Treatment of Psychotic Disorders

With a focus on Bipolar Disorder

Outline

• History of Bipolar Disorder

• Symptoms of Bipolar Disorder

• Diagnosis of Bipolar Disorder

• Treatment of Bipolar Disorder

• Future of Bipolar Disorder

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)

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

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

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

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.

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.

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.

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

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.

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.

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

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.

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.

Works Cited

• www.drugs.com• www.wikipedia.org• www.wrongdiagnosis.com• www.helpguide.org• http://richardgpettymd.blogs.com/my_weblog/neurotoxicity