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Antipsychotic Update 2/23/2019 Antipsychotic Update Carrie L. Kreps Pharm.D., BCGP, FASCP 1 Objectives ● Define and classify antipsychotic drugs (APD). ● Explain the mechanism of action of antipsychotic drugs. ● List various indications of APDs. ● Explain adverse effects of antipsychotic drugs. ● Understand how a pharmacist can monitor side effects. ● Describe new atypicals on the market. ● Explain differences in cost of APDs. ● Recognize which APDs are long-acting injectables. ● Predict which APDs are more/less desirable in various scenarios. 2 Definition ● Class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia, or disordered thoughts) ● Increasingly being used in the management of non- psychotic disorders 3 1 2/23/2019 Most Common Uses ● Schizophrenia ● Schizoaffective disorder ● Bipolar disorder ● Psychotic depression ● Treatment resistant major depression ● Adjunctive treatment in some anxiety disorders ● Acute treatment of agitation ● Dementia or insomnia where no other treatments have worked 4 Classification of Antipsychotics Typical (1st generation) APD ● D2 antagonist ● Higher risk of EPS Atypical (2nd generation) APD ● D2/5-HT2A antagonist ● Higher risk of metabolic effects ● Lower risk of EPS 5 APD Effects Pathways Function 1st Generation APD 2nd Generation APD Nigrostriatal Movement Higher risk for EPS Lower risk for EPS Mesolimbic Arousal, memory, Decreased positive Decreased positive motivation symptoms symptoms Mesocortical Cognition, Increased negative Decreased or no effect communication, symptoms on negative symotins social function, response to stress Tuberoinfundibular Regulates prolactin Higher risk for Lower risk for release Hyperprolactinemia Hyperprolactinemia 6 2 2/23/2019 Extrapyramidal Symptoms (EPS) https://youtu.be/2xfu-d_aYWs 7 Extrapyramidal Symptoms (EPS) EPS Acute Dystonia Akathisia Pseudoparkinsonism Tardive dyskinesia Looks like Stiff neck, muscle rigidity, “Ants in pants”, severe Shuffling gait, Involuntary eye deviation, trouble internal restlessness, expressionless face, movement of facial swallowing, spasm of the can’t sit still rigidity/tremors muscle, jerky limb body movement Onset Hours to days of treatment ≤ 1-4 weeks of treatment ≤ 1-3 months of After Months to initiation or dosage initiation or dosage treatment initiation or years of therapy increase increase dosage increase Treatment 1. parenteral: -beta blocker -anticholinergic -valbenazine -anticholinergic (Cogentin) (propanolol) (Cogentin) (Ingrezza) or benadryl -benzodiazepine(ativan) -amantadine -deutetrabenazine -benzodiazepine (ativan) -anticholinergic (Austedo) 2. Follow-up with oral (Cogentin) anticholinergic (Cogentin) 8 APDs: Dirty Drugs Other receptors Dopamine inhibition Alpha-1 Orthostatic hypertension H-1 Sedation, weight gain 5-HT2C Weight gain, mood, cardiovascular effect Muscarinic receptors anti-SLUD effects, tachycardia, impaired cognition/memory 9 3 2/23/2019 1st Generation (Typical) Low potency High potency ● Chlorpromazine ● Fluphenazine ● Prochlorperazine ● Haloperidol ● Thioridazine ● Pimozide ● Thiothixene 10 2nd Generation (Atypical) ● Asenapine (Saphris) ● Olanzapine (Zyprexa) ● Clozapine (Clozaril) ● Quetiapine (Seroquel) ● Iloperidone (Fanapt) ● Paliperidone (Invega) ● Ziprasidone (Geodon) ● Risperidone (Risperdal) ● Lurasidone (Latuda) 11 Newer Atypical ● D2 partial agonist ○ Aripiprazole (Abilify) 2002 ○ Brexpiprazole (Rexulti) 2015 ● D3-preferring D3/D2 receptor partial agonist ○ Cariprazine (Vraylar) 2015 ● 5HT2A inverse agonist/antagonist with no D2 affinity ○ Pimavanserin (Nuplazid) 2014 12 4 2/23/2019 Cost ● LAIs can cost up to four times as much as the oral equivalent, but this cost increase can be offset by a reduction in hospitalization related medical costs. ● Most 2nd gen APDs cost >$1000/month 13 Long-acting Injectables (LAI) ● LAIs ensure medication delivery, NOT efficacy. ● Ideally used in patients who respond to and tolerate antipsychotic medications that are available in LAI formulations. ● Allows for better ability to distinguish between lack of efficacy and poor adherence. ● Not for short-term therapy (<3 months). ● Consider for any patient with schizophrenia and risk factors for non- adherence (history on non-adherence, substance abuse, cognitive impairment, ambivalence towards medicine). 14 LAI Dosing 1. Start or convert patient to an oral dosage form of the desired antipsychotic medicine (one that has an LAI formulation) 2. Give trial of oral dosage form to determine clinical response, tolerability, and effective dose (at least 3-7 days) 3. Convert from oral dosage form to LAI 15 5 2/23/2019 LAIs and Dosing Intervals ● Risperdal consta - every 2 weeks ● Fluphenazine decanoate - every 2-3 weeks ● Zyprexa relprevv - every 2-4 weeks ● Haloperidol decanoate - every 4 weeks ● Invega sustenna - every 4 weeks ● Abilify maintena - every month ● Aristada (aripiprazole lauroxil) - every 1-2 months ● Invega trinza - every 3 months 16 LAI Advantages vs Disadvantages Disadvantages Advantages ● Varying pharmacokinetics ● Improved adherence and dosing intervals ● Reduced risk of overdose ● Adverse effects may persist ● Reduced hospitalization rates after stopping/reducing ● Bypasses pharmacokinetic dose hurdles of absorption and ● Injection related adverse first pass hepatic elimination effects ● Improved relapse prevention ● Some patients may feel a lack of autonomy ● High cost 17 6.
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