When an atypical antipsychotic is also an agent - Canadian ...

gic 1 receptors (H 1 ), hence one can expectsedation and weight gain. The medicalliterature shows that quetiapine XR is associatedwith a lower intensity of self-reported“excessive sedation” compared with theimmediate-release formulation. 27 Interestingly,quetiapine’s low affinity for serotonergic5HT 2C and muscarinic 3 (M 3 ) receptorsis thought to limit the weight gainpredicted by blockade of H 1 receptors.Quetiapine’s anticholinergic (M 1 ) effectsare weak which might explain why it has minimaldetrimental effects on cognitive function.Clinically, this attribute is relevant as manypatients suffering from MDD are cognitivelyimpaired (concentration, attention, etc.) 8Akin to all antipsychotics, quetiapine hasthe capacity to block postsynaptic dopamine 2receptors (D 2 ). In contrast to other agents suchas risperidone or paliperidone that bind tightlyto these receptors, quetiapine (like clozapine)is considered a loose binder. It is thought thatloose binders are associated with a lower incidenceof extrapyramidal symptoms and tardivedyskinesia, dysphoria and prolactin-relatedside effects (osteoporosis, amenorrhea, sexualdysfunction, etc.) than tight binders. 28,29Atypical antipsychotics block the postsynapticserotonergic 5HT 2 receptors. Someantidepressants, such as mirtazapine, are alsoantagonists of this neuronal system. Stimulationof the postsynaptic 5HT 2 receptors cantrigger various clinical problems that areoften seen with SSRIs, venlafaxine, desvenlafaxineor duloxetine. These include sleepdisruption, anxiety, akathisia, agitation, sexualdysfunction, extrapyramidal symptoms,among others. It should also be noted thatserotonin (via its action at these receptors)can set off a state of hypodopaminergism andof hyponoradrenergism. 30Quetiapine’s affinity for serotonergic 5HT 7receptors could explain its beneficial effectson sleep architecture. 31-33Recent data show that one of quetiapine’smetabolites, norquetiapine (also known asN-desalkyl quetiapine), inhibits the norepinephrinereuptake transporter, therebypotentiating noradrenaline neurotransmission.34 This attribute is shared by manyantidepressants such as duloxetine, desvenlafaxine,venlafaxine (when used at dosesabove 150–225 mg/day) and most of thetricyclics. The metabolite norquetiapine alsoacts as a partial serotonin 5HT 1A agonist (abuspirone-like effect); a feature that mightexplain the anxiolytic effects that can beseen with quetiapine XR. 34,35Clinical studies ofquetiapine in unipolarmajor depressive disorderThe clinical development program thatassessed the efficiency of quetiapine XR as amonotherapy in unipolar major depressivedisorder consisted of six studies; two of whichhave been published at this time. 36,37Quetiapine XR was effective as a monotherapyfor the treatment of MDD. From atolerability standpoint, let’s note that quetiapineXR’s safety profile differed from its comparators.For example, in the Cutler et al.study, 36 the most frequent adverse eventsnoticed with quetiapine XR were dry mouth,somnolence and sedation. For duloxetine,which was used as the comparator in this trial,nausea, headache, dizziness and dry mouthwere the most common side effects reported.In the quetiapine XR group, sedation andsomnolence were the adverse events that ledpatients to stop their treatment most often (afinding that was also replicated in the Weisleret al. trial). 37 In the duloxetine group, nauseaand sedation caused the majority of tolerability-relatedtreatment terminations. 36 Cliniciansmust also remember that general safetyissues of atypical antipsychotics such as weightgain, hyperlipidemia, hyperglycemia, tardiveTable 1 Tolerability issues with currently-marketed antidepressants 8,9,26,31,36,38,42,43SSRIs * SNRIs Mirtazapine Bupropion Quetiapine XRNausea ++++ ++++ 0 0/+ 0/+Sexual dysfunction ++++ ++++ + 0/+ ++Sleep disturbances ++++ ++++ 0/+ + 0/+Agitation / Anxiety/Restlessness/ Akathisia+++ +++ 0/+ + 0/+Withdrawal symptoms(when drug is discontinued)• Very common withparoxetine, can besevere• Less common withfluoxetine• Very common withvenlafaxine XR,can be severe• Need more datawith duloxetine0/+Usually mild0/+Usually mild+/++Usually mildNotes : ++++ : very common ; 0 : uncommon; SSRIs: citalopram, escitalopram, paroxetine, sertraline, fluoxetine, fluvoxamine; * : differences might exist between agents;SNRIs: duloxetine, desvenlafaxine, venlafaxine (when doses are > 150-225 mg/day)November 2009 | Answer online at www.canadianhealthcarenetwork.ca When an atypical antipsychotic is also an agent of choice in the treatment of major depressive disorder | 3

Table 2 Quetiapine XR: dose and titration vs indicationsIndication Target dose Titration CommentsSchizophrenia and Mania400–800 mg/dayMaximal dose in productlabeling: 800 mg/dayday 1: 300 mg/dayday 2: 600 mg/dayafter day 2: up to 800 mg/dayBipolar depression300–600 mg/dayMaximal dose in productlabeling: 600 mg/dayday 1: 50 mg/dayday 2: 100 mg/dayday 3 : 200 mg/dayday 4 and thereafter: 300 mg/dayIn clinical trials, doses of 300 mg/day and of 600 mg/day were evaluated;the optimal dose seems to be300 mg for most patientsUnipolar majordepressive disorder50–300 mg/dayTarget dose seems to be150 mg/day in most patientsday 1: 50 mg/dayday 2: 50 mg/dayday 3: 150 mg/dayafter day 4: up to 300 mg/daydyskinesia and neuroleptic malignant syndromemust be taken into account as quetiapineXR is a member of this class. 26Quetiapine XR :pharmacokinetics anddrug interactionsQuetiapine XR, a dibenzothiazepine derivative,undergoes a very significant first-passeffect; its bioavailability being only 9%. TheTmax of the immediate-release formulationof quetiapine (Seroquel ® ) is about one hour;for the XR formulation, the Tmax is aboutsix hours. CYP3A4 appears to be the mainisoenzyme involved in the biotransformationof quetiapine. 26Via CYP3A4, the metabolism of quetiapineyields norquetiapine, a metabolite with antidepressantproperties. This metabolite has alonger plasma half-life than the parent drugand is also metabolized by CYP3A4. 34As for clinically relevant pharmacokineticdrug interactions, inhibitors of CYP3A4 canincrease quetiapine plasma levels by up to10-fold, and inducers of CYP3A4 can decreasequetiapine plasma levels very substantially.Table 3 Atypical antipsychotics – indications in Canada (as monotherapy)Quetiapine XR Olanzapine Risperidone ZiprasidoneSchizophreniaAcute √ √ √ √Bipolar Disorder– acute mania √ √ √ √Bipolar Disorder– acute depression √Unipolar Major DepressiveDisorder√Sources: AstraZeneca Canada Inc. Seroquel XR® product monograph. May 27, 2009; Eli Lilly Canada. Zyprexa® productmonograph. February 23, 2009; Janssen-Ortho. Risperdal® product monograph. June 30, 2008; Pfizer Canada. Zeldox®product monograph. December 18, 2008.Quetiapine is not affected by the smokingstatus of the patient.Quetiapine is a substrate of p-glycoprotein.It is 83% bound to plasma proteins. Theelimination half-lives of quetiapine andnorquetiapine are approximately seven and12 hours respectively. 26 The relevance oftherapeutic drug monitoring with quetiapineis still a matter of debate.Pharmacist’s rolePatient counsellingPharmacists must remember that almost halfof all patients stop their antidepressant medicationduring the first month of therapy, andnearly 75% of them do so within the first threemonths.As a community pharmacist, bear in mindthat the depressed patient might not have the“strength” or enough “drive” to pick up hismedication at the pharmacy. For some, to justanswer the phone is a gargantuan task.Quetiapine XR tablets should be swallowedwhole and not split, chewed or crushed.Quetiapine XR can be administered with orwithout food. The product monograph statesthat quetiapine XR should be administeredgenerally in the evening (to respect the Tmaxof the formulation).Be vigilant when you hand a patient an4 | When an atypical antipsychotic is also an agent of choice in the treatment of major depressive disorder Answer online at www.canadianhealthcarenetwork.ca | November 2009

information sheet because it would be awkwardfor someone receiving quetiapine XR forunipolar depression to read on the patientinformation leaflet: “This medication has beenprescribed for your psychosis”.Here are a few concepts that could beshared with your patients:Even if you start feeling better, do not stopyour quetiapine XR because antidepressantssometimes require many weeks or months fortheir full effect to be noticeable.Quetiapine XR is a psychotropic (i.e., adrug that acts on the brain) with many clinicaluses, depression being one of them. It is alsovery effective against symptoms such asanxiety, “inner tension”, restlessness andinsomnia.Even just after a few days, you will noticebeneficial effects of quetiapine XR: you willsleep better and you will feel “less sad”. Butremember that many weeks or monthsmight be needed for its “full effect” to benoticeable.Clinical pearlsQuetiapine XR, an “antipsychotic/antidepressant”,can be used for unipolar depression inpatients that do not exhibit “psychotic”symptoms.The optimal dose of quetiapine XR variesaccording to the indication (see Table 2).Quetiapine XR’s tolerability profile isdifferent (see Table 1). In contrast to otherantidepressants, quetiapine XR is less likely tocause nausea, sexual dysfunction, sleep disruption,anxiety, agitation, etc. Even though it isa dopaminergic-blocking drug, the risk ofextrapyramidal (EPS) symptoms (pseudoparkinsonism,tremor, etc.) is lower withquetiapine XR (at MDD doses) than it iswith some serotonergic antidepressants. In theCutler et al. study, 36 EPS-like symptoms weremore frequent in duloxetine than in quetiapineXR patients (150 mg and 300 mg).The most common adverse events associatedwith the use of quetiapine XR as a monotherapyin the treatment of MDD were drymouth, sedation, somnolence, dizziness andfatigue. 26 Pharmacists must remember that theXR formulation of quetiapine is associatedwith less orthostatic hypotension and “excessivesedation” than the immediate-releaseformulation. 27Quetiapine XR and sleep: sleep disturbancesare a cardinal symptom of MDD; subjectsoften complain of difficulty in initiatingand maintaining sleep as well as nocturnalawakenings. 38 Unfortunately, most antidepressantshave deleterious effects on sleep(e.g., REM suppression, decrease in the qualityof sleep). Quetiapine XR differs in thisregard since it normalizes sleep and has beneficialeffects on its architecture, similar towhat one might expect with mirtazapine ortrazodone. Also, although it has sedativeeffects, quetiapine XR does not seem to havea negative impact on daytime alertness. Somepatients might experience “excessive” sedationduring the titration period, after whicha tolerance develops. 20,32Withdrawal symptoms: Some antidepressants,especially paroxetine and venlafaxineXR, can cause severe manifestations of withdrawal,such as dizziness, mood symptoms(anxiety, suicidal thoughts), paresthesias, flulikesymptoms, etc. It is encouraging to seethat quetiapine XR is associated with a milderwithdrawal syndrome. In the Cutler et al.trial, 36 nausea, insomnia and headache werethe most commonly-cited symptoms duringits discontinuation. In the Weisler et al.study 37 , stopping quetiapine XR causedinsomnia (5.2%), nausea (4.7%), headache(3.2%), and diarrhea (2.4%). In the placebogroup, the most common adverse events thatemerged during the discontinuation phasewere insomnia (3.9%), headache (1.7%),diarrhea (3.9%), irritability (1.7%) andabnormal dreams (1.7%).Risk of mania induction: Antidepressantscan all induce a manic phase in vulnerablepatients. Interestingly, there was nosignificant difference in the incidence of“treatment-emergent mania” betweenquetiapine / quetiapine XR and placebo ineither of the main studies that evaluatedquetiapine / quetiapine XR as a monotherapyin the management of bipolardepression. 22,23Metabolic effects: Similar to all other atypicalantipsychotics, cholesterol, triglycerides,glucose, weight and waist circumferenceshould be monitored. In the Weisler et al.study, 37 mean weight gain after eight weekswas similar in the quetiapine XR and placebogroups (about 1 kg). The proportion ofpatients experiencing ≥ 7% increase in weightwas 0.6% for the quetiapine XR 50 mg/daygroup, 3.6% for the quetiapine XR 150 mg/day group, 4.5% for the quetiapine XR 300mg/day group, and 1.1% for the placebogroup. 37ConclusionNot many years ago, few clinicians would havethought that an antipsychotic would be prescribedas a treatment for unipolar depression.That is to say that we are dealing with verycomplex pharmacological entities that aresimply more than just plain anti-schizophrenicagents. 33,39,40Atypical antipsychotics are not all createdequal. For example, the risk of extrapyramidalsymptoms is not as important with clozapineas it is with risperidone, and the riskof weight gain differs between olanzapineand ziprasidone; the former being associatedwith much greater weight gain than the latter.29 The clinician might think that if oneatypical is helpful in MDD, then all theatypicals possess that attribute. However, ifone looks at the latest guidelines for thetreatment of bipolar depression 41 , quetiapineXR is a first-line agent, olanzapine is a firstlinechoice only when combined with fluoxetine,and aripiprazole is not recommendeddue to negative trials. Finally, let’s note thata major clinical caveat lies in the fact thatthere are no predictive factors of response toquetiapine XR, or any other antidepressant.42,43 Therefore, several trials of variousantidepressants might be needed beforeattaining remission.November 2009 | Answer online at www.canadianhealthcarenetwork.ca When an atypical antipsychotic is also an agent of choice in the treatment of major depressive disorder | 5

References1. American Psychiatric Association: Diagnostic andStatistical Manual of Mental Disorders, Fourth Edition,Text Revision. Washington, DC, APA, 2000.2. Kessler RC, Birnbaum H, Bromet E et al. Age differencesin major depression: results from the NationalComorbidity Survey Replication (NCS-R). Psychol Med2009;17:1-13.3. Murray CJ, Lopez AD. Alternative projections of mortalityand disability by cause 1990-2020: Global Burdenof Disease Study. Lancet 1997;349:1498-1504.4. Michaud CM, Murray CJ, Bloom BR. Burden ofdisease - implications for future research. JAMA 2001;285:535-9.5. Ustün TB, Ayuso-Mateos JL, Chatterji S et al. Globalburden of depressive disorders in the year 2000. Br JPsychiatry 2004;184:386-92.6. Greenberg PE, Kessler RC, Birnbaum HG et al. Theeconomic burden of depression in the United States: howdid it change between 1990 and 2000? J Clin Psychiatry2003;64:1465-75.7. Trivedi MH, Rush AJ, Wisniewski SR et al. Evaluationof outcomes with citalopram for depression using measurement-basedcare in STAR*D: implications for clinicalpractice. Am J Psychiatry 2006;163:28-40.8. Bauer M, Bschor T, Pfennig A et al. World Federationof Societies of Biological Psychiatry (WFSBP) guidelinesfor biological treatment of unipolar depressive disordersin primary care. World Journal of Biological Psychiatry2007;8:67-104.9. Lam RW, Kennedy SH, Grigoriadis S et al. CanadianNetwork for Mood and Anxiety Treatments (CANMAT)clinical guidelines for the management of major depressivedisorder in adults. III. Pharmacotherapy. J AffectDisord 2009 (in press).10. Fava M, Davidson KG. Definition and epidemiologyof treatment-resistant depression. Psychiatr Clin NorthAm 1996;19:179-200.11. Blier P. The pharmacology of putative early-onsetantidepressant strategies. Eur Neuropsychopharmacol2003;13:57-66.12. Wade A, Friis Andersen H. The onset of effect forescitalopram and its relevance for the clinical managementof depression. Current Medical Research and Opinion2006;22:2101-10.13. Olfson M, Marcus SC, Tedeschi M et al. Continuityof antidepressant treatment for adults with depression inthe United States. Am J Psychiatry 2006;163:101-8.14. Bull SA, Hu XH, Hunkeler EM et al. Discontinuation ofuse and switching of antidepressants: influence of patientphysiciancommunication. JAMA 2002;288:1403-9.15. Berman RM, Marcus RN, Swanink R et al. Theefficacy and safety of aripiprazole as adjunctive therapyin major depressive disorder: a multicenter, randomized,double-blind, placebo-controlled study. J Clin Psychiatry2007;68:843-53.16. Marcus RN, McQuade RD, Carson WH et al. Theefficacy and safety of aripiprazole as adjunctive therapyin major depressive disorder: a second multicenter, randomized,double-blind, placebo-controlled study. J ClinPsychopharmacol 2008;28:156-65.17. Papakostas GI, Shelton RC, Smith J et al. Augmentationof antidepressants with atypical antipsychoticmedications for treatment-resistant major depressive disorder:a meta-analysis. J Clin Psychiatry 2007;68:826-31.18. Shelton RC, Papakostas GI. Augmentation of antidepressantswith atypical antipsychotics for treatmentresistantmajor depressive disorder. Acta Psychiatr Scand2008;117:253-9.19. Daly EJ, Trivedi MH. A review of quetiapine in combinationwith antidepressant therapy in patients withdepression. Neuropsychiatr Dis Treat 2007;3:855-67.20. Baune BT, Caliskan S, Todder D. Effects of adjunctiveantidepressant therapy with quetiapine on clinicaloutcome, quality of sleep and daytime motor activity inpatients with treatment-resistant depression. Hum Psychopharmacol2007;22:1-9.21. Weisler RH, Calabrese JR, Thase ME et al. Efficacyof quetiapine monotherapy for the treatment of depressiveepisodes in bipolar I disorder: a post hoc analysis of combinedresults from 2 double-blind, randomized, placebocontrolledstudies. J Clin Psychiatry 2008;69:769-82.22. Calabrese JR, Keck PE Jr, Macfadden W et al. Arandomized, double-blind, placebo-controlled trial ofquetiapine in the treatment of bipolar I or II depression.Am J Psychiatry 2005;162:1351-60.23.Thase ME, Macfadden W, Weisler RH et al. for theBOLDER II Study Group. Efficacy of quetiapine monotherapyin bipolar I and II depression: a double-blind,placebo-controlled study (the BOLDER II study). J ClinPsychopharmacol 2006;26:600-9.24. McElroy S, Young AH, Carlsson A et al. A doubleblind,placebo-controlled study with acute and continuationphase of quetiapine and paroxetine in adults withbipolar depression (EMBOLDEN II) (abstract). BipolarDisord 2008;10(suppl 1):59.25. Young AH, McElroy S, Chang W et al. A double-blind,placebo-controlled study with acute and continuationphase of quetiapine and lithium in adults with bipolardepression (EMBOLDEN I) (abstract). Int J Neuropsychopharmacol2008;11:187.26. AstraZeneca Canada Inc. Seroquel XR® productmonograph. May 27, 2009.27. Datto C, Berggren L, Patel JB et al. Self-reportedsedation profile of immediate-release quetiapine fumaratecompared with extended-release quetiapine fumarateduring dose initiation: a randomized, double-blind,crossover study in healthy adult subjects. Clin Ther2009;31:492-502.28. Kapur S, Zipursky R, Jones C et al. A positron emissiontomography study of quetiapine in schizophrenia: apreliminary finding of an antipsychotic effect with onlytransiently high D2 receptor occupancy. Arch GenPsychiatry 2000;57:553-9.29. Weiden PJ. EPS profiles: the atypical antipsychoticsare not all the same. J Psychiatric Practice 2007;13:13-24.30. Dremencov E, El Mansari M, Blier P. Effects ofsustained serotonin reuptake inhibition on the firing ofdopamine neurons in the rat ventral tegmental area. JPsychiatry Neurosci 2009;34:223-9.31.Cohrs S, Rodenbeck A, Guan Z et al. Sleep-promotingproperties of quetiapine in healthy subjects. Psychopharmacology(Berl) 2004; 174:421-9.32. Todder D, Caliskan S, Baune BT. Night locomotoractivity and quality of sleep in quetiapine-treated patientswith depression. J Clin Psychopharmacol 2006;26:638-42.33. Millan MJ. Dual- and triple-acting agents for treatingcore and co-morbid symptoms of major depression: novelconcepts, new drugs. Neurotherapeutics 2009;6:53-77.34. Jensen NH, Rodriguiz RM, Caron MG et al. N-desalkylquetiapine,a potent norepinephrine reuptake inhibitorand partial 5-HT1A agonist, as a putative mediator ofquetiapine’s antidepressant activity. Neuropsychopharmacology2008;33:2303-12.35. Baune BT. New developments in the managementof major depressive disorder and generalized anxietydisorder: role of quetiapine. Neuropsychiatr Dis Treat2008;4:1181-91.36. Cutler AJ, Montgomery SA, Feifel D et al. Extendedrelease quetiapine fumarate monotherapy in majordepressive disorder: a placebo- and duloxetine-controlledstudy. J Clin Psychiatry 2009;70:526-39.37. Weisler R, Joyce JM, McGill L et al. Extended releasequetiapine fumarate monotherapy for major depressivedisorder: results of a double-blind, randomized, placebocontrolledstudy. CNS Spectr 2009;14:299-313.38. Jindal RD, Thase ME. Treatment of insomnia associatedwith clinical depression. Sleep Med Rev 2004;8:19-30.39. Rakofsky JJ, Holtzheimer PE, Nemeroff CB. Emergingtargets for antidepressant therapies. Current Opinionin Chemical Biology 2009;13:1-12.40. Daws LC. Unfaithful neurotransmitter transporters:focus on serotonin uptake and implications for antidepressantefficacy. Pharmacology & Therapeutics 2009;121:89-99.41. Yatham LN, Kennedy SH, Schaffer A et al. CanadianNetwork for Mood and Anxiety Treatments (CANMAT) andInternational Society for Bipolar Disorders (ISBD) collaborativeupdate of CANMAT guidelines for the managementof patients with bipolar disorder: update 2009.Bipolar Disord 2009;11:225-55.42. Möller HJ. Antidepressants: controversies abouttheir efficacy in depression, their effect on suicidality andtheir place in a complex psychiatric treatment approach.World J Biol Psychiatry 2009 (in press)43. Papakostas GI, Fava M. Predictors, moderators,and mediators (correlates) of treatment outcome inmajor depressive disorder. Dialogues Clin Neurosci2008;10:439-51.6 | When an atypical antipsychotic is also an agent of choice in the treatment of major depressive disorder Answer online at www.canadianhealthcarenetwork.ca | November 2009

QUESTIONS - Answer online at www.canadianhealthcarenetwork.ca, CE section, “More CCCEP-approved” dept.1. Which of these medications will causean increase in quetiapine XR’s plasmaconcentrations?a) inhibitors of CYP1A2b) inducers of CYP3A4c) inhibitors of CYP3A4d) inhibitors ofUDP-glucuronosyltransferase (UGT)2. Which of the following statements istrue regarding quetiapine XR’s effectson sleep?a) It suppresses the REM phase.b) By its important anti-H1 effects, itcauses daytime drowsiness.c) It has beneficial effects on sleeparchitecture.d) It has benzodiazepine-like effectson delta sleep.3. Recent US data suggests that thelifetime prevalence of depression isof about:a) 60%b) 4%c) 6%d) 20%4. When using quetiapine XR in thetreatment of major depressive disorder,the starting dose should be:a) 300 mg / dayb) 100 mg /dayc) 50 mg / dayd) 25 mg / day (i.e., one-half of a50 mg tablet)5. Quetiapine’s pharmacokineticsare influenced by caffeine intake.a) trueb) false6. When using quetiapine XR in thetreatment of schizophrenia, the startingdose should be:a) 300 mg / dayb) 100 mg /dayc) 50 mg / dayd) 800 mg / day7. By which mechanism of action isquetiapine XR thought to exert itsantidepressant effect?a) inhibition of monoamine-oxidaseb) stimulation of melatonin receptorsc) antagonism of alpha1-adrenergicreceptorsd) inhibition of the norepinephrinereuptake pump8. Most patients suffering from MDDtake their antidepressant as it isprescribed. This statement is:a) trueb) false9. Quetiapine XR :a) should only be prescribed to patientswho are psychoticb) can be cut in half or crushedc) should always be administered in themorningd) can be taken with or without foodCase Study (Questions 10–17)Karen is a 39-year-old woman who works asan interior designer. A few years ago, sheexperienced a major depressive episode. Thisled to a sick leave lasting more than a yearand she eventually lost her position in oneof the leading companies in the country. Forthat first episode, she refused medication;she did not want any “chemicals” andopted instead to see a psychologist.Three months ago, she went to theneighbourhood walk-in clinic, seeking help forwhat appeared to be an episode of depression.The physician on duty prescribed venlafaxinewith the following dosage schedule:37.5 mg/day for 3 days, 75 mg/day for 3days, 112.5 mg/day for 3 days, 150 mg/dayfor 3 days, 225 mg/day thereafter.Six weeks later, Karen decides to go tothe hospital. She says that she is “really notfeeling like herself anymore” — she can’tsleep, has difficulty concentrating, and feelsextremely anxious. She reveals that twoweeks ago, she tried to cut her dose of venlafaxinein half. As soon as she realized thatthis strategy made her feel worse (she experiencedvertigo, paresthesias, worsening of heranxiety), she resumed the original dose.The emergency department psychiatristprescribes quetiapine XR 50 mg/day at supperfor two days, to be increased to quetiapineXR 150 mg/day at supper thereafter.To learn more about her new medication,Karen decides to consult the Internet anddiscovers that quetiapine XR is classed asan antipsychotic. To add to her confusion,she finds a website where quetiapine XR ispromoted as a cure for manic-depressivedisorder.10. To reassure Karen, the pharmacistshould explain that:a) Quetiapine has been prescribed for herpsychotic depression.b) Quetiapine is a new antidepressantsimilar to fluoxetine.c) Quetiapine is a complex medicine withmany uses; the treatment of depressionbeing one of them.November 2009 | Answer online at www.canadianhealthcarenetwork.ca When an atypical antipsychotic is also an agent of choice in the treatment of major depressive disorder | 7

QUESTIONS - Answer online at www.canadianhealthcarenetwork.ca, CE section, “More CCCEP-approved” dept.11. The pharmacist should point out thefollowing to his patient:a) Quetiapine XR and venlafaxine are differentantidepressants and, for example,they do not cause the same side effects.b) You will only have to take the quetiapineXR for about three months.c) You can crush the quetiapine tablet andmix it with applesauce.12. If Karen abruptly stops herquetiapine XR, she will probablyexperience the same withdrawalsymptoms as she did when she cuther dose of venlafaxine in half.This statement is:a) trueb) false13. The target dose of quetiapine XRthat we should aim for to optimallytreat Karen’s MDD is:a) 50 mg / dayb) 600 mg / dayc) 150 mg / dayd) 450 mg / day14. Can inhibitors of CYP3A4 increaseplasma levels of quetiapine?a) yesb) no15. Regarding side effects that canbe caused by quetiapine XR, thepharmacist should mention to Karenthat the most common adverse eventsare:a) tremor and headachesb) psoriasisc) sedation and dry mouthd) headache and dry mouth16. Regarding side effects that can becaused by quetiapine XR, the pharmacistshould mention to Karen that:a) Bothersome sedation and drowsinessusually occur during the first few weeksof treatment, after which a tolerancedevelops.b) Headaches will usually respond to adose increase.c) Since it can “stimulate,” the medicationshould be taken in the morning.17. Karen smokes 15–20 cigarettes perday. Will this have an effect on thepharmacokinetics of quetiapine XR?a) yesb) no18. Quetiapine XR’s target dose inunipolar major depressive disorder islower than in the treatment of mania.This statement is:a) trueb) false19. Which of these agents is classedas an SSRI?a) bupropionb) mirtazapinec) quetiapine XRd) escitalopram20. Which of these medications is afirst-line option in the treatment ofunipolar major depressive disorder?a) escitalopramb) quetiapine XRc) trazodoned) clozapineFaculty: When an atypical antipsychotic is also an agent of choice in the treatment of major depressive disorderAbout the authorFor the past ten years, Benoît Rouleau hasbeen actively involved in psychiatric pharmacy,including roles as teacher and a solicitedspeaker. He also conducts psychopharmacologicalresearch, with a special focus on the therapeuticdrug monitoring of psychotropics. Benoit is thepresident of the Quebec Psychiatric PharmacyGroup.ReviewersAll lessons are reviewed by pharmacists foraccuracy, currency and relevance to currentpharmacy practice.This lesson is valid until October 16, 2012.Information about the treatment of majordepressive disorder may change over the course ofthis time. Readers are responsible for determiningthe most current aspects of this topic.CE DesignerShawn Samson, TwoCreative.caFor information about CE marking, please contactMayra Ramos at (416) 764-3879, fax (416) 764-3937 or mayra.ramos@rci.rogers.com. No partof this CE lesson may be reproduced, in wholeor in part, without the written permission ofthe publisher. © 2009Continuing Education Project ManagerSheila McGovern, Toronto, Ont.8 | When an atypical antipsychotic is also an agent of choice in the treatment of major depressive disorder Answer online at www.canadianhealthcarenetwork.ca | November 2009

To answer this CE lesson onlineIf currently logged into our Online Ce Program, please return to the “LessonsAvailable Online” Page and click on “Link to questions” for this CE Lesson.If not logged in but already registered to our Online Ce Program, pleaseclick here:http://ce.pharmacygateway.com/Pharmacy/login/index.aspIf you have not registered for our Online Ce Program and wish to answer online,please click here: http://ce.pharmacygateway.com/Pharmacy/login/adduser.aspIf you have any questions please contact:Mayra RamosPharmacy Practice, Pharmacy Post, Drugstore Canada, Novopharm CE Series,More CCCEP-approved CEs or Tech Talk CEs (English and French)Fax: (416) 764-3937Email: mayra.ramos@rci.rogers.comFrancine BeauchampQuebec Pharmacie and L’actualite PharmaceutiqueFax: (514) 843-2183Email: francine.beauchamp@rci.rogers.com