Pharmacotherapy II: Schizophrenia & Bipolar Disorder PDF

Pharmacotherapy II: Schizophrenia and Bipolar disorder Augsburg PA Program, Spring 2025 Clinton Billhorn, PA-C, CAQ-HM  Learning Objectives Schizophrenia & Bipolar Chapter 26 1. Review the clinical presentation and etiology of...

Pharmacotherapy II: Schizophrenia and Bipolar disorder Augsburg PA Program, Spring 2025 Clinton Billhorn, PA-C, CAQ-HM  Learning Objectives Schizophrenia & Bipolar Chapter 26 1. Review the clinical presentation and etiology of schizophrenia. 2. Differentiate between positive and negative symptoms of schizophrenia. 3. Classify the 1st and 2nd generation antipsychotics by potency and incidence of extrapyramidal side effects. 4. Define early and late extrapyramidal side effects, the features, and management, including tardive dyskinesia. 5. Discuss the approach to other adverse effects (non-extrapyramidal) of antipsychotic medications (NMS, anticholinergic effects, hypotension, agranulocytosis, dysrhythmias, etc). 6. Know the black box warnings and lab monitoring for clozapine. 7. Summarize the key prescribing considerations and patient education for a patient receiving treatment with 1st and 2nd generation antipsychotics. 8. Discuss benefits and risks for the use of depot antipsychotic preparations. 9. Know the 3 major objectives of drug therapy for schizophrenia. 10. Outline the general approach to drug selection, dosing, routes, initial therapy, maintenance therapy, adherence, and non-drug therapy for schizophrenia. Chapter 28 11. Review the characteristics of bipolar disorder, including types, patterns, and etiology. 12. Describe the 3 major types of drugs used to treat bipolar disorder. 13. Differentiate between the drugs of choice for acute therapy for manic episodes, depressive episodes, and long-term prevention. 14. Summarize the key prescribing considerations, lab monitoring, and patient education for a patient receiving treatment with Lithium. 15. Know the black box warnings for lithium, carbamazepine, lamotrigine, and antipsychotics (in older populations). For the following representative medications (included on the Unit Representative Medication List), know the medication class, mechanism of action, indications, adverse effects, contraindications, interactions (common), monitoring (if needed), and patient education. Chlorpromazine Haloperidol Clozapine Aripiprazole Olanzapine Lithium Carbamazepine Lamotrigine Valproic Acid Risperidone Quetiapine  Chlorpromazine - Antipsychotic Medication names: Thorazine MOA: Dopaminergic antagonist, serotonergic antagonist Indication: Schizophrenia, Bipolar I, agitation Adverse effects: Xerostomia, Dizziness, Urinary retention, Sedation Contraindications: Hypotension, poorly controlled seizure disorder Major interactions: CNS depressants, Levodopa/Carbidopa, SSRIs Patient Education/Clinical Pearls: Don’t take w/alcohol, risk of TD/akathisia (lower than others) Chlorpromazine - Antipsychotic Black box warning: Increased mortality in Elderly patients with dementia related psychosis  Haloperidol - Antipsychotic Medication names: Haldol MOA: Dopaminergic antagonist Indication: Schizophrenia, Tourette syndrome, severe behavioral disorders OFF LABEL → agitation, mania Adverse effects: Dystonia, Akathisia, Neuroleptic Malignant Syndrome, Parkinsonism, Tardive Dyskinesia, weight gain, xerostomia Contraindications: Parkinsons, dementia Major interactions: CNS depressant Patient Education/Clinical Pearls: Often utilized for patients w/dementia in settings of delirium/agitation Haloperidol - Antipsychotic Black box warning: Increased mortality in Elderly patients with dementia related psychosis  Clozapine - Antipsychotic Medication names: Clozaril MOA: Dopamine and serotonin antagonist, impacts alpha-adrenergic, histamine, and cholinergic receptors as well Indication: Psychosis, Resistant Bipolar, Resistant Schizophrenia Adverse effects *High risk drug*: Severe neutropenia, seizures, bradycardia, myocarditis, small bowel obstruction Contraindications: Myeloproliferative disorders, severe renal or cardiac disease Major interactions: QT Prolonging medications Patient Education/Clinical Pearls: Requires close monitoring during titration with frequent blood draws. You need help from PharmD. Clozapine - Antipsychotic Black box warning 1. Increased mortality in Elderly patients with dementia related psychosis 2. Neutropenia 3. Orthostatic hypotension 4. Seizures 5. Myocarditis and mitral valve incompetence Clozapine - Antipsychotic  Aripiprazole - Antipsychotic Medication names: Abilify MOA: Quinolinone antipsychotic, dopamine/serotonin antagonist/agonist Indication: Bipolar/Acute mania, aggression, schizophrenia Adverse effects: Sedating, akathisia, dystonia Contraindications: Bariatric surgery, CV disease, Parkinsons, Seizures Major interactions: QT prolonging medications Patient Education/Clinical Pearls: Fairly safe, well tolerated Aripiprazole - Antipsychotic Black box warning: Increased mortality in Elderly patients with dementia related psychosis and increased suicidality in children/young adults  Olanzapine - Antipsychotic Medication names: Zyprexa MOA: Serotonergic and dopaminergic antagonist Indication: Agitation, Bipolar I, Schizophrenia Adverse effects: Hyperprolactinemia, Contraindications: QT prolonging medications Major interactions: Anticholinergic medications Patient Education/Clinical Pearls: Sedating, fast acting Olanzapine - Antipsychotic Black box warning: Increased mortality in Elderly patients with dementia related psychosis  Lithium - Antimanic Medication names: Lithobid MOA: Unknown, possibly due to cation transport Indication: Bipolar I, MDD Adverse effects: Pseudotumor cerebri, serotonin syndrome Contraindications: Dehydration/Renal disease Major interactions: MAOI Patient Education/Clinical Pearls: Need to be well hydrated, narrow therapeutic window  Lithium - Antimanic Black box warning: Lithium toxicity can occur at doses close to therapeutic levels, plan for close monitoring must be in place prior to initiating  Carbamazepine - Antimanic Medication names: Tegratol MOA: Depresses activity in thalamus, limits sodium ion influx Indication: Bipolar disorder, seizures Adverse effects: Aplastic anemia, heart failure, hyponatremia, ataxia, dizziness, drowsiness Contraindications: Known blood disorder, caution in heart failure Major interactions: Apixaban (decrease effect), MAOIs, Rivaroxaban (decrease effect), HIV meds Patient Education/Clinical Pearls: Patients w/Asian ancestry should be screened for HLA-B*1502 allele variant → high risk of SJS/TEN Carbamazepine - Antimanic Black box warning: Serious dermatologic effects (HLA- B*1502), and Aplastic anemia  Lamotrigine - Antiseizure Medication names: Lamictal MOA: Inhibits glutamate and sodium channels Indication: Bipolar disorder, seizures Adverse effects: Blood disorders, increase SI Contraindications: Known blood disorders Major interactions: No major interactions Patient Education/Clinical Pearls: Weight gain Lamotrigine - Antiseizure Black box warning: Serious dermatologic reactions  Valproic Acid - Antimanic Medication names: Depakote MOA: Increased GABA, sodium channel inhibition Indication: Bipolar, seizure, Migraines Adverse effects: Dizziness, Blood disorders, hepatotoxicity, hyperammonemia Contraindications: Liver failure Major interactions: No major interactions Patient Education/Clinical Pearls: Generally well tolerated, be aware of the hyperammonemia on initiation if patient gets acutely confused Valproic Acid - Antimanic Black box warning: Hepatotoxicty, increased risk with mitochondrial disease, major congenital malformations, life- threatening pancreatitis  Risperidone - Antipsychotic Medication names: Risperdal MOA: Serotonergic and dopaminergic antagonist Indication: Bipolar, Delusional disorder, MDD, Schizophrenia Adverse effects: Akathisia, drowsiness, hyperlipidemia, dystonia, hyperglycemia, QT prolongation, weight gain Contraindications: No absolute contraindications Major interactions: No major interactions Patient Education/Clinical Pearls: Metabolic impacts Risperidone - Antipsychotic Black box warning: Increased mortality in Elderly patients with dementia related psychosis  Quetiapine - Antipsychotic Medication names: Seroquel MOA: Dopaminergic and serotonergic antagonist Indication (Therapeutic Use): Bipolar disorder, Delusional disorder, MDD, PTSD, Schizophrenia Adverse effects: Constipation, urinary retention, hyperlipidemia, hyperglycemia, weight gain, QT prolongation Contraindications: No absolute contraindications Major interactions: QT prolonging medications, Patient Education/Clinical Pearls: Metabolic effects Quetiapine - Antipsychotic Black box warning: Increased mortality in Elderly patients with dementia related psychosis and increased suicidality in children/young adults Schizophrenia  Schizophrenia Etiology Presentation Neurodevelopmental disorder Syndrome made up of positive with neuropathological changes and negative symptoms, that begin in utero cognitive impairments, mood/anxiety disorders  Symptoms Positive Negative Hallucinations Typically presents first Delusions Resistant to treatment Disorganization Blunted affect Apathy Asociality Alogia (Thought blocking)  Symptoms Cognitive impairment Mood/Anxiety Process speed Higher rates Attention Working memory Learning (verbal/visual) Reasoning Social  Antipsychotic Generations 1st Generation 2nd Generation Haloperidol Ariprazole Chlorpromazine Quetiapine Olazapine Clozapine Risperidone  Antipsychotic Generations 1st Generation Common AEs Haloperidol Higher risk of EPS Chlorpromazine Higher sedation Weight gain  Antipsychotic Generations Common AEs 2nd Generation Higher risk of metabolic syndrome Ariprazole Higher risk of QT prolongation Quetiapine Olazapine Clozapine Risperidone  Extrapyramidal Side Effects Early Late Acute dystonia Pseudoparkinsonism Neuroleptic Malignant Syndrome Tardive Dyskinesia Akathesia Management Management Benztropine Amantadine Dantroline + Benzos Discontinue offending agent Propranolol Benzos Extrapyramidal Symptoms (EPS)  Management of other AEs Limit dose Anticholinergic Frequent water Oral-balance Dysrhythmias QT monitoring IV Magnesium Avoid other QT agents  Key Prescribing/Patient Ed Key prescribing considerations Patient education Check A1c Sedation Baseline lipids Weight gain Baseline ECG Cholesterol risk  Depot Preparations Benefits Risks Improved adherence Delayed clinical improvement Reduced hospitalization Adverse effects persist Duplicate slides to repeat Predictable format. Perceived lack of autonomy Less risk of overdose High acquisition costs Bypasses hepatic elimination Special storage  Treatment of Schizophrenia 3 Major Objectives Reduce symptoms Prevent relapses Improve Quality of Life  General Treatment Approach Drug selection/Route/Dose Maintenance therapy Aripiprazole < weight gain Usually can titrate down once stable If rapid improvement needed → Olanzapine/Haldol Lowest effective dose Consider degree of sxs for route Non-drug therapy Adherence CBT 50-60% Dialogue Side effects Poor discharge planning Social skill training Assertive Community Treatment Vocational rehab 1.Get into groups of 4 2.Each group will take one case and develop plan (medication selection, labs, education, monitoring, follow-up) 3.5-10 minutes to discuss 4.Pick one person to present your answer to the class  Case #1 23 year old patient presents to psychiatric clinic with concern for lack of motivation and paranoid thinking. The symptoms are not affecting their day to day life, however they’re worried they have schizophrenia because their mom had similar symptoms at this age.  Case #2 Cops called for 30 year old patient spitting on a restaurant window and yelling at customers inside. Patient was brought to the emergency department and is yelling that they’re being held hostage and that the FBI is trying to kill them.  Case #3 27 year old patient on their 4th admission this year for decompensated schizophrenia for medication non-adherence. Once compensated he states that his pills always get stolen/lost at the shelter.  Case #4 25 year old patient with schizophrenia who attempted suicide via ingestion of 45 tablets of olanzapine. ECG obtained and QTc 650 and patient noted to have twisting/jerking movements. Bipolar disorder  Bipolar Disorder Types Bipolar I (Mania) Characteristics Bipolar II (Hypomania) Cyclothymic (Mild depression) Patterns Etiology Certain times of day Multi-factorial Year Genetic components Rapid Cycling (4+x/year) Trauma  Bipolar Disorder: Drug Classes Anticonvulsants 3 major types Valproic Acid Lamotrigine Mood stabilizers Antipsychotics Lithium Quetiapine  Bipolar Disorder Acute Mania Medication Selection Quetiapine Olanzapine Depressive Episodes Long term Valproic Acid Monotherapy or combination of Lamotrigine other agents Lithium  Lithium Management Prescribing Considerations Patient Education Kidney disease Ability to monitor Intake Small therapeutic window Hydration Lab Monitoring Routine monitoring TSH Risk of thyroid disease Creatinine Lithium Levels 1.Get into groups of 4 2.Each group will take one case and develop plan (medication selection, labs, education, monitoring, follow-up) 3.5-10 minutes to discuss 4.Pick one person to present your answer to the class  Case #1 22-year-old woman, has been feeling unusually depressed for the past few weeks, struggling to get out of bed in the mornings and feeling like nothing will ever get better. She has trouble concentrating and feels hopeless about her future. However, during the last few days, she has experienced moments of extreme excitement, staying up late into the night with ideas flooding her mind. She has been calling friends non-stop, starting projects, and feeling incredibly creative, but then crashing again into depressive episodes shortly after.  Case #2 29-year-old woman, is brought to the emergency department by her family after she became increasingly agitated and reckless over the past few days. She has a history of bipolar disorder but has been stable on medication for over a year. Recently, stopped taking her prescribed mood stabilizers because she felt "better than ever" and didn't need them. For the past week, her behavior has been increasingly erratic. She hasn't been sleeping, staying up for days at a time, and engaging in impulsive activities, such as driving long distances without a clear destination, spending large sums of money on luxury items she doesn’t need, and making grandiose plans that she can’t realistically follow through with. She has been talking excessively, her speech is rapid, and she has difficulty staying focused on a single topic. Her family is worried about her safety, as she has also exhibited poor judgment, including offering a large sum of money to strangers she met online.  Case #3 40-year-old man, has a long history of cycling moods. In the past, he’s experienced weeks of feeling overly happy, productive, and energetic, followed by episodes of extreme sadness, loss of interest in hobbies, and fatigue. Currently, he’s in a hypomanic phase. He feels unusually confident at work, takes on excessive responsibilities, and often interrupts colleagues in meetings. He also feels unusually flirtatious with his coworkers and has been impulsively spending on items he doesn’t need. He’s aware of these changes but is having trouble managing them.  Case #4 25-year-old woman, has recently been feeling irritable and unusually energetic. Over the past few days, she has been planning to travel internationally and starting multiple projects without completing any of them. She goes from being overly cheerful and sociable one moment to snapping at her friends and family the next. Her thoughts feel jumbled, and she’s overwhelmed by ideas. Her sleep is disrupted, and she finds herself unable to stay still for long periods. Recently, her energy crashed, and she began feeling hopeless, with difficulty getting out of bed for days.  References Assigned chapters UptoDate [email protected]