Presentation on theme: "Sleep Medicine on the Fly- What Every Physician Should Know \Integration of Psychiatry into Primary Health Care Conference- January 2014 Raed Hawa MD,"— Presentation transcript:
1Sleep Medicine on the Fly- What Every Physician Should Know \Integration of Psychiatry into Primary Health Care Conference- January 2014Raed HawaMD, FRCP, DABSM, DABPNDeputy Psychiatrist in Chief- UHNAssociate ProfessorDepartment of Psychiatry, University of Toronto Diplomate American Board of Psychiatry and NeurologyDiplomate American Board of Sleep MedicineSpecialty Certification in Psychosomatic MedicineSpecialty Certification in Sleep Medicine1
2Disclosure: Dr. Raed Hawa Advisory board, speakers’ bureaus, grant, financial or research supportNo conflict of interest and no financial interest or other affiliation to declare
3A Road Map?At the end of today's session participants are expected to:1. improve their knowledge of sleep medicine as it pertains to their practice2. become aware of the options that are available to treat these sleep disorders3. appreciate the complexity and co-morbidity between psychiatric disorders and sleep disorders*It is all about how it applies to your practice*
4Why should physicians be interested in sleep disorders? Sleep/tiredness/sleepiness complaintsInsomnia is often an early presentation of a psychiatric or medical illnessMany sleep disorders may mimic psychiatric illnesses ( sleep apnea and depression)Medications affect sleepOur patient population can benefit from basic sleep hygiene practices
6Clinical VingetteDavid, a 48 yo married male, a banker, and a father of 2 ages 14 and 16.Long history of recurrent major depressive episodes with multiple trials of SSRIs, SNRIs and BupropionCurrently of Venlafaxine XR 225mg/dayCurrent complaints of increased irritability and missing work that he attributes to poor sleepWhat might be the causes for David’s insomnia?Primary sleep disorderResidual depressionMedication related? Poor sleep hygieneAlcohol/caffeine intakeSomething else
8SLEEP Awake – low voltage – random, fast Drowsy – 8 to 12 cps – alpha wavesN1-Stage 1 – 3 to 7 cps – theta wavesN2-Stage 2 – 12 to 14 cps – sleep spindles and K complexesN3 -Delta Sleep – 1 1/4 to 2 cps – delta waves > 75 mVR-REM Sleep – low voltage – random fast with sawtooth waves
9Normal Sleep Histogram REMWN1N2N31 - light sleep, 5-10% of total sleep time, transition between awake and asleep% of total sleep time3,4 - deep or delta wave sleep, occurs mostly early in the nightREM sleep, 20-25% of sleepAll 4 stages repeat in ultradian rhythm of about 90 minutes1234567Hours of Recording
10Is it a primary sleep disorder? Obstructive sleep apnea (4-8%)Restless leg syndrome (2-15%)Insomnia (10-30%)Parasomnia ( 5-10% )EDS ( <5% )
11OSASCessation of breathing lasting at least 10 seconds with desaturations and arousals.Some of the signs and symptoms:Snoring, gasping for air, stopping breathing at night, memory complaints, irritability, depression, morning headaches, sexual problems, restless sleep, and sedation or tiredness during the day.
13OSAS Why treat? High blood pressure Heart problems- 8 to 10 times more likely to have heart attacks or strokesMore health care money- 2.5 times more likely to visit a doctorMore likely to die in their sleep- 2.5 times more likelyPoor quality of life and 3 times more likely to be involved in car accidents
14OSAS Rx Didgeridoo!! Weight loss/ Bariatric Surgery EPAP Surgery/ Pillar procedure/ MaxillofacialDental DeviceCPAP – gold standard
15If (s)he snores suspect apnea ALSO CONSIDER STOPBANG & MALLAMPATI
16STOP BANG questionnaire S do you SnoreT do you feel Tired, fatigued or sleepyO have you been Observed to stop breathingP high blood PressureB BMI >35A Age >50N Neck circumference >40G Gender: MaleAnesthesiology 2008; 108:
21Restless leg syndrome First described by Willis in 1672 Diagnostic Criteria ( strictly clinical ):Desire to move limbs ( creepy crawly sensation, itchy and aching feeling, crampy and painful ) withMotor restlessnessWorse at restTemporary relief by activityWorse at nightInternational RLS Study Group 2006
22Periodic limb movements PLMS: Diagnosis is based on PSG findings.PLMD: PLMS plus sleep dysfunction.80% of RLS patients have PLMSAsymptomatic PLMS does not require treatment.
23RLSRule out:Iron deficiency, Uremia, RA, Peripheral neuropathy, Diabetes, Pregnancy, Spinal cord lesion, Medications.“The Mimics”Akathisia ( drug induced or positional ), peripheral neuropathy, nocturnal leg cramps, sleep starts, anxiety, and psychosis.
24Pathophysiology RLSSPECT/PETReduction of caudate and putamen D2 receptor bindingBrain Iron TransportCSF ferritin low- abnormal iron transportfMRIDecreased thalamic blood flow during RLS symptoms
25Treatment RLS Dopamine Agonists Ropinirole-- 0.25 to 3 mg (D2 agonist) Pramipexole to 1.5 mg (D2 and D3 agonist)Cabergoline-- 1 to 4 mgPergolide to 0.75 mgBromocriptine– 5 to 20 mgLdopa-carbodopa– 25 to 400 mg
27If your patient has RLS/PLMD? R/O other causesCheck ferritin levelsIf less than 50 – treat with FeAdd vitamin CIf no help, try medications
28B. Wayne Blount, MD, MPH Professor, Emory S.O.M. insomniaB. Wayne Blount, MD, MPHProfessor, Emory S.O.M.
29Insomnia- Scope of the Problem Prevalence: 30% of general population have complaints of sleep disruption and 10% have associated functional impairmentAlmost all major mental illness is associated with “some” sleep complaintInsomnia can be the presenting complaint for anxiety, depression or a sign of abuse potentialMany medical problems can have sleep complaints as part of the presentationBidirectional model between depression and insomnia, between anxiety and insomnia
30Insomnia- Definitions Global dissatisfaction with sleep and one of:1.Difficulty initiating sleep2. Difficulty maintaining sleep3. Early morning awakeningWith distress or impairment3 nights/week for 3 months3 monthsDespite adequate opportunity for sleepEpisodic, persistent or recurrentTransient- do not seek medical attention- usually related to stress/minor event/change in environmentShort term and chronic- seek medical attentionPrimary include idiopathic or sleep state misperception or fatal familial insomniaSecondary- related to psych or medical rpoblems/ meds/circadian problems
31Pathophysiology of Insomnia Disorder of hyperarousal - hypervigilance during day with difficulty initiating/maintaining sleep during the nightCognitive modelPhysiologic modelNeuroendocrine modelIncreased autonomic activity in sleep ( HR, MR, BP,Temperature ,NE secretion, HPA activation)Increased beta/gamma and decreased delta EEG activityIncreased brain glucose metabolism Sleep Med Rev (1):9-15Spielman – behavioural model predisposing factors( heightened arousals, family hx, prior hx,) external factors (stress), produce insomnia perpetuated by maladaptive coping strategiesMorin- cognitive model ruminative thoughts around bedtime is the central component; cognitive arousal leads to physiological arousal, with time and repetition there is pairing between temporal and environmental cues and sleeplessness.Physiologic model- RAS interacting with hypothalamus ( anterior) and thalamus.Increased body temp near sleep onsetIncreased HR during sleep, decreased heart period variability during sleep; increased whole body metabolic rate during sleep in INSOMNIACSElevated beta activity during NREM in insomnia- this is even more substantiated in insomnia plus depression where there is even more beta activity and metabolic activity in the orbitofrontal cortex ( decreased activity in the dorsolateral prefrontal cortex during wake )Increased cortisol and ACTH before and during the first half of sleep
32Why care about insomnia? Insomnia prevalence increases with greater medical comorbidityThere is increased prevalence of medical disorders in those with insomniaInsomnia with objective short sleep duration is associated with high risk for hypertensionInsomnia with objective short sleep duration is associated with high risk for type 2 diabetesInsomnia with objective short sleep duration is associated with neuropsychological deficitsSleep 2009;32:Sleep 2010;33:Sleep 2007;30920:
33Treatment Options I. Behavioural and Cognitive therapies II. Prescription medications
34Behavioural and Cognitive Therapies Standards of Practice Stimulus controlRelaxation therapyCognitive behavioural therapy CBT-ISleep restrictionSleep hygieneSleep 2006;29:Stimulus control: conditioning between sleep environment and sleepinessHOW- go o bed only when feeling sleepy; in no sleep in minutes then leave bed and bedroom; use bed for sleep; no naps and no snoozes.Bed restriction- increase sleep driveHOW? Strict bedtimes and rising time limited to hours of sleep reported in one night; increase time in bed by advancing bedtime by minutes when efficiency is at least 85%; keep wakeup time fixed; if efficiency is still less than 85% after 10 days, delay bedtime by minutesSleep hygiene- limit caffeine, alcohol, stimulants; no naps, no clock watching and exercise regularlyRelaxation- guided imagery and jacobson’s progressive muscle relaxationCognitive restructuring- overall overestimation/fear/ apprehension
35Clinical Practice Point Most behavioural treatments studied are six one-hour sessions by trained therapistsThere are a few basic principles that can be utilized in your practiceEstablish a rapport with your patient, listen, instill hope and follow-upRely on principle of conditioning and good sleep hygiene practicesSelf monitoring , treatment rationale, and homework
36Psychological & Behavioural Treatments For Chronic Insomnia Standard therapies (Level 1 Evidence)Guideline therapies (Level 2 or 3 Evidence)Psychological / behavioural interventionsStimulus control therapyRelaxation trainingCognitive behaviour therapy ± relaxationSleep restrictionMulticomponent*Paradoxical intentionBiofeedbackKEY MESSAGE:Several types of psychological and behavioural interventions have been shown to be effective for chronic insomnia; the recommendations outlined here may be applied to patients with MDD. For chronic insomnia, CBTi (which includes sleep hygiene practices) is a treatment of choice because its benefits are more long-term compared to medications that can help short-term.ADDITIONAL DISCUSSION NOTES:Stimulus control therapy: interventions that train the insomnia patient to reassociate the bed and bedroom with sleep and reestablish a consistent sleep-wake schedule.Relaxation training: methods aimed at reducing somatic tension (e.g., progressive muscle relaxation, autogenic training) or intrusive thoughts at bedtime that interfere with sleep.Sleep restriction: curtailing the amount of time in bed to the actual amount of time spent asleep, thereby creating a mild sleep deprivation, and then lengthening sleep time as sleep efficiency improves.Cognitive behavioral therapy: various combinations of cognitive and behavioural components aimed at changing patients’ beliefs and attitudes about insomnia, as well as therapies such as stimulus control, sleep restriction, or relaxation training. Sleep hygiene education is also often included.Multicomponent therapy (without CBT): combines stimulus control therapy, relaxation training and sleep hygiene education.Paradoxical intention: instructing the patient to remain passively awake and avoid any effort (i.e., intention) to fall asleep. The goal is to eliminate performance anxiety, as it may inhibit sleep onset.Biofeedback: provides visual or auditory feedback to patients to help them control some physiologic parameters (e.g., muscle tension) in order to seek reduction in somatic arousal.There is insufficient evidence to recommend sleep hygiene education as a single therapy for chronic insomniaMorgenthaler et al. Sleep 2006;11:*stimulus control + relaxation + sleep hygiene OR stimulus control + sleep restriction + sleep hygiene.
37FDA Approved Insomnia Treatment Immediate Release benzodiazepines Dose (mg) T1/2 (hr)Estazolam (ProSom®) 1,Flurazepam (Dalmane®) 15,Quazepam (Doral®) 7.5,Temazepam (Restoril®)Triazolam (Halcion®) .125,Immediate Release Non-benzodiazepinesEszopiclone (Lunesta®) 1,2,3 5-7Zaleplon (Sonata®) 5,10 1Zopiclone (Imovane®*) 5,Zolpidem (Ambien®) (Sublinox *) 5,Selective Melatonin Receptor AgonistRamelteon (Rozerem®)Doxepin----3m and 6 mg(for maintenance insomnia)* Available in Canada and not in USA
38Benzodiazepine Receptor Agonists All BDZ receptor agonists are GABA modulators at the GABAA receptor complexGABAA-receptor: pentamerAllows chloride ions to enterGreater polarization and hence inhibitoryNon benzodiazepines have a higher degree of alpha1 subtype selectivity
39Recommendations For the Management of Insomnia: Pharmacotherapies Line of therapyClass of medicationExample medications1st lineShort-intermediate acting benzodiazepinesMelatonin receptor agonistZolpidem, eszopiclone,* zaleplon,* temazepamEx: agomelatine*2nd lineAlternate short-intermediate acting benzodiazepinesSedating antidepressantsTrazodone, amitriptyline, doxepin, mirtazapineInsomnia + comorbid mood disorderCombined benzodiazepine and sedating antidepressantsAnticonvulsantsGabapentin, tiagabine*Atypical antipsychoticsQuetiapine, olanzapineKEY MESSAGE:This slide outlines recommended pharmacological treatments for insomnia in the general adult population. Specific recommendations are made for patients with comorbid insomnia and mood disorders, with agents that target both disorders figuring prominently.Short-term hypnotic treatment should be supplemented with behavioural and cognitive therapies when possibleAdapted from Schutte-Rodin et al. J Clin Sleep Med 2008;4:*not available in Canada.
45Insomnia and Depression Up to 90% of MDE patients complain of insomniaUp to 40% of patients complaining of insomnia could have a mood disorderSubjective complaints of difficulty initiating, maintaining sleep or early awakeningObjective findings: decreased REM latency, increased % REM, increased first REM period and decreased SWS
46Antidepressants and Sleep SSRIVenlafaxineDuloxetineBUPROPIONMIRTAZAPINETCA
47SSRIs and SleepIdiosyncratic effects: can cause insomnia or agitation in any individual patientUp to 60% of patients on SSRIs are also on a hypnoticAll SSRIs decrease SE, suppress REM, delay REM onset, and increase S1 sleepThere appears to be a trend where:Fluvoxamine and paroxetine are more sedatingFluoxetine is more stimulatingSertraline, citalopram and escitalopram are neutralClonazepam plus Prozac- WT Smith 2002Zolpidem with SSRIs in depression Asnis 1999
48Clinical Practice Point Trazodone, TCAs and mirtazapine are commonly used to help insomnia complaints in patients who suffer from depression or anxiety disordersSSRI could be used alone or with a BDZ/hypnotic to help insomnia complaints in depressionAdjusting dose or timing can be helpfulCombining medication with CBT is an option
49Are Antidepressants To Blame For Sleep Disturbances? ClassDrugInsomniaSedationHeadacheTremorDry MouthSweatingNauseaDiarrheaConstipationFatigueAnxietySSRICitalopramEscitalopramFluoxetineFluvoxamineParoxetineSertralineSNRIDuloxetineVenlafaxineDesvenlafaxineOthersBupropionMirtazapine>50%Quetiapine XRKEY MESSAGE:Residual symptoms of sleep disturbance can also be side effects of antidepressant treatment. Insomnia has been associated with many SSRIs and SNRIs, whereas sedation has been associated with all classes of antidepressants. Sertraline having been associated with fatigue and excess sleepiness as well.0-9%10-29%≥30%Data from placebo-controlled trials from respective product monographs; not for direct comparison between agents. Adapted from Lam et al. J Affect Disord 2009:17:S26-43 and Seroquel XR Product Monograph (2011).
50Role for Antipsychotics A 45 year-old male was referred to see me for a sleep assessmentBy the time I saw him he was already put on olanzapine 2.5mg po qhs and has been “doing great”. He was not sure why he needed to see me nowWhat are the effects of antipsychotics on sleep parameters?What is the evidence for use of antipsychotics in insomnia and in complicated insomnia?
51Antipsychotics and Sleep Typical antipsychoticsClozapineRisperidoneOlanzapineQuetiapineZiprasidoneTotal Sleep Time+++Sleep EfficiencyHowever consider:Weight gain and therefore worsening of apneaIncreased leg restlessnessHyperlipidemiaGlucose dysregulationQT prolongation
52Important Quotes- NIH Chronic Insomnia Panel “all (antipsychotics) agents have significant risks, and thus their use in the treatment of chronic insomnia cannot be recommended”Eszopiclone and zolpidem extended release are not indicated for “short term” useIntermittent vs regular prescriptionShort term vs long term prescription
53Clinical Practice Point Antipsychotics are commonly used in patients who have psychosis and bipolar illness to help with sleep complaintsAntipsychotics are sometimes used in patients whose depression is successfully treated but still complain of their sleepPotential effects on weight, lipids and glucoseQuetiapine is commonly used for “psychiatric insomnia”
54Back to David Is David’s insomnia most likely... A primary sleep disorder?A residual symptom of depression?Medication-induced?Due to poor sleep hygiene?Due to something else?Use this question as an opportunity for participants to share their experience with one another and to ask expert facilitators for guidance as it relates to challenging cases.
55Back to DavidDavid is exhibiting residual symptoms of depression and mild anxietyHis insomnia is affecting his work functioningWould you change his treatment plan? If yes, how?Use this case vignette as an opportunity for participants to share their experience with one another and to ask expert facilitators for guidance as it relates to challenging cases.It is important to address any issues pertaining to sleep hygiene, maladaptive behaviours or cognitive distortions (e.g., I am going to die if I do not sleep).
56Treatment of InsomniaWhat is the most common prescribed medication for the treatment of insomniain the United States?in Kuwait?
57Clinical aspects of Insomnia Treatment of insomnia is based upon the following principles:A. Insomnia is always a symptom of a larger psychiatric disorderB. Insomnia may lead to hypertension and diabetesC. Reduction of depressive symptoms can improve insomniaD. Sleep studies are always helpful in confirming the diagnosis of insomniaB and C are right answers
58Depression and sleepPolysomnographic features of depression seen in 50% of patients diagnosed with depression include:Abbreviated REM sleep onsetIncreased REM amountsDecreased slow wave sleepIncreased sleep fragmentation and arousalsSleep studies are indicated in cases of suspected depressionE is incorrect
59Case of Mr. BMr. B is a healthy 20 yo male whom you have been seeing in therapy for treatment of anxiety. According to his roommate, the patient has been waking up screaming, with severe sweating and difficulty to communicate with during these episodes. The patient had severe nightmares as a child. The events typically occur after missing his normal amount of sleep because of social events or studying for tests.Q: How would you treat these “nightmares”?
60Events during sleep Nightmares Night terrors Panic attacks (nocturnal) REM behaviour disorderSleep walkingNocturnal seizuresCONSIDER: prior history, age, dreaming episode, time of occurrence, ability to console, autonomic arousability, and behaviours during episode.
61Screening for Parasomnias 1. do you or your bed partner believe that you move your arms, legs, or body too much or have unusual behaviour during sleep?2. do you move while dreaming as though you are attempting to carry out a dream?3. have you ever hurt yourself or your partner while asleep?4. do you eat or drink without full awareness during the night?5. review medication(hypnotic) list/alcohol intake
62Events during the night Fuseli’sFuseli’s nightmare
63Nightmares vs Night terrors REM relatedLast 1/3 of nightScaredLittle movementRemember dreamConsolableDelayed back to sleepNon REM relatedFirst half of nightConfusedActiveAmnesia in morningNot consolableEasy back to sleep
64Nightmares REM related events Last third of the night Vivid dreams Dreams are rememberedAutonomic hyperarousability- mildNo confusion or disorientation
65Nightmares- cont’dTreatment to be directed for culprit- medications, withdrawal, sleep disorder, sleep deprivationNo harm results from awakenings- ReassuranceImagery rehearsal treatmentPrazosin in cases of PTSD related n/mTryptophan?
66Night terrors Occur out of SWS ( N3 )* First half of the night Positive hx of sleep walkingBehaviour is stereotypicalExtreme autonomic dischargeDifficult to consolePotential self harm/ harm to others* in children out of N1/N2High amplitude and Hypersynchroonous bursts of slow waves preceed the abnormal behavioursIn children can occur out of stage 1 and 2Tachycardia, tachypnea, prespiratoin, screaming with confusion, glassy eyes, pick at blankets, get up and walk around.Family history of sleepwalking-Incidence of somnambulism and related parasomnias increases aqs follows:22% when remote relative has it44% when one parent has it and60% when both parents affected
67Night terrors- cont’dMay be triggered by: febrile illness, alcohol, sleep deprivation, stress.Medications can induce such events- hypnotics/neuroleptics/stimulants/anti-histamines and antiarrhythmic medsR/O brain insult, brain glioma, epilepsy, cardiac insufficiency.
68Night terrors- cont’d Treatment of NREM Parasomnia Education and reassuranceSafety precautions- if sleep walkingBDZ/ TCARelaxationHypnosis
69Unusual dreamsA 66 yo male who you see for depression presented to your office with bruises to his hands and feet after falling off the bed few days earlier. He recalls having a dream where he had to defend himself from a snake. On further inquiry he indicated that his wife has been scared to sleep with him in the same bed due to his excessive movements at night. His sleep record epoch shows the following:2/3 of males above 50 with RBD will develop Parkinsonian type disorder within a mean interval of 13 years.
71Unusual dreamsA 66 yo male who you see for depression presented to your office with bruises to his hands and feet after falling off the bed few days earlier. He recalls having a dream where he had to defend himself from a snake. On further inquiry he indicated that his wife has been scared to sleep with him in the same bed due to his excessive movements at night.This man likely:Has loss of muscle atonia during his REM sleepHas REM sleep behaviour disorder (RBD)Would benefit from an SSRIWill develop neuropathy with Guillain Barre-like illnessWill benefit from Clonazepam2/3 of males above 50 with RBD will develop Parkinsonian type disorder within a mean interval of 13 years.
72ONE LAST, VERY EFFECTIVE TREATMENT OPTION For apnea, RLS, Insomnia, parasomnias with com0rbid depression and anxiety is:
73ONE LAST, VERY EFFECTIVE TREATMENT OPTION For apnea, RLS, Insomnia, parasomnias and com0rbid depression with anxiety is:Review this lecture
74EXTRAsIf we have time we can cover: Excessive Daytime Sleepiness
77Sleepy!The "switch" for sleep is considered to be the ventrolateral preoptic nucleus (VLPO) of the anterior hypothalamus.VLPO uses GABA and galanin to initiate sleep by inhibiting the arousal regions of the brain.VLPO inhibits the wake-promoting regions of the brain including the tuberomammillary nucleus, lateral hypothalamus, locus coeruleus, dorsal raphe, laterodorsal tegmental nucleus, and pedunculopontine tegmental nucleus.Hypocretin (orexin) neurons in the lateral hypothalamus help to stabilize this switch
78EDSA 45 yo female has been referred to a sleep clinic for assessment of day time sleepiness and fatigue.How do you differentiate between EDS and fatigue?Is there a role for a sleep study? MSLT? MWT?What are the causes for EDS?
83Final questionOf the following which is the most specific finding in a patient who is known to have narcolepsy?MSLT with average sleep onset of 6 minutesImprovement of EDS when drinking coffeeSleep paralysisHypnagogic HallucinationsCataplexy
84BibliographyAn update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep 2004:27(3):Brower KJ. Alcohol’s effects on sleep in alcoholics. Alcohol Research and Health ;25(2):Kushida CA,Littner MR,Hirshkowitz M etal. Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep related breathing disorders. Sleep 2006:29(3):Morgenthaler T,Kapen S,Lee-Chiong T etal. Practice parameters for the medical therapy of obstructive sleep apnea. Sleep 2006;29(8):Morin CM,Bootzin RR,Buysse DJ etal. Psychological and behavioural treatment of insomnia. Update of the recent evidence. Sleep 2006;29(11):Neubauer DN. The evolution and development of insomnia pharmacotherapies. JCSM ;3(5): S11-S15Peterson MJ and Benca RM. Sleep in mood disorders. Psychiatr Clin N 2006;29:Roth T. Insomnia: Definition, prevalence, etiology, and consequences. JCSM 2007;3(5): S7- S10Schenck C, Mahowald M. Parasomnias. Post Med 2000;107(3):Silber MH. Chronic insomnia. NEJM. 2005;353:803-10
85Fun Websites The sleep IQ test: Sleep meditation quilt square: A couple of simple things to remember and a cool site. t/Water_files/water14_help_with_sleep/help_with_sleep.htmlPractice parameters for treating chronic primary insomnia in the elderly. Nat’l. Guideline Clearinghouse;
86QUESTIONSIf you have any questions I could be reached at the following address:Raed Hawa MD FRCPC DABPN DABSMAssociate Professor, Department of PsychiatryDeputy Psychiatrist in Chief, University Health NetworkDeputy Clerkship Director, UME, University of TorontoDirector, Undergraduate Psychiatry Program, UME, University of Toronto
88Agomelatine and SleepBASLEEP EFFICIENCYSLEEP LATENCY29.729.98078.978.93028.478.878.378.426.728.127.87978.27877.22523.5777622.5Sleep Efficiency (%)7576.576.42075.875.77422.214.171.1249.620.274.818.818.818.97315Agomelatine72AgomelatineSertalineSertaline717010123456123456WeekWeekP value–<.0001.018.001<.001.007Agomelatine n1171121059988Sertraline n11411310193877971KEY MESSAGE:Although not yet available in Canada (except through a Special Access program), agomelatine has a favourable effect on the relative amplitude of the circadian rest-activity/sleep-wake cycle in depressed patients as early as week 1, reflecting improvement in sleep and daytime functioning.P value–<.001.003.005Agomelatine n1171121059988Sertraline n11411310193877971Double-blind, randomized, controlled clinical trial of agomelatine mg/d (n=154) vs. sertraline mg/d (n=159) over 6 weeks.Agomelatine is only available in Canada through a Special Access program.Kasper et al. J Clin Psychiatry 2010:71:
89Efficacy of Adjunctive Modafinil In Partial Responders To SSRIs With Persistent Fatigue & Sleepiness Placebo681012141618Mean = SEM HAM-D-17 Score*†‡Week124Final VisitaBaselineOther significant improvements for adjunctive modafinil vs. placebo:↑ CGI-I scores↓ fatigueKEY MESSAGE:This study supports the efficacy and safety of modafinil as augmentation therapy in patients who are partial responders to SSRI therapy. Benefits were noted in terms of both depressive symptomatology, fatigue / sleepiness, and overall clinical condition.Double-blind, randomized, placebo-controlled clinical trial of 60 depressed, insomniac outpatients receiving open-label fluoxetine plus add-on eszopiclone 3 mg or placebo at bedtime for 8 weeks. CGI-I: Clinical Global Impression – Improvement.*P=0.07; † p=0.06; ‡p<0.08.Fava et al. J Clin Psychiatry 2005:66:85-93.
90Quetiapine XR: Significant Effect On Sleep In Patients With MDD Pooled analysis of two 8 week†, RCTs of quetiapine XR in patients with MDD (n=968)KEY MESSAGE:In this pooled analysis of two of the registration studies for quetiapine XR, sleep quality was significantly improved by both doses of the active agent compared to placebo.*p<0.001; †6 week randomization phase, 2 week discontinuation phase; results shown are at week 6. PSQI: Pittsburg Sleep Quality Index.Weisler et al. Int Clin Psychopharmacol 2012; 27: