The Drug Revolution for Mental Health

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The Drug Revolution for Mental Health. Medicine for Madness. Demonic Possession. St. Zenobius exorcises devils (seen fleeing from the mouths of the possessed). A hole in the head: Trepannation. Benjamin Rush. (1745-1813) Treated mentally ill at Pennsylvannia hospital Madness as disease
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The Drug Revolution forMental Health Medicine for Madness Demonic Possession
  • St. Zenobius exorcises devils (seen fleeing from the mouths of the possessed)
  • A hole in the head: Trepannation Benjamin Rush
  • (1745-1813)
  • Treated mentally ill at Pennsylvannia hospital
  • Madness as disease
  • Used talk therapy
  • Humane treatment
  • Holistic approach
  • Phillipe Pinel
  • (1745-1826)
  • “Treatise on Insanity” 1791
  • Removed chains from mental ill patients at Paris asylum (1792)
  • Pinel freeing patients Dorothea Lynde Dix
  • (1802-1887)
  • Found mentally ill housed in jails (MA)
  • Helped found hospitals in 15 states & Canada
  • Humane care
  • Supervised nursing corp: US Civil War
  • Early Treatment
  • The spinning chair
  • One of Rush’s invention
  • Treatments not very effective
  • Early 20th century treatments
  • Insulin coma
  • Lobotomy
  • First generation “shock” treatment
  • Restraints
  • Restrictions
  • Warehousing
  • State hospitals growing every year
  • Deinstitutionalization KW 6-9 Mental health movement
  • Move patients to less restrictive environments (out of state hospitals)
  • Follow up with community mental health
  • Monitor continued drug treatment
  • Patient rights
  • Change in commitment laws
  • Drug can Modify KW 6-5 Mood Disorders
  • Mood Disorders
  • characterized by emotional extremes
  • Major Depressive Disorder
  • no apparent reason,
  • experiences two or more weeks of depressed moods,
  • feelings of worthlessness, and
  • diminished interest or pleasure in most activities
  • Depression
  • Major Depressive Disorder
  • Defined-long-term sadness and helplessness
  • Demographics
  • Observed more often in women than men
  • Peak frequency between 25 and 44
  • About 19% of all people suffer a bout of depression at least once in their lives
  • Genetics
  • Depression does have a genetic link
  • Gene has not been located
  • 10% 8 6 4 2 0 Percentage depressed Females Males 12-17 18-24 25-34 35-44 45-54 55-64 65-74 75+ Age in Years Gender Differences in Depression 70 60 50 40 30 20 10 0 Suicides per 100,000 people The higher suicide rate among men greatly increases in late adulthood 15-24 25-34 35-44 45-44 55-64 65-74 75-84 85+ Females Males Mood Disorders- Suicide Depression
  • Reactive
  • Related to traumatic life event
  • Can be triggered by an event (ex: death of a loved one, birth of a child, etc)
  • Endogenous Source from within More likely to be related to neurochemical differences
  • Depression Physiology of Depression Two Conclusions Mood depends on the effects of a combination of transmitters Different depressed people have somewhat different transmitter abnormalities Video Brain chemistry Cognition Mood Mood Disorders-Depression
  • Altering any one component of the chemistry-cognition-mood circuit can alter the others
  • Depression
  • Drug Treatments
  • Antidepressants
  • Tricyclics-prevent reuptake of serotonin or norepinephrine/epinephrine
  • MAO Inhibitors-block MAO from breaking down serotonin and norepinephrine/epinephrine
  • SSRI’s-Selective Serotonin Reuptake inhibitor: inhibits reuptake of serotonin
  •  Routes of action of antidepressantsTricyclics block the reuptake of dopamine, norepinephrine, or serotonin.SSRIs specifically block the reuptake of serotonin. MAOIs block the enzyme MAO, which converts dopamine, norepinephrine, or serotonin into inactive chemicals. Serotonin and Depression KW 6-11 Prozac MDMA Casues Cell Damage
  • MDMA Changes the density of serotonin axons in monkeys
  • Normal brain on left
  • Brain on right 18 months following treatment
  • Depression: Other treatments
  • ECT
  • Applied every other day for two weeks
  • Muscle relaxants and anesthetics minimize discomfort
  • Memory loss can be a side-effect (limited if shock is given to right hemisphere only
  • Altered Sleep Patterns
  • Treat patient like someone with difficulty adjusting to changing time zones
  • Biomedical Therapies
  • Electroconvulsive Therapy
  • Seasonal Affective Disorder Defined-depression that regularly recurs in a particular season Usually treated by bright light therapy Mood Disorders
  • Manic Episode
  • a mood disorder marked by a hyperactive, wildly optimistic state
  • Bipolar Disorder
  • alternates between the hopelessness of depression and the overexcited state of mania
  • formerly called manic-depressive disorder
  • Bipolar Disorder Defined-alternate between mania and depression Demographics May last only days or for a year or more 1% of people have a mild case at some time in life Average age of onset is early 20’s Genetics Concordance rate is .50 No specific gene has been identified Depressed state Manic state Depressed state Mood Disorders-Bipolar
  • PET scans show that brain energy consumption rises and falls with emotional swings
  • Bipolar Disorder Treatments Lithium Stabilizes mood Mechanism unknown Side effect: toxicity Anticonvulsant drugs (like Depakote) Mechanism of action on cortex (lower activity) Schizophrenia Definitions
  • Schizophrenia
  • literal translation “split mind”
  • a group of severe disorders characterized by:
  • disorganized and delusional thinking
  • disturbed perceptions
  • Schizophrenia Symptoms
  • Delusions
  • false beliefs, often of persecution or grandeur, that may accompany psychotic disorders
  • Hallucinations
  • false perceptual experiences such as seeing something without any external visual stimulus
  • Prevalence
  • Schizophrenia affects about 1% of the population and range in severity.
  • Occurs in all parts of the world, but is 10 to 100 times more common in the United States and Europe than in third-world countries.
  • More common in men than in women by a ration of about 7 to 5.
  • More severe and earlier age of onset for men (early 20’s versus late 20).
  • Likelihood increases as the age of the father increases.
  • Characteristics of Schizophrenia Characteristics Deteriorating ability to function Accompanied by delusions, hallucinations, thought disorder, movement disorder and inappropriate emotional expression Behavioral Symptoms Positive Symptoms-behavior that are present that should be absent Delusions, hallucinations, thought disorders Negative Symptoms-behavior that is absent that should be present Weak social interactions, emotional expression, speech, and working memory  Probabilities of developing schizophreniaThe closer the genetic relationship to someone with schizophrenia, the higher the probability of developing it oneself. Schizophrenia and Genetics Genetics Concordance rate is 50% However, genes are not the only influence A gene has not been located for schizophrenia Hypotheses of Causation in Schizophrenia
  • Neurodevelopmental
  • Either genes or difficulties early in life impair brain development in ways that lead to schizophrenic-like symptoms in early adulthood
  • Dopamine Hypothesis-Excess dopamine activity causes behavioral changes associated with schizophrenia
  • Supported by drug treatments that target dopamine
  • Glutamate Hypothesis-the problem is deficient glutamate activity
  • Neurodevelopmental
  • The neurodevelopmental hypothesis suggests abnormalities in the prenatal or neonatal development of the nervous system.
  • Leads to subtle abnormalities of brain anatomy and major abnormalities in behavior.
  • Abnormalities could result from genetics, difficulty during birth, or a combination of both.
  • Causation
  • Supporting evidence for the neurodevelopmental hypothesis includes:
  • Several kinds of prenatal or neonatal difficulties are linked to later schizophrenia.
  • People with schizophrenia have minor brain abnormalities that originate early in life.
  • Abnormalities of early development could impair behavior in adulthood.
  • Prenatal Risk Factors
  • Prenatal risk factors increasing the likelihood of schizophrenia include:
  • Poor nutrition of the mother during pregnancy.
  • Premature birth.
  • Low birth weight.
  • Complications during delivery.
  • Head injuries in early childhood are also linked to increased incidence of schizophrenia.
  • Season of Birth
  • Certain viral infections may be an alternative or supplement genetic influences.
  • The seasoned-of-birth effect refers to the tendency for people born in winter to have a slightly (5% to 8%) greater probability of developing schizophrenia.
  • More pronounced in latitudes far from the equator.
  • Might be explained by complications of delivery, nutritional factors, or increased likelihood of viral infections
  • Schizophrenia and Brain
  • Schizophrenia is associated with mild brain abnormalities:
  • Strongest deficits found in the left temporal and frontal lobe of the cortex.
  • Larger than normal ventricles.
  • Especially common in those with complications during birth.
  • Areas that mature slowly such as the dorsolateral prefrontal cortex.
  • Schizophrenics have deficits in working memory.
  • MRI Scans of Schizophrenia Normal Twin Schizophrenic Twin CBF in Schizophrenia Treatment
  • Antipsychotic/neuroleptic drugs are drugs that tend to relieve schizophrenia and similar conditions.
  • Chlorpromazine (thorazine) is a drug used to treat schizophrenia that relieves the positve symptoms of schizophrenia.
  • Relief usually experienced 2-3 weeks after taking the drug, which must be taken indefinitely.
  • Schizophrenia Treatment
  • Antipsychotic Drugs-All block postsynaptic dopamine receptors
  • First Generation Antipsychotics (FGA’s)
  • Phenothiazines-chlorpromazine
  • Butyrophenones-haloperidol
  • Dopamine and Psychosis KW 6-10 Antipsychotics Dopamine hypothesis
  • The dopamine hypothesis of schizophrenia suggests that schizophrenia results from excess activity at dopamine synapses in certain areas of the brain.
  • Substance-induced psychotic disorder is characterized by hallucinations and delusions resulting from repeated large doses of amphetamines, methamphetamines, or cocaine.
  • Each prolongs activity of dopamine at the synapse, providing further evidence for dopamine hypothesis.
  • Pathways affected
  • The mesolimbocortical system is a set of neurons that project from the midbrain tegmentum to the limbic system.
  • Site where drugs that block dopamine synapses produce their benefits.
  • Drugs also block dopamine in the mesostriatal system, which project to the basal ganglia.
  • Result is tardive dyskinesia, characterized by tremors and other involuntary movements.
  • Fig. 15-20, p. 479 SGA’s
  • Second-generation antipsychotics (atypical antipsychotics) are a class of drugs used to treat schizophrenia but seldom produce movement problems.
  • Examples: clozapine, risperidone.
  • More effective at treating the negative symptoms and are now more widely used.
  • Have less effect on dopamine D2 receptors and more strongly antagonize serotonin type 5-HT2 receptors.
  • TGA’s?
  • Third Generation Antipsychotics.
  • Abilify® (aripiprazole)
  • Act on both dopamine and serotonin.
  • Regulates, rather than blocks, dopamine.
  • May help both positive and negative symptoms.
  • Side effects: restlessness, constipation, sleepiness, involuntary movement.
  • Schizophrenia Conclusions
  • Schizophrenia cannot be explained by a single gene or single transmitter.
  • Dopamine and glutamate may play important roles in schizophrenia to different degrees in different people.
  • Schizophrenia involves multiple genes and abnormalities in dopamine, glutamate, serotonin and GABA.
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