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PSY 320 - Ch 8 - Psychotherapeutics

by: Elliana

PSY 320 - Ch 8 - Psychotherapeutics PSY 320

Marketplace > University of Miami > Psychlogy > PSY 320 > PSY 320 Ch 8 Psychotherapeutics
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Combined class lecture & textbook notes
Drugs & Behavior
Dr. Marc Gellman
Class Notes
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This 11 page Class Notes was uploaded by Elliana on Monday March 21, 2016. The Class Notes belongs to PSY 320 at University of Miami taught by Dr. Marc Gellman in Spring 2015. Since its upload, it has received 20 views. For similar materials see Drugs & Behavior in Psychlogy at University of Miami.


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Date Created: 03/21/16
PSY 320 Drugs & Behavior Chapter 8 Psychotherapeutics Mental Disorders: Medical Model • Model: ◦ Symptoms -> diagnosis -> determina▯on of cause -> treatment -> cure • Limita▯ons of model: ◦ Usually the only symptoms of mental disorders are behavioral ◦ Behaviors are varied & have many causes • Model guides much of current thinking: ◦ Psychoac▯ve drugs are used to control symptoms of mental illness ◦ Researchers seek to iden▯fy chemical imbalances associated w/ specific mental disorders Classifica▯on of Mental Disorders • DSM-5 ◦ Developed by American Psychiatric Associa▯on ◦ Provides diagnos▯c criteria & defini▯ons for disorders des u y l ed◦ iW Research Domain Criteria Project (RDoC) • Classifies disorders based on behavioral dimensions & neurobiological measures • Uses modern research approaches in gene▯cs, neuroscience, & behavioral science • Framework for developing hypotheses & evalua▯ng results when inves▯ga▯ng mechanisms of psychopathology • Matrix of func▯onal dimensions grouped into domains Treatment of Mental Disorders • Mental Disorder - Impairment in normal behavioral, cogni▯ve, or emo▯onal func▯on ◦ Highly prevalent ◦ WHO es▯mates 450 million ppl qualify for a mental disorder diagnosis History & Consequences of Drug Treatments for Mental Illness • Historically, pa▯ents were hidden in dungeons or ins▯tu▯ons • 1917 "Malaria Therapy" ◦ Many ppl suffered from general paresis (syphili▯c infec▯on of the nervous system) ◦ Fever associated w/ malaria produced improvement ◦ Later discovery of an▯bio▯cs curing syphilis eliminated need for Malaria Therapy • Replaced w/ shock therapies, insulin therapies, etc. ◦ 1920s "Narcosis therapy:" • Depressants & barbiturates used to induce sleep for a week or more ◦ 1930s Intravenous thiopental sodium (truth serum): • Used in psychotherapy to help pa▯ents express repressed thoughts ◦ Insulin-shock therapy: • Used to treat schizophrenia • Ineffec▯ve, caused agita▯on ◦ Electroconvulsive therapy: • Ineffec▯ve to treat schizophrenia PSY 320 Drugs & Behavior • S▯ll used to treat severe depression that doesn't respond to medica▯on • First an▯depressant drugs emerged in 1950s ◦ Paraldehyde most commonly used, had a horrible odor • Mental hospitals' popula▯on decreased since 1950s • 1963 Community Mental Health Act ◦ Provided federal support to states to develop community-based mental health centers ◦ Intended to treat pa▯ents closer to home in a more natural/accessible se▯ng • Medicare & Medicaid in 1965 moved elderly pa▯ents w/ demen▯a into nursing homes • "Libera▯on" of mental pa▯ents to mainstream society ◦ Prescrip▯ons o▯en replaced psychotherapy ◦ 1/3rd of homeless ppl in the US have some form of mental illness that they cannot afford to treat or do not have access to medica▯ons for DSM-5 Anxiety Disorders Characterized by excessive worry, fears, or avoidance • Specific phobia - Excessive or unreasonable fear of a specific object or situa▯on • Social anxiety disorder - A marked fear or anxiety about one or more social situa▯ons • Panic disorder - Recurrent & unexpected panic a▯acks, which consist of abrupt surges of intense fear or discomfort • Agoraphobia - Fear or anxiety about 2 or more of these situa▯ons: using public transporta▯on, being in open spaces, being in shops or theaters, standing in line, or being outside of the home alone • Generalized anxiety disorder - Excessive anxiety & worry about a number of events or ac▯vi▯es, las▯ng for a period of 6 months or longer Mental Disorders • Psychosis - Mental disorder involving loss of contact with reality ◦ Organic psychoses - Known physical cause ◦ Func▯onal psychoses - No known cause or obvious physical cause ◦ Schizophrenia - Severe, life-long mental illness consis▯ng of disturbed thought processes & poor emo▯onal responsiveness • Posi▯ve symptoms - Hallucina▯ons, delusions, thoughts of persecu▯on • Nega▯ve symptoms - Reduced emo▯onal responsiveness, social withdrawal, reduced movement, lack of mo▯va▯on • Types of schizophrenia: ▪ Paranoid type - posi▯ve symptoms ▪ Catatonic type - nega▯ve symptoms ▪ Disorganized type - disorganized/immature behaviors ▪ Undifferen▯ated type - doesn't fit into other categories ▪ Residual type - pa▯ents who currently exhibit few symptoms ▪ Prodromal phase - Years before a diagnosis, early/subtle signs & schizophrenic-like symptoms occurring less frequently & w/ less severity • Schizophrenia affects 1% of world popula▯on • Around 1/3rd of pa▯ents w/ schizophrenia qualify as treatment-resistant pa▯ents: Minimal or no improvements a▯er 2 trials of either typical or atypical an▯psycho▯c drugs • Schizophrenic individuals typically have deficits in cogni▯ve func▯oning including: Working memory, reference memory, a▯en▯on, & execu▯ve func▯oning PSY 320 Drugs & Behavior • Many pa▯ents demonstrate sensory-ga▯ng deficit: Diminished capacity to filter out unimportant s▯muli in one's environment • Features of schizophrenia: ▪ Delusional thinking - Firmly held beliefs of: persecu▯on, jealousy, sin/ guilt, grandiosity, religious ▪ Hallucina▯ons - percep▯ons experienced w/o external s▯muli, auditory hallucina▯ons including commands & commentary ▪ Disorganized speech (thought disorder) ▪ Disorganized or bizarre behavior: catatonic stupor, inappropriate mannerisms, deteriora▯on of grooming, dress, home, social behavior, etc. ▪ Incongruity of affect - I.E. inappropriate smiling ◦ Chronic psychosis characterized by 2 of the following: • Delusions, hallucina▯ons, disorganized speech, disorganized behavior, lack of emo▯onal response • Causes significant interference w/ social/occupa▯onal func▯oning • Mood disorders - Characterized by depressed or manic symptoms ◦ Depression 4th leading cause of disability worldwide ◦ Due to prevalence & drama▯c effects on life ◦ Major depressive disorder • Characterized by at least 5 of the depressive symptoms, las▯ng at least 2 weeks • Depressed mood, lack of interest/pleasure, change in body weight & sleeping pa▯erns, fa▯gue, feelings of worthlessness, difficulty thinking/concentra▯ng, recurrent thoughts of death • Prevalence during life▯me is 16% ◦ Dysthymic disorder • Depressed mood occurring nearly every day for at least 2 years ◦ Major depression w/ psycho▯c features • Presence of depression, hallucina▯ons, & delusions related to depressed mood ◦ Bipolar disorder - Characterized by abnormal changes btwn depressive & manic mood states • Depressive symptoms same as with depressed individuals • Mania consists of abnormal elevated or irritated mood, arousal, or energy levels ▪ Manic behavior: fast speaking, rapidly changing ideas, impulsive decision making • Bipolar 1 disorder - At least 1 manic episode & possible alterna▯ng depression • Type 1 bipolar disorder - Exhibits depression & episodes of severe mania • Type II - Exhibits depression along w/ episodes of less-severe mania • The most common incorrect diagnosis for bipolar disorder is depression • Bipolar depression far less prevalent than unipolar depression Categories of currently used an▯depressants: • Monoamine oxidase (MAO) inhibitors ◦ Monoamine hypothesis of depression: ◦ Monoamine neurotransmi▯er deficiency cause depressive mood ◦ An▯depressant drugs designed based on this hypothesis PSY 320 Drugs & Behavior ◦ Originally discovered in 1950s when trea▯ng pa▯ents for tuberculosis ◦ Alter metabolism of amino acid tyramine • "Cheese reac▯on" - Severe headache, palpita▯ons, nausea, & vomi▯ng may occur when ea▯ng cheese & could possibly result in deadly stroke • Tricyclic an▯depressants ◦ Block presynap▯c receptors/transporters for serotonin, dopamine, & norepinephrine ◦ Block different numbers of postsynap▯c receptors for acetylcholine & histamine ◦ Main histamine effect is drowsiness ◦ Mul▯ple ac▯on of TCAs some▯mes advantageous, promotes sleep ◦ All TCAs are toxic to the heart @ high doses ◦ Make effec▯ve agents of suicide, fueled search for other an▯depressants ◦ Adverse effects: • Dry mouth, dry eyes, cons▯pa▯on, urinary reten▯on - caused by muscarinic receptors • Dangerous cardiovascular effects - caused by inhibi▯on of a1 adrenoceptors • Seda▯ve effects - caused by inhibi▯on of histamine H1 receptors • Weight gain, type II diabetes ◦ Imipramine (Tofranil) discovered as modifica▯on of phenothiazine (an▯psycho▯c) ◦ Amitriptyline (Elavil) higher seda▯ve & an▯cholinergic effects, affects serotonin more than imipramine does ◦ Clomipramine (Anafranil) has highest serotonin effect of TCAs w/ li▯le an▯cholinergic or seda▯ve ac▯on • Selec▯ve serotonin reuptake inhibitors (SSRIs) ◦ By late 1970s researchers began to dis▯nguish btwn behavior-s▯mula▯ng & mood- enhancing effects of an▯-depressants ac▯ng on NE & 5-HT systems • Believed that behavior-s▯mula▯ng effects for mediated by blocking NE reuptake, while mood-enhancing effects were mediated by 5-HT • Research focused on developing drugs to specifically enhance 5-HT transmission while simultaneously minimizing effects on histamine & Ach receptors: the cause of most side effects ◦ 1988 fluoxe▯ne (Prozac) was approved • Increase extracellular levels of 5-HT by inhibi▯ng reuptake into presynap▯c cell, increasing level of 5-HT available to bind to receptors • Primarily used to treat clinical depression • Also used to treat anxiety disorders, social phobia, OCD, ea▯ng disorders, chronic pain, PTSD ◦ Fluoxe▯ne (Prozac) first SSRI, one of the most prescribed drugs in history ◦ Sertaline (Zolo▯) quick ac▯on, less side effects ◦ Paroxe▯ne (Paxil) for OCD & panic ◦ Fluvoxamine (Luvox, 1995) for OCD/panic/PTSD ◦ Serotonin Syndrome - Life-threatening condi▯on characterized by agita▯on, restlessness, cogni▯ve impairments, & hallucina▯ons ◦ Serotonin discon▯nua▯on syndrome - Caused by abrupt withdrawal of an▯depressant drug, resul▯ng in sensory/sleeping impairments, disequilibrium, flulike symptoms, gastrointes▯nal effects • Serotonin-norepinephrine reuptake inhibitors PSY 320 Drugs & Behavior ◦ Enhance levels of serotonin & norepinephrine by blocking serotonin & norepinephrine transporters ◦ Dual-ac▯on an▯depressants ◦ Need for new class of an▯depressant drugs resulted from: • Adverse effects of SSRIs, par▯cularly sexual side effects • Failure of significant # of pa▯ents to respond to SSRIs/other drugs ) 4991 , roxeffE ( en i xa f a l n ◦e V • First & most commonly used SRNI • Reuptake effects are dose dependent ▪ Low doses act just on 5-HT ▪ Moderate doses on 5-HT & NE ▪ High doses also affect DA transmission ◦ Duloxe▯ne (Cymbalta) approved 2004 ◦ Effexor similar mechanism, shorter half-life • Atypical an▯depressant drugs ◦ Reduce depression thru mechanisms that differ from those of other an▯depressant drug classifica▯ons ◦ One of the most prescribed is bupropion (Wellbutrin) • Reuptake inhibitor for norepinephrine & dopamine • Binds selec▯vely to dopamine transporter, tho behavioral effects are a▯ributed to its inhibi▯on of NE reuptake • Also acts as nico▯nic Ach receptor antagonist • Effect an▯depressant on its own • Par▯cularly popular as an add-on medica▯on in the cases of incomplete response to SSRIs • Doesn't cause weight gain, even shoes mild-moderate weight loss or appe▯te suppression • Bupropion currently 4th-most prescribed an▯depressant in the US a▯er sertraline (Zolo▯), escitalopram (Lexapro), & fluoxe▯ne (Prozac) ◦ Bupropion (Zyban) • Ini▯ally researched/marketed as an▯depressant • Subsequently found to be effec▯ve as smoking cessa▯on aid Limita▯ons in An▯depressant Drug Effec▯veness & Development • All an▯depressant drugs have a lengthy response ▯me ◦ Clinically significant effects occur a▯er 2 weeks of treatment ◦ Full effects a▯er 4 weeks • Treatment-resistant depression ◦ Successive failed a▯empts at significantly reducing depressive symptoms ◦ Btwn 29-46% of pa▯ents are treatment-resistant • To gain FDA approval, new an▯depressants must be tested in clinical trials compared to placebos ◦ Clinically significant improvements o▯en occur in placebo-treated pa▯ents ◦ Strong placebo effects + cau▯ous nature of clinical drug tes▯ng = failure to find clinically significant an▯depressant effects • Most an▯depressant drugs elevate brain serotonin levels • An▯depressant drugs increase dopamine concentra▯ons in prefrontal cortex PSY 320 Drugs & Behavior • Neuronal growth occurs during an▯depressant treatment • Risks: ◦ Individuals first star▯ng an▯depressants may be anxious, irritable, hos▯le, impulsive, or restless ◦ Combina▯on of severe depression & restlessness especially dangerous ◦ An▯depressants may elevate energy enough for individuals to carry out suicide plans ◦ Advisory drugs: Prozac, Zolo▯, Wellbutrin, Zyban, Paxil, Celexa, Effexor, Serzone, Luvox, Remeron Typical An▯psycho▯cs PSY 320 Drugs & Behavior Atypical An▯psycho▯cs Mood Stabilizers & Other Drugs • For bipolar disorder • Few drugs are considered pure mood stabilizers: drugs that reduce both depressive & manic symptoms • Beyond mood stabilizers, other treatments include an▯convulsant drugs & an▯psycho▯c drugs • Lithium ◦ One of the oldest & most effec▯ve treatments for bipolar disorder ◦ Effec▯veness first realized by John Cade in 1949 ◦ Provides greater efficacy for mania than for depression ◦ Requires 10-15 days before symptoms decrease ◦ Acts as mood-normalizing agent for manic depression ◦ Has serious side effects: • Nausea, vomi▯ng, diarrhea • Narrow therapeu▯c index • Lithium's mechanisms of ac▯on ◦ Lithium affects: • Second-messenger ac▯ons • Gene expression • Neuroprotec▯ve effects • Inhibi▯on of glycogen synthase kinase 3 (GSK-3): Protein kinase that promotes apoptosis & regulates inflamma▯on • An▯convulsants: ◦ O▯en also used as mood stabilizers ◦ Valproic acid (Depakote), carbamazepine (Tegretol), lamotrigine (Lamictal) PSY 320 Drugs & Behavior ◦ Don't require blood levels to be monitored History of Schizophrenia Treatment • 1952 Henri Laborit administered preanesthe▯c agent chlorpromazine to manic pa▯ents ◦ Had calming effect on pa▯ents w/ psychosis • Efficacy of chlorpromazine for schizophrenia formally studied by Jean Delay & Pierre Deniker ◦ Revolu▯onized treatment of schizophrenia • Butyrophenones: ◦ Haloperidol (Haldol, 1967) & doperidol (Inapsine, mainly an▯nausea/an▯eme▯c) • Aripiprazole (Ambilify) ◦ Atypical an▯-psycho▯c & an▯-depressant ◦ Approved in 2002 to treat schizophrenia ◦ Approved in 2004 for manic episodes of bipolar disorder ◦ Approved in 2007 as adjunct for major depressive disorder, but not as a monotherapy for MDD ◦ Approved in 2009 to treat irritability in kids w/ au▯sm An▯psycho▯c Drugs • Dopamine hypothesis - Posi▯ve symptoms of schizophrenia arise from excessive dopamine release ◦ An▯psycho▯c drugs act as antagonists for D2 receptors ◦ Amphetamine causes psycho▯c symptoms via increases in dopamine release • Classes of an▯psycho▯cs 1. Typical or conven▯onal an▯psycho▯cs • All same efficacy • Block pathway from ventral tegmental area (VTA) to basal ganglia, limbic structure, & frontal cortex • Many generic equivalents now available • Prototype - Phenothiazines ◦ Pharmacokine▯cs: • 24-48 hr half-life • Unpredictable absorp▯on & metabolism ◦ Pharmacodynamics: • Blocks D2 receptors • Also blocks ACh, 5-HT, NE, & histamine: seda▯ng, sympathomime▯c, an▯eme▯c ◦ Decrease sensi▯vity to emo▯onal expression ◦ Decrease RAS sensi▯vity to external s▯muli ◦ Acute extrapyrimidal effects • Akathesia: anxious pacing, rocking, fiddling • Dystonia: spasms & posturing • Parkinsonsim ◦ Tardive dyskinesia • Butyrophenones ◦ Longer half-life: drug holidays of 3 days ◦ More specific D2 blocker ◦ Fewer side effects, li▯le seda▯on PSY 320 Drugs & Behavior ◦ Parkinsonian effects like those of high-potency phenothiazines 2. Atypical an▯psycho▯cs • Block typical pathways & 5-HT pathway from raphe nucleus to basal ganglia, limbic structures, & en▯re cortex • Different side effect profiles • Much more expensive • Clozapine (Clozaril, 1990) ▪ Some▯mes drama▯c improvement ▪ Relieves posi▯ve & nega▯ve symptoms of schizophrenia ▪ Agranulocytosis, NMS ▪ Acts on DA, 5-HT, ACh, & histamine • Risperidone (Risperdal, 1994) ▪ Inhibits D2 & serotonin-2 receptors ▪ Low side effects: first-line treatment • Pimazode (Orap, 1996) ▪ Used in US for Toure▯e's disorder, in Europe & South America for schizophrenia ▪ May also help delusional disorder • Olanzapine (Zyprexa, 1996) ▪ Like clozapine, but no agranulocytosis • Ser▯ndole (Serlect, 1997) ▪ Serotonin, adrenalin, & cor▯cal DA2; dual ac▯on • Quetapine (Seroquel, 1997) ▪ Treats posi▯ve & nega▯ve symptoms ▪ Selec▯ve 5-HT & D2 antagonist • An▯cholinergic side effects: dry mouth, blurred vision, rapid heart rate (tachycardia), urine reten▯on, cons▯pa▯on, confusion & memory impairment • Main side effects: ▪ EPS - Cogwheel rigidity, coarse tremor, hypokinesia, shuffling gait ▪ Tardive Dyskinesia - Involuntary/o▯en irreversible movements in the face, tongue, jaw, hands, & feet ▪ NMS - Life-threatening syndrome w/ "lead pipe" muscular rigidity, hyperthermia, unstable vitals, agita▯on ▪ Dystonia - Painful muscle contrac▯on in the jaw, neck, tongue ▪ Orthosta▯c hypotension, prolac▯nemia, akathisia/restlessness, lower seizure threshold, drug interac▯ons Mechanism of Ac▯on • Phenothiazines & other conven▯onal an▯psycho▯cs produce pseudoparkinsonsim ◦ Ini▯al effect blocks D2 dopamine receptors ◦ Tho lag effect requires 10-14 days to see an▯psycho▯c effects ◦ Ul▯mate mechanism remains unknown ◦ Involves some response of the nervous system to repeated administra▯on of dopamine antagonists • Clozapine ◦ Risk of deadly suppression of white blood cell produc▯on PSY 320 Drugs & Behavior ◦ Use requires periodic blood samples to monitor white cells ◦ Affects mul▯ple receptor types ◦ Blocks D2 dopamine & 5HT2A serotonin receptors • Serotonin-dopamine antagonists: ◦ Atypical an▯psycho▯cs ◦ Risperidone, olanzepine, etc. ◦ Don't affect white blood cells ◦ Reduce pseudoparkinsonsim Ac▯ons to Effects Ac▯ons: • Microdialysis studies find atypical an▯psycho▯c drugs increase dopamine concentra▯ons in the prefrontal cortex • Ac▯ons of atypical an▯psycho▯cs on 5-HT & D2 receptors may account for effects on cor▯cal dopamine neurotransmission ◦ As well as ability to improve cogni▯ve impairment & nega▯ve symptoms in schizophrenia Side Effects: • Don't produce drug dependence • Extremely difficult to use to commit suicide • Jaundice, skin rashes • Photosensi▯vity in skin to light (sunburns easily) • Agranuloctosis - low white blood cell count ◦ May result in high mortality rate • Facial ▯cs • Symptoms similar to Parkinson's disease • Weight gain, metabolic changes in children & increased risk for obesity or diabetes • Cardiovascular risk for the elderly Typical vs. Atypical: • Atypical ◦ 2nd genera▯on an▯psycho▯cs ◦ Marketed as offering greater efficacy in reducing psycho▯c symptoms w/ less side effects ◦ Effects o▯en lacked robustness ◦ Assump▯on increasingly challenged w/ increase in atypical prescrip▯ons ◦ One review found no differences, another found atypicals to be just moderately more efficacious ◦ Olanzapine appears superior in terms of reducing psychopathology, tho associated w/ huge gains in weight & increase in fat/cholesterol ◦ 3rd genera▯on an▯psycho▯cs slightly less effec▯ve than Olanzapine but safer for type II diabetes risk Long-Term Management of Chronic Mental Illness • Several studies suggest medica▯ons may be less effec▯ve for outcomes that ma▯er most to ppl w/ serious mental illness: a full return to well-being & a produc▯ve place in society • Long-term follow-up studies: ◦ In the first 6-10 months a▯er discon▯nua▯on: 25-55% of pa▯ents relapse PSY 320 Drugs & Behavior ◦ For those who don't relapse during this period, subsequent relapses are much less frequent even a▯er prolonged periods off medica▯on • For some, remaining on medica▯on long-term may impede a full return to wellness • For others discon▯nuing medica▯on could be disastrous • Reducing posi▯ve symptoms may be necessary but is rarely sufficient for a full return to normal func▯oning • Neither 1st or 2nd genera▯on an▯psycho▯cs help much with nega▯ve symptoms or problems w/ a▯en▯on & judgment • Family educa▯on, supported employment, & cogni▯ve behavioral therapy have all shown efficacy in reducing likelihood of relapse


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