Lecture 11 Psychopharmacological Medications PDF

Psychopharmacology Psychotherapeutic Medications Psychotherapeutic Medications: Introduction An Age-Old Question: How do we treat Mental Illness? Prehistoric Approaches to Treating Mental Illness Assumption: Abnormal behavior was due to “evil sp...

Psychopharmacology Psychotherapeutic Medications Psychotherapeutic Medications: Introduction An Age-Old Question: How do we treat Mental Illness? Prehistoric Approaches to Treating Mental Illness Assumption: Abnormal behavior was due to “evil spirits” which were removed by: Letting them out through Beating Bleeding holes drilled in the skull them out them out (“Trephining”) Later Approaches: Isolation and Constraint  Later Approaches: Sensory Based Sensory Deprivation Sensory Shock Tranquilizer Chair designed by Founding Father, Benjamin Rush  Historical Medical Interventions Assumption: Brain is fixed. Thus, drastic procedures to “shock” the brain into normalcy. Insulin Shock Therapy Electroconvulsive Therapy Convulsant Drugs ❖Developed in 1927 by Manfred Sakel, ❖Developed in 1937 by Ugo Cerletti, ❖Developed in 1933 by Ladislaus von a Polish neurophysiologist. an Italian neurophysiologist. Meduna, a Hungarian M.D. ❖Excessive insulin leads to glucose ❖Remains a widely used approach for ❖Used IM metrazol to induce deficit in brain the treatment of depression convulsions ❖Falsely claimed 70% improvement ❖Used in conjunction with muscle ❖No longer practiced ❖No longer practiced. relaxants and anesthesia Goal was to create convulsions to shake the brain back to normal functioning. Medical Interventions: Pre-Frontal Lobotomies Surgical treatment to sever connections in the prefrontal cortex Developed in 1936 by Egas Moniz, a Transorbital Lobotomy popularized in U.S. Portuguese neurophysiologist. Awarded the by Walter Freeman who developed a Nobel Prize for medicine in 1949. transorbital procedure In its heyday, lobotomy was one of the most popular forms of therapy  A New Style Intervention: Psychotherapy Sigmund Freud developed psychoanalysis in 1900 Psychotherapy: An interactive experience with a trained professional, working on understanding and changing behavior, thinking, relationships, and emotions Goal: To use intensive exchanges between client and therapist to identify and correct the psychological problems underlying mental illness Major forms are Psychoanalysis, Humanistic, Cognitive, Behavioral  Schizophrenia: Description and Symptoms Quick Facts Demographics ❖Dementia praecox ❖ about 1% (Emil Kraeplin, 1896) ❖ mostly young ❖ An example of ❖ equal male and female psychosis (a loss of ❖ more prevalent in African contact with reality) Americans* ❖ Different etiologies, ❖ more prevalent in inner behaviors, outcomes cities The Schizophrenic Spectrum  Schizophrenia: Symptoms Positive Symptoms Negative Symptoms (Behaviors that are present, but shouldn’t be) (Behaviors that are absent, but should be present) ❖ Disorganized Thoughts and Delusions ❖ Social Withdrawal ❖ Disturbed Perceptions (Hallucinations) ❖ Anhedonia (loss of pleasure) ❖ Disorganized Speech ❖ Alogia (loss of speech) ❖ Unusual Movements ❖ Amotivational (loss of motivation) Social/Occupational Dysfunction No One ❖ Employment Symptom Defines ❖ Interpersonal Relationships Schizophrenia ❖ Self Care Cognitive Symptoms Mood Symptoms ❖ Attentional Difficulties ❖ Dysphoria (Anxiety, ❖ Memory Issues Depression, Unease) ❖ Executive Functions (Decision ❖ Inappropriate Emotions Making, Planning, Judgment, etc.) ❖ Suicidality ❖ Hopelessness  Schizophrenia: Treatment Options Treatment Options for Schizophrenia were Scarce and Ineffective Psychoanalysis? The Chlorpromazine Revolution Freud said No. Neo-Freudians attempted with mixed success. Psychosurgery? Not terribly successful for schizophrenics Pharmacologic Approaches? Most significant advancement in Heavy Doses of Barbiturates the treatment of psychiatric or Benadryl (to tranquilize) disorders EVER By 1955, half of all psychiatric patients were schizophrenic  The Chlorpromazine Revolution Importance Deinstitutionalization: ❖First demonstration that mental illness Ultimately led to 80% reduction Rights sold to Smith- in mental hospital residents from could be treated pharmacologically Kline & French peak of 560,000 ❖Ultimately led to 80% reduction in mental hospital residents 1950 1952 1955 Mid-1960s 1989 ❖Led to the field of Psychopharmacology Developed in ❖Demonstrated brain was malleable France Approved in US for Second generation of treatment of (Laboratoires psychiatric problems antipsychotics (the atypicals) Rhone-Poulenc)  The Chlorpromazine Revolution Chlorpromazine Effects on Dopamine ❖ Dopamine antagonist (blocks D2 dopaminergic receptor sites) ❖ Ultimately, reduces DA synthesis and release ❖ Sustained Depolarization of membrane potentials, reducing firing ❖ Affects mesolimbic, mesocortical, and nigrostriatal areas Insufficient Levels NT Activity is along a Continuum Excessive Activity Normal Range Behavioral Effects ❖ Greatly reduces positive symptoms ❖ Less effective for negative symptoms Parkinson’s Disease ❖ Approximately 70% respond with Schizophrenia Viral Encephalitis significant improvement Tourette’s Syndrome Stimulant OD  Chlorpromazine Side Effects Significant Side Effects (Major role in Medication Noncompliance) Movement side effects mediated by basal ganglia Tardive Dyskinesia Parkinson’s- like Symptoms (The Thorazine Shuffle!) Acute Dystonia Akathisia  Antipsychotics (Major Tranquilizers) Typical Antipsychotics: 1st Atypical Antipsychotics: 2nd Generation Generation (1955 with Thorazine) (1989 with Clozapine) ❖Target D2 receptors ❖D2, but also Serotonin, NE, ACh, and Histamine ❖Similar benefits and side effects ❖Specific to mesolimbic & mesocortical systems (including the movement problems) ❖Less likely to produce motor disturbances ❖Greater efficacy in reducing negative symptoms ❖Exs., Thorazine, Prolixin, Serentil, ❖Wider clinical profile (helps more patients) Trilafon, Compazine, Haldol, Navane ❖Risk of agranulocytosis (loss of white blood cells) ❖Exs., Risperdal, Zyprexa, Seroquel, Abilify Atypicals are usually the first line of treatment, but concerns remain about treatment noncompliance The Mood Disorders Mood Disorders: Disorders where a disturbance in emotional mood is the main underlying feature The Mood Disorders: Major Depression Major Depression: Disorder in which The Common Cold of Mental Illness symptoms occur for two or more weeks without a notable cause  Characteristics of Major Depression The Vicious Cycle of Major Depression Depression is Cyclic Depression is Often Comorbid with Anxiety The depressed mood changes a person’s style of thinking and interacting in a way that makes stressful experience more likely.  Causes of Major Depression: A Biopsychosocial Approach The Heritability of Various Psychological Disorders (Bienvenu et al., 2011) Studies of identical and fraternal twins Psychotherapeutic Medications for Major Depression Antidepressants are a direct consequence of Thorazine revolution Most effective treatment for depression is combination of medication and therapy Depression treatment is largely physician-based JAMA Intern Med. 2016;176(10):1482-1491. doi:10.1001/jamainternmed.2016.5057 Three Major Classes of Antidepressants Three generations of antidepressants ❖1957: MAO inhibitors ❖1957- 1958: Tricyclics ❖1987: SSRIs  Monamine Oxidase Inhibitors (MAOIs) MAO: Intraneuronal deactivation of the catecholamines and serotonin Most effective anti-depressants,… but The Downside of MAOIs: Potentially fatal side effects by producing major hypertensive crisis ❖Interactions with diet (foods containing tyramine) ❖Interactions with other medications (tricyclics, psychostimulants, l-dopa) ❖Thus, the third line of treatment 2006: Transdermal patch of selegiline (no GI issues) MAO inhibitors prevent the deactivation of these neurotransmitters.  Tricyclics: The Second Generation Three-ringed molecules (hence the name, tricyclics) Effects ❖Promotes feelings of confidence ❖Improves mood ❖Reduces physical complaints ❖Relieves suicidal ideation The Downside ❖Relatively low Therapeutic Index (about 8) ❖Responsible for 25% of all fatal overdoses in U.S. ❖Can produce seizures, cardiac arrhythmia, hypotension ❖Usual side effects include constipation, dry mouth, blurred vision Reuptake Inhibitors for norepinephrine, dopamine, and serotonin  Selective Serotonin Reuptake Inhibitors (SSRIs) Third Generation of Antidepressants. Least Effective… ❖Blocks serotonin reuptake Brand Name Generic Name Prozac Fluoxetine specifically (thus, a more Zoloft Sertraline targeted effect) Paxil Paroxetine ❖ Guided Missile versus Luvox Fluvoxamine Carpet Bombing! Lexapro Escitalopram oxalate Celexa Citalpram ❖Typically, a 4 to 6-week course of action …but Best Tolerated. Hence, the First Line of Treatment. Benefits and Side Effects of SSRIs Typical side effects are generally mild Potential for Serotonin Syndrome ❖ Occurs in combination with other serotoninergic medications ❖ Disorientation/confusion, agitation, shivering, fevers, diarrhea, involuntary muscle contractions ❖ Potentially life-threatening if not diagnosed in time  An Herbal Approach: St. John’s Wort St. John’s Wort is a Supplement, not a Drug. ❖Hypericum perforatum from Hypericum genus of plants (about 370 invasive weed species) ❖Traditionally harvested on June 24th (St. John’s Day) ❖Generally considered as effective for mild to moderate depression as tricylics or SSRIs; no effect for moderate to severe depression ❖Mechanism of action is unknown, but it may function as a serotonergic reuptake inhibitor  Other Available Antidepressants Re-Uptake Inhibitors Norepinephrine Norepinephrine- Selective Serotonin- Serotonin- Medication reuptake inhibitors dopamine reuptake Serotonin norepinephrine norepinephrine- (NRIs) inhibitors (NDRIs): Reuptake reuptake inhibitors dopamine reuptake Inhibitors (SNRIs): inhibitors (SSRIs) (SNDRIs) Depression Depression Depression Depression Depression Uses Anxiety ADHD Anxiety Bipolar depression ADHD panic disorder Narcolepsy ADHD, GAD, OCD chronic pain Narcolepsy chronic nerve pain binge-eating ADHD fibromyalgia. disorder Ludiomil Ritalin Celexa, Lexapro Cymbalta Effexor Examples Strattera Wellbutrin Luvox, Paxil Fetzima Serzone Vivalan (bupropion) Prozac, Zoloft Spravato (esketamine): FDA-approved Used in conjunction with an oral antidepressant nasal spray as an adjunct for the treatment of depression (2019) Only given in physician’s office of approved s-enantiomer of ketamine practices (limited distribution) The Mood Disorders: Bipolar Disorder (Manic-Depression) Depression Bipolar Disorder Mania Disorder in which individuals Mental condition Period of hyper- have wild alterations between characterized by depression and mania elevated mood that is feelings of severe euphoric, giddy, easily despondency and irritated, hyperactive, dejection, feelings of impulsive, overly inadequacy and guilt, optimistic, and even lack of energy, appetite grandiose. and sleep disturbances. Contrasting Symptoms Depressed mood: stuck feeling “down,” with: Mania: euphoric, giddy, easily irritated, with: ❖ exaggerated pessimism ❖ exaggerated optimism ❖ social withdrawal ❖ hypersociality and sexuality ❖ lack of felt pleasure ❖ delight in everything ❖ inactivity and no initiative ❖ impulsivity and overactivity ❖ difficulty focusing ❖ racing thoughts; the mind won’t settle down ❖ fatigue and excessive desire to sleep ❖ little desire for sleep  Treatment for Bipolar Disorder Lithium ❖Light metal chemical element commonly found in nature ❖No known physiological role for humans or animals ❖No psychoactive effect at all on normal subjects Effects in Bipolars Extremely low Therapeutic Index How Does It Work? ❖ Relieves mania without causing sedation or inducing depression (around 2 or 3) ❖ May affect ionic flow through membrane (thus ❖ Produces remission and mood altering action potentials) stability in 60-80% of bipolars ❖May stabilize receptor ❖Levels behavior (reduces highs, densities to level neural activity increases the lows)  Treatment Approaches to Major Depression Pharmacologic Intervention Electroconvulsive Therapy Psychotherapy Medications designed to treat biochemical Electrically induced seizure used for Talk Therapy: The treatment of mental imbalances in the brain: Three Classes severe depression. disorder by psychological means.  What Works Best? A Biopsychosocial Approach BioMedical Therapies Psychological Therapies ❖ Insight-Oriented Psychotherapy ❖ Drug Therapies ❖ Psychoanalysis ❖ Electro-Convulsive Therapy ❖ Humanistic ❖ Trancranial Magnetic Stimulation ❖ Cognitive ❖ Behavior-Oriented Psychotherapy Social/Community Approaches ❖ Family Therapy ❖ Community Treatment ❖ Prevention Programs