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    Depression: Types Symptoms Diagnosis Causes Treatment

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    Thea Mallari
    This document discusses depression, including its types, symptoms, diagnosis, causes, and treatment. It describes major depression, chronic depression, atypical depression, bipolar disorder, and seasonal affective disorder. Common symptoms include persistent sadness, loss of pleasure, feelings of guilt, changes in appetite or sleep, and thoughts of death. Diagnosis involves patient history, physical exams, and using criteria from the DSM-IV. Causes may include genetics, death, abuse, and certain medications. Treatment involves psychotherapy, electroconvulsive therapy, medications like SSRIs and SNRIs, and natural alternatives.

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    Depression: Types Symptoms Diagnosis Causes Treatment

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    Thea Mallari
    79 views32 pages
    This document discusses depression, including its types, symptoms, diagnosis, causes, and treatment. It describes major depression, chronic depression, atypical depression, bipolar disorder, and seasonal affective disorder. Common symptoms include persistent sadness, loss of pleasure, feelings of guilt, changes in appetite or sleep, and thoughts of death. Diagnosis involves patient history, physical exams, and using criteria from the DSM-IV. Causes may include genetics, death, abuse, and certain medications. Treatment involves psychotherapy, electroconvulsive therapy, medications like SSRIs and SNRIs, and natural alternatives.

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    This document discusses depression, including its types, symptoms, diagnosis, causes, and treatment. It describes major depression, chronic depression, atypical depression, bipolar disorder, and seasonal affective disorder. Common symptoms include persistent sadness, loss of pleasure, feelings of guilt, changes in appetite or sleep, and thoughts of death. Diagnosis involves patient history, physical exams, and using criteria from the DSM-IV. Causes may include genetics, death, abuse, and certain medications. Treatment involves psychotherapy, electroconvulsive therapy, medications like SSRIs and SNRIs, and natural alternatives.

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    © All Rights Reserved
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    Download as pdf or txt
    79 views32 pages

    Depression: Types Symptoms Diagnosis Causes Treatment

    Uploaded by

    Thea Mallari
    This document discusses depression, including its types, symptoms, diagnosis, causes, and treatment. It describes major depression, chronic depression, atypical depression, bipolar disorder, and seasonal affective disorder. Common symptoms include persistent sadness, loss of pleasure, feelings of guilt, changes in appetite or sleep, and thoughts of death. Diagnosis involves patient history, physical exams, and using criteria from the DSM-IV. Causes may include genetics, death, abuse, and certain medications. Treatment involves psychotherapy, electroconvulsive therapy, medications like SSRIs and SNRIs, and natural alternatives.

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    © All Rights Reserved
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    of 32

    DEPRESSION

    Types
    Symptoms

    Diagnosis

    Causes

    Treatment
    TYPES OF DEPRESSION
    Major depression
    Chronic depression (Dysthymia)

    Atypical depression

    Bipolar disorder/Manic depression

    Seasonal depression (SAD)


    SYMPTOMS
    persistently sad, anxious, or empty moods
    loss of pleasure in usual activities (anhedonia)
    feelings of helplessness, guilt, or worthlessness
    crying, hopelessness, or persistent pessimism
    fatigue or decreased energy
    loss of memory, concentration, or decision-making capability
    restlessness, irritability
    sleep disturbances
    change in appetite or weight
    physical symptoms that defy diagnosis and do not respond to
    treatment (especially pain and gastrointestinal complaints)
    thoughts of suicide or death, or suicide attempts
    poor self-image or self-esteem (as illustrated, for example, by
    verbal self-reproach)
    DIAGNOSIS
    Extensive patient and family history
    Blood test for hypothyroidism

    Current medication

    DSM-IV
    One of the first two symptoms
    Five other symptoms
    CAUSES OF DEPRESSION
    Genetics
    Death/Abuse

    Medications
    TREATMENT FOR DEPRESSION
    Psychotherapy
    Electroconvulsive therapy

    Natural alternatives

    Medication
    SSRIs
    MAOIs

    TCAs

    SNRIs

    NDRIs

    TeCAs
    NEUROTRANSMITTERS AND THE
    CATECHOLAMINE HYPOTHESIS
    Neurotransmitters pass along signal
    Smaller amount of neurotransmitters causes
    depression
    MONOAMINE OXIDASE (MAO) AND
    DEPRESSION
    MAO catalyze deamination of intracellular
    monoamines
    MAO-A oxidizes epinephrine, norepinephrine,
    serotonin
    MAO-B oxidizes phenylethylamine
    Both oxidize dopamine nonpreferentially

    MAO transporters reuptake extracellular


    monoamine
    MONOAMINE OXIDASE INHIBITORS
    (MAOIS)
    History
    Isoniazid
    Iproniazid

    Current Drugs
    Mechanism of Action

    Side Effects Isoniazid

    Iproniazid
    MAOIS ON THE MARKET
    MAO Inhibitors (nonselective)
    Phenelzine (Nardil)
    Tranylcypromine (Parnate)
    Isocarboxazid (Marplan)

    MAO-B Inhibitors (selective for MAO-B)


    Selegiline (Emsam)
    MAOIS MECHANISM OF ACTION
    MAO contains a
    cysteinyl-linked
    flavin
    MAOIs covalently
    bind to N-5 of the
    flavin residue of
    the enzyme
    MAOIS SIDE EFFECTS
    Drowsiness/Fatigue Muscle twitching
    Constipation Weight gain

    Nausea Blurred vision

    Diarrhea Headache

    Dizziness Increased appetite

    Low blood pressure Restlessness

    Lightheadedness, Shakiness

    Decreased urine output Weakness

    Decreased sexual Increased sweating


    function
    Sleep disturbances
    MAOIS SIDE EFFECTS
    Side effects have put MAOIs in the second or
    third line of defense despite superior efficacy
    MAO-A inhibitors interfere with breakdown of
    tyramine
    High tyramine levels cause hypertensive crisis (the
    cheese effect)
    Can be controlled with restricted diet

    MAOIs interact with certain drugs


    Serotonin syndrome (muscle rigidity, fever, seizures)
    Pain medications and SSRIs must be avoided
    THE RECEPTOR SENSITIVITY
    HYPOTHESIS
    Supersensitivity and up-regulation of post-
    synaptic receptors leads to depression
    Suicidal and depressed patients have increased
    5HT-2 receptors
    TRICYCLIC ANTIDEPRESSANTS
    (TCAS)
    History
    Imipramine
    Current Drugs
    Mechanism of Action

    Side Effects

    Imipramine
    TCAS ON THE MARKET
    Amitriptyline
    Desipramine (Norpramin)

    Doxepin (Sinequan)

    Imipramine (Tofranil, Tofranil-PM)

    Nortriptyline (Pamelor)

    Protriptyline (Vivactil)

    Trimipramine (Surmontil)
    TCAS MECHANISM OF ACTION
    TCAs inhibit serotonin,
    norepinephrine, and dopamine
    transporters, slowing reuptake
    TCAs also allow for the
    downregulation of post-
    synaptic receptors
    All TCAs and SSRIs contain
    an essential amino group that
    appears to interact with Asp-
    98 in hSERT
    TCAS SIDE EFFECTS
    Muscarinic M1 receptor antagonism - anticholinergic
    effects including dry mouth, blurred vision,
    constipation, urinary retention and impotence
    Histamine H1 receptor antagonism - sedation and
    weight gain
    Adrenergic receptor antagonism - postural
    hypotension
    Direct membrane effects - reduced seizure threshold,
    arrhythmia
    Serotonin 5-HT2 receptor antagonism - weight gain
    (and reduced anxiety)
    TCAS SIDE EFFECTS
    Nonselectivity results in
    greater side effects
    TCAs can also lead to
    cardiotoxicity
    Increased LDH leakage
    Slow cardiac conduction

    High potency can lead to


    mania
    Contraindicated with
    persons with bipolar
    disorder or manic depression
    TETRACYCLIC ANTIDEPRESSANTS
    (TECAS)
    Current Drugs
    Mirtazapine (Remeron)
    Mechanism of Action
    Same as TCAs
    Side Effects
    SELECTIVE SEROTONIN REUPTAKE
    INHIBITORS
    Most commonly prescribed class
    Current drugs

    Mechanism of action

    Side effects

    Serotonin
    SSRIS ON THE MARKET
    citalopram (Celexa)
    dapoxetine (Priligy)

    escitalopram (Lexapro)

    fluoxetine (Prozac)

    fluvoxamine (Luvox) Fluoxetine 1:1

    paroxetine (Paxil)

    sertraline (Zoloft)

    zimelidine (Zelmid) (discontinued)

    indalpine (Upstene) (discontinued)

    Sertraline
    SSRIS MECHANISM OF ACTION
    Exact mechanism remains uncertain
    Ser-438 residue in the human serotonin
    transporter (hSERT) appears to be a determining
    factor in SSRI potency
    Antidepressants interact directly with hSERT

    http://www.mayoclinic.com/health/antidepressant
    s/MM00660
    SSRIS SIDE EFFECTS
    Anhedonia Fatigue
    Apathy Changes in sexual

    Nausea/vomiting behavior
    Drowsiness or Suicidal thoughts

    somnolence
    Headache

    Bruxism (involuntarily
    grinding of the teeth)
    Extremely vivid and
    strange dreams
    Dizziness
    SSRIS SIDE EFFECTS
    Many disappear within 4 weeks (adaption phase)
    Side effects more manageable compared to
    MAOIs and TCAs
    Sexual side effects are common

    SSRI cessation syndrome


    Brain zaps
    Sexual dysfunction
    SEROTONIN-NOREPINEPHRINE
    REUPTAKE INHIBITORS (SNRIS)
    Slightly greater efficacy than SSRIs
    Slightly fewer adverse effects than SSRIs

    Current drugs
    Venlafaxine (Effexor)
    Duloxetine (Cymbalta)

    Mechanism of Action
    Very similar to SSRIs
    Works on both neurotransmitters
    Venlafaxine 1:1
    Side effects Duloxetine
    Similar to SSRIs
    Suicide
    NOREPINEPHRINE-DOPAMINE
    REUPTAKE INHIBITORS (NDRIS)
    Current drugs
    Bupropion (Wellbutrin)
    Mechanims of Action
    Similar to SSRIs and SNRIs
    More potent in inhibiting dopamine
    Also an3-4 nicotinic antagonist
    Bupropion 1:1
    Adverse effects
    Lowers seizure threshold
    Suicide
    Does not cause weight gain or sexual dysfunction
    (even used to treat the two)
    ASSIGNED READING
    An Introduction to Medicinal Chemistry, by
    Graham L. Patrick, Chapter 20, pp. 593-8.
    Kelly, John. Novel therapeutic targets for the
    treatment of depression. Current Medicinal
    Chemistry: Central Nervous System Agents
    (2003), 3(4), 311-322.

    Optional Reading:

    Wong, David T.; Perry, Kenneth W.; Bymaster, Frank P. Case


    History: The Discovery of Fluoxetine Hydrochloride (Prozac).
    Nature Reviews Drug Discovery (2005), 4(9), 764-774.

    Krishnan, K. Ranga. Revisiting monoamine oxidase inhibitors.


    Journal of Clinical Psychiatry (Memphis, TN, United States)
    (2007), 68(Suppl. 8), 35-41.
    HOMEWORK QUESTIONS
    1. Many of the medications to treat depression are thought to involve
    systems utilizing the monoamine neurotransmitters, noradrenaline,
    dopamine, and serotonin (5-HT). Draw the structures of these
    neurotransmitters. Why are they called monoamines? Illustrate their
    structural resemblance to one another.
    2. Monoamine oxidase inhibitors (MAOIs) increase CNS synaptic
    concentrations of these monoamines by inhibiting an enzyme responsible
    for their degradation. Draw the reaction scheme for the biological
    degradation of noradrenaline by monoamine oxidase.
    3. Illustrate how the TCAs and SSRIs might resemble the monoamine
    neurotransmitters, providing one example of each class of antidepressant.
    REFERENCES
    http://ajp.psychiatryonline.org/cgi/reprint/157/11/1901
    http://www.webmd.com/depression/
    http://pn.psychiatryonline.org/content/41/24/21.full
    http://www.mayoclinic.com/health/maois/MH00072
    http://www.springerlink.com/content/b9b8668ff59f89d7/fulltext.pdf
    http://www.emsam.com/pi_emsam.pdf
    http://www.nevdgp.org.au/info/topics/depression_theory.htm
    http://www.uspharmacist.com/content/t/psychotropic_disorders/c/11467/
    http://www.jbc.org/content/284/15/10276.full.pdf+html
    http://www.aafp.org/afp/981200ap/cadieux.html
    http://www.mayoclinic.com/health/antidepressants/MH00071
    http://books.google.com/books?id=R0W1ErpsQpkC&pg=PA565&lpg=PA565&dq=tcas+mechanism+
    of+action&source=bl&ots=oASle2Z-
    pr&sig=36CB_3JY4uD3LIYvqXWmAb3nliY&hl=en&ei=HzfFS9OrB4Tu9gTD6_ixDg&sa=X&oi=boo
    k_result&ct=result&resnum=8&ved=0CCoQ6AEwBw#v=onepage&q=tcas%20mechanism%20of%2
    0action&f=false
    http://www.informaworld.com/smpp/content~content=a916036122&db=all

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