their common pathway of expression through deficits in executive function (8). For example, impulsivity as a chronic intermittent condition may well reflect chronic emotional lability, which often is seen as part of chronic dysthymia or borderline personality organization or, less often, reflects a frank mood disorder. Stimulant medication would not be expected to improve emotionally based impulsivity; it would more likely worsen it. The current Canadian Medical Association guidelines on driving safety include road rage as a subcategory of emotional disorder (9). The latest edition includes ADHD as a reportable condition if it is uncontrolled and associated with impulsive driving. Impulsive road rage may reflect separate orthogonal variables of cognitive impulsivity and emotional lability, which may require quite different treatment modalities. Further careful research into this nonspecific syndrome, which appears to be presenting with increasing prevalence, seems to have merit, both for public health measures and, possibly, for psychiatric practice.

6. Jerome L, Segal A. Benefit of long-term stimulants on driving in adults with ADHD. J Nerv Ment Dis 2001;189:36 64. 7. Cloninger RC. Assessment of the impulsive-compulsive spectrum of behavior by the seven-factor model of temperament and character. In: Oldham MJ, Hollander E, Skodol AE, editors. Impulsivity and compulsivity. Washington (DC) American Psychiatric Press Inc; 1996. p 815. 8. Jerome L, Segal A. ADHD, executive function and problem driving. The ADHD Report 2000;8:711. 9. Canadian Medical Association. Determining medical fitness to drive. A guide for physicians. 6th ed. Ottawa (ON) CMA; 2000.

assess impulse-control disorders, explosive behaviours, or aggression. Virtually all its items deal with depression, anxiety, and feelings of stress. No questions probe aggression, hostility, or impulse control. Future research in this area would therefore profitably consider these potentially important factors. Much remains to be done in research on road rage and psychiatric distress. Both victims and perpetrators of road rage should be examined with psychiatric instruments that allow for the identification of ADHD and impulse-control disorders as well as depression and anxiety. As Dr Jerome suggests, mood disorders may underly impulsivity. At present, we also know nothing of how road rage behaviour in young people may relate to various psychiatric problems. It is also important to note that our work does not allow the disentanglement of causeeffect relations; thus we must keep in mind the importance of considering road rage as a cause of such problems as depression and posttraumatic stress disorder (PTSD) (for example, 7). Available evidence makes it clear that motor vehicle collisions wherein road rage may have played an important role (8) are a major source of injuries and premature death in Canada and also a major source of psychiatric problems such as PTSD (9,10). Additional efforts to understand the role of psychiatric problems as both precursors to and results of motor vehicle collisions should be considered as a research priority. We completely agree with Dr Jerome that further understanding of road rage may have important implications for public health and psychiatric practice.

Laurence Jerome, MB, ChB, FRCPC London, Ontario

Reply: Ancient Wine but Still Potent?

Dear Editor: We are grateful for Dr Jeromes contribution to the debate about road rage and its relation to psychiatric distress. He makes the important point that a significant literature exists on psychiatric issues and driving and correctly notes how several different psychiatric problemssuch as explosive disorders, attention-deficit hyperactivity disorder (ADHD), and impulsive behaviour may relate to road rage (for example, 1,2) Road rage is sometimes portrayed as a new phenomenon, but as Dr Jerome points out, it has a long history. There are literary and historical references to road rage that point to a relation with psychiatric distress. In Sophocles play Oedipus the King, written about 420 BC, a road rage incident is the ostensible reason for which Oedipus kills his father (3). Oedipus is characterized as impulsive and easily provoked to violence. Sophocles based his Oedipus story on a folk tale, and he may have included the road rage incident because his audience would believe and accept it. The poet Lord Byron was involved in a serious road rage case in 1822 (4). It concerned a dispute over the right-of-way on a road, lasted several hours, and resulted in a serious injury to the supposed perpetrator. Lord Byron was subject to depression at many times during his life, but it is not clear whether this contributed directly to the road rage incident. Byron was also subject to irritation and sudden bouts of violence (4). We have used the General Health Questionnaire (GHQ) in our own research (5). The GHQ, a general psychiatric screening instrument for identifying people experiencing psychiatric distress, has proved very useful in survey research (6). However, it does not

References
1. Tillmann WA,Hobbs GE. The accident-prone automobile driver: a study of the psychiatric and social background. Am J Psychiatry 1949;:32131. 2. Smart GR, Asbridge M, Mann RE, Adlaf EM. Psychiatric distress among road rage victims and perpetrators. Can J Psychiatry 2003;48:681 8. 3. Nada-Raja S, Langley JD, McGee R, Williams SM, Begg DJ, Reeder AI. Inattentive and hyperactive behavior and driving offences in adolescence. J Am Acad Child Adolesc Psychiatry 1997;36:51522. 4. Barkley RA, Murphy KR, DuPaul GR, Bush T. Driving in young adults with ADHD: knowledge, performance, adverse outcomes and the role of executive functions. Journal of the International Neuropsychological Society 2002;8:65572. 5. Cox DJ, Merkel RL, Kovatchev B, Seward R. Effect of stimulant medication on driving performance of young adults with attention-deficit hyperactivity disorder. J Nerv Ment Dis 2000;188;230 4.

References
1. Nada-Raja S, Langley JD, McGee R, Williams SM, Begg DJ, Reeder AI. Inattentive and hyperactive behavior and driving offences in adolescence. J Am Acad Child Adolesc Psychiatry 1997;36:51522. 2. Jerome L, Segal A. Benefit of long-term stimulants on driving in adults with ADHD. J Nerv Ment Dis 2001;189:36 64. 3. Roche P. Sophocles: the complete plays. New York: Signet; 2001. 4. Marchand LA. Byron: a portrait. New York: Alfred A Knopf; 1970. 5. Smart RG, Asbridge M, Mann RE, Adlaf E. Psychiatric distress among road rage victims and perpetrators. Can J Psychiatry 2003;48:681 8 6. Pevalin DJ. Multiple applications of the GHQ-12 in a general population sample: an investigation of long-term retest effects. Soc Psychiatry Psychiatr Epidemiol 2001;35:508 12. 7. Breslau N. Epidemiological studies of trauma, posttraumatic stress disorder, and other psychiatric disorders. Can J Psychiatry 2002;47:9239.

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8. Smart RG, Mann RE. Deaths and injuries from road rage: cases in Canadian newspapers. CMAJ 2002;167:7612. 9. Health Canada. The economic burden of illness in Canada. Ottawa: Health Canada; 2002. 10. Mayou R, Bryant B, Duthie R. Psychiatric consequences of road traffic accidents. BMJ 1993;307:64751.

Reginald G Smart, PhD Mark Asbridge, PhD Robert E Mann, PhD Edward Adlaf, PhD Toronto, Ontario

The Effect of Quetiapine on Cannabis Use in 8 Psychosis Patients With Drug Dependency
Dear Editor: Approximately one-half of all patients with schizophrenia abuse or depend on psychoactive substances at some point during their lives (1), but few studies to date have proposed an integrated pharmacologic treatment for this schizophreniaaddiction comorbidity. Because of their strong dopamine D2 receptor antagonism, conventional antipsychotics such as haloperidol should in theory be the treatment of choice for comorbid schizophrenia and substance abuse. In practice, however, such treatment has not been demonstrated to be consistently effective and has only controlled drug abuse in special cases (2). A few pilot studies suggest that, among the conventional antipsychotics, flupenthixol may reduce cravings in schizophrenia patients with cocaine addiction (3). To date, the most promising results have been obtained with clozapine, a prototype of the atypical antipsychotics (4). Sharing certain key properties with clozapine (for example, 5-HT2 D2 ratio) (5), quetiapine may also reduce drug cravings in psychosis patients with addictions. A pilot study of 12 patients suffering from bipolar disorder (BD) and cocaine addiction appears to support this hypothesis (6). To expand on this promising result, we report case histories for 8 psychosis patients whose

cannabis use habits significantly improved Acknowledgement after treatment with quetiapine. The authors would like to pay tribute to Jean-Yves Roy, a pioneer psychiatrist in Case Report dual diagnosis in Montreal, who passed The group of patients (5 men and 3 women) away in April 2004. included 4 patients with schizophrenia and 4 with affective BD. All patients had cannabis Funding and Support dependency, and 2 also had a cocaine use disWe received no financial support, either order, according to DSM-IV criteria. Their from pharmaceutical companies or from mean age was 38.5 years (range 25 to 46 public research institutions, to gather the years). Before quetiapine was initiated, they data described in this letter. received antipsychotics (5 patients), antidepressants (2 patients), lithium (2 patients), Note clonazepam (2 patients), and procyclidine (1 This report was previously presented at the patient). All 8 patients were given quetiapine annual meeting of the International Society for an average of 5.8 months, at dosages rang- of Addiction Medicine; October 2002; ing between 100 and 1200 mg daily. Concom- Reykjavic (Iceland). itantly, 4 patients received antidepressants, 2 received gabapentin, and 1 was on methadone References maintenance treatment. Overall, an average 97.3% reduction in their weekly cannabis use 1. Regier DA, Faemer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, and others. Comorbidity of mental was observed with an average quetiapine dosdisorders with alcohol and other drug abuse: results age of 388 mg daily. When interviewed, from the Epidemiological Catchment Area (ECA) Study. JAMA 1990;264: 2511 8. patients reported consuming an average of 2. Brady KT, Anton R, Ballenger JC, Lydiard B, 35.6 g weekly of cannabis (range 18 to 56 g) Adinoff B, Selander J. Cocaine abuse among before quetiapine introduction. After quetiaschizophrenic patients. Am J Psychiatry pine treatment, patients reported an average 1990;147:1164 7. cannabis consumption of 1.1 g weekly. 3. Levin FR, Evans SM, Coomaraswanny S, Collins Like clozapine, quetiapine has proven benefits when compared with conventional antipsychotics (7,8). First, clozapine and quetiapine have a beneficial effect on mood. Showing mesolimbic selectivity, these agents do not appear to cause extrapyramidal symptoms. Further, these medications produce little or no neuroleptic-induced dysphoria. Last, it is possible that these atypical antipsychotics (mainly clozapine) alleviate the negative and cognitive symptoms of schizophrenia more than do conventional antipsychotics. To the extent that some patients with schizophrenia may take substances as a form of selfmedication, the clinical data presented here suggest that quetiapine, like clozapine, could form the basis of an integrated pharmacologic treatment for the psychosisaddiction comorbidity. Further controlled research is needed to validate the preliminary data collected to date.
ED, Regent N, Kleber HD. Flupenthixol treatment for cocaine abusers with schizophrenia: a pilot study. Am J Drug and Alcohol Abuse 1998;24:343 60. 4. Drake RE, Xie H, McHugo GJ, Green AI. The effects of clozapine on alcohol and drug use disorders among patients with schizoprenia. Schizophr Bull 2000;26:4419. 5. Gefvert O, Lundberg T, Wieselgren I-M, Bergstrom M, Langstrom B, Wiesel F-A, and others. D2 and 5HT2a receptor occupancy of different doses of quetiapine in schizophrenia: a PET study. Eur Neuropsychopharmacol 2001;11:10510. 6. Brown ES, Netjek VA, Perantie DC, Bobadilla L. Quetiapine in bipolar disorder and cocaine dependence. Bipolar Disord 2002;4:406 11. 7. Young CR, Longhurst JG, Bowers MB, Mazure CM. The expanding indications for clozapine. Exp Clin Psychopharmacol 1997;5:216 34. 8. Kasper S, Mller-Spahn F. Review of quetiapine and its clinical applications in schizophrenia. Exp Op Pharmacother 2000;1:783 801.

Stphane Potvin, MA, Doctoral Candidate Emmanuel Stip, MD, MSc, CFPQ Jean-Yves Roy, MD, FRCP, CSAM Montreal, Quebec

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