Antipsychotics dosing ranges

Key CPZ equiv dose = Chlorpromazine equivalent dose.This concept is of value in comparing the potency of classical antipsychotics. Dose ranges are not specified as they are extremely wide and drugs are normally titrated up from low starting doses (e.g. chlorpromazine 25 mg or equivalent) until an adequate antipsychotic effect is achieved or the maximum dose reached.The chlorpromazine equivalent dose concept is of less value for atypical antipsychotics since minimum effective doses (Min. eff. dose) and narrower therapeutic ranges have been defined. Maximum dose (Max. dose) can be exceeded only under specialist supervision. 

Compared to antipsychotics, there are even fewer studies on the prescribing patterns of antidepressants done in Asian countries. Pi etal. (1985) conducted a survey of psychotropic prescribing practices reported by psychiatrists in 29 medical schools in 9 Asian countries. Daily dose range of tricyclic antidepressants (TCAs) such as amitriptyline, imipramine, and nortriptyline in Asian countries was comparable to the practice in USA. This is despite differences found between Asian and non-Asian populations in the pharmacokinetics of TCAs (Pi et al, 1993). A questionnaire on the practical prescribing approaches in mood disorders administered to 298 Japanese psychiatrists was reported by Oshima et al. (1999). As first-line treatment, the majority of respondents chose newer TCAs or non-TCAs for moderate depression and older TCAs for severe depression. Combination of antidepressants and anxiolytics was preferred in moderate depression, while an antidepressant and antipsychotic combination was common in severe psychotic depression. Surprisingly, sulpiride was the most favored drug for dysthymia. In a naturalistic, prospective follow-up of 95 patients with major depression in Japan, the proportion of patients receiving 125 mg/day or less of imipramine was 69% at one month and 67% at six months (Furukawa et al., 2000). 

In partial responders who are tolerating the antipsychotic well, it may be reasonable to titrate above the usual dose range. 

TABLE 4.5. Typical Antipsychotics and Their Dosing Ranges... 

Quetiapine (Seroquel). Quetiapine is the fourth of the atypical antipsychotics introduced in the United States. It is effective in both positive and negative symptoms of schizophrenia within a dose range of 150 to 750mg/day in two divided... 

Antipsychotic agent Approx. equiv. dose (mg) Usual oral adult daily dose range (mg) Sedation EPS Anticholinergic effects ... 

Tiapride and sulpiride are neuroleptics of the substituted benzamide class. These selective Dj blockers have weak antipsychotic properties and are not available in the United States, although they are commonly used in Europe for the treatment of tics. In a pair of 6-week controlled trials involving 27 children with TS, at doses ranging from 4 to 6 mg/kg/day, tiapride was superior to placebo and produced a 30%-44% decrease in videotaped tic counts (Eggers et ah, 1988). 

In general, the untoward effects of antipsychotics in children are similar to those seen in adults. However, within the therapeutic dose range, parkinsonism is rare in preschool-age children (Campbell et al., 1999). No... 

Preclinical and clinical data indicate that olanzapine may have antipsychotic effects at doses below its EPS threshold. Although early clinical results substantiated a lesser propensity to cause EPS at the low end of the dose-response curve, with dose escalation there was a concomitant increase in the use of antiparkinsonian medication (473). In this context, it should be noted that studies that used higher olanzapine doses found them to be more effective than low to intermediate doses (117). Thus, olanzapine may be similar to risperidone in that both drugs have a therapeutic dose range in which the antipsychotic effect can be achieved without inducing significant EPS. 

Clozapine. Clozapine produces seizures at a greater rate than other antipsychotics, especially in the dose range of 600 to 900 mg/day. Fortunately, these levels are substantially above the usual therapeutic range of 300 to 400 mg/day, but seizures can occur on lower doses, as well. A more rapid escalation of the clozapine dose may also predispose to the development of seizures. According to the drug s manufacturer, the reported incidence of seizures, based on daily dosage, is as follows ... 

Puech A, Fleurot O, Rein W. Amisulpride, and atypical antipsychotic, in the treatment of acute episodes of schizophrenia a dose-ranging study vs. haloperidol. The Amisulpride Study Group. Acta Psychiatr Scand 1998 98(l) 65-72. 

A moderately priced atypical antipsychotic within the therapeutic dosing range... 

How are neuroleptics and atypical antipsychotics classified and how do they differ in potency, dosing range, and adverse effects ... 

Olanzapine has a very low incidence of EPS when used within the approved dose range of 10 to 20 mg daily. However, many patients are being treated at doses above the currently recommended limit in the approved product labeling of 20 mg/day. Quetiapine is an efficacious antipsychotic with an excellent EPS profile. Although contrary to efficacy studies, doses above 500 mg are often used to achieve optimal effects, with dose titration to 800 mg/day being a... 

Minimal research evidence supports the use of antipsychotic doses beyond the dose range in the Food and Drug Administration (FDA) approved product labeling. Clinicians frequently titrate doses above the approved range, and often attest to symptom improvement when this is done. 

Adult Antipsychotic Oral Dose Range (Daily) Single IM Dose ... 

Dosages in older adults are usually in the lower range. Because older adults are more susceptible to cardiovascular and neuromuscular reactions to the antipsychotic drugs the nurse must dosely monitor them. It is important to increase the dosages gradually. 

FIGURE 58-7 The IC50 values (ordinate) are the concentrations of the antipsychotic drugs that reduce the stereospecific component of 3H-haloperidol binding by 50%. The abscissa indicates the average values (and ranges) of doses used for schizophrenia. (From Seeman, P. et al. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 261 717-719,1976)... 

Most antipsychotics have half-fives of elimination in the range of 20 to 40 hours. After dosage stabilization, most antipsychotics (except quetiapine and ziprasidone) can be dosed once daily. It may be possible to dose SGAs less often than their plasma kinetics would suggest. 

In addition to parkinsonism, another extrapyramidal side effect is the so-called acute dystonic reaction in which muscles (usually of the face or neck) go into an acute spasm. A dystonic reaction is painful and unpleasant, usually occurs early in treatment, and sometimes occurs after the very first dose of an antipsychotic. Another extrapyramidal symptom is akathisia, a restless inability to relax and sit still. Akathisia can range from a mild restlessness to extreme agitation. Rarely, patients have been known to attempt suicide during severe episodes of akathisia. It is easy to overlook akathisia, because it can easily be mistaken for a worsening of psychosis or anxiety. 

There have been numerous trials of use of the atypical antipsychotics in patients with developmental disabilities, but most of these trials were uncontrolled open-labeled studies or case reports (Aman and Madrid, 1999). Findings were reported for 86 adults and 1 child with prominent self-injury. The reports of adults assessed clozapine (1 report) and risperidone (4 reports). Improvement was observed for a majority of participants in all of these trials. The patients presented with a multitude of conditions, ranging from nonspecific MR and associated behavior problems, to pervasive developmental disorders (including autism), to various psychiatric disorders, including schizophrenia and manic disorder. Self-injury appeared to respond to treatment regardless of concomitant condition. In the only clozapine report with a child (who had autistic disorder), a mean dose of 283 mg/day caused a transient reduction in self-injury. 

Customary oral daily doses (third column) the smallest and largest recommended daily doses of the same medication may differ by a factor of 3 20. These wide dosage ranges are due to the fact that antipsychotics are used for various indications and that their efficacy and tolerability vary... 

---