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INFLUENTIAL PUBLICATIONS   |    
International Consensus Study of Antipsychotic Dosing
David M. Gardner, Pharm.D., M.Sc.; Andrea L. Murphy, Pharm.D.; Heather O’Donnell, B.Sc. Pharm.; Franca Centorrino, M.D.; Ross J. Baldessarini, M.D.
FOCUS 2014;12:235-243. doi:10.1176/appi.focus.12.2.235
Abstract

Objective  Potency equivalents for antipsychotic drugs are required to guide clinical dosing and for designing and interpreting research studies. Available dosing guidelines are limited by the methods and data from which they were generated.

Method  With a two-step Delphi method, the authors surveyed a diverse group of international clinical and research experts, seeking consensus regarding antipsychotic dosing. The authors determined median clinical dosing equivalents and recommended starting, target range, and maximum doses for 61 drugs, adjusted for selected clinical circumstances.

Results  Participants (N=43) from 18 countries provided dosing recommendations regarding treatment of psychotic disorders for 37 oral agents and 14 short-acting and 10 long-acting parenteral agents. With olanzapine 20 mg/day as reference, estimated clinical equivalency ratios of oral agents ranged from 0.025 for sulpiride to 10.0 for trifluperidol. Seventeen patient and treatment characteristics, including age, hepatic and renal function, illness stage and severity, sex, and diagnosis, were associated with dosing modifications.

Conclusion  In the absence of adequate prospective, randomized drug-drug comparisons, the present findings provide broad, international, expert consensus-based recommendations for most clinically employed antipsychotic drugs. They can support clinical practice, trial design, and interpretation of comparative antipsychotic trials.
(Reprinted with permission from the American Journal of Psychiatry 2010; 167(6): 686–693) 

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Table 1.Clinical Dosing Equivalencies and Dosing Recommendations of Oral Antipsychotics
Table Footer Note

a Respondents were asked what dose they consider to be clinically equivalent to 20 mg/day of olanzapine in treatment of the reference case, a moderately symptomatic adult man with DSM-IV schizophrenia with ≥2 years of antipsychotic treatment and not considered treatment refractory. Median confidence levels for the clinically equivalent doses are reported as low (L), moderate (M), or high (H).

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b Respondents were asked to indicate their usual starting dose, target dosing range, and maximum daily dose for the reference case after being untreated for over 1 month. The target dose range reflects the median lower and upper doses of ranges recommended.

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Table 2.Clinical Dosing Equivalencies and Dosing Recommendations for Short-Acting Injectable Antipsychotics
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a Respondents were asked what dose they consider to be clinically equivalent to a single, 5-mg intramuscular dose of haloperidol in treatment of the reference case, an adult man with DSM-IV schizophrenia not treated for 2 weeks, presenting with delusions, auditory hallucinations, agitation, poor cooperation, threatening behavior, and who is refusing oral medications. Median confidence regarding clinically equivalent dosing was reported as moderate for all agents except mesoridazine, prochlorperazine, and trifiuopromazine, for which confidence was rated low.

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b Respondents were asked to indicate their usual initial intramuscular dose, the dose range per injection, and the maximum intramuscular dose per 24 hours for the reference case. Range of doses/injection reflects the median lower and upper doses of ranges recommended.

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Table 3.Clinical Dosing Equivalencies and Dosing Recommendations for Long-Acting Injectable Antipsychotics
Table Footer Note

a Respondents were asked what dose and interval they considered clinically equivalent to oral olanzapine, 20 mg/day, in the treatment of the reference case, a moderately symptomatic adult man with DSM-IV schizophrenia, not considered treatment-refractory with ≥2 years of antipsychotic treatment. The reported clinically equivalent doses are adjusted to correspond to the median dosing interval. Confidence in the clinically equivalent dose was moderate for all agents.

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b Respondents were asked to indicate their usual dosing interval, initial dose, target dose range, and maximum dose for the reference case, who differed from the above description in that recent use of an oral antipsychotic had been intermittent due to poor treatment adherence. The oral antipsychotic and dose were not specified. Initial and maximum doses are adjusted to match the median dosing intervals. Target dose range reflects the median lower and upper doses of the ranges recommended.

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Table 4.Factors for Which Antipsychotic Dosing Changes Are Recommendeda
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a Reported are numbers of responses and percentage of respondents recommending dosing changes, ranked by median magnitude and direction (decrease or increase) of recommended daily oral dose adjustments, for factors deviating from the reference case, a moderately symptomatic adult Caucasian man of normal weight with DSM-IV schizophrenia, not considered refractory, with >2 years of antipsychotic treatment but untreated for>1 month. Other patient characteristics not considered to require dosing adjustment included being overweight (BMI 25–30 kg/m2) or obese (BMI >30.0); being black or Hispanic; ≥15 years of illness and antipsychotic drug use; being hospitalized versus ambulatory; disorders other than schizophrenia (schizoaffective, delusional, manic or mixed states of bipolar disorder, or unspecified psychosis); comorbid substance use or anxiety disorders; average clinical quality of prior antipsychotic treatment responses; rapid-dissolving tablet or oral liquid formulations.

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