Psychopathology and Treatment PDF

Psychopathology and Treatment Anxiety Disorders Depressive Disorders Schizophrenia  Class Objectives Learn and define terminology relevant to treatment Describe the various treatment considerations and identify the threats to patient adherence. Id...

Psychopathology and Treatment Anxiety Disorders Depressive Disorders Schizophrenia  Class Objectives Learn and define terminology relevant to treatment Describe the various treatment considerations and identify the threats to patient adherence. Identify the pharmacological and psychological treatments for anxiety, depression and schizophrenia. Differentiate between the pharmacological treatment groups based on their mechanisms of action for anxiolytics, antidepressants and antipsychotics. Identify the side effects of each drug category (classification and generation) for anxiolytics, antidepressants and antipsychotics. Identify the various forms of psychological treatment for each disorder and be able to provide an opinion as to why combination therapy is most beneficial  Terminology Clinical guidelines and principle recommendations Patient adherence First line medication Non-selective v. Selective agents Immediate (Short-acting) v. long-term relief Acute v. Chronic treatment Primary Effects v. Secondary and Side Effects Agonist, Antagonist, Partial Agonist Reuptake inhibitor Enzyme degradation Treatment Considerations Which method of treatment is best?  Treatment Considerations Is treatment necessary? – Symptom severity How should it be treated? – Concomitant treatment; patient history Will the patient adhere to treatment recommendations and to the plan? – Delayed desired effects; immediate side effects Anxiety Disorders  Pathophysiology of Anxiety Anxiety is the result of a decrease in GABAergic neurotransmission within the amygdala (For review Nemeroff, 2009) GABA to Amygdala  What if… GABA to Amygdala?  Pharmacological Treatment First Generation (Barbiturates) Second Generation (Benzodiazepines) Third Generation (Z-Drugs) Alternatives  Pharmacological Treatment Anxiolytics – “anti-anxiety” medications Goal – GABAergic anxiolytics mechanism of action ??? – to __________ neurotransmission to the Amygdala  Pharmacological Treatment: Barbiturates First Generation – Indication: anxiolytic, sedative, antiepileptic – Secondary effects: CNS depressant, profound sedation – Concern: toxicity, abuse Mechanism of action – GABA-A agonist (increase Cl- channel opening); enhance GABA neurotransmission Examples – phenobarbital (Bayer’s Luminal; antiepileptic 1912 (Darling, 1923) – pentobarbital (Lundbeck/Akorn’s Nembutal; injectable restrictions for lethal executions) (Jolly, 2011)  Pharmacological Treatment: Benzodiazepines Second Generation – Indication: acute anxiolytic, sedative – Secondary Effects: CNS depressant, sedation – Concerns: tolerance, abuse liability, toxicity Mechanism of Action: – GABA agonist at benzodiazepine site; Enhance GABA neurotransmission Examples: – alprazolam (Xanax) panic disorder, agoraphobia – diazepam (Valium) alcohol withdrawal management, seizures – lorazepam (Ativan) long lasting or multiple seizures – clonazepam (Klonopin) panic disorder, agoraphobia, seizures  Pharmacological Treatment: (non-benzos) Z-drugs Third Generation – Indication: Chronic treatment of anxiety and insomnia – Secondary effect: cognitive impairment; sleep-related behaviors – Concerns: abuse liability and toxicity (less than) Mechanism of Action: – GABA receptor modulator; indirect GABA agonist; Enhance GABA neurotransmission Examples – zolpidem (Ambien)  Pharmacological Treatment: Alternatives antihistamines, beta-blockers azaspirodecanedione (azas-piro-de-ca-nedione) – Mechanism of Action: Serotonin and Dopamine agonist (effectiveness; Koen and Stein, 2011; MOA = 5-HT1a and DA) – Example: Buspar (buspirone); minimal sedation Antidepressants – First-line treatment for acute and chronic treatment, no abuse liability, anxiety/depression comorbid presentations – Examples: escitalopram (Lexapro; SSRI), sertraline (Zoloft; SSRI), venlafaxine (Effexor; SNRI) – Side effects – nausea, headache, insomnia, sexual dysfunction  Psychological Treatment Psychotherapy (generally preferred) – Exposure Therapy (behavior-based) Phobias – Cognitive Behavioral Therapy Change patterns of thinking and behavior Problem-solving technique Generalized Anxiety Disorder – Psychodynamic Psychotherapy Reveal the unconscious to decrease psyche tension Relaxation – panic disorder Panic disorder  Preferred Treatment Pharmacological Treatment – SSRI Psychological Treatment – Psychotherapy approach, dependent on disorder Combined Treatment – Both – to provide short-term relief of symptoms to increase efficacy of psychological treatment Depressive Disorders  Psychopathology: Depression Monoamine Theory – 3 neural systems Serotonin – Emotion regulation – Sadness Dopamine – Reward/Motivation – Anhedonia Norepinepherine – Energy – Lethargy  Pathophysiology of Depression Monoamine Theory of Depression: – Depressive symptoms are the result of a decrease in the monoamines serotonin, norepinephrine, dopamine  What if…. serotonin, norepinepherine, dopamine?  Pharmacological Treatment First Generation antidepressants Second Generation antidepressants Third Generation antidepressants (atypicals)  Pharmacological Treatment: MAOIs First Generation Monoamine oxidase inhibitors (MAOIs) – Non-selective – MOA: monomaine enzyme inhibitor (inhibits the enzyme that breaks down monoamines) Examples – iproniazid (Euphozid; 1950s; 1st)* – phenelzine (Nardil; 1961) – selegiline (Emsam) – isocarboxazid (Marplan) – tranylcypromine (Parnate)  Pharmacological Treatment: TCAs First Generation Tricyclic Antidepressants (TCAs) – Non-selective – MOA: monoamine reuptake inhibitor (increases 5-HT and NE - as well as DA to some degree -by inihibiting reuptake) Examples – imipramine (Tofranil; 1950s; the 1st) – amitriptyline (Elavil)  Pharmacological Treatment First Generation antidepressants – MAOIs and TCAs Second Generation antidepressants Third Generation antidepressants (atypicals)  Pharmacological Treatment: SSRIs Second Generation Selective Serotonin Reuptake Inhibitors (SSRIs) – Selective – MOA: serotonin reuptake inhibitor (increases serotonin by preventing reuptake) Examples – fluoxetine (Prozac; 1980s; revolutionary) – paroxetine (Paxil) – escitalopram (Lexapro) – sertraline (Zoloft)  Pharmacological Treatment First Generation antidepressants – MAOIs and Tricyclics Second Generation antidepressants – SSRIs Third Generation antidepressants (atypicals)  Pharmacological Treatment: SNRIs Third Generation Serotonin Norepinepherine Reuptake Inhibitors (SNRIs) – Selective – MOA: 5-HT and NE reuptake inhibitors (increases serotonin and norepinephrine - and dopamine to a small degree - by preventing reuptake) Examples – venlafaxine (Effexor; 1993; 1st) – duloxetine (Cymbalta) – buproprion (Wellbutrin; DA and NE reuptake inhibitor)  Pharmacological Treatment: Treatment Considerations weeks to see improvements ~50% success rate Discontinuation syndrome Withdrawal symptoms with abrupt discontinuation Side effects – dry mouth, constipation and weight gain MAOIs and TCAs – tremors; food and drug restrictions SSRIs – sexual dysfunction SNRIs – initial nervousness, insomnia, excessive sweating  Psychological Treatment Psychotherapy (generally preferred) – Cognitive Behavioral Therapy Change patterns of thinking and behavior Problem-solving technique – Cognitive Therapy Change patterns of thinking Challenge negative thoughts/perceptions of the world Mild-moderate depression  Preferred Treatment Pharmacological Treatment – SSRI/SNRI – Delayed desired effects but immediate side effects Psychological Treatment – Psychotherapy approach Combined Treatment – Both – to provide short-term relief of symptoms to increase efficacy of psychological treatment Schizophrenia  Schizophrenia Neuropathology Disconnection of reality; psychosis is associate with… Monoamine Theory of Schizophrenia – 2-Factor Dopamine Hypothesis – Dopamine and Serotonin Hypothesis Hypofunctionality Hypothesis – Dysregulation of glutamatergic neural system Cortical hypofunction of glutamatergic neural signaling (decreased NMDA receptor function) Cholinergic Hypothesis – Dysregulation of cholinergic neural system Cholinergic receptor systems regulate downstream neural systems (e.g., DA and GLU) are dysfunctional Decrease in ACh neurotransmission 34  Defining Schizophrenia Monoamine Theory of Schizophrenia: – Schizophrenia symptoms are the result of excess dopamine (DA) in the mesolimbic pathway (+) and DA deficiency in the mesocortical pathway [(-) and cognitive)] DA in mesolimbic DA in mesocortical Antipsychotics No treatment for psychotic features until the 1950s  Antipsychotic Treatment 1950s chlorpromazine (Thorazine) was synthesized (antihistamine) – (comprehensive) History Considered as the greatest scientific advancement in psychiatric care Contributed to nearly 50% psychiatric discharges  Neuropathophysiology: Schizophrenia 4 Major Dopamine Pathways Symptomology? Side Effects? Mesolimbic Mesocortical Nigrostriatal Tuberoinfundibular  Neuropathophysiology: Schizophrenia 4 Major Dopamine Pathways Symptomology? Side Effects? Mesolimbic Mesocortical Nigrostriatal Tuberoinfundibular  Pharmacological Treatment First Generation Antipsychotics – chlorpromazine (Thorazine) Second Generation Antipsychotics Third Generation Antipsychotics  Pharmacological Treatment: Dopamine Antagonists First Generation (typical) Dopamine antagonist – blocks dopamine everywhere Desired Effects – Alleviation of positive symptoms Example – chlorpromazine (Thorazine)  Pharmacological Treatment: Dopamine Antagonists First Generation (typical) Dopamine antagonist – blocks dopamine everywhere Desired Effects – Alleviation of positive symptoms Example – chlorpromazine (Thorazine)  Pharmacological Treatment: Dopamine Antagonists First Generation (typical) Dopamine antagonists chlorpromazine (Thorazine) Side effects – Extrapyramidal symptoms (4) Dystonia (muscle contraction) akathisia (restlessness) Parkinsonism (bilateral tremor, rigidity) tardive dyskinesia (repetitive muscle contraction) – Psychomotor slowing Neurolepsis – Blocks dopamine in the nigrostriatal pathway  Pharmacological Treatment: Dopamine Antagonists First Generation (typical) Dopamine antagonists chlorpromazine (Thorazine) Side effects – Hyperprolactinemia – Gynecomastia – Blocks dopamine in the tuberoinfundibular pathway  Pharmacological Treatment First Generation Antipsychotics – Typical – chlorpromazine (Thorazine) – Blocks dopamine function Second Generation Antipsychotics Third Generation Antipsychotics  Pharmacological Treatment First Generation Antipsychotics – Typical – chlorpromazine (Thorazine) – Blocks dopamine function Second Generation Antipsychotics – Atypical – clozapine (Clozaril) – Blocks dopamine and serotonin function (although to a lesser effect) Third Generation Antipsychotics  Pharmacological Treatment: Dopamine/Serotonin Antagonists Second Generation (atypical) Dopamine/Serotonin antagonist – blocks dopamine and serotonin Desired Effects – Alleviation of positive and negative symptoms Example – clozapine (Clozaril)  Pharmacological Treatment: Dopamine/Serotonin Antagonists Second Generation (typical) Dopamine/Serotonin antagonist – blocks dopamine and serotonin Desired Effects – Alleviation of positive and negative symptoms Example – clozapine (Clozaril)  Pharmacological Treatment: Dopamine/Serotonin Antagonists Side Effects Lower incidents of extrapyramidal symptoms Decreased risk of hyperprolactemia and gynecomastia Weight gain (metabolic syndrome)  Pharmacological Treatment First Generation Antipsychotics – Typical – chlorpromazine (Thorazine) – Blocks dopamine function – Positive Symptoms Second Generation Antipsychotics – Atypical – clozapine (Clozaril) – Blocks dopamine and serotonin function – Positive and Negative Symptoms Third Generation Antipsychotics  Pharmacological Treatment First Generation Antipsychotics – Typical - chlorpromazine – Blocks dopamine function – Positive Symptoms Second Generation Antipsychotics – Atypical – clozapine – Blocks dopamine and serotonin function – Positive and Negative Symptoms Third Generation Antipsychotics  Pharmacological Treatment: Dopamine/Serotonin Partial Agonists Third Generation (atypical) Dopamine/Serotonin partial agonist – Restores dopamine and serotonin neural activity where needed Desired Effects – Alleviation of positive, negative and cognitive symptoms Example – aripiprazole (Abilify)  Pharmacological Treatment: Dopamine/Serotonin Partial Agonists Third Generation (atypical) Dopamine/Serotonin partial agonist – Restores dopamine and serotonin neural activity where needed Desired Effects – Alleviation of positive, negative and cognitive symptoms Example – aripiprazole (Abilify)  Pharmacological Treatment: Dopamine/Serotonin Partial Agonists Third Generation (atypical) Dopamine/Serotonin partial agonist – Restores dopamine and serotonin neural activity where needed Desired Effects – Alleviation of positive, negative and cognitive symptoms Example – aripiprazole (Abilify)  Pharmacological Treatment: Dopamine/Serotonin Partial Agonists Side Effects (Same as Second Generation) Lower incidents of pseudoparkinsoniasm Decrease risk of hyperprolactemia and gynecomastia Weight gain (metabolic syndrome)  Pharmacological Treatment: Dopamine/Serotonin Partial Agonists First Generation Antipsychotics – Typical – chlorpromazine (Thorazine) – Blocks dopamine function – Relief of positive symptoms Second Generation Antipsychotics – Atypical – clozapine (Clozaril) – Blocks dopamine and serotonin function – Relief of positive and negative symptoms Third Generation Antipsychotics – Atypical – aripiprazole (Abilify) – Restores dopamine and serotonin function where needed – Relief of positive, negative and some cognitive symptoms  Pharmacological Treatment: First Generation Antipsychotics – Typical – chlorpromazine (Thorazine) – Blocks dopamine function – Relief of positive symptoms Second Generation Antipsychotics – Atypical – clozapine (Clozaril) – Blocks dopamine and serotonin function – Relief of positive and negative symptoms Third Generation Antipsychotics – Atypical – aripiprazole (Abilify) – Restores dopamine and serotonin function where needed – Relief of positive, negative and some cognitive symptoms  Pharmacological Treatment: First Generation Antipsychotics Second Generation Antipsychotics Third Generation Antipsychotics “Fourth Generation” Antipsychotics – Paradigm Shift – Cholinergic agents Pharmacological Treatment: Muscarinic M1/M4 Agonists Aim of antipsychotic medications? Restore dopamine and serotonin function While minimizing side effects  Key Concepts Patient adherence is threatened by lack of immediate effects (antidepressants), side effects (anxiolytics and antidepressants) and resources (i.e., money, insurance, transportation, services). First line medication for anxiety and depression are SSRI and SNRIs. All anxiolytics and antidepressants aim to increase GABA and monoamine neurotransmission, respectively. However, the various generations and classification of drugs are different based on their mechanism of action and side effect profile. Chlorpromazine is defined as the biggest scientific advancement and Cobenfy (xanomeline and trospium chloride) is regarded as the contributor to the recent paradigm shift in schizophrenia treatment. Antipsychotic drugs are classified based on the mechanism of action. The side effect profile decreased with the development of each generation. Psychotherapy (Exposure, Cognitive Behavioral, Cognitive and Psychodynamic Therapy) in conjunction with pharmacological treatment may provide the greatest therapeutic effect.