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| Feature | Aripiprazole [First Line] | Olanzapine | Quetiapine | Clozapine [Refractory] | Risperidone (Paliperidone) | Lurasidone | Loxapine [FGA] | Haloperidol [FGA] | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Injectable? | ✓, LAI | ✓, LAI | | | ✓, LAI | ✓ | | ✓, LAI | | Affinity | | | ↓↓↓ | ↓↓↓ | +++ | | | +++ | | Agitation | | ✓ (5-10 Q2h) | | | | | ✓ (25 Q1h) | ✓ (2-5 Q1h) | | Mania | ✓ | | ✓ | | ✓ | | | | | Depression | Mono (Adj) | | Bipolar | | | Bipolar | | | | Sedation | | +++ | ++ | ++++ | + | | + | | | EPS | | ↓↓ | ↓↓↓ | ↓↓↓ | | | + | +++ | | Metabolic | | +++ | + | +++ | + | + | | | | Seizure | | | | ++ | ↓↓↓ | | | | | QT | | | + | | | | | + | | Prolactin ↑ | | | | | + | | + | |

Left = high, right = low (affinity)

High Affinity A/E
Dopamine Blockage
EPS, hyperprolactinemia

Low Affinity A/E
Muscarinic AchR Blockage
Tachycardiac, Hypotenson, Constipation
Anti-histamine Effect
Sedation, Metabolic effect (weight gain)
K channel blockage
Ventricular arrhythmia (LQT)
<aside>
First-line:
Olanzapine (Zyprexa®) - most similar MOA to clozapine, some evidence more effective than others

Treatment-resistant Sc (tried 2 different drugs)
Consider A/E Profile, Monitor side-effects, adherence (LAI)
Not very effective in improving patient QoL outcomes (negative and cognitive symptoms…) </aside>