chapter 25: psychopharmacology copyright © 2012, 2007 mosby, inc., an affiliate of elsevier inc....
TRANSCRIPT
Chapter 25:Chapter 25:
PsychopharmacologyPsychopharmacology
Copyright © 2012, 2007 Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved. Copyright © 2012, 2007 Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.
22Copyright © 2012, 2007 Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved. Copyright © 2012, 2007 Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.
Did You Know?Did You Know?
During any given year, 1 in 4 adults suffer fromDuring any given year, 1 in 4 adults suffer from
a diagnosable mental disorder.a diagnosable mental disorder.
The percent of Americans who will experience: The percent of Americans who will experience: A mental illness in their lifetime, especially in A mental illness in their lifetime, especially in
their teen years: 46.6%their teen years: 46.6% A mood disorder: 20%A mood disorder: 20% An anxiety disorder: 28.8%An anxiety disorder: 28.8% An impulse control disorder: 24.8%An impulse control disorder: 24.8% A substance abuse disorder: 14.6%A substance abuse disorder: 14.6%
33Copyright © 2012, 2007 Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved. Copyright © 2012, 2007 Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.
NeurotransmittersNeurotransmitters
Acetylcholine (Ach)Acetylcholine (Ach) Dopamine (DA)Dopamine (DA) Serotonin (5-HT)Serotonin (5-HT) Glutamate (Glu)Glutamate (Glu)
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AcetylcholineAcetylcholine
Receptors:Receptors: Nicotine Nicotine MuscarinicMuscarinic MemoryMemory Anticholinergic side effectsAnticholinergic side effects
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DopamineDopamine
Receptors:Receptors: Nigrostriatal: movementNigrostriatal: movement Mesolimbic: pleasure, Mesolimbic: pleasure,
delusions/hallucinationsdelusions/hallucinations Mesocortical: mediates positive and negative Mesocortical: mediates positive and negative
symptoms, cognitive side effectssymptoms, cognitive side effects Tuberoinfundibular: prolactin releaseTuberoinfundibular: prolactin release
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SerotoninSerotonin
Inhibitory catecholamineInhibitory catecholamine Mediates:Mediates:
Cognitive effectsCognitive effects Emotions, including panicEmotions, including panic Memory and anxietyMemory and anxiety Violence and aggressionViolence and aggression Sexual functionSexual function Sleep-wake cyclesSleep-wake cycles
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GlutamateGlutamate
Excitatory neurotransmitterExcitatory neurotransmitter
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Variables that Affect Drug Variables that Affect Drug Therapy Therapy
Mode/mechanism of actionMode/mechanism of action Dosage formDosage form BioavailabilityBioavailability Onset, peak, duration of actionOnset, peak, duration of action Serum, half-lifeSerum, half-life Elimination methodElimination method Side effects/toxicitiesSide effects/toxicities CostCost
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Patient-Related VariablesPatient-Related Variables
DiagnosisDiagnosis Other disease statesOther disease states Age Age WeightWeight Anticholinergic susceptibilityAnticholinergic susceptibility History of side effectsHistory of side effects Previous responsePrevious response ComplianceCompliance Financial/insuranceFinancial/insurance Support systemSupport system
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Antipsychotic MedicationsAntipsychotic Medications
Conventional or TypicalConventional or Typical Block DBlock D22 receptors in limbic region receptors in limbic region Differ in potency and side effectsDiffer in potency and side effects
AtypicalAtypical Differ in mode of action, side effect, potencyDiffer in mode of action, side effect, potency Fewer EPSFewer EPS Greater efficacy with negative symptoms, Greater efficacy with negative symptoms,
cognitive symptoms, refractory illnesscognitive symptoms, refractory illness Lower potential to increase prolactinLower potential to increase prolactin
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Symptom Dimensions of PsychosisSymptom Dimensions of Psychosis
1.1. Positive symptoms: overactive dopamine Positive symptoms: overactive dopamine neurons in mesolimbic pathwayneurons in mesolimbic pathway
Examples:Examples: Delusions, hallucinations Delusions, hallucinations Disorganized speech, behavior Disorganized speech, behavior CatatoniaCatatonia AgitationAgitation
Relieved by typical antipsychotics, anticipate Relieved by typical antipsychotics, anticipate response 2 to 8 weeksresponse 2 to 8 weeks
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Symptom Dimensions of Symptom Dimensions of Psychosis, cont’d.Psychosis, cont’d.
2.2. Negative symptoms: dopamine deficiency in Negative symptoms: dopamine deficiency in mesocortical pathwaymesocortical pathway
Examples:Examples: Blunted affect, decreased spontaneityBlunted affect, decreased spontaneity Passivity, social apathy/withdrawalPassivity, social apathy/withdrawal Alogia, avolition, anhedoniaAlogia, avolition, anhedonia
Best treated with atypical antipsychotics, Best treated with atypical antipsychotics,
response: slowresponse: slow
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Symptom Dimensions of Symptom Dimensions of Psychosis, cont’d.Psychosis, cont’d.
3.3. Cognitive symptomsCognitive symptoms
Examples:Examples: Thought disorderThought disorder IncoherenceIncoherence Loose associationLoose association Difficulty processing informationDifficulty processing information
Atypical antipsychotics may improve cognitive Atypical antipsychotics may improve cognitive
functionfunction
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Symptom Dimensions of Symptom Dimensions of Psychosis, cont’d.Psychosis, cont’d.
4.4. Aggressive symptomsAggressive symptoms
Examples:Examples: HostilityHostility Verbal abuseVerbal abuse AssaultAssault Sexual acting outSexual acting out Poor impulse controlPoor impulse control
Treated with typical antipsychotics, response Treated with typical antipsychotics, response
within hourswithin hours
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Symptom Dimensions of Symptom Dimensions of Psychosis, cont’d.Psychosis, cont’d.
5.5. Depressive/anxious symptomsDepressive/anxious symptoms
Examples:Examples: WorryWorry GuiltGuilt IrritabilityIrritability AnxietyAnxiety DepressionDepression
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Goals of TherapyGoals of Therapy
Enable patient to:Enable patient to: Return to normal daily functionsReturn to normal daily functions Provide self-careProvide self-care
Minimize side effects:Minimize side effects: Use lowest possible doseUse lowest possible dose Manage side effects to increase complianceManage side effects to increase compliance
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Absorption, Distribution, Absorption, Distribution, Metabolism, and ExcretionMetabolism, and Excretion
AbsorptionAbsorption Well absorbed by GI tractWell absorbed by GI tract Influenced by:Influenced by:
FoodFood
AntacidsAntacids
AnticholinergicsAnticholinergics
SmokingSmoking
DistributionDistribution Depends on route of administrationDepends on route of administration
IM: greater bioavailabilityIM: greater bioavailability
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Absorption, Distribution, Absorption, Distribution, Metabolism, and Excretion, cont’d.Metabolism, and Excretion, cont’d.
MetabolismMetabolism Half-life: 20 to 40 hoursHalf-life: 20 to 40 hours Metabolized in liverMetabolized in liver
ExcretionExcretion Via kidneysVia kidneys
Serum level monitoringSerum level monitoring Not routinely usefulNot routinely useful
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Acute Episode Acute Episode
Olanzapine (Zyprexa) 10-20 mg dailyOlanzapine (Zyprexa) 10-20 mg daily Risperidone (Risperdal) 3-6 mg dailyRisperidone (Risperdal) 3-6 mg daily Quetiapine (Seroquel) 300-800 mg dailyQuetiapine (Seroquel) 300-800 mg daily Ziprasidone (Geodon) 120-180 mg dailyZiprasidone (Geodon) 120-180 mg daily Aripiprazole (Abilify) 10-30 mg dailyAripiprazole (Abilify) 10-30 mg daily
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Anticholinergic Side EffectsAnticholinergic Side Effects
Low Potency Conventional Antipsychotics Atropine-like Low Potency Conventional Antipsychotics Atropine-like side effects:side effects:
Dry mouthDry mouth Blurred visionBlurred vision Sinus tachycardiaSinus tachycardia Urinary retentionUrinary retention ConstipationConstipation Nasal congestionNasal congestion Ejaculatory inhibitionEjaculatory inhibition
Treatment: supportive measuresTreatment: supportive measures
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Adverse Effects of AntipsychoticsAdverse Effects of Antipsychotics
Extrapyramidal Side Effects (EPS)Extrapyramidal Side Effects (EPS) Dystonia:Dystonia: IM diphenhydramine or benztropine followed IM diphenhydramine or benztropine followed
by oral antiparkinsonism drugby oral antiparkinsonism drug PseudoparkinsonismPseudoparkinsonism: change to low-potency drug: Oral : change to low-potency drug: Oral
antiparkinsonism drugantiparkinsonism drug AkathisiaAkathisia: decrease antipsychotic dose: Propranolol : decrease antipsychotic dose: Propranolol
(Inderal)(Inderal) Tardive dyskinesiaTardive dyskinesia: change to atypical antipsychotic: change to atypical antipsychotic Neuroleptic Malignant SyndromeNeuroleptic Malignant Syndrome: medical emergency, : medical emergency,
initia; treatment involves admission to ICUinitia; treatment involves admission to ICU
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Neuroleptic Malignant SyndromeNeuroleptic Malignant Syndrome
Level of consciousnessLevel of consciousness Muscle toneMuscle tone Autonomic dysfunctionAutonomic dysfunction
HyperpyrexiaHyperpyrexia Labile hypertensionsLabile hypertensions TachycardiaTachycardia TachypneaTachypnea DiaphoresisDiaphoresis DroolingDrooling
MyoglobinuriaMyoglobinuria
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Treatment of NMSTreatment of NMS
Discontinue antipsychoticsDiscontinue antipsychotics HydrateHydrate AcetaminophenAcetaminophen HeparinHeparin Management of arrhythmias Management of arrhythmias DantroleneDantrolene DopaminergicsDopaminergics
Bromocriptine, amantadineBromocriptine, amantadine
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Cardiovascular Side EffectsCardiovascular Side Effects
Postural hypotensionPostural hypotension Arrhythmias Arrhythmias PalpitationsPalpitations Changes in QT interval Changes in QT interval
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Side Effects Related to Clozapine, Side Effects Related to Clozapine, Olanzapine, Low-Potency Typical Olanzapine, Low-Potency Typical
AntipsychoticsAntipsychotics
SedationSedation Weight gainWeight gain
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Other Side EffectsOther Side Effects
PhotosensitivityPhotosensitivity PoikilothermiaPoikilothermia GalactorrheaGalactorrhea GynecomastiaGynecomastia
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Depot MedicationDepot Medication
Fluphenazine decanoateFluphenazine decanoate Intramuscularly or subcutaneouslyIntramuscularly or subcutaneously
Haloperidol decanoateHaloperidol decanoate IntramuscularlyIntramuscularly
Administration PointersAdministration Pointers Inspect solution.Inspect solution. Use dry syringe and needle.Use dry syringe and needle. Do not exceed 3 ml per site.Do not exceed 3 ml per site.
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Atypical Antipsychotic: ClozapineAtypical Antipsychotic: Clozapine
High receptor affinity for DHigh receptor affinity for D44 and 5HT2 and 5HT2 Reserved for refractory illnessReserved for refractory illness Risk: agranulocytosisRisk: agranulocytosis Side effects:Side effects:
Anticholinergic, extrapyramidalAnticholinergic, extrapyramidal NMSNMS Tachycardia, postural hypotensionTachycardia, postural hypotension Weight gainWeight gain HypersalivationHypersalivation Fever, seizuresFever, seizures
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Figure 25-1 A transaxial positron emission tomography (PET) scan image at the level of Figure 25-1 A transaxial positron emission tomography (PET) scan image at the level of the basal ganglia. (Data from Tamminga CA et al., Maryland Psychiatric Research the basal ganglia. (Data from Tamminga CA et al., Maryland Psychiatric Research Center, University of Maryland at Baltimore, unpublished research.)Center, University of Maryland at Baltimore, unpublished research.)
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Other Atypical AntipsychoticsOther Atypical Antipsychotics
Risperidone (Risperdal)Risperidone (Risperdal) Olanzapine (Zyprexa)Olanzapine (Zyprexa) Quetiapine (Seroquel)Quetiapine (Seroquel) Ziprasidone (Geodon)Ziprasidone (Geodon)
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AntidepressantsAntidepressants
Selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs)(SSRIs)
Tricyclic antidepressantsTricyclic antidepressants Monoamine oxidase inhibitorsMonoamine oxidase inhibitors
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Figure 25-2 Neurotransmitter responses to antidepressant therapy. Figure 25-2 Neurotransmitter responses to antidepressant therapy. AA, In the depressed , In the depressed state, sparse amounts of neurotransmitter are available in the synapse of a depressed state, sparse amounts of neurotransmitter are available in the synapse of a depressed person.person.
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Figure 24-2 Neurotransmitter responses to antidepressant therapy. Figure 24-2 Neurotransmitter responses to antidepressant therapy. BB, With treatment, the , With treatment, the reuptake of neurotransmitter is blocked by the antidepressant drug (in red). The result is reuptake of neurotransmitter is blocked by the antidepressant drug (in red). The result is increased amounts of neurotransmitter in the synapse, and, finally, after several weeks increased amounts of neurotransmitter in the synapse, and, finally, after several weeks the postsynaptic receptors have decreased (i.e., downregulated), which is associated the postsynaptic receptors have decreased (i.e., downregulated), which is associated with resolving depression. with resolving depression.
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Selective Serotonin Reuptake Selective Serotonin Reuptake Inhibitors (SSRIs)Inhibitors (SSRIs)
Approved for depression, panic, OCD, PTSD,Approved for depression, panic, OCD, PTSD,
bulimia nervosa, social phobiabulimia nervosa, social phobia Citalopram (Celexa)Citalopram (Celexa) Escitalopram (Lexapro)Escitalopram (Lexapro) Fluvoxamine (Luvox)Fluvoxamine (Luvox) Paroxetine (Paxil)Paroxetine (Paxil) Sertraline (Zoloft)Sertraline (Zoloft)
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Serotonin SyndromeSerotonin Syndrome
ConfusionConfusion HypomaniaHypomania RestlessnessRestlessness MyoclonusMyoclonus HyperreflexiaHyperreflexia DiaphoresisDiaphoresis ShiveringShivering TremorTremor DiarrheaDiarrhea
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Tricyclic Antidepressants: Tricyclic Antidepressants: Second-Line TherapySecond-Line Therapy
Amitriptyline (Elavil)Amitriptyline (Elavil) Clomipramine (Anafranil)Clomipramine (Anafranil) Desipramine (Norpramin)Desipramine (Norpramin) Imipramine (Tofranil)Imipramine (Tofranil) Nortriptyline (Aventyl)Nortriptyline (Aventyl) Protriptyline (Vivactil)Protriptyline (Vivactil) Trimipramine (Surmontil)Trimipramine (Surmontil)
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Response to AntidepressantsResponse to Antidepressants
Week 1Week 1 AnxietyAnxiety Improved sleepImproved sleep
Weeks 1 to 3Weeks 1 to 3 Activity, self-care, sex driveActivity, self-care, sex drive Concentration, memoryConcentration, memory Psychomotor retardationPsychomotor retardation
Weeks 2 to 4Weeks 2 to 4 Relief of depressed moodRelief of depressed mood HopelessnessHopelessness Suicidal ideation subsidesSuicidal ideation subsides
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MAOI Dietary RestrictionsMAOI Dietary Restrictions
Prohibited:Prohibited: Aged cheese, ripe avocadosAged cheese, ripe avocados Ripe figs, anchovies, bean curdRipe figs, anchovies, bean curd Broad beans, yeast, liverBroad beans, yeast, liver Deli meats, pickled herringDeli meats, pickled herring Meat extracts, fermented foodsMeat extracts, fermented foods Chianti and sherryChianti and sherry
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MAOI Dietary MAOI Dietary Restrictions, cont’d. Restrictions, cont’d.
Moderate use:Moderate use: Beer, aleBeer, ale Wine, distilled spiritsWine, distilled spirits Cottage cheese, cream cheeseCottage cheese, cream cheese Yogurt, sour creamYogurt, sour cream Coffee, chocolateCoffee, chocolate Spinach, raisins, tomatoes, eggplantSpinach, raisins, tomatoes, eggplant
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Other Restrictions Other Restrictions with Use of MAOIswith Use of MAOIs
Anti-asthmaticsAnti-asthmatics AntihypertensivesAntihypertensives EpinephrineEpinephrine Allergy, hay fever decongestantsAllergy, hay fever decongestants Cough and cold productsCough and cold products BuspironeBuspirone MeperidineMeperidine SSRIsSSRIs YohimbineYohimbine
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Hypertensive CrisisHypertensive Crisis
HeadacheHeadache Stiff neckStiff neck SweatingSweating Nausea and vomitingNausea and vomiting
TreatmentTreatment NifedipineNifedipine Monitor vital signsMonitor vital signs
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Other AntidepressantsOther Antidepressants
Venlafaxine (Effexor)Venlafaxine (Effexor) NefazodoneNefazodone TrazodoneTrazodone BupropionBupropion MirtazapineMirtazapine
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Treatment of Bipolar DisorderTreatment of Bipolar Disorder
LithiumLithium ValproateValproate CarbamazepineCarbamazepine OxcarbazepineOxcarbazepine LamotrigineLamotrigine GabapentinGabapentin TopiramateTopiramate TiagabineTiagabine ZonisamideZonisamide LevetiracetamLevetiracetam
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Lithium Side Effects Within Lithium Side Effects Within Therapeutic RangeTherapeutic Range
Fine tremorFine tremor Nausea, vomiting, diarrheaNausea, vomiting, diarrhea Mild polydipsia, polyuriaMild polydipsia, polyuria Lethargy, muscle weaknessLethargy, muscle weakness Weight gainWeight gain Increased WBCIncreased WBC Acne, alopeciaAcne, alopecia HypothyroidismHypothyroidism
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Lithium Side Effects: Lithium Side Effects: Moderate ToxicityModerate Toxicity
Lithium level >1.5 mEq/LLithium level >1.5 mEq/L Coarsening of tremorCoarsening of tremor Worsening GI symptomsWorsening GI symptoms Confusion, slurred speechConfusion, slurred speech Sedation, lethargySedation, lethargy
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Lithium Side Effects: Lithium Side Effects: Severe ToxicitySevere Toxicity
Lithium level >2.5 mEq/LLithium level >2.5 mEq/L ArrhythmiasArrhythmias AB block AB block BradycardiaBradycardia MyocarditisMyocarditis SeizuresSeizures ComaComa DeathDeath
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Generalized Anxiety DisorderGeneralized Anxiety Disorder
AntidepressantsAntidepressants VenlafaxineVenlafaxine SSRIsSSRIs ImipramineImipramine NefazodoneNefazodone MirtazapineMirtazapine
BenzodiazepinesBenzodiazepines ClonazepamClonazepam LorazepamLorazepam AlprazolamAlprazolam
BuspironeBuspirone
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Obsessive Compulsive DisorderObsessive Compulsive Disorder
AntidepressantsAntidepressants SSRIsSSRIs ClomipramineClomipramine
Augmentation therapyAugmentation therapy
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Posttraumatic Stress DisorderPosttraumatic Stress Disorder
AntidepressantsAntidepressants SSRIsSSRIs
BenzodiazepinesBenzodiazepines ClonazepamClonazepam
Mood stabilizersMood stabilizers
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Social PhobiaSocial Phobia
AntidepressantsAntidepressants SSRIsSSRIs
BenzodiazepinesBenzodiazepines GabapentinGabapentin
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HypnoticsHypnotics
BenzodiazepinesBenzodiazepines Triazolam (Halcion)Triazolam (Halcion) Temazepam (Restoril)Temazepam (Restoril) Flurazepam (Dalmane)Flurazepam (Dalmane)
NonbenzodiazepinesNonbenzodiazepines Zolpidem (Ambien)Zolpidem (Ambien) Zaleplon (Sonata)Zaleplon (Sonata)
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Other Agents Used for SleepOther Agents Used for Sleep
TrazodoneTrazodone Chloral hydrate (Notec)Chloral hydrate (Notec) Diphenhydramine (Benadryl)Diphenhydramine (Benadryl) Melatonin (Circadian)Melatonin (Circadian) Herbal productsHerbal products
Kava-kavaKava-kava ValerianValerian
BarbituratesBarbiturates
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Acute Agitation and Aggression Acute Agitation and Aggression
AntipsychoticsAntipsychotics HaloperidolHaloperidol ZiprasidoneZiprasidone QuetiapineQuetiapine RisperidoneRisperidone OlanzapineOlanzapine
BenzodiazepinesBenzodiazepines LorazepamLorazepam Trazodone (for older adults)Trazodone (for older adults)
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Chronic AggressionChronic Aggression
SchizophreniaSchizophrenia AntipsychoticsAntipsychotics
ManiaMania LithiumLithium ValproateValproate
Seizure disorderSeizure disorder CarbamazepineCarbamazepine ValproateValproate
Older adultsOlder adults TrazodoneTrazodone