Chlorpromazine antipsychotic dose

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). 

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. 

Chlorpromazine equivalents Approximate dose equivalent of a first-generation antipsychotic to 100 mg of chlorpromazine (relative potency). 

These medications cannot be dosed solely based on their dopamine receptor blocking potency, because they also have effects on other receptors that must be factored into their dosing (see Table 4.6). For example, it is not unusual to begin treatment of a psychotic patient with a 5 mg dose of haloperidol. In terms of dopamine receptor blocking potency, 5 mg of haloperidol is more or less equivalent to 500 mg of chlorpromazine. If a patient were immediately treated with 500 mg of chlorpromazine, however, he/she would likely have side effect problems such as dizziness and excessive sedation. This is because the medications with the lowest dopamine receptor blocking potency are the most potent at other receptor systems responsible for these side effects. (See Table 4.7) The evolution of antipsychotics from low to medium to high potency has been driven not only by the desire to find... 

Several studies have evaluated the use of low doses of the typical antipsychotics. These include studies of high potency antipsychotics such as haloperidol, medium potency antipsychotics such as loxapine, and low potency antipsychotics such as chlorpromazine and thioridazine. In general, the studies have shown that antipsychotics reduce impulsivity and protect from psychotic decompensation. 

Tardive dyskinesia can occur in manic patients on neuroleptics alone, the frequency may be greater than in schizophrenics who are more likely to be on continuous medication. One possible explanation for this lies in the fact that neuroleptics are often administered to manic patients for short periods only, sufficient to abort the active episode, and then abruptly stopped. Thus high doses of neuroleptics are separated by drug-free periods, leading to a situation most likely to precipitate tardive dyskinesia. The recent increase in prescribing high potency neuroleptics such as haloperidol instead of low potency drugs such as chlorpromazine or thioridazine has undoubtedly increased the frequency of tardive dyskinesia. Clearly, use of the atypical antipsychotics with the very low frequency of EPS makes them the treatments of choice. 

Although normally administered in comparatively large doses the concentration of unaltered chlorpromazine in plasma is usually too low to be measured except by sensitive GLC methods (C6, C15). Using such a technique, Curry et al. (C18) have shown that the optimum antipsychotic effect appears to occur at plasma levels which are lower than those causing side effects in chronically treated patients but higher than those causing these effects in acutely treated patients. ... 

Two early publications (Delay et al., 1959 Di Mascio et al., 1963) deal with the subjective effects of the first antipsychotics in relatively high doses. Chlorpromazine at single doses of 100 200 mg gave rise to the following effects in healthy volunteers ... 

Antipsychotic drugs with strong sedative clinical effects (e.g. chlorpromazine. clozapine, olanzapine) produce subjective and objective sedation and impair most areas of performance in healthy volunteers, usually at doses far below those typically used in patients. Antipsychotic drugs with little sedative clinical action (e.g. pimozide, sulpiride, amisulpride) produce few subjective and objective effects in healthy... 

Treatment Implications. A review of response rates found that only 35% of patients with psychotic depression responded to treatment with a tricyclic antidepressant alone versus 67% of patients with nonpsychotic depression (Table 6-6) (13). Yet these patients have a better response to electroconvulsive therapy (ECT) (14). These patients have also been found to respond to combined treatment with an antidepresssant and an antipsychotic in comparison with either an antidepressant or antipsychotic alone (15). Despite these data, one study found that less than 50% of patients with psychotic depression referred to an ECT service had been treated with an antipsychotic and only 15% had received a daily dose equivalent to 200 mg or more or chlorpromazine ( 16). 

Three subfamilies of phenothiazines, based primarily on the side chain of the molecule, were once the most widely used of the antipsychotic agents. Aliphatic derivatives (eg, chlorpromazine ) and piperidine derivatives (eg, thioridazine ) are the least potent. These drugs produce more sedation and weight gain. Piperazine derivatives are more potent (effective in lower doses) but not necessarily more efficacious. Perphenazine, a piperazine derivative, was the typical antipsychotic drug used in the CATIE study described in the following text. The piperazine derivatives are also more selective in their pharmacologic effects (Table 29-1). 

Most antipsychotic drugs are readily but incompletely absorbed. Furthermore, many undergo significant first-pass metabolism. Thus, oral doses of chlorpromazine and thioridazine have systemic availability of 25-35%, whereas haloperidol, which has less first-pass metabolism, has an average systemic availability of about 65%. 

Deposits in the anterior portions of the eye (cornea and lens) are a common complication of chlorpromazine therapy. They may accentuate the normal processes of aging of the lens. Thioridazine is the only antipsychotic drug that causes retinal deposits, which in advanced cases may resemble retinitis pigmentosa. The deposits are usually associated with "browning" of vision. The maximum daily dose of thioridazine has been limited to 800 mg/d to reduce the possibility of this complication. 

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