Antipsychotics dosing

TABLE 34-6. First-Generation (Typical) Antipsychotic Dosing of Decanoate Preparations... 

The overall mean chlorpromazine-equivalents per day (CPZe) dose prescribed differed significantly, with lower dosing in Thailand compared with Malaysia and Australia (p < 0.001) (see Table 11.4). Pairwise comparisons revealed that the mean typical antipsychotic dose was significantly higher in Malaysia compared with Thailand (p < 0.001) and NWMH (p < 0.001). There were significant differences observed (p < 0.001) while comparisons of the mean atypical antipsychotic dose showed that Australia was significantly higher compared with Thailand (p < 0.001) and Malaysia (p < 0.001). 

In general, rapid titration of antipsychotic dose is not recommended. 

Treatment with AChs is disappointing, and reduction in antipsychotic dose may be the best intervention. Another alternative is to switch to an SGA, although akathisia occasionally occurs with the SGAs. Quetiapine and clozapine appear to have the lowest risk for causing akathisia. 

Initial dosage The initial dose should not exceed 100 mg regardless of previous antipsychotic dose requirements. If the conversion requires more than 100 mg of haloperidol decanoate as an initial dose, administer that dose in 2 injections (maximum of 100 mg initially followed by the balance in 3 to 7 days). 

In addition to the somatic side-effects of neuroleptics, there are a number of important psychiatric side-effects, such as demotivation or indifference (a direct effect of most drugs, actually part of the definition of the neuroleptic effect). This may mimic the negative features of the illness and may lead to prescriptions of an antidepressant when a reduction in dose or change of antipsychotic may be more appropriate. A second key problem is anxious activation or akathisia. This dose-dependent dysphoric state may lead to an apparent worsening in the clinical picture and accordingly an increase in antipsychotic dose rather than decrease and may be so intolerable as to lead on to suicide. 

TABLE 5-4. Summary of atypical antipsychotic dosing in acute mania... 

Dose required to control the patient s clinical state, with lower doses combined with a BZD preferable to more aggressive antipsychotic doses... 

Lorazepam. Lorazepam has been increasingly studied for control of psychotic aggressivity ( 157,158, 159,160, 161,162, 163,164, 165,166 and 167). One reason is that, of all the BZDs available in parenteral form, lorazepam has a pharmacokinetic profile (quick, reliable absorption) that makes it particularly suitable for this type of use. Open, retrospective, and controlled studies indicate that oral or parenteral lorazepam added to an antipsychotic controls disruptive behavior safely and effectively for most patients. The combination may also permit an overall reduction of the antipsychotic dose, although this assumption requires further study ( 162, 164, 166). 

As noted above, OC failure may lead to accidental pregnancy and exposure of the developing fetus to potentially teratogenic properties of CBZ ( 383). Therefore, OC levels should be closely monitored and patients should notify their physician of spotting, an indicator of OC failure. Prothrombin time and the International Normalized Ratio (INR) should be monitored when patients are on warfarin and CBZ concomitantly. Patients stabilized on an antipsychotic may decompensate when CBZ is added. This may necessitate an increase in the antipsychotic dose and is one indication for TDM of antipsychotic drug levels ( 384). Conversely, when CBZ is discontinued, the dose of these other agents may need to be lowered to avoid toxicity. In summary ... 

On the other hand, when an inducer of 1A2 is given concomitantly with either of the two antipsychotic substrates of 1A2, the level of the antipsychotic may fall. This happens when a patient begins to smoke, because smoking induces 1A2, and this would cause levels of olanzapine and clozapine to fall (Fig. 11—45). Theoretically this might cause patients stabilized on an antipsychotic dose to relapse if the levels fell too low. Also, cigarette smokers may require higher doses of these atypical antipsychotics than nonsmokers. 

On the other hand, if carbamazepine is stopped in a patient receiving one of these four atypical antipsychotics, the antipsychotic dose may need to be reduced, because the autoinduction of 3A4 by carbamazepine will reverse over time (Fig. 11—51). 

Correct choice = D. Tardive dyskinesia appears to be produced to the same degree and frequency by all the neuroleptic drugs when used in equieffective antipsychotic doses. 

Woerner et al. (1998) studied a group of neuroleptic-naive patients aged 55 and above, evaluated them at baseline before the start of neuroleptics, and followed up at 3-month intervals. Relatively low doses of conventional neuroleptics were used The rates of TD were 25%, 34%, and 53% after 1, 2, and 3 years of cumulative antipsychotic treatment. Once again, the rates were astronomically high A greater risk of TD was associated with history of [electroconvulsive therapy] treatment, higher mean daily and cumulative antipsychotic doses, and presence of extrapyramidal signs early in treatment. ... 

Decanoate injection initial dose 10-15 times the previous oral dose for patients maintained on low antipsychotic doses (e.g., up to equivalent of 10 mg/day oral haloperidol) initial dose may be as high as 20 times the previous oral dose for patients maintained on higher antipsychotic doses maximum dose 100 mg, if higher than 100 mg dose is required the remainder can be administered 3-7 days later administer total dose every 4 weeks... 

Many patients experience and/or can be significant in amount at effective antipsychotic doses... 

Since the potency (therapeutic efficacy in relation to weight) of antipsychotic agents varies markedly between compounds, it is useful to think of the effective antipsychotic dose of classical agents in terms of chlorpromazine equivalents (see Table 19.5). For example, haloperidol has a relatively high anh-psychotic potency, such that 2-3 mg is equivalent to chlorpromazine 100 mg, whereas sulpiride 200 mg (low potency) is required for the same antipsychotic effect. 

For each antipsychotic agent there is a licensed maximum dose for example up to 1000 mg of chlorpromazine/day may be given under the United Kingdom licence. Prescribing beyond the licensed maximum dose requires specialist consent. When two antipsychotics are co-prescribed, the maximum antipsychotic dose should not exceed 1000 mg of chlorpromazine equivalents/day except under specialist supervision. For some antipsychotics the licenced maximum dose is considerably less than 1000 mg of chlorpromazine equivalents/day. For instance, the licenced maximum dose of thioridazine was reduced to 600 mg/day following concerns about its cardiovascular toxicity. Note... 

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. 

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