Antipsychotics & Mood Stabilizers ppt
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Questions and Answers

What is the primary mechanism by which antipsychotics reduce psychotic symptoms?

  • By stimulating the hypothalamic-pituitary-adrenal axis
  • By increasing dopaminergic neurotransmission in the mesolimbic system
  • By blocking dopamine receptors in the mesocortical pathway
  • By reducing dopaminergic neurotransmission in the mesolimbic system (correct)

    • Which of the following is a negative symptom of psychosis?

  • Delusions
  • Hallucinations
  • Anxiety
  • Avolition (correct)

    • What is the primary concern when using antipsychotics in elderly patients with dementia-related psychosis?

  • Sedation
  • Increased mortality (correct)
  • Risk of addiction
  • Weight gain

    • Which of the following is an example of a delusion?

    <p>Believing that external forces are controlling one's thoughts</p> Signup and view all the answers

    What is the dopamine hypothesis of psychosis?

    <p>Hyperdopaminergic activity in the mesolimbic system leads to positive symptoms</p> Signup and view all the answers

    What is alogia?

    <p>Poverty of speech</p> Signup and view all the answers

    Why do some patients report dysphoria when taking antipsychotics?

    <p>Because antipsychotics block normal thoughts as well as delusions</p> Signup and view all the answers

    What is the result of antipsychotics on delusions and hallucinations?

    <p>They allow patients to work through symptoms in other ways, making delusions and hallucinations dormant</p> Signup and view all the answers

    What is the primary mechanism of action of first-generation antipsychotics?

    <p>D2 receptor antagonists</p> Signup and view all the answers

    Which of the following is NOT a side effect of first-generation antipsychotics?

    <p>Hypertension</p> Signup and view all the answers

    What is the primary mechanism of action of partial agonists in the prefrontal cortex?

    <p>Increasing the action of dopamine</p> Signup and view all the answers

    Which of the following antipsychotics is associated with blue-grey skin pigmentation?

    <p>Chlorpromazine</p> Signup and view all the answers

    What is the primary treatment for neuroleptic malignant syndrome?

    <p>Dantrolene sodium</p> Signup and view all the answers

    Which of the following is a common side effect of first-generation antipsychotics due to blockade of dopamine in the hypothalamus?

    <p>Increased prolactin levels</p> Signup and view all the answers

    What is the primary mechanism of action of third-generation antipsychotics?

    <p>Partial agonists</p> Signup and view all the answers

    Which of the following is a side effect of first-generation antipsychotics due to blockade of muscarinic receptors?

    <p>Anticholinergic effects</p> Signup and view all the answers

    What is the primary indication for antipsychotics?

    <p>Schizophrenia/schizoaffective disorder</p> Signup and view all the answers

    Which of the following is a side effect of first-generation antipsychotics due to blockade of H1 receptors?

    <p>Sedation</p> Signup and view all the answers

    What is the primary mechanism of action of Valbenazine (Ingrezza) in reducing tardive dyskinesia severity?

    <p>VMAT2 inhibitor</p> Signup and view all the answers

    What is the primary goal of conservative dosing in preventing tardive dyskinesia?

    <p>Minimizing dosage to reduce side effects</p> Signup and view all the answers

    What is the typical timeframe for observing a decrease in tardive dyskinesia severity with Valbenazine (Ingrezza) treatment?

    <p>6 weeks</p> Signup and view all the answers

    What is the cost of 30 capsules of Valbenazine (Ingrezza) at a dose of 80 mg?

    <p>$6,225</p> Signup and view all the answers

    What is the primary advantage of 2nd Generation (Atypical) Antipsychotics compared to traditional antipsychotics?

    <p>Reduced risk of extrapyramidal symptoms</p> Signup and view all the answers

    What is the recommended initial dosing strategy for antipsychotics in order to minimize side effects?

    <p>Start low, go slow</p> Signup and view all the answers

    What percentage of schizophrenia patients have limited antipsychotic response?

    <p>30%</p> Signup and view all the answers

    What is the minimum dosage of chlorpromazine required for a trial to be considered adequate for treatment-resistant schizophrenia?

    <p>600mg</p> Signup and view all the answers

    What is the recommended reduction in symptoms required to consider a patient 'minimally improved' on the Clinical Global Impression-Schizophrenia Scale?

    <p>&lt;20%</p> Signup and view all the answers

    What is the estimated response rate to clozapine in treatment-resistant schizophrenia patients who did not respond to prior antipsychotics?

    <p>75%</p> Signup and view all the answers

    What is the estimated mortality rate due to agranulocytosis associated with clozapine?

    <p>2.7-3.0%</p> Signup and view all the answers

    What is the recommended clozapine dose reduction when a patient stops smoking?

    <p>30%</p> Signup and view all the answers

    What is the estimated percentage of people with schizophrenia who smoke?

    <p>70-80%</p> Signup and view all the answers

    What is the purpose of the Risk Evaluation Mitigation Strategy (REMS) program/registry for clozapine?

    <p>To ensure safe distribution and use</p> Signup and view all the answers

    What is a predictor of good response to clozapine in treatment-resistant schizophrenia?

    <p>Prior response to a drug</p> Signup and view all the answers

    What is the term for non-adherence to medication that may masquerade as treatment-resistant schizophrenia?

    <p>Pseudo-resistance</p> Signup and view all the answers

    Which of the following mood stabilizers is associated with a decrease in the risk of suicide?

    <p>Lithium</p> Signup and view all the answers

    In patients with bipolar disorder, what is the recommended duration of maintenance therapy after an acute manic episode?

    <p>Indefinite therapy</p> Signup and view all the answers

    What is the primary mechanism of action of lithium in bipolar disorder?

    <p>Inhibition of postsynaptic D2 receptor supersensitivity</p> Signup and view all the answers

    What is the contraindication for lithium use in the first trimester of pregnancy?

    <p>Risk of Epstein's anomaly</p> Signup and view all the answers

    What is the recommended serum therapeutic range for lithium?

    <p>0.6-1.2 mEq/L</p> Signup and view all the answers

    What is the most common adverse effect of lithium therapy?

    <p>Leukocytosis</p> Signup and view all the answers

    What is the recommended frequency for monitoring lithium levels after initiation?

    <p>Every 5 days</p> Signup and view all the answers

    What is the primary treatment for lithium toxicity?

    <p>IV fluids and monitoring</p> Signup and view all the answers

    What is the risk associated with abrupt discontinuation of lithium therapy?

    <p>Increased risk of relapse</p> Signup and view all the answers

    Which of the following medications can alter lithium levels?

    <p>All of the above</p> Signup and view all the answers

    What percentage of people with bipolar disorder report at least one stressful life event before a manic or depressive episode in the preceding 6 months?

    <p>60%</p> Signup and view all the answers

    What is the hallmark of bipolar I disorder?

    <p>A manic episode</p> Signup and view all the answers

    What is the primary difference between bipolar I and bipolar II disorder?

    <p>The presence of hypomanic episodes</p> Signup and view all the answers

    What is the primary treatment for rapid cyclers?

    <p>Valproate</p> Signup and view all the answers

    What is the primary mechanism of action of mood stabilizers?

    <p>Modulating intracellular signaling pathways to enhance cell survival and plasticity</p> Signup and view all the answers

    What is the primary reason why patients with bipolar disorder may not adhere to their medication regimen?

    <p>All of the above</p> Signup and view all the answers

    What is the primary risk factor for suicide in patients with bipolar disorder?

    <p>Depressive episodes</p> Signup and view all the answers

    What is the primary effect of lithium on suicide rates in patients with bipolar disorder?

    <p>It decreases suicide rates</p> Signup and view all the answers

    What is the goal of minimizing extrapyramidal symptoms and other side effects during antipsychotic treatment?

    <p>To promote adherence to the treatment regimen</p> Signup and view all the answers

    What is the recommended approach to titrating medication during the initial 7-day period of antipsychotic treatment?

    <p>Titrate the medication close to or to the effective dose</p> Signup and view all the answers

    What is the primary characteristic of cyclothymia?

    <p>Brief episodes of hypomania and depression</p> Signup and view all the answers

    What is the primary reason why patients with bipolar disorder experience a decreased life expectancy?

    <p>All of the above</p> Signup and view all the answers

    Which of the following antipsychotics is associated with a high risk of prolactin elevation and breast cancer in women?

    <p>Paliperidone</p> Signup and view all the answers

    What is the primary goal of antipsychotic treatment during the 2-3 week period?

    <p>To promote socialization and self-care habits</p> Signup and view all the answers

    Which of the following antipsychotics is associated with a high risk of seizures?

    <p>Ziprasidone</p> Signup and view all the answers

    What is the recommended approach to managing treatment-resistant psychosis?

    <p>To try another atypical antipsychotic</p> Signup and view all the answers

    Which of the following side effects is commonly associated with olanzapine?

    <p>Weight gain</p> Signup and view all the answers

    What is the primary goal of antipsychotic treatment during the 6-8 week period?

    <p>To reach the target dose and maintain it</p> Signup and view all the answers

    Which of the following antipsychotics is associated with a high risk of orthostatic hypertension?

    <p>Brexpiprazole</p> Signup and view all the answers

    What is the recommended approach to managing psychotic symptoms that persist after 2 atypical antipsychotics have been tried?

    <p>To consider clozapine</p> Signup and view all the answers

    Above which level of serum valproic acid does dialysis become indicated?

    <p>2.5 mEq/L</p> Signup and view all the answers

    What is the typical range of effective serum levels for valproic acid?

    <p>50-100</p> Signup and view all the answers

    Which of the following is a rare but fatal adverse effect of valproic acid?

    <p>Hepatotoxicity</p> Signup and view all the answers

    What is the primary concern when using carbamazepine in patients of Asian ancestry?

    <p>HLA-B*15:02 allele</p> Signup and view all the answers

    What is the primary advantage of oxcarbazepine over carbamazepine?

    <p>Less hepatic toxicity</p> Signup and view all the answers

    What is the most common adverse effect of oxcarbazepine?

    <p>Hyponatremia</p> Signup and view all the answers

    What is the recommended dosing strategy for lamotrigine?

    <p>Start low, go slow</p> Signup and view all the answers

    What is the primary concern when using mood stabilizers in women of childbearing age?

    <p>Teratogenicity</p> Signup and view all the answers

    What is the recommended approach to mood stabilizer treatment?

    <p>Use a mood stabilizer in every phase of treatment</p> Signup and view all the answers

    What is the primary concern when using antidepressants in patients with bipolar disorder?

    <p>Switch to mania or hypomania</p> Signup and view all the answers

    Study Notes

    Psychosis

    • Functionally disruptive symptoms with abnormal psychomotor behaviors, negative symptoms, cognitive impairments, and emotional disturbances
    • Presence of delusions or hallucinations without insight, or both
    • Defining feature of Schizophrenia Spectrum Disorders
    • Many psychiatric, neurodevelopmental, neurological, and medical conditions can cause psychosis

    Positive and Negative Symptoms

    • Positive (+) Symptoms:
      • Hallucinations (audio, tactile, visual)
      • Delusions (untrue, irrational, firm fixed beliefs)
    • Negative (-) Symptoms:
      • Neglect personal hygiene
      • Need assistance with ADLs
      • Thought disorders (alogia, thought blocking, word salad, perseveration)
      • Flat affect
      • Avolition (decrease in initiation of goal-directed behavior)
      • Anhedonia (lack of pleasure in activities, social interactions)

    Dopamine Hypothesis

    • Hyperdopaminergic activity in the Mesolimbic system: (+) symptoms
    • Hypodopaminergic activity in the Mesocortical pathway: (-) symptoms, cognition, and affect

    Antipsychotics

    • All reduce dopaminergic neurotransmission
    • Do not erase delusions, but block dopamine to allow patients to work through symptoms
    • Can cause dysphoria, which increases non-adherence

    Antipsychotic Terminology

    • Full agonist: binds to the receptor to induce a full biological response
    • Full antagonist: binds to the receptor and blocks the action of the endogenous neurotransmitter
    • Partial agonist: has lower intrinsic activity at the receptor than a full agonist
    • D2 antagonists: block D2 receptors (1st and 2nd generation antipsychotics)

    Antipsychotic Indications

    • Schizophrenia/schizoaffective disorder
    • Bipolar disorder
    • Acute psychosis (mania)
    • Major depressive disorder with psychotic features
    • Borderline personality disorder
    • Tourette syndrome

    1st Generation Antipsychotics (FGAs)

    • MOA: D2 receptor antagonists
    • Antipsychotic effect: relief of positive symptoms
    • Induction of extrapyramidal side effects (EPS)
    • Other MOA: 5-HT2c receptor antagonist, alpha 1 antagonist, H1 antagonist, M1 antagonist

    1st Generation Antipsychotic Adverse Drug Reactions (ADRs)

    • Extrapyramidal side effects (abnormal, involuntary movements)
    • Neuroleptic malignant syndrome
    • Anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision, confusion)
    • Moderate weight gain
    • Sedation
    • Orthostatic hypertension
    • Increased prolactin levels

    2nd Generation Antipsychotics (SGAs)

    • MOA: 5-HT2A/D2 antagonists
    • First-line pharmacotherapy
    • Less EPS (extrapyramidal symptoms)
    • (+) Sx relief; impact (-) sxs by improving apathy, social withdrawal, decreased motivation, and cognitive impairment
    • MOA: D2 receptor antagonists (+) Sx improvement; 5-HT2A antagonist (-) Sx improvement

    2nd Generation Antipsychotic ADRs

    • Moderate to severe weight gain
    • Metabolic syndrome
    • Sedation
    • Increased QT prolongation
    • Neuroleptic malignant syndrome
    • Seizures
    • Prolactin-elevation antipsychotics

    3rd Generation Antipsychotics (TGAs)

    • MOA: Partial D2/5-HT1 agonist/5HT2A antagonist
    • Indications: Schizophrenia, Bipolar Mania, Major Depressive Disorder
    • ADRs: Weight gain, headache, agitation, insomnia, anxiety

    Treatment-Resistant Schizophrenia (TRS)

    • Definition: Limited antipsychotic response, high burden to patients, families, and society
    • Treatment recommendations: Clozapine, currently the only indicated and evidence-based pharmacologic treatment for TRS

    Mood Stabilizers

    • Definition: Treat episodic course, relatively stereotyped features with clear subtypes, or variable presentation

    • Symptoms: Inability to remain in homeostasis, interaction of genetic, epigenetic, neurochemical, and environmental factors

    • Predictors of good response: Prior response to a drug, absence of EtOH or drug abuse, acute onset/short duration of illness, affective symptoms, family history of affective illness, medication compliance### Bipolar Disorder Treatment

    • Lithium and mood stabilizers are associated with an increase in gray matter volume

    • Acute mania, acute depression, and reduction of future episodes are treated with maintenance regimens

    • Mixed episodes are characterized by high highs and low lows

    Maintenance Treatment

    • Patients are at high risk of relapse for up to 6 months after remission of an acute episode
    • Lithium, valproate, lamotrigine, carbamazepine, and oxcarbazepine are recommended for maintenance treatment
    • Best empirical evidence supports the use of lithium and valproate in maintenance treatment

    Mood Stabilizers

    Lithium

    • Indicated for 1st-line and maintenance treatment of bipolar disorder
    • MOA: inhibits postsynaptic D2 receptor supersensitivity and alters cation transport in nerve and muscle cells
    • Narrow serum therapeutic range: 0.6-1.2 mEq/L (0.4-0.8 mEq/L for elderly)
    • Dosing considerations: abrupt discontinuation can lead to relapse
    • Contraindications/precautions: severe cardiovascular disease, pregnancy (1st trimester), unstable renal function, dehydration, and sodium depletion
    • Monitoring: check levels at steady state (5 days), before/after every dose change, and with change in other medications
    • Warnings: suicide risk, nephrogenic diabetes insipidus, polyuria/polydipsia, hypercalcemia, and hyperthyroidism
    • Adverse reactions: leukocytosis, dry mouth, hand tremor, confusion, vertigo, decreased memory, and EKG changes

    Lithium Toxicity

    • >1.2 mEq/L: nausea, diarrhea, tremor, ataxia, cognitive slowing
    • >1.5 mEq/L: coarse tremor, dizziness, vomiting, diarrhea, ataxia, confusion
    • >2.0 mEq/L: delirium, EEG changes, impaired renal function, arrhythmias, coma
    • >2.5 mEq/L: ARF, seizures; treated with IVFs and monitoring, and dialysis if necessary

    Valproic Acid

    • Indicated for acute mania and maintenance treatment
    • Effective serum levels: typically 50
    • Adverse reactions: mild and transient LFT elevation, rare fatal hepatotoxicity, N/V/D, sedation, ataxia, tremor, weight gain, and thrombocytopenia
    • Teratogenicity: neural tube defects in fetus
    • DDI: weak inhibitor of CYP2C9 and CYP2C19, highly protein bound

    Carbamazepine (Tegretol)

    • Indicated as an anticonvulsant in lieu of lithium or valproic acid or as an adjunct
    • DDI: protein bound, metabolized by liver, auto-inducer of own hepatic enzymes
    • Adverse reactions: ↑ risk of SJS and TEN, HLA-B 15:02 allele in Asian ancestry, rare aplastic anemia and agranulocytosis, non-dose-related idiosyncratic hepatitis
    • Pregnancy category D: risk of neural tube defects

    Oxcarbazepine (Trileptal)

    • Indicated as an anticonvulsant in lieu of lithium or valproic acid or as an adjunct
    • No levels needed
    • Adverse reactions: hyponatremia (25%), SJS (check HLA-B*15:02), ↓ estrogen OCP levels

    Lamictal

    • Indicated for bipolar maintenance and bipolar depression
    • Dosing considerations: start low, go slow, target dose 100 mg/d
    • Adverse reactions: rash, which may lead to SJS, especially in children

    Mood Stabilizer Strategies

    • Use a mood stabilizer in every phase of illness
    • Tailor treatment to phase of illness
    • Optimize proven treatments before trying unproven ones
    • Renal disease: generally avoid lithium
    • Liver disease: generally avoid valproate
    • Sensitivity to EPS: generally avoid aripiprazole and risperidone
    • Obesity: generally avoid olanzapine, quetiapine, and risperidone
    • Women of childbearing age: avoid valproate

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