Most of the drugs in the second generation, known as atypical antipsychotics, have been developed more recently, although the first atypical antipsychotic, clozapine. Both generations of medication tend to block receptors in the brain's dopamine pathways, but antipsychotic drugs encompass a wide range of receptor targets.
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Antipsychotics are mainly used to treat the symptoms of schizophrenia and bipolar disorder, but can also be used to treat major depression, dementia, and some specific childhood disorders.
Conventional antipsychotics can cause movement disorders, known as extrapyramidal side effects. These include tardive dyskinesia: repetitive movements that patients are unable to control, such as grimacing. Newer "atypical" antipsychotics such as olanzapine and risperidone are less likely to cause extrapyramidal side effects.
| DOSING AND TITRATION OF COMMONLY USED ANTIPSYCHOTICS | ||||
|---|---|---|---|---|
| Brand (Generic & Formulation) | Indication(s) | Adult Initial Dose* | Adult Therapeutic Dose | Titration |
| FIRST-GENERATION ANTIPSYCHOTICS | ||||
| Fluphenazine HCl (tabs, elixir, oral conc) | Psychosis | 2.5–10mg daily in 3–4 divided doses | <20mg dose should be optimal; max 40mg/day | When symptoms are controlled, can reduce gradually to daily maintenance doses of 1mg or 5mg, often given as a single daily dose |
| Haldol (haloperidol lactate inj) | Schizophrenia | 2–5mg IM every 4–8 hrs or up to hourly if needed | — | Switch to oral form 12–24 hrs after last injection |
| Trifluoperazine HCl (tabs) | Psychosis | 2–5mg twice daily | 15–20mg/day | — |
| Thioridazine HCl (tabs) | Schizophrenia unresponsive to (preferably 2) other antipsychotics | 50–100mg three times daily | 200–800mg/day in 2–4 divided doses | May increase gradually to max 800mg/day |
| Chlorpromazine HCl (tabs) | Psychosis Mania | Less acutely disturbed: 25mg three times daily Outpatient: 10mg 3–4 times daily or 25mg 2–3 times daily Severe cases: 25mg three times daily | Inpatient: 500–1000mg/day Less acutely disturbed: 400mg/day Outpatient: 200–800mg/day | Increase dose gradually until symptoms are controlled. Continue optimum dosage for 2 weeks; then gradually reduce to lowest effective maintenance dose. See literature. |
| SECOND-GENERATION ANTIPSYCHOTICS | ||||
| Abilify (aripiprazole tabs, soln) Abilify Discmelt (aripiprazole ODT) | Schizophrenia | 10mg or 15mg once daily | 15mg/day; max 30mg/day | May increase at intervals of at least 2 weeks |
| Clozaril (clozapine tabs) | Refractory severe schizophrenia Reduce risk of recurrent suicidal behavior in schizoaffective disorders | Schizophrenia: 12.5mg 1–2 times daily Recurrent suicidal behavior: 300mg/day | Schizophrenia: 300–450mg/day in divided doses Recurrent suicidal behavior: 300mg/day (12.5–900mg daily; treat for at least 2 years) | May increase by increments of 25–50mg/day to 300–450mg/day in divided doses by the end of 2 weeks. Then may increase once or twice weekly in increments of up to 100mg; max 900mg/day. Reduce gradually over 1–2 weeks if discontinuing; may discontinue abruptly if necessary (eg, leukopenia, myocarditis; may cause relapse or cholinergic rebound). Retitrate if stopped for ≥2 days. |
| Fanapt (iloperidone tabs) | Acute treatment of schizophrenia | 1mg twice daily on day 1, 2mg twice daily on day 2, 4mg twice daily on day 3, 6mg twice daily on day 4, 8mg twice daily on day 5, 10mg twice daily on day 6, 12mg twice daily on day 7 | 6–12mg twice daily; max 24mg/day | Retitrate if stopped for >3 days |
| FazaClo (clozapine ODT) | Refractory severe schizophrenia Reduce risk of recurrent suicidal behavior in schizoaffective disorders | Schizophrenia: 12.5mg 1–2 times daily Recurrent suicidal behavior: 300mg/day | Schizophrenia: 300–450mg/day in divided doses Recurrent suicidal behavior: 300mg/day (12.5–900mg daily; treat for at least 2 years) | May increase by increments of 25–50mg/day to 300–450mg/day in divided doses by the end of 2 weeks. Then may increase once or twice weekly in increments of up to 100mg; max 900mg/day. Reduce gradually over 1–2 weeks if discontinuing; may discontinue abruptly if necessary (eg, leukopenia, myocarditis; may cause relapse or cholinergic rebound). Retitrate if stopped for ≥2 days. |
| Geodon (ziprasidone HCl caps) | Schizophrenia | 20mg twice daily, max 80mg twice daily | 20–80mg twice daily | May increase at intervals of at least 2 days |
| Geodon for Injection (ziprasidone mesylate for inj) | Rapid control of acute agitation | 10–20mg as needed | Max 40mg/day (10mg every 2 hrs; or 20mg every 4 hrs); treat for max 3 days | Switch to oral form as soon as possible |
| Invega (paliperidone ext-rel tabs) | Schizophrenia. Acute treatment of schizoaffective disorder | 6mg once daily in AM | 3–12mg once daily; max 12mg/day | May increase in increments of 3mg/day at intervals of >5 days (for schizophrenia) or >4 days (for schizoaffective disorder) |
| Invega Sustenna (paliperidone ext-rel inj) | Schizophrenia | 234mg on day 1, then 156mg one week later | 117mg (39–234mg) monthly | — |
| Latuda (lurasidone HCl tabs) | Schizophrenia | 40mg once daily | 40–80mg once daily; max 80mg/day | — |
| Risperdal (risperidone tabs, soln) Risperdal M-Tabs (risperidone ODT) | Schizophrenia | 2mg/day in 1–2 doses | 4–16mg/day; max 16mg/day | May increase by 1–2mg/day at intervals of at least 24 hrs to target dose 4–8mg/day |
| Risperdal Consta (risperidone long-acting inj) | Schizophrenia | Give with oral risperidone (or other antipsychotic) for 3 weeks, then stop oral form | 25mg IM every 2 weeks; max 50mg every 2 weeks | May adjust dose every 4 weeks |
| Saphris (asenapine SL tabs) | Schizophrenia | Acute: 5mg twice daily Maintenance: 5mg twice daily | Acute: 5mg twice daily; max 20mg/day Maintenance: 10mg twice daily; max 20mg/day | Maintenance: Increase to max 10mg twice daily after 1 week |
| Seroquel (quetiapine fumarate tabs) | Schizophrenia | 25mg twice daily on day 1; increase by 25–50mg 2–3 times daily on days 2 and 3; target 300–400mg/day in 2–3 divided doses by day 4 | 150–750mg/day; max 800mg/day, all in divided doses | May adjust at 2-day intervals by 25–50mg twice daily |
| Seroquel XR (quetiapine fumarate ext-rel tabs) | Schizophrenia | 300mg once daily in the PM | 400–800mg/day; max 800mg/day | May increase at 1-day intervals in increments of up to 300mg/day |
| Zyprexa (olanzapine tabs) Zyprexa Zydis (olanzapine ODT) | Schizophrenia | 5–10mg once daily, increase to 10mg once daily within several days | 10–20mg/day; max 20mg/day | May adjust by 5mg/day at intervals of 1 week |
| Zyprexa IntraMuscular (olanzapine inj) | Agitation due to schizophrenia | 2.5–10mg/dose IM; up to 3 doses | — | Switch to oral form when appropriate |
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