Treatment of Psychotic Disorders

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Treatment of Psychotic Disorders

• With a focus on Bipolar Disorder

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Outline

• History of Bipolar Disorder
• Symptoms of Bipolar Disorder
• Diagnosis of Bipolar Disorder
• Treatment of Bipolar Disorder
• Future of Bipolar Disorder

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History of Bipolar Disorder

• The earliest written descriptions of a
  relationship between mania and melancholia are
  attributed to Aretaeus of Cappadocia. Aretaeus
  was an eclectic medical philosopher who lived in
  Alexandria somewhere between 30 and 150 AD.
  Aretaeus is recognized as having authored most of
  the surviving texts referring to a unified
  concept of manic-depressive illness, viewing both
  melancholia and mania as having a common origin
  in black bile.
• Emil Kraepelin (1856-1926), a German psychiatrist
  categorized and studied the natural course of
  untreated bipolar patients long before mood
  stabilizers were discovered. Describing these
  patients in 1902, he coined the term manic
  depressive psychosis. He noted in his patient
  observations that intervals of acute illness,
  manic or depressive, were generally punctuated by
  relatively symptom-free intervals in which the
  patient that was able to function normally.

• In 1949, John Cade discovered that lithium
  carbonate could be used as a successful treatment
  of manic depressive psychosis
• In the 1950s, U.S. hospitals began experimenting
  with lithium on their patients.
• By the mid-1960s, reports started appearing in
  the medical literature regarding lithium's
  effectiveness.
• The U.S. Food and Drug Administration did not
  approve of lithium's use until 1970.

Emil Kraepelin (1856-1926)
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Symptoms of Bipolar Disorder

• Mania -
• Feeling very high on life
• Talking rapidly
• Feeling grandiose
• Racing thoughts and speech
• Erratic and impulsive actions
• Delusions and hallucinations (severe)
• Hypomania -
• Like but less severe that mania
• Euphoric, energetic and productive
• No hallucinations or delusions
• Characterized by an unusually good mood
• Depression -
• Feeling hopeless, sad or empty
• Fatigue, energy and concentration loss
• Thoughts of death or suicide

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Diagnosis Bipolar Disorder

• What is it?
• Not a single disorder but one of Mania and
  Depression
• Usually involves Rapid Cycling
• Subdivided
• Bipolar I - one or more manic or mixed episodes
  with or without depressive episode
• Bipolar II - one or more Major Depressive
  Episodes along with at least one Hypomanic
  episode
• Cyclothymia - one or more Hypomanic episodes and
  Dysthymic (chronic depression) episodes

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Brain scans indicating the differences in brain
activity when a patient is switching between a
depressive episode and hypomanic episode
Brain scans showing the increased amount of brain
matter with the use of lithium utilizing the
growth promoter called brain-derived neurotrophic
factor
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Treatments

• Medications
• Mood stabilizers - Lithium (Lithobid, Lithane,
  Eskalith, ect.)
• Anticonvulsants - Depakote, Tegretol
• Bipolar Depression - Lamotrigine
• Antipsychotic - Seroquel, Zyprexa, Risperdal,
  ect.
• Antidepressants are questionable due to the fact
  that some believe that it induces a manic episode
  especially if there is no mood stabilizers used.
• Hospitalization
• May occur, especially with manic episodes. This
  can be voluntary or involuntary.
• Long-term inpatient stays are now less common due
  to deinstitutionalization, although can still
  occur.
• Following a hospital admission, support services
  available can include drop-in centers, visits
  from members of a community mental health team or
  Assertive Community Treatment team, supported
  employment and patient-led support groups.

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Mood Stabilizer - Lithium

• Recent research suggests three different
  mechanisms which may act together to deliver the
  mood-stabilizing effect of this ion.
• The excitatory neurotransmitter glutamate is the
  key factor in understanding how lithium works.
• Other mood stabilizers such as valproate and
  lamotrigine exert influence over glutamate,
  suggesting a possible biological explanation for
  mania.
• The other mechanisms by which lithium might help
  to regulate mood include the alteration of gene
  expression and the non-competitive inhibition of
  an enzyme called inositol monophosphatase.

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Mood Stabilizer - Lithium

• Absorption
• Readily absorbed from the GI tract. Absorption is
  not significantly impaired by food. T max is 0.5
  to 3 h. Therapeutic serum level is 0.4 to 1
  mEq/L. Steady state is reached in 5 to 7 days
• Distribution
• Distribution space of lithium approximates that
  of total body water. Not protein bound.
  Distribution across the blood-brain barrier is
  slow however, the CSF lithium level is about 40
  of the plasma concentration
• Elimination
• About 95 eliminated by the kidney primarily
  excreted in the urine. Renal excretion is
  proportional to its plasma concentration. The
  half-life is about 24hrs.

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Eskalith

• Preclinical studies have shown that lithium
  alters sodium transport in nerve and muscle cells
  and effects a shift toward intraneuronal
  metabolism of catecholamines, but the specific
  biochemical mechanism of lithium action in mania
  is unknown.
• Indicated in the treatment of manic episodes of
  manic-depressive illness. Maintenance therapy
  prevents or diminishes the intensity of
  subsequent episodes in those Bipolar patients
  with a history of mania.
• Fine hand tremor, polyuria, and mild thirst may
  occur during initial therapy for the acute manic
  phase, and may persist throughout treatment.
• Transient and mild nausea and general discomfort
  may also appear during the first few days of
  lithium administration.These side effects usually
  subside with continued treatment or a temporary
  reduction or cessation of dosage.
• If persistent, cessation of lithium therapy may
  be required.
• Diarrhea, vomiting, drowsiness, muscular
  weakness, and lack of coordination may be early
  signs of lithium intoxication, and can occur at
  lithium levels below 2.0 mEq/L
• Because lithium theraputic levels are so close to
  the toxic levels lithium concentration levels
  must be monitored constantly and before treatment
  is given

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Depakote

• Dissociates to the valproate ion in the
  gastrointestinal tract. The mechanisms by which
  valproate exerts its therapeutic effects have not
  been established. It has been suggested that its
  activity in epilepsy is related to increased
  brain concentrations of gamma-aminobutyric acid
  (GABA).
• Depakote ER (divalproex sodium extended-release)
  is indicated for the treatment of acute manic or
  mixed episodes associated with bipolar disorder,
  with or without psychotic features
• Side Effects
• Fever, sore throat, body aches, diarrhea,
  tremors, ect.

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Lamotrigine

• Lamotrigine tablets are indicated for the
  maintenance treatment of Bipolar I Disorder to
  delay the time to occurrence of mood episodes
  (depression, mania, hypomania, mixed episodes) in
  patients treated for acute mood episodes with
  standard therapy.
• If used in conjunction with valproate (Depakote)
  the dosing should be cut in half due to the
  absorption rate in its presence.
• Side effects
• Dizziness, headache, blurred or double vision,
  nausea, vomiting, rash, ect.

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Seroquel

• Used in the treatment of both depressive episodes
  and acute manic episodes associated with Bipolar
  I disorder
• It has been proposed that the efficacy of
  Seroquel in its mood stabilizing properties in
  bipolar depression and mania are mediated through
  a combination of dopamine type 2 (D2) and
  serotonin type 2 (5HT2) antagonism.
• Antagonism at receptors other than dopamine and
  5HT2 with similar receptor affinities may explain
  some of the other effects of Seroquel.

• Tardive Dyskinesia - A syndrome of potentially
  irreversible, involuntary, dyskinetic movements
  may develop in patients treated with
  antipsychotic drugs.
• Chronic antipsychotic treatment should generally
  be reserved for patients who appear to suffer
  from a chronic illness that (1) is known to
  respond to antipsychotic drugs, and (2) for whom
  alternative, equally effective drugs have no
  effect

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Problems with Bipolar Disorder

• Many things are unknown about Bipolar Disorder
  including
• Mechanisms
• Causes
• Exact Treatments
• Prevention

• Not only are these things not known about the
  disorder but the implications of the drugs on the
  body are not completely known either.
• The complete mapping of the human genome will
  help with these issues and the research being
  done on neurotransmitters will also help.

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Future of Disorder

• It has been discovered that lithium protects
  neurons by increasing the levels of a
  neuroprotective protein called Bcl-2.
• Lithium has been found to help stimulate the
  production of new neurons (neurogenesis) in the
  hippocampus part of the limbic system that
  control emotions and behavior.
• A major breakthrough came in 2000, with the
  demonstration that lithium increases the amount
  of gray matter in the human brain, probably by
  stimulating the production of a growth promoter
  called brain-derived neurotrophic factor
• When the researchers compared the brains of
  bipolar patients on lithium with those of people
  without the disorder and those of bipolar
  patients not on lithium, they found that the
  volume of gray matter in the brains of those on
  lithium was as much as 15 percent higher in the
  cingulate and paralimbic regions of the brain,
  that are critical for attention, motivation and
  emotional control.

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Works Cited

• www.drugs.com
• www.wikipedia.org
• www.wrongdiagnosis.com
• www.helpguide.org
• http//richardgpettymd.blogs.com/my_weblog/neuroto
  xicity