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Pharmacology of Anxiolytic/ Sedative-Hypnotics

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Title: Pharmacology of Anxiolytic/ Sedative-Hypnotics


1
Pharmacology of Anxiolytic/ Sedative-Hypnotics
  • Philip G. Janicak, MD
  • Professor of Psychiatry and Pharmacology
  • University of Illinois at Chicago

2
Abstract
pharmacology of anxiolytic/sedative-hypnotics
  • Recent anxiolytic and sedative-hypnotic agents
    offer comparable efficacy, fewer serious adverse
    effects, and less risk of a fatal consequence due
    to accidental or intentional overdose in
    comparison to alcohol, barbiturates and other
    non-barbiturate agents (e.g., meprobamate).
    Unfortunately, they have not entirely eliminated
    the hazards of tolerance, dependency, and
    withdrawal syndromes, although they have a lower
    abuse potential than their predecessors.
  • For these reasons, it is important to become
    knowledgeable about the basic pharmacology of
    these drugs, in addition to their appropriate
    clinical indications, dosages, and duration of
    usage. Most importantly, their limitations must
    receive as much attention as their assets.

3
Objectives
pharmacology of anxiolytic/sedative-hypnotics
  • Review different classes of antianxiety and
    sedative-hypnotic agents in terms of their
    pharmacodynamics pharmacokinetics adverse
    effects and potential for drug interactions
  • Review diagnostic indications for anxiolytic/
    sedative-hypnotics
  • Review treatment strategies for anxiety and sleep
    disorders

4
Anxiety
pharmacology of anxiolytic/sedative-hypnotics
  • Natural human experience
  • Subjective qualities of fear or related emotions
  • Ensures survival and adaptation
  • In excess, can cripple and destroy
  • Subjective, physiological, behavioral aspects

5
Anxiety Symptoms
pharmacology of anxiolytic/sedative-hypnotics
  • Anxiety symptoms are associated with numerous
    medical conditions
  • Cardiovascular disease
  • Endocrine disease
  • Gastrointestinal disease
  • Neurologic disease
  • Drug-induced

6
Lifetime And 12-Month Prevalence Of Anxiety
Disorders In The NCS
Anxiety Disorders Lifetime () 12-Month ()
Panic Disorder 3.5 2.3 Agoraphobia without
panic 5.3 2.6 Social Phobia 13.3 7.9 Simple
Phobia 11.3 8.8 Generalized Anxiety 5.1 3.1Disord
er Posttraumatic Stress 7.6 3.9Disorder Any
anxiety disorder 28.7 19.3
Kessler et al. Arch Gen Psychiatry. 1994518.
7
ANTIANXIETY AGENTS
Generic Names Trade Names Daily Dosage (mg/day)
BENZODIAZEPINES Chlordiazepoxide Librium,
others 10-100 Diazepam Valium,
others 2-40 Oxazepam Serax, others 30-120 Chlora
zepate Tranxene, others 15-60 Lorazepam Ativan 1
-10 Prazepam Centrax 20-60 Halazepam Paxipam 60-
160 Alprazolam Xanax 0.75-4 AZAPIRONES Buspiron
e Buspar 15-60 ANTIDEPRESSANTS SSRI Sertraline,
others 25-250 Venlafaxine Effexor 75-375
8
SEDATIVE-HYPNOTICS
Generic Names Trade Names Daily Dosage (mg
/day) BENZODIAZEPINES Long-acting Flurazepam
Dalmane 15-45 Quaz
epam Doral 7.5-15 Intermediate-acting Estazol
am Prosom 0.5-2 Temazepam Restoril 15-45 Shor
t-acting Triazolam Halcion 0.125-0.25 NONBE
NZODIAZEPINE Zolpidem Ambien 5-20 Zaleplon
Sonata 5-20 SEDATING ANTIDEPRESSANTS Trazodo
ne Dyserel 25-100 BARBITURATE-LIKE Chloral
Hydrate Notec 500-1500 OTHER Melatonin 0.
3-2
9
Pharmacodynamics
pharmacology of anxiolytic/sedative-hypnotics
  • Benzodiazepines
  • Specific binding site associated with GABAA
    receptor-chloride ion channel
  • Potentiate GABA
  • Serotonergic effects (e.g., clonazepam)
  • Azapirone (e.g., buspirone)
  • 5-HT1A agonist acutely, ? firing, in dorsal
    raphe nuclei chronically, receptor
    desensitization ? ? activity
  • Beta-blockers
  • ? receptors central and peripheral, post synaptic
  • Clonidine
  • Agonist at ?2 receptors, central, pre-synaptic
  • Antidepressants

10
GABA Function and Distribution
pharmacology of anxiolytic/sedative-hypnotics
  • Inhibitory neurotransmitter
  • Widely distributed throughout CNS
  • Local inhibitory action, therefore rapidly alters
    neuronal output
  • Desensitization to inhibitory effects with
    chronic stimulation of GABA

11
GABAA-BZD Supramolecular Complex
12
GABAA Receptor Structure
S.M. Paul, 1995
13
pharmacology of anxiolytic/sedative-hypnotics
14
BZD Receptors
pharmacology of anxiolytic/sedative-hypnotics
  • Type I
  • Predominates in cerebellum
  • Anxiolytic properties
  • Less sedative properties
  • Type II
  • Located in cortex, hippocampus, spinal cord
  • No anxiolytic properties
  • Sedative properties
  • Type III
  • Located in peripheral tissue
  • No anxiolytic properties
  • ? other properties

15
BZD Receptor Activity
pharmacology of anxiolytic/sedative-hypnotics
16
Non-Benzodiazepine Agents
pharmacology of anxiolytic/sedative-hypnotics
  • Imidazopyridines (e.g., zolpidem, alpidem)
  • Pyrazolopyrimidine (e.g., zaleplon)
  • Cyclopyrralone (e.g., zopiclone)
  • Sedating antidepressants (e.g., trazodone)

17
Non-Benzodiazepine Agents (cont)
pharmacology of anxiolytic/sedative-hypnotics
  • Antihistamines (e.g., diphenhydramine)
  • Natural Remedies (e.g., melatonin, valerian)
  • B-carbolines (e.g., abecarnil)
  • BZD structural derivatives (e.g., biretazanil)

18
Serotonin Model
pharmacology of anxiolytic/sedative-hypnotics
  • Majority of 5-HT pathways originate in the dorsal
    raphe (DR)
  • DR innervates cortex, hypothalamus, thalamus, and
    limbic system
  • 5-HT mediates behavioral effects in animal models
    and humans

19
Serotonin Receptors
pharmacology of anxiolytic/sedative-hypnotics
  • 5-HT1A -Anxiety, alcoholism, sexual function
  • 5-HT1C -Anxiety, migraine pain
  • 5-HT1D -Migraine pain
  • 5-HT2 -Anxiety, depression, schizophrenia
    negative symptoms, sexual function
  • 5-HT3 -Migraine pain, emesis, schizophrenia
    (e.g., ondansetron)
  • 5-HT4 -Anxiety, schizophrenia?

20
Serotonin Agents Indications forAnxiety-Related
Disorders
pharmacology of anxiolytic/sedative-hypnotics
  • SSRI
  • Sertraline - OCD PD PTSD
  • Paroxetine - OCD PD SAD GAD
  • Fluoxetine - OCD BN PMDD
  • Fluvoxamine - OCD
  • Venlafaxine - GAD
  • Buspirone - GAD

21
Noradrenergic Model
pharmacology of anxiolytic/sedative-hypnotics
  • Hypersensitivity to autonomic nervous system
  • Locus coeruleus (LC)
  • Stimuli norepinephrine release stimulation of
    the sympathetic nervous system

22
Norepinephrine Receptors
pharmacology of anxiolytic/sedative-hypnotics
  • Locus coeruleus
  • Alpha -2 adrenergic receptors
  • somatodendritic autoreceptors
  • terminal autoreceptors
  • negative feedback system
  • antagonists are anxiogenic
  • agonists may be anxiolytic and decrease
    withdrawal symptoms (e.g., clonidine)
  • Beta adrenergic receptors
  • Beta-blockers (e.g., propranolol)
  • Social phobia
  • Performance anxiety

23
Pharmacokinetics Benzodiazepines
pharmacology of anxiolytic/sedative-hypnotics
  • Absorption rapid absorption, except clorazepate
  • Onset of action increase lipid solubility ?
    faster onset
  • Duration of action single dose with increased
    lipid solubility ? faster redistribution to fat
    tissues? shorter duration of action. Chronic
    use in equilibrium with fat tissues
  • Half life In part, determines duration of
    action
  • Metabolism lorazepam, oxazepam, temazepam not
    metabolized by liver

24
Drug Interactions Benzodiazepines
pharmacology of anxiolytic/sedative-hypnotics
  • Additive pharmacodynamic effects (e.g., alcohol)
  • BZD withdrawal when other drugs that increase
    seizure risk are also taken
  • Inhibit BZD metabolism (e.g., nefazodone via P450
    3A 3/4 inhibits metabolism of triazolam)
  • Diazepam may increase levels of digoxin and
    phenytoin

25
Adverse Effects Benzodiazepines
pharmacology of anxiolytic/sedative-hypnotics
  • Sedation and impairment of performance
  • Psychomotor skills driving engaging in
    dangerous physical activities using hazardous
    machinery, especially during initial phase of
    treatment
  • Memory impairment
  • Anterograde amnesia (desired before surgery,
    other procedures).
  • Dose-related, and tolerance may not develop.
  • Most likely with triazolam
  • Disinhibition
  • Possible risk factors history of aggression,
    impulsivity, borderline or antisocial personality

26
Abuse, Dependence, Withdrawal, and Rebound
Anxiety Benzodiazepines
pharmacology of anxiolytic/sedative-hypnotics
  • Abuse potential decreased when properly
    prescribed and supervised.
  • Dependence may occur at usual doses taken beyond
    several weeks.
  • Withdrawal may occur even when discontinuation is
    not abrupt (e.g., by 10 every 3 days). Symptoms
    include tachycardia, increased blood pressure,
    muscle cramps, anxiety, insomnia, panic attacks,
    impairment of memory and concentration,
    perceptual disturbances, derealization,
    hallucinations, hyperpyrexia, seizures. May
    continue for months.
  • Rebound anxiety return of target symptoms, with
    increase intensity.

27
Pharmacokinetics/Pharmacodynamics Buspirone
pharmacology of anxiolytic/sedative-hypnotics
  • Onset of action (i.e., weeks versus days)
  • No sedation or impairment of performance
  • No cross-tolerance with BZDs
  • No tolerance or withdrawal
  • No abuse potential

28
Adverse Effects Buspirone
pharmacology of anxiolytic/sedative-hypnotics
  • Nausea
  • Headache
  • Insomnia, nervousness
  • Restlessness
  • Dizziness, lightheadedness

29
Indications for Antianxiety/Sedative-Hypnotics
pharmacology of anxiolytic/sedative-hypnotics
  • Generalized anxiety disorder (GAD)
  • Phobic disorders
  • Anxiety disorder due to general medical condition
  • Panic disorder
  • Obsessive-compulsive disorder
  • Posttraumatic stress disorder
  • Sleep disorders (dyssomnias parasomnias)

30
GAD
pharmacology of anxiolytic/sedative-hypnotics
  • Represents up to 50 of anxious patients seen by
    physicians
  • Increased annual medical expenses
  • Often unnecessary medical consultations
  • 55 million prescriptions for BZDs in 1989
  • Anxiolytic agents fourth most prescribed class of
    medication

31
Treatment Strategy for GAD
CLINICAL PRESENTATION TREATMENT STRATEGY
  • Acute anxiety (mild)

PSYCHOTHERAPY Supportive, Cognitive-Behavioral
or Insight-Oriented
(may start)
(insufficient response)
(may add)
Acute anxiety (more severe)
(start)
Benzodiazepine (BZD) plus Psychotherapy
(insufficient response)
(may try)
32
Treatment Strategy for GAD
CLINICAL PRESENTATION TREATMENT STRATEGY
  • Chronic anxiety
  • (no prior BZD therapy)

Buspirone (up to 90 mg/day for up to 6 weeks)
plus CBT
(may start)
(insufficient response)
Venlafaxine
(insufficient response)
33
Treatment Strategy for GAD
CLINICAL PRESENTATION TREATMENT STRATEGY
Buspirone or Venlafaxine plus BZD initially, then
taper BZD plus CBT
  • Chronic anxiety,
  • prior BZD therapy

(may start)
(insufficient response)
Buspirone or Venlafaxine plus BZD for longer
period plus CBT
(insufficient response)
Chronic anxiety with panic or depressive symptoms
(may start)
Other Antidepressants (TCA, SSRI, MAOI) w/wo a
BZD or Buspirone
34
Phobic Disorders
pharmacology of anxiolytic/sedative-hypnotics
  • Disabling anxiety (at times associated with panic
    attacks) and avoidance
  • Agoraphobia
  • Social phobia (Social Anxiety Disorder)
  • Specific phobia

35
Treatment Strategyfor PHOBIC Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
  • Social Phobia, Generalized (Social Anxiety
    Disorder)

Cognitive Behavioral Therapy
(may start)
(or)
(insufficient response)
Selective Serotonin Reuptake Inhibitor (e.g.,
Paroxetine)
(insufficient response)
36
Treatment Strategyfor PHOBIC Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
BEHAVIORAL THERAPY PLUS SSRI
(insufficient response)
MAOI (must wait at least 2 weeks after
discontinuation of SSRI longer for fluoxetine
before starting MAOI)
or Alprazolam or Clonidine
37
Treatment Strategyfor PHOBIC Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
  • Cognitive Behavioral Therapy
  • Systematic desensitization
  • Specific Phobia

(start)
(insufficient response)
B-blocker (e.g., performance anxiety)
(insufficient response)
MAOI (e.g., phenelzine)
38
Anxiety Disorder due toGeneral Medical Condition
pharmacology of anxiolytic/sedative-hypnotics
  • Psychologically meaningful environmental stimuli
  • Temporally related to the initiation or
    exacerbation of a physical condition
  • Demonstrable organic pathology (e.g., rheumatoid
    arthritis)
  • Known physiological process (e.g., migraine)

39
Panic Disorder
pharmacology of anxiolytic/sedative-hypnotics
  • Sudden, spontaneous, unexpected feelings of
    terror and anxiety
  • The autonomic equivalence of anxiety
  • The desire to flee the situation and return to a
    safe place
  • A phobic avoidance of the places where such
    attacks occur

40
Symptomatology of Panic Attacks
pharmacology of anxiolytic/sedative-hypnotics
  • Shortness of breath /smothering sensations
  • Dizziness, unsteady feelings, or faintness
  • Palpitations/tachycardia
  • Trembling/shaking
  • Sweating
  • Choking
  • Nausea/abdominal distress
  • Depresonalization/ derealization
  • Paresthesias
  • Flushes/chills
  • Chest pain or discomfort
  • Fear of dying
  • Fear of going crazy or doing something
    uncontrolled

41
Treatment Strategy for PANIC Disorder with or
without Agoraphobia
CLINICAL PRESENTATION TREATMENT STRATEGY
  • Panic attacks (mild) w/wo agoraphobia
  • Behavioral Therapy only
  • (may require several months)
  • Cognitive
  • In-vivo exposure
  • Relaxation
  • Systematic desensitization

(start)
(insufficient response)
(may add)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ
Jr. Principles and Practice of Psychopharmacothera
py. 3rd ed. Philadelphia, PA Lippincott Williams
Wilkins 2001.
42
Treatment Strategy for PANIC Disorder with or
without Agoraphobia
CLINICAL PRESENTATION TREATMENT STRATEGY
  • Panic attacks (moderate) w/wo agoraphobia

SSRI plus Behavioral Therapy
(may start)
(or)
(insufficient response)
Other Antidepressant (e.g., Venlafaxine, TCA)
plus Behavioral Therapy
(insufficient response)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ
Jr. Principles and Practice of Psychopharmacothera
py. 3rd ed. Philadelphia, PA Lippincott Williams
Wilkins 2001.
43
Treatment Strategy for PANIC Disorder with or
without Agoraphobia
CLINICAL PRESENTATION TREATMENT STRATEGY
ALPRAZOLAM/CLONAZEPAM plus Behavioral Therapy
(insufficient response)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ
Jr. Principles and Practice of Psychopharmacothera
py. 3rd ed. Philadelphia, PA Lippincott Williams
Wilkins 2001.
44
Treatment Strategy for PANIC Disorder with or
without Agoraphobia
CLINICAL PRESENTATION TREATMENT STRATEGY
TCA/SSRI and Behavioral Therapy
  • Panic attacks (severe) w/wo agoraphobia

(start)
(plus)
  • Alprazolam/Clonazepam
  • for first month

(insufficient response)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ
Jr. Principles and Practice of Psychopharmacothera
py. 3rd ed. Philadelphia, PA Lippincott Williams
Wilkins 2001.
45
Treatment Strategy for PANIC Disorder with or
without Agoraphobia
CLINICAL PRESENTATION TREATMENT STRATEGY
TCA/SSRI and Behavioral Therapy
(plus)
  • Alprazolam/Clonazepam
  • indefinitely

(insufficient response)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ
Jr. Principles and Practice of Psychopharmacothera
py. 3rd ed. Philadelphia, PA Lippincott Williams
Wilkins 2001.
46
Treatment Strategy for PANIC Disorder with or
without Agoraphobia
CLINICAL PRESENTATION TREATMENT STRATEGY
  • MONOAMINE OXIDASE INHIBITOR (N.B. SSRI) must be
    stopped prior to beginning MAOI
  • Fluoxetine, at least 5 weeks
  • Other SSRIs, at least 2 weeks

(insufficient response)
(may try)
Valproate w/wo BZD
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ
Jr. Principles and Practice of Psychopharmacothera
py. 3rd ed. Philadelphia, PA Lippincott Williams
Wilkins 2001.
47
Obsessive-Compulsive Disorder (OCD)
pharmacology of anxiolytic/sedative-hypnotics
  • Recurrent obsessions and/or compulsions
  • Cause marked distress, are time-consuming, or
    interfere with functioning
  • Are recognized as excessive or unreasonable
  • Are not due to the effect of a substance or
    general medical condition

48
Obsessions in OCD
pharmacology of anxiolytic/sedative-hypnotics
  • Contamination
  • Pathological doubt
  • Aggressive impulses
  • Somatic concerns
  • Need for symmetry
  • Sexual impulses

49
Compulsive Behaviors in OCD
pharmacology of anxiolytic/sedative-hypnotics
  • Cleaning
  • Washing
  • Checking
  • Excessive ordering/arranging
  • Counting
  • Repeating
  • Collecting

50
Treatment Strategy for OBSESSIVE-COMPULSIVE and
Related Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
(may start)
  • Mild symptoms

Behavioral Therapy (e.g., exposure and response
prevention)
(insufficient response)
(may add)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ
Jr. Principles and Practice of Psychopharmacothera
py. 3rd ed. Philadelphia, PA Lippincott Williams
Wilkins 2001.
51
Treatment Strategy for OBSESSIVE-COMPULSIVE and
Related Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
  • Moderate to severe symptoms
  • SSRI
  • Fluvoxamine
  • Sertraline
  • Paroxetine
  • Citalopram
  • Fluoxetine

(start)
(or)
Clomipramine
(plus)
Behavioral Therapy
(insufficient response)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ
Jr. Principles and Practice of Psychopharmacothera
py. 3rd ed. Philadelphia, PA Lippincott Williams
Wilkins 2001.
52
Treatment Strategy for OBSESSIVE-COMPULSIVE and
Related Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
Alternate SRI
(insufficient response)
Clonazepam/Buspirone plus SRI
(insufficient response)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ
Jr. Principles and Practice of Psychopharmacothera
py. 3rd ed. Philadelphia, PA Lippincott Williams
Wilkins 2001.
53
Treatment Strategy for OBSESSIVE-COMPULSIVE and
Related Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
Pimozide/Haloperidol/Risperidone or Lithium w/wo
SRI
  • Trichotillomania
  • Tics (e.g., Tourettes)
  • Delusional symptoms

(may start)
(insufficient response)
MAOI (SRI must be completely cleared first)
(insufficient response)
(may consider)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ
Jr. Principles and Practice of Psychopharmacothera
py. 3rd ed. Philadelphia, PA Lippincott Williams
Wilkins 2001.
54
Treatment Strategy for OBSESSIVE-COMPULSIVE and
Related Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
  • Severe, unremitting course (e.g., 5 years failed
    trials with SSRI, CMI, MAOI severe dysfunction)
  • Somatic Therapy
  • ECT
  • Neurosurgery
  • TMS (?)

(consider)
From Janicak PG, Davis JM, Preskorn SH, Ayd FJ
Jr. Principles and Practice of Psychopharmacothera
py. 3rd ed. Philadelphia, PA Lippincott Williams
Wilkins 2001.
55
Posttraumatic Stress Disorder (PTSD)
pharmacology of anxiolytic/sedative-hypnotics
  • Due to an unusual experience that would be very
    stressful for almost anyone (e.g., combat, rape,
    sudden unexpected death of a loved one)
  • Symptoms include
  • Intrusive recollections frightening dreams
    sense of event recurring
  • Intensive physiological stress hyperarousal
  • Emotional numbing
  • Persistent avoidance of stimuli associated with
    the trauma
  • High comorbidity with other psychiatric disorders
  • Increase suicide attempt risk
  • Female-to-male lifetime prevalence ratio of 21

56
pharmacology of anxiolytic/sedative-hypnotics
PTSD COMPLICATIONS
  • Symptoms overlap with
  • Major depression
  • Other anxiety disorders
  • Substance abuse disorders
  • Significant disability, including
  • Occupational
  • Psychiatric
  • Medical
  • Psychosocial

57
Treatment Strategy for POSTTRAUMATIC STRESS
DISORDER
CLINICAL PRESENTATION TREATMENT STRATEGY
  • ANTIDEPRESSANT (especially with depressive
    features)
  • SSRI (e.g., sertraline)
  • TCA
  • MAOI (caution advised in bulimic patients)

may start
Posttraumatic stress disorder
(insufficient response)
Exposure or Cognitive behavioral therapy
58
Sleep Disorders
pharmacology of anxiolytic/sedative-hypnotics
  • Dyssomnias (difficulty initiating or maintaining
    sleep or not feeling rested)
  • Primary Insomnia
  • Primary Hypersomnia
  • Circadian Rhythm Disorder
  • Parasomnias (abnormal event)
  • Nightmare Disorder
  • Sleep Terror Disorder
  • Sleepwalking Disorder

59
Treatment Strategy for SLEEP Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
(first)
  • Transient or short-term insomnia
  • Clarify diagnosis
  • treat any medical or psychiatric disorder
  • check for non-prescribed drugs

(insufficient response or no other disorder
discovered)
Adapted from Janicak PG, Davis JM, Preskorn SH,
Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA
Lippincott Williams Wilkins 2001.
60
Treatment Strategy for SLEEP Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
  • Nonpharmacological therapies
  • Stimulus control
  • Sleep restriction
  • Relaxation techniques
  • Paradoxical intention
  • Sleep hygiene techniques

(insufficient response)
Adapted from Janicak PG, Davis JM, Preskorn SH,
Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA
Lippincott Williams Wilkins 2001.
61
Treatment Strategy for SLEEP Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
Short- to intermediate-acting BZD
Sedative-Hypnotic (e.g., estazolam 0.5-1 mg QHS)
(or)
Zolpidem or Zaleplon (5-20 mg QHS)
(insufficient response)
Adapted from Janicak PG, Davis JM, Preskorn SH,
Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA
Lippincott Williams Wilkins 2001.
62
Treatment Strategy for SLEEP Disorders
CLINICAL PRESENTATION TREATMENT STRATEGY
Non-pharmacological therapies w/wo sedating
antidepressant
  • Chronic insomnia (³7-12 weeks)

(start)
  • e.g., trazodone (25-50 mg QHS)

(insufficient response)
COMBINED TREATMENT non-pharmacological and
intermittent, sedative-hypnotic when necessary
Adapted from Janicak PG, Davis JM, Preskorn SH,
Ayd FJ Jr. Principles and Practice of
Psychopharmacotherapy. 3rd ed. Philadelphia, PA
Lippincott Williams Wilkins 2001.
63
References
pharmacology of anxiolytic/sedative-hypnotics
  • Ayd FJ Jr, Janicak PG, Davis JM, Preskorn SH.
    Advances in the pharmacotherapy of
    anxiety-related disorders. In Janicak PG, ed.
    Principles and Practice of Psychopharmacotherapy
    Update. Baltimore, MD Williams Wilkins 1996.
    Vol 1.
  • Janicak PG, Ayd FJ Jr. Sedatives and hypnotics in
    the elderly patient. In Nelson JC, ed. Geriatric
    Psychopharmacology. New York, NY Marcel-Dekker
    1998347-366.
  • Janicak PG, Davis JM, Preskorn SH, Ayd FJ Jr.
    Principles and Practice of Psychopharmacotherapy.
    3rd Ed. Philadelphia, PA Lippincott Williams
    Wilkins 2001463-558.
  • Israni TH, Janicak PG, Davis JM. Obsessive
    compulsive disorder. In Flaherty JA, Davis JM,
    Janicak PG, eds. Psychiatry diagnosis and
    therapy. 2nd ed. Norwalk, CN Appleton Lange
    1993145-155.
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