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Psychopharmacology 101

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Title: Psychopharmacology 101


1
Psychopharmacology 101
  • Its all in the neurotransmitters

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  • Neurotransmitters are the chemicals that
  • communicate between neurons.
  • The most common are norepinephrine, dopamine,
    serotonin,
  • GABA, and acetylcholine.
  • Each neuron has its
  • own neurotransmitter, which is received by a
  • special receptor on an adjacent nerve cell, then
  • released and taken up again by the original
  • sending nerve.
  • When enough neurotransmitters are
  • received, the nerve fires.

6
  • The relationship between neurotransmitters,
  • nerve connections, special areas of the
  • brain, and behavior/symptoms of mental
  • illness is very complicated and not yet
  • understood.
  • Beware of oversimplified explanations.

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  • Psychotropic drugs apparently effect
    neurotransmission in several ways
  • Synthesis
  • Storage
  • Release
  • Degradation
  • Access/Reuptake

10
How most psychoactive medicines work
  • Blocks receptor sites
  • Counteracts effects of neurotransmitter
  • Attaches to receptor sites
  • Increases effects of nerves action
  • Blocks the enzyme that breaks down the
    neurotransmitter
  • Increases neurotransmitter-increases activity of
    nerve
  • Blocks the reuptake of the neurotransmitter
  • Increases neurotransmitter-increases activity of
    nerve

11
MECHANISMS OF ACTION
  • The etiopathology of psychiatric illnesses is
    still unknown
  • Most psychotropics have been developed
    serendipitiously, and their mechanism of action
    is unknown We know these drugs work, but we have
    very little idea how
  • However, there are reliable hypotheses on what
    the first step may be of the cascade of events
    that leads to symptoms improvement after a
    medication is administered.

12
  • Current research indicates that the primary
  • mechanism of psychotropic drugs may not
  • be a direct effect on neurotransmitters, but
  • effects on the internal mechanisms of the
  • cell, including the DNA transcription of
  • proteins that promote cell death. These
  • pathways will be the targets of the next
  • generation of psychiatric medications.

13
NEUROTRANSMITTERS
  • ACH
  • MUSCARINIC RECEPTORS
  • NICOTINIC RECEPTORS
  • MONOAMINES
  • Cathecolamines (Dopamine, Norepinephrine,
    Epinephrine)
  • Serotonin
  • Histamine
  • NEUROPEPTIDES
  • e.g., Opioids (endorphins)
  • AMINOACIDS
  • GABA, Glycine Inhibitory
  • Glutammate, Aspartame Excitatory

14
Basic Neurotransmission
  • RECEPTORS
  • CELL MEMBRANE PROTEINS THAT
  • ARE STIMULATED BY SPECIFIC
  • NEUROTRANSMITTERS
  • PROTEIN KINASE
  • ION CHANNELS
  • G PROTEIN COMPLEXES
  • NEUROTRANSMITTERS
  • CHOLINERGIC
  • MONOAMINES
  • NEUROPEPTIDES
  • AMINOACIDS

15
Neurotransmitter Activity
16
Neurotransmitter roles
  • Dopamine
  • Acts on the nervous system to increase heart rate
    and blood pressure. Controls movements. In
    frontal lobe helps with memory, attention and
    problem solving. A disruption has been linked to
    psychosis and schizophrenia.

17
Neurotransmitter roles
  • Serotonin
  • Involved with depression, bipolar disorder and
    anxiety

18
Neurotransmitter roles
  • Norepinephrine
  • Involved in control of alertness and wakefulness.
    Disturbances implicated in affective disorders

19
Neurotransmitter roles
  • GABA
  • Works to inhibit the re-firing of a neuron. May
    interfere with memory formationmay regulate
    activity underlying sleep and arousal

20
Cytochrome P450 Monooxidase System
  • More than 200 enzymes
  • At least 40 in humans
  • 6 Enzymes are responsible for about 90 of all
    the metabolic activity of P450 enzymes 1A2,
    3A4, 2C9, 2C19, 2D6, and 2E1
  • Induction and Inhibition is relatively common

21
  • The cytochrome p450 family of genes, expressed
    primarily in the liver, affect psychotropic and
    other medications.
  • There are three main ones
  • CYP3A4 -lots of drug effects, few polymorphism
  • CYP2D6 -lots of drug effects, lots of
    polymorphism
  • CYP2C19 -few effects, lots of polymorphism

22
CYP 2D6
  • Antidepressants
  • desipramine, fluoxetine, nortriptyline,
    paroxetine, venlafaxine
  • Antipsychotics
  • fluphenazine, perphenazine, risperidone
  • Stimulants
  • atomoxetine
  • Other
  • codeine, dextromethorphan, oxycodone
  • beta blockers

23
2C19
  • Antidepressants
  • amitriptyline, clomipramine, imipramine,
    citalopram, escitalopram, sertraline
  • Benzodiazepines
  • diazepam
  • Other
  • phenytoin
  • propanolol

24
Examples
  • SSRIs Increase serotonin at brain neurons by
    blocking serotonin reuptake, long-term probably
    affect receptor numbers and distribution.
  • MAOIs Inhibit the action of MAO-A and B enzymes
    that metabolize 5-HT, DA, NE
  • Benzodiazepines Bind to the BDZ-GABA-Cl receptor
    complex, facilitating the action of GABA
    (inhibitory neurotransmitter) on CNS excitability
  • Antipsychotics Antagonism or partial agonism of
    dopamine receptors

25
Classes of Psychotropic Medications
  • Antidepressants
  • SSRIs
  • SNRIs
  • Tricyclics
  • MAOIs
  • Other
  • Psychostimulants
  • Antipsychotics
  • Typical
  • Atypical

26
Classes of Psychotropic Medications
  • Mood Stabilizers
  • Lithium
  • Divalproex
  • Carbamazepine
  • Lamotrigine?
  • Anti-anxiety
  • Benzodiazepine
  • Non Benzodiazepine

27
Classes of Psychotropic Medications
  • Dementia Drugs
  • Antiparkinsonians
  • Medications for Substance Dependence

28
Diagnostic and Therapeutic Dilemmas with
Behavioral Disorders
  • How to quantify disorder
  • No blood culture
  • How to decide behavior that is target
  • Often one behavior may respond better than other
    to various psychotropic medication
  • How to manage divergent reporting

29
Psychopharmacology in Preschoolers
  • Less published data regarding outcome
  • Less straight forward
  • Less clear guidelines for use

30
Choosing a Medication
  • Diagnosis
  • Symptoms
  • Risk/Benefits
  • Alternative Treatments
  • Comorbid Medical Diagnoses
  • Concurrent Treatments

31
Factors that affect dosing
  • The following can effect the appropriate dosage
    of
  • medication by a factor of 10
  • Age, concurrent disease, other medications
  • Height, weight
  • Lean/fat ratio
  • Diet
  • Exercise
  • Smoking
  • Alcohol use

32
Treatment Adherence
  • 80 adherence is anticipated by studies.
  • Good adherence increases the likelihood of
  • a good outcome by a factor of 2.88.
  • Doctors estimate compliance at 95.
  • Electronic monitoring indicates 47 and
  • declines over time.

33
Treatment Adherence
  • Adherence seems to be worse in younger clients
    and African-Americans.
  • SGAs do not have better adherence, although
    clients like them better.
  • Non-adherence to health behavior recommendations
    is twice the rate of medication non-adherence.

34
  • Interventions must be complex with a focus on
    enhancing client convenience, providing
    information, reinforcement and enlisting social
    support.
  • Written materials are less effective than
    telephone, individual, or group formats.
  • Even the most effective interventions have only a
    modest effect.

35
Non adherence
  • inadvertent or intentional
  • Different responses needed
  • Cognitive adaptation training may be useful for
    inadvertent non-adherence
  • This training includes signs, alarms on
    medication containers, single-dose packs,
    notebooks for recording side-effects, etc.
  • CBT can be adapted for intentional non-adherence.

36
Improved Medication Adherence
  • Treatment obviously helps
  • Transportation and medical care available
  • Monotherapy, single dosing, blister paks, depot,
    liquid, sublingual
  • Good physician communication and rapport
  • Serious, painful, acute treatment problem
  • Nice treatment setting
  • Subjective sense of well being
  • Social support
  • Skill training, modeling, memory enhancement,
    motivational interviewing techniques

37
Behavioral Treatment Adherence
  • 40 terminate therapy prematurely.
  • Modal number of sessions is 1.

38
Improved Adherence
  • First impression of therapist is confident and
    competent
  • Belief in therapy and prediction of how many
    appointments are needed
  • Strong therapeutic alliance
  • Education about therapy before beginning
  • Contracting for homework
  • Motivational interviewing techniques

39
The Placebo Effect
  • The placebo effect is improvement in health,
    often
  • measurable and observable, that is not
    attributable
  • to treatment.
  • Placebos have successfully treated
  • depression, pain, asthma, arthritis,
    hypertension,
  • warts, colitis, insomnia, and other conditions.
  • Placebos can also cause negative effects
    including
  • vomiting, dizziness, fatigue, numbness, hives,
  • rashes, tremor, and death (voodoo.)
  • The placebo effect probably accounts for most of
  • the benefit due to acupuncture, aromatherapy,
  • homeopathy, and most other alternative
    treatments.
  • and 33 of the response to antidepressants.

40
Placebos in Psychiatric Disorders
  • Panic disorder is highly responsive to placebos
    -
  • 50 improvement in symptoms.
  • PTSD, GAD placebo improvement is 30-40.
  • 73 of improvement with antidepressants is
    placebo.
  • OCD and psychosis do not show much placebo
    response.
  • The overwhelming majority of studies that
    compared CBT to pill placebo show no difference.

41
The Placebo Effect
  • Conditions which cause significant psychological
  • distress are most likely to respond to placebo.
  • Possible mechanisms
  • Psychological theory our beliefs effect our
    biochemistry and behavior, supported by fMRI
    studies
  • Nature taking its course we often get better
    if we do nothing at all
  • Process of treatment administering the placebo,
    touching, caring, attention, communication -may
    cause a response

42
PositiveElements of the Treatment Situation
  • Recognized healer
  • Healing symbols
  • Evaluation
  • Healing rituals
  • Diagnosis
  • Prognosis
  • Plausible treatment

43
Using the placebo effect
  • Convey honest, appropriate, positive
    expectations
  • Find out what your patients believe about their
    illness
  • Suggest placebo type treatments (a lot of people
    get better drinking this tea, following this
    diet, etc)

44
Using the Placebo Effect
  • Inspire confidence
  • Look professional
  • Display symbols of healing
  • Make notes
  • Take time, ask questions
  • Provide a diagnosis
  • Perform simple diagnostic tests
  • Enhance response to treatment
  • Elicit patients beliefs and select consistent
    treatment
  • Offer optimistic prognosis
  • Use a prescription pad

45
Best messages to improve adherence
  • Take pills daily
  • The antidepressant may not work right away
  • Continue taking it even if you feel better
  • Dont stop without talking to your doctor
  • Feel free to call

46
AD/HD Primary v. Secondary
  • Much of information on response to medication
    based on plain AD/HD
  • Long term outcome worrisome
  • Co-morbid conditions increase with age including
    LD, CD
  • Short term response to stimulant medication high
  • Many children have AD/HD as a result of another
    condition ESPECIALLY young children
  • Anxiety, Specific Learning disability, Mood
    disorders, Poor environmental conditions in home

47
Stimulants
  • More information available than for other
    medication types
  • Several long term studies
  • Affects primarily both dopamine and
    norepinephrine neuro-transmitter systems
  • Various preparations available

48
Stimulant Drugs to Treat ADHD
  • The side effects are the same among the
    medications
  • decreased appetite, initial sleep difficulty,
    headaches, tics, and irritability.
  • Growth suppression, if at all, appears dose
    related, and childrens height and weight should
    be monitored.
  • There is no evidence of tolerance or later
    substance abuse.
  • Sudden cardiac death has been a concern with
    stimulants

49
Drugs to Treat ADHD
  • Attention deficit hyperactivity disorder is the
    most common psychiatric disorder in childhood.
  • Stimulant medication has become the mainstay
    treatment, methylphenidates being first choice.
  • All of these medications seem to be equally
    effective with about a 70 response rate.
  • Some children do not respond to medication and do
    not experience total remission of symptoms.

50
Stimulants
  • Dexmethylphenidate
  • Short acting
  • Focalin
  • Long acting
  • Focalin XR
  • Methylphenidate
  • Short acting
  • Ritalin, Methylin
  • Intermediate
  • Metadate ER,
  • Ritalin SR, Methylin ER
  • Extended release
  • Concerta,
  • Daytranatransdermal patch,
  • MetadateCD,
  • Ritalin LA
  • Dextroamphetamine
  • Short acting
  • Dexedrine, Dextrostat
  • Intermediate
  • Dexedrine CR (spansules)
  • Amphetamine Mixed Salt
  • Intermediate
  • Adderall
  • Long acting
  • Adderall XR

51
Non stimulant medications
  • Atomoxetine (Strattera)
  • Affects noradrenergic transport and has similar
    improvement to the stimulants.
  • Adverse effects include decreased appetite, GI
    problems, dizziness, and sedation. The most
    serious is the potential for severe liver injury
    and the possibility of suicidal thinking.
  • Tenex/Clonidine
  • Beta blocker (antihypertensive)
  • Used for aggressive kids

52
Side effects
  • Methylphenidate, dexedrine
  • Appetite and weight
  • Height
  • Insomnia
  • Cognitive blunting
  • Atomoxetine
  • Nausea
  • Sedation
  • Tenex
  • Sedation

53
Antidepressants?
  • Wrong name for category
  • Often used for anxiety
  • Also used in AD/HD
  • Rarely used alone

54
Choosing an Antidepressant
  • Previous Response/Tolerability
  • Family History
  • Comorbid Psychiatric Symptoms
  • Comorbid Psychiatric Diagnoses
  • Comorbid Medical Diagnoses
  • Concurrent treatments

55
Antidepressant Adherence
  • 10 never fill prescription, 16 stop first
    week,
  • 41 in 2 weeks, 68 by 1 month
  • Risks of non-adherence
  • Side effects
  • Cost
  • Improvement
  • Lack of education about illness and treatment
  • Delayed onset of benefit
  • Fear of dependence
  • Stigma

56
Treating Depression
  • Clients seen weekly for six weeks show more
  • improvement than those seen less often.
  • Clients are more likely to tolerate side effects
    if
  • they know they are going to see the doctor in a
  • few days.
  • Using scales to assess outcome improves care,
  • client satisfaction, and overall treatment
    outcome.

57
Antidepressants and Suicide
  • On October 15, 2004, the FDA issued its
  • strongest possible warning (black box) for
  • all antidepressants stating that these
  • medications may increase the risk of
  • suicidal thinking and behavior in children
  • and adolescents with major depressive or
  • other psychiatric disorders.

58
Archives of General Psychiatry(March 2006)
  • All PC studies submitted to FDA (4,582
  • patients, 24 trials)
  • 16 studies looked at MDD, 8 at anxiety
  • disorders
  • 4 trials had no events in drug or placebo
  • group

59
  • Results
  • No completed suicides
  • The overall relative risk was 1.95
  • Risk was lower in the MDD group (1.66)
  • Risk varied greatly among different trials
  • Annualized rate of suicide attempts from data
  • General population0.6
  • Adult antidepressant trials2.6
  • Child/adolescent trials3.9

60
Hypotheses
  • Subjects are recruited early in the illness when
    suicide risk is high
  • Adverse selection of treatment resistant
    subjects into the trial
  • Intense monitoring for events
  • Delay of antidepressant effects
  • Antidepressants do not reduce short-term suicide
    risk
  • Antidepressant induction of mixed or psychotic
    states
  • Rate inflation due to identifying suicidal
    events in brief time samples early in acute
    illness

61
Antidepressants and Suicide
  • We are left with a great deal of uncertainty
    regarding
  • the use of antidepressants, especially in young
    people
  • under 18. There seems to be evidence that
    suicidal
  • ideation may emerge during early treatment with
  • antidepressants. There is no evidence that this
  • increases the risk of completed suicide. (No
    suicides in
  • 4,000 children in any of these studies.)
    Completed
  • suicides have also fallen during the last ten
    years, a
  • time of increased usage of antidepressants in
    this age
  • group.
  • The best approach is to monitor everyone
  • who is started on an antidepressant closely
  • for the appearance of suicidal ideation,
  • agitation, and irritability, especially during
  • the initial months of therapy, and be sure
  • that the risk is discussed during the
  • informed consent process.

62
Classifications of Antidepressants
  • Tricyclic antidepressants (TCAs)
  • Monoamine Oxidase Inhibitors (MAOI)
  • Strong serotonin reuptake Inhibitors (SSRIs)
  • Serotonin and Norepinephrine Reuptake Inhibitors
    (SNRIs)

63
TCA
  • Introduced for depression in 1950s
  • Hundreds of studies demonstrating efficacy in
    adult depression studies
  • Introduced in children in 1960s as alternative to
    stimulants
  • Concern of reports of sudden deaths has limited
    use

64
TCA
  • Imipramine, desipramine, amitryltiline
  • Uses
  • Depression
  • AD/HD
  • Enuresis
  • OCD
  • Effective EXCEPT for depression in children in
    studies

65
TCA
  • Sudden death and cardiac effects
  • Related to prolonged conduction
  • First reported in 1990
  • All cases associated with desipramine

66
Tricyclic Antidepressants
  • amitriptyline(Elavil)
  • amoxapine(Asendin)
  • clomipramine(Anafranil)
  • desipramine(Norpramin)
  • doxepin(Adapin, Sinequan)
  • imipramine(Tofranil)
  • maprotiline(Ludiomil)
  • nortriptyline(Pamelor)
  • protriptyline-(Vivactil)
  • trimipramine-(Surmontil)

67
Tricyclic Antidepressants
  • Advantages
  • Inexpensive
  • Sedating
  • Provides weight gain and pain relief in
    medically ill, useful in Parkinsons, treatment
    resistance
  • Clomipramine works in OCD.
  • Disadvantages
  • Fatal in overdose
  • Anticholinergic side effects, orthostatic
    hypotension
  • Cardiac effects
  • Hard to dose
  • No antidepressant efficacy in children and
    adolescence

68
MAO Inhibitors
  • React with other medications
  • FDA endorsed for depression in ages gt16

69
Monoamine Oxidase Inhibitors
  • isocarboxazid(Marplan)
  • phenelzine (Nardil)
  • tranylcypromine(Parnate)
  • transdermalselegiline(EmSam)
  • Advantages
  • May help in atypical depression
  • Disadvantages
  • Requires special diet
  • Cause dizziness
  • Fatal with other drugs and in overdose

70
SSRIs
  • Fluvoxetine (Prozac)
  • Fluvoxamine (Luvox)
  • Sertraline (Zoloft)
  • Citalopram (Celexa)
  • Escitalopram (Lexapro)
  • Paroxetine (Paxil)

71
SSRIs
  • Seven different families of re-uptake
    inhibitionall a little different
  • Also are 5HT receptor agonists included in
    category
  • Nefazodone (Serzone)
  • Mirtazapine (Remeron)

72
SSRIs
  • Side effects
  • CNS headache, insomnia, anxiety, tremor
  • GI nausea, constipation, anorexia, dyspepsia,
    weight gain
  • Sexual dysfunction decreased libido, impotence
  • Pediatric specific Aggressiveness, epistaxis,
    sinusitis, urinary incontinence, hyperkinesia

73
SSRIs
  • Serotonin syndrome
  • Fever, confusion, muscle rigidity, diaphoresis,
    agitation, hyper-reflexia, caridac, renal and
    liver problems
  • Discontinuation syndrome
  • Flu-like symptoms

74
Stopping the Medication
  • All antidepressants, particularly SSRIs can
    cause a withdrawal syndrome. The reactions may be
    more common and severe with short-acting drugs
    like paroxetine and venlafaxine.
  • Common symptoms (usually resolve in 2-3 weeks)
  • Neurosensory(vertigo, parathesia, shock-like,
    myalgia)
  • Neuromotor(tremor, myoclonus, ataxia, visual,
    piloerection)
  • Gastrointestinal (nausea, vomiting, diarrhea)
  • Psychiatric (anxiety, depression, suicidality,
    irritabililty)

75
SSRIs
  • Adverse effect suicides and suicide ideation
  • NO suicide in pediatric trials
  • Increased risk for all patients with major
    depressive disorder
  • Current concerns over Paxil and Prozac with major
    depressive disorder patients

76
SSRI differences
  • Paroxetine higher somnolence (23) higher
    constipation (13), and slightly lower diarrhea
    (11) rate. Inhibits CYP-450 2D6
  • Paroxetine is only SSRI with significant
    anticholinergic effects.

77
SSRI differences
  • Fluoxetine higher agitation and lower somnolence
    rate, longer half life. Inhibits CYP-450 2D6
  • Fluvoxamine has higher rate for nausea (40) and
    insomnia (21). Inhibits CYP-450 1 A2

78
SSRI differences
  • Sertraline Generally low in side effects, weaker
    inhibitor of 2 D6 enzyme system, maximum
    absorption requires full stomach.

79
Preexisting Conditions
  • Obsessive-compulsive disorder SSRI,
    clomipramine, SNRI usually first choice.
  • Panic disorder avoid trazodone and bupropion
    because they are relatively ineffective for
    panic.
  • Bipolar disorder avoid TCAs

80
Comorbid Conditions-ADs are used for
  • Agoraphobia
  • Borderline personality disorder
  • Depression (unipolar / bipolar)
  • Dysthymic disorder
  • Generalized Anxiety Disorder (GAD)
  • Hypochondriasis

81
Comorbid Conditions-ADs are used for
  • Obsessive-Compulsive Disorder
  • Panic Disorder
  • Premenstrual Syndrome (PMS)
  • Post-Traumatic Stress Disorder (PTSD)
  • Schizoaffective disorder
  • Social Phobia

82
Side Effects
  • General side effects may abate after a few
    weeks of Tx
  • For sustained SEs, the pt will not necessarily
    experience the same SEs if switched to another
    drug within the same class.
  • Beware of drug interactions

83
The SNRIs
  • Venlafaxine (Effexor)
  • Duloxetine (Cymbalta)

84
Venlafaxine
  • Potent reuptake inhibitor of 5-HT, with less
    potent effect on NE and dopamine. 30 fold higher
    affinity for 5-HT transporters than NE
    transporters. In healthy humans, whereas 75 mg/d
    was sufficient to block platelet 5-HT uptake,
    only at 375 mg/d was NE function affected.
  • May Increase diastolic blood pressure

Effexor XR. Prescribing Information. PDR 2006,
Thompson Eds, 2006 Wellington et al. CNS Drugs
2001 15643-69
85
Bupropion
  • Does not increase serotonin
  • Approved also for quitting smoking
  • Very low sexual side effects
  • May have therapeutic window
  • Caution in patients with seizure risk

Wellbutrin XL Prescribing Information. PDR 2006,
Thompson Eds, 2006 Stahl. Essential
Psychopharmacology. Cambridge University Press,
2005 Masand et al. Ann Clin Psych 2002 14175-182
86
Mirtazapine
  • Acts as a central antagonist at presynaptic
    alpha-2 receptors, thought to result in an
    increase in central noradrenergic and
    serotonergic activity
  • Potent antagonist of 5-HT2 and 5-HT3 receptors
  • Potent antagonist of H1 receptors, accounting for
    sedative effects
  • Moderate antagonist of peripheral alpha-1
    receptors and muscarinic receptors, accounting
    for occasional orthostatic hypotension and
    anticholinergic effects, respectively.

87
Mood Stabilizers
  • Controversy more over what is childhood Bipolar
    Affective Disorder
  • What constitutes Bipolar in prepubertal children?
  • Irritibility
  • Few periods of normal functioning
  • Different at different times of day
  • Often overlaps with children already diagnosed as
    AD/HD

88
Mood Stabilizers
  • Lithium
  • Antiepileptics
  • Tegretol
  • Depakote
  • Possibly
  • Klonopin
  • Trileptil
  • Lamictal
  • Antipsychotics, esp. atypicals

89
Mood Stabilizers
  • Lithium
  • Divalproex
  • Carbamazepine
  • Lamotrigine
  • Lithium daily dose (mg) 100.5 752.7 x
    expected lithium concentration -3.6 x age (years)
    7.2 x weight - 13.7 x BUN (Terao, 1999)

90
Antipsychotics
  • Indications
  • Typical (Classic) antipsychotics
  • Haloperidol
  • Chlorpromazine
  • Perphenazine
  • Other

91
Second Generation Antipsychotics
  • All of these medications work on dopamine
  • receptors, like the typical antipsychotics,
  • but they are more selective at certain sites,
  • and also effect serotonin receptors.
  • Because of this, their effects -both positive and
  • negative -are quite different. They are also very
    different from each other
  • Another ongoing area of interest is whether or
    not
  • SGAs are also mood stabilizers. They probably
  • are, but it is not clear how they are distinct
    from
  • each other, or what advantages they have over
  • lithium and the anticonvulsants.

92
Newer (Atypical) Antipsychotics
  • Lower side effects
  • Lower risk of TD
  • Lower EPS
  • Better in negative symptoms (deficits in
    emotional responsiveness, flattening of affect,
    poverty of speech, lack of volition and drive,
    loss of feeling, social withdrawal and decreased
    spontaneous movement)
  • Lower cognitive impairment
  • Mood stabilizing properties

93
Atypical antipsychotics
  • Clozapine (Clozaril)
  • Risperidone (Risperdal)
  • Olanzapine (Zyprexa)
  • Quetiapine (Seroquel)
  • Zisprasidone (Geodone)
  • Aripiprazole (Abilify)

94
Side Effects
  • PROLACTIN
  • Increased with all antipsychotics except
    clozapine, ziprasidone, aripiprazole and maybe
    quetiapine.
  • SSRIs, particularly paroxetine, may increase
    prolactin and exacerbate neuroleptic-induced
    prolactinemia.

Metabolic Risks
  • Increased with all atypical antipsychotics but
    Aripiprazole and Ziprasidone have a lower risk

Agranulocytosis
  • Clozapine. Common presentation Acute sore throat,
    high fever, mouth sores and ulcers.

TD - EPS
  • More common for classic/typical Neuroleptics

95
Chronic Side Effects
  • Weight gain/Metabolic Syndrome
  • Certain SGAs increase the risk for metabolic
    syndrome
  • -increased weight, high blood pressure, diabetes,
  • increased serum cholesterol and triglycerides
  • Clients need to be monitored for these findings
  • because of the risk of cardiovascular
    complications.
  • The medications most likely to increase weight
    are
  • clozapine, olanzapine, divalproex, and lithium

96
Antianxiety
  • Benzodiazepines
  • Buspirone
  • SSRIs
  • Antihistamine

97
Benzodiazepines for Anxiety
  • Advantages
  • Well-tolerated
  • Quick onset
  • Effective
  • Safe in overdose
  • Low Cost
  • Disadvantages
  • Withdrawal reactions
  • Sedation
  • Risk of abuse
  • Poor antidepressant effect

98
SSRIs for Anxiety
  • Advantages
  • Effective
  • Safe
  • No risk of abuse
  • Effective on depression
  • Disadvantages
  • Possible increase in anxiety during initial
    period of use
  • Sexual side-effects

99
Dementia Medications
  • Donepezil (Aricept)
  • Rivastigmine (Exelon)
  • Galantamine (Reminyl)

100
Anticholinergics
  • Benztropine (Cogentin)
  • Diphenhydramine (Benadryl)

Used for EPS and acute dystonia
101
Substance Abuse Meds
  • Disulfiram (Antabuse)
  • Aldehyde dehydrogenase inhibitor
  • When ETOH consumed, results in flushing, anxiety,
    nausea, sweating, dyspnea, tremor, confusion,
    headache, nausea/vomiting
  • Naltrexone (ReVia)
  • Opioid receptor antagonist
  • Decreases craving for ETOH

102
Latest information on Web
  • www.nimh.nih.gov
  • Patient/provider handouts
  • www.aacap.org
  • Facts for families
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