First-generation antipsychotic medications for maintenance treatment of schizophrenia in adult patients: Oral dosing, pharmacokinetics, and selected characteristics

Agent	Initial dose (mg/day)	Usual dose range (mg/day)	Maximum dose (mg/day)	Half-life (hours)	Metabolism and clearance	Selected characteristics
Chlorpromazine^*	25 to 100	200 to 800	800	Approximately 30	CYP2D6, other CYPs, and glucuronidation to active and inactive metabolites	Doses greater than 800 mg/day approved by some regulatory authorities are not recommended QTc prolongation risk; assess baseline and on-treatment ECG Routinely given in 2 to 4 divided doses May adjust daily dose by 20 to 50 mg increments every ≥3 days Avoid use in older adults Other formulation: Short-acting IM
Fluphenazine	2.5 to 10	5 to 20	40	14 to 16	CYP2D6	Routinely given in 1 to 2 divided doses May adjust daily dose by 5 mg increments at weekly intervals Oral absorption is highly variable; dose must be individualized Dose adjustment may be needed with CYP2D6 inhibitor drugs^¶ Avoid use in hepatic impairment (per manufacturer) Other formulations: Oral solution, short-acting IM, LAI
Haloperidol	1 to 10	2 to 20	100 Most patients are treated with doses of ≤30 mg/day	14 to 37	CYP2D6, 3A4, and glucuronidation; some metabolites active and potentially neurotoxic	Daily dose administered in 1 to 3 divided doses May adjust daily dose by 1 to 10 mg increments every 3 to 7 days Oral bioavailability approximately 60%; adjust accordingly when switching between oral and short-acting parenteral formulations Variable dose requirements due to CYP2D6 metabolizer phenotype QTc prolongation risk increased with IV doses greater than 2 mg (off-label route); for IV use assess baseline and on-treatment ECG Other formulations: Oral solution, short-acting IM/IV, LAI
Loxapine	20	20 to 100	250 mg	6 to 8 (parent) 12 (active metabolites)	CYP1A2, 2D6, 3A4 and glucuronidation to active and inactive metabolites	Routinely given in 1 to 2 divided doses May adjust daily dose by 10 mg increments every 3 to 5 days Other formulations: Inhalation for acute treatment in health care setting; oral solution and short-acting IM available in some areas (not United States)
Molindone	50 to 75	15 to 100	225	1.5	CYP2D6
Perphenazine	8 to 16	8 to 32	64	9 to 12 (parent) 10 to 19 (active metabolites)	CYP2D6, 3A4, and other CYPs to active and inactive metabolites	Routinely given in 2 to 3 divided doses daily May adjust daily dose by 8 mg increments every 4 to 7 days Variable dose requirements due to CYP2D6 metabolizer phenotype Avoid use in hepatic impairment (per manufacturer)
Pimozide	1 to 2	2 to 4	10	55 150 (CYP2D6 poor metabolizers)	CYP1A2, 2D6, 3A4 and others	QTc prolongation risk; assess baseline and on-treatment ECG Oral bioavailability is variable due to extensive hepatic first-pass metabolism Maximum dose 4 mg/day in CYP2D6 poor metabolizers Avoid use with CYP2D6 inhibitors^¶
Thioridazine^*	150 to 300	200 to 600	800	4 to 10 (parent) 21 to 25 (active metabolites)	CYP2D6 and other CYPs to active (mesoridazine) and inactive metabolites	Given in 1 to 3 divided doses May adjust daily dose by 100 to 150 mg increments every 3 to 4 days QTc prolongation risk; assess baseline and on-treatment ECG Due to an increased risk of ocular toxicity, UpToDate contributors avoid doses >600 mg/day unless required for a robust response Avoid use with CYP2D6 inhibitors^¶
Thiothixene	6 to 10	15 to 30	60	34	CYP1A2 and others	Given in 1 to 3 divided doses May adjust daily dose by 5 to 10 mg increments every 3 to 5 days Oral bioavailability is variable; dose must be individualized based on patient response Tobacco smoking may decrease levels
Trifluoperazine	4 to 10	15 to 20	40	3 to 12 (parent drug) 22 (active metabolites)	CYP1A2 and other CYPs to active and inactive metabolites	Given in 1 to 2 divided doses May adjust daily dose by 5 to 10 mg increments every 3 to 5 days Oral bioavailability is variable; dose must be individualized based on patient response Tobacco smoking may decrease levels

This table is intended for use in conjunction with UpToDate content on treatment of schizophrenia. Doses shown are total daily dose, oral administration, for maintenance treatment of schizophrenia in adult patients with normal kidney and liver function. Refer to UpToDate drug monographs for dose adjustments.
Antipsychotic medications are to be used with caution and at significantly reduced doses (eg, reduced by 50% or more) in older adults, those who are medically ill or with a first episode of psychosis.
The dosing and other information provided in this table differs from dosing used in management of behavioral symptoms of dementia in older adults; in general, these medications are not recommended for that use. For additional information, refer to the relevant UpToDate clinical topics.
Although several first-generation antipsychotic medications are subject to drug interactions via CYP metabolism as listed above, they are not themselves important inhibitors or inducers of metabolism of other drugs (exception: thioridazine moderately inhibits CYP2D6).

CYP: cytochrome P450; ECG: electrocardiogram; IM: intramuscular (short-acting); IV: intravenous; LAI: long-acting injectable (eg, depot).

* More prominent adverse effects relative to other antipsychotics including orthostatic hypotension, sedation, QTc prolongation, anticholinergic effects, and pigmentary retinopathy (thioridazine). Refer to UpToDate topic on pharmacology of first-generation antipsychotic medications.

¶ Dose adjustment may be necessary if coadministered with medication(s) that alter drug metabolism (eg, CYP2D6 or 3A4). Lists of CYP2D6 and 3A4 inhibitors and inducers are available as separate tables in UpToDate; refer to the drug interactions program for specific interactions.

Data from:

American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia, 3rd ed, American Psychiatric Association 2021.
UpToDate Lexidrug. More information available at https://online.lexi.com/.

Graphic 144806 Version 5.0

خرید پکیج

First-generation antipsychotic medications for maintenance treatment of schizophrenia in adult patients: Oral dosing, pharmacokinetics, and selected characteristics